Event ID: 1167873
Event Started: 12/1/2008 7:46:05 AM ET
Please stand by for real-time relay captioning.
We have an interesting agenda -- later today we will -- some of the issues discussed in oversight report, we will look at federal initiatives -- through standards development. And tomorrow we will continue to discuss, refine, future study priorities and plans. Finally we will discuss the draft progress report for the new administration.
At our last meeting, which was in July, in addition to preparing a progress report for the incoming Secretary we decided to write a letter to secretary Leavitt. We discussed the main points and finalized via e-mail after the meeting. In addition to thanking the Secretary for the high priority to private sector solutions and resources to address the policy challenges associated with the development of genetic technologies, we took the opportunity to highlight several issues we thought were in need of critical attention over the remay understander of htion entour.
We urged -- recommendations, beginning to address the practical -- surrounding establishment of laboratory tests and taking steps to create inceptives for laboratories to make test menus analytical and clinical validity available through gene tests or post on their own website.
In the area of pharmacogenomics onlyics, the FDA issues draft -- pharmacogenomics drugs, changes in medical coverage, billing policys to facilitate the integration of genetic technology based on history of family disease and access to genetic counseling services. A copy of the letter is in tab seven of the briefing books, and through our website.
With regard to the FDA codevelopment guide guidance for pharmacogenomics -- series of meetings over the fall on the guidance and work continues on that. With regard to the other issues raised regarding coverage, I am told to expect to receive a letter from the secretary addressing some of those issues as well.
I also want to take note of the report, which you see here on the screen, that secretary Leavitt released about two weeks ago to provide an update on personalized healthcare. The report discusses many of the issues we have been addressing as a committee. It outlined some of the important steps taken to advance personalized medicine and offers a frank account of how much more will need to be done before personalized healthcare is a fully developed and applied system. The report contains case studies, commission papers that are very relevant to a number of issues we are likely to take up in the years ahead. It's available to the website at the URL you see on the screen. Those of you on the committee should have receive said copies of that as well.
We have seen significant progress on the family history front, a demonstration of the secretary-general's family history tool, demo of the secretary-general's family history tool was shown on March 25, and we will have stories of that, to be ri leased in late December. Several -- CDC and -- supporting research through development, contracts to enhance the utility of family history in electronic health information to support risk assessment and prevention. Focus on implementing development, HH is S, Department of Labor, treasury, EEOC. We understand proposed rule will be issued coven by the EEOC on the employment provisions of the law, multiple teams working across the agencies on the health insurance provisions. Those take effect May of 2009 and employee in November of 29
I would like to note since the last meting the work meeting the leadership of Dr. McGrath -- the task force formed three groups to -- public healthcare providers, patients and consume everies. They are currently in a data collecting phase and hope to begin the draft report in February. I would like to thank the ex officio members they will receive a survey next month from the task force, education activities within your agencies. We hope you will take the time to complete the survey which should be returned by the end of January. During the course of information gathering, the counsel on linkages between academia and public health practice was revising it's core competencies between -- and since competency and genetics is not currently addressed the forum would like SACGHS to -- and genomics as they relate broadly to public health. The first under tab 7, accepting comments until -- review over the next two days and let Cathy -- know if you have suggested edits.
In particular I want to thank sill Sylvia and Joseph for making sure this gets in there. Tomorrow we will be delving into the discussion of future study priorities. You recall in July we came to preliminary conclusions about the issues, areas we thought needed to be pursued. Our goal at this meeting will be to come to final consensus on issues, agree on a workplan for addressing them. We will be mindful of the priorities of the new administration into our ultimate workplan.
This end we will discuss a new draft report to the administration. Should take the form of concise summary, discuss the growing importance of personalized msdz and the complex issues it raises. Should sum up our work and key recommendations over the past six years and focus going forward, how to be most helpful to the new secretary and make it clear we are ready to adjust priorities as needed.
We are in a time of transition in more ways than one. This will be the last SACGHS meeting for several members, Scott McLean, Matt Guy glt nard and Steve Gutman, retiring at end of the year. Let me say we deep appreciate your services and many contributions to our work. We admire your commitment to public and military work, fulfilling your agency's important missions. Steve, I thought I saw you, there, sitting where I can't see him. I know you were involved in the secretary's advisory committee on genetic testing, the predecessor, and probably are among the longest-serving ex officios, you deserve extra exin addition and measure of appreciation. We wish you all the best in all your endeavors. [Applause]
We know FDA and Department of Defense will appoint new ex officio members, we look forward to working with them. Matt's rement at FTC will be Sarah -- attorney in division of advertising practices, should be here tomorrow. We will meet her then.
I also wanted to take the opportunity to thank Joe Boone, I don't think is here, the associate director for science in the laboratory systems at CDC, for his contributions to SACGHS, and -- retiring at the end of the year. I have known Joe since my CDC days, 30 years. Been a transition at the EEOC. Peter gray, served as commissioner -- number of years, moved to the civil rights division of the Department of Justice. We appreciated Peter's dedication very much and before he left EEOC was working on development of regs implementing employment provisions of -- now represented the a the staff level by Kerry liebig, senior attorney adviser in the office of counsel. Joining us tomorrow as well, and we welcome her to SACGHS, thanks to all of you for your service and advice.
Dr. is serving as alternative ex officio today, Dr. Fox will be tomorrow. We have a new -- to welcome, where's darren, there, joined the team in August, put to immediate work. Has undergraduate work in biology and a law degree, worked z a dewriter and journalist.
I have a personal transition, my first day of retirement from work, leaving the private sector, will be rejoining the public health community as chief science officer at the LA County health department, be here in a different capacity.
I would like to call your attention to, like all federal advisory committee, SACGHS has a two-year charter and it was extended for another two years. Good news. We have a new web address, new site, as you will see on the screen, the new URL is shown here. There's a handout at the registration desk. Hopefully we will find people, materials, even more successful than up until now. So Sarah, this is the time that we all know and love, when we get to hear the important reminder about the ethics rules, cleernl important.
Very important. As you know, you have been appointed to this committee as a special government employee, and although you are in this special categories, you are nonetheless subject to the rules of conduct. I will highlight two of those, that about conflict of interest and the rule about lobbying. First, conflict of interest, before every meeting you provide us with information about your personal, professional and financial interests, information we use to determine whether you have any real, potential or A conflicts of interests that could compromise your ability to be neutral -- we believe your ability to be objective will not be -- we rely on you to be attentive to the possibility that an issue will arise that could effect or appear to effect your interest in a specific way. Provided each of you with a list of your financial relationships that could an a conflict. If this happens we ask you to recuse yourself from the discussion ask leave the room. Prohibited from lobbies, may not lobby as professional or individual, if you lobby as private individual it's important you keep it separate from activity on this committee. Secretary's Advisory Committee on Genetics, Health, and Society is a advisory commit eye to the secretary of health and human services, does not advise the Congress. I thank you for being attentive to these rules and appreciate how conscience eous you all are.
Since we serve in multiple capacities, things where your name appear, involving SACGHS should be reviewed by the committee. With that, important reminder, thank you, Sarah, we are ready too get started on the first agenda item. As you are more than a little aware the task force for gene patent and licenses has been working more than two years to carry out a study on whether gene patenting licensing -- leadership of deb Warner, started out, somewhere, there, good morning, Deb. Continued to serve as ad hoc member, joined today in that capacity. Thanks for your continuing service and welcome back. As always.
Into the breach stepped one Jim Evans. Has been ably guiding the task force's work ever since, reached an important milestone and goal today is to decide whether the draft report the task force has developed is ready to be released for public comment.
Tab 3, of the briefing book, preliminary findings conclusions, developed a range of potential policy options for the public consideration. Jim will review the key elements and facilitate a discussion of the draft report and policy options. The task force devoted countless hours, and I thank the task force, especially to Jim for his leadership, commitment, thank you very much, and take it away.
Jim Evans: It has been quite a while since the full committee has heard of our progress on the patents and licensing issues. I do want to start off by thanking everyone who has been involved in this. This has turned out to be a gargantuan task, true for a couple of reasons. It's simply a very broad and deep field. There's a huge history of patent law, licensing issues, patents obviously go way back to the U.S. Constitution. It's technically a demanding subject and we are very fortunate to have a broad range of expertise on the task force.
I think the other thing that make its difficult is that there are many stakeholders, and the stakeholders, when it comes to patents and licensing are not always in synch with their own interests, right. They are sometimes mutually exclusive interests. This becomes a complex issues, as well as one that can become contentious as well. Again, I want to thank the task force for the many, many hours, conference calls, some two-hour conference call that's went into three hours; I am apologizing for that. I want to thank Steve for had his guidance in this, he's been there at critical junctures as we have come across are certain issues that needed to be hammered out. I want to especially, a huge public thank you to Yvette -- and -- none of this would have happened without them, they are fantastic. You see the roster of people involved in this. Today I want to march through these, apologies, 130 slides.
We have several hours to do this, we can -- as we do it, I have humor slides to show before breaks to wake you up. I do think it behooves us to review what we have done, where we started with this as we go forward. The last couple of hours, what I want to do is, go over this range of policy options. This is a little bit unusual, the way we approached this, because it's so complex and potentially -- issue, the way we tailored this will serve will the public's interest in having some framework from which to comment.
Then at our next meeting we will, after that public comment period try to finalize our recommendations. So, just the history of this in March of ' 04, gene patents were identif as a priority. We deferred further effort at that point, and our C-report, at that point in progress had not come out yet. It subsequently came out in the fall of 2005, a small group formed to review the report and determine whether they had done our work for us and we didn't need to go on or whether there were things for the SACGHS to take up.
So in march of 2006, the NRC's general thrust was endorsed by this committee, but there were important limitations in our minds, and that had to do with clinical patient access. The NRC report was focused primarily on research. We felt at that time we needed to investigate the issue of how gene patents and licensing play out in the realm of patient care, something that was not really a focus of NRC, not a deficiency, just wasn't their primary focus.
In June of 2006 we had informational session, decided at that point to move forward with an in-depth study to focus on gene patent and licensing as they relate to patient access to genetic tests. We discussed the study's scope, workplan at that point, and established task force on gene patents and licensing practices. In October 2006, two years ago, we had the first task force meeting where we refined the proposed scope of the study, outlined potential approaches for the study and shortly after that, in November, at the full meeting of SACGHS we presented the study, scope and workplan, which were approved by the full committee.
Then, in February 2007 there was a task force meeting to discuss the study, scope and workplan. At that time we met with somebody else I want to give thanks to, right here, Bob [indiscernible], as well as the rest of the members of his team at Duke's center for law, ethics and policy. Bob is a well-respected leader in this field and his group agreed to develop literature and relevant case studies to help us make sense of, learn what we could in a systemic organized way, in this broad field and try to ultimately come to some conclusions that could lead to recommendations in necessary.
In March of '07 we had a meeting, discussed next steps, on the very next day we, at the SACGHS meeting, had a primmer session on gene patents and licensing practices, which I think many of us who only glancingly had dealt with in the past, through clinical activities, really benefited from, because it's laid out a lot of the fundamentals, nut and bolts on patenting, which can get quite ar cane and complex.
We received an update from dike on Duke on the status of -- in July of '07 at the success SACGHS meeting we received a briefing. At that time we had an international round table on, this is not an issue that is by any means unique to the U.S., this is, the issue of gene patent losing, very much front and center for many countries and felt it would be foolish to ignore the experience of other countries. We therefore received an overview of the international gene patent and licensing landscape, reviewed the status of the test nothing Canada, U .K., since their -- cab such a visible in the gene licensing landscape. We learned about comparisons of the patent system, U.S. and several other countries and reviewed international reports and recommendations regarding these subjects.
So the purpose of the today's session is really three-fold. One is, we want to review and discuss the public consultation draft report on gene patent and licensing practices, and their impact on patient access to genetic tests. In tab 3. We also want to review, discuss the range of how -- a range of how policy options for public consideration. Because this is so complex, we did not feel that it would be fair to the full committee, to ourselves, or most importantly, to the public, to settle on conrecommendations to be transmitted to the secretary. Rather, we created a range of possible recommendations, and those are up for discussion today, will be then transmitted when finalized to the public, the public can use those as a framework from which to comment and make observations. We can then come back, armed with those comments and settle on final recommendations. It would have been presumptioneous of the task force to come to concrete recommendations at this point.
We also then want to seek the committee's approval of the draft report and decide on a range of options for public consideration. A standard 60-day public comment period in early 2009. Now, since it has been so long since we talked about gene patents and licensing and because this is our field with some technical issues that need to be understood as we go forward, we felt it would be useful to spend a few minutes reviewing the back ground of all patents to some extent in general, obviously specifically how they relate to gene licensing and -- so some have been taken from the earlier session in which we are received a primmer, I went back and reviewed the slides of Jorges Goldstein, back to the Constitution, it's really to promote progress in the science and arts. We want to promote the geepment development of ideas. Intellectual property should be seen as something whose end is to promote the creation of additional property, to promote its use, promote the investment in ideas and allow and encourage openness and discourage secretness to further development. As a clinician, those of you who are clinicians will understand something I have not understood prior to this. In clinical medicine we frequent Lee talk about an artery being open, blood can flow-through. I never understood why patent was spelled the same way as patent. The whole role is to keep the field open. That crystallized for me, the purpose of patents, to keep the field open. There's also a philosophical intent, behind intellectual property, to reward innovation, the idea of natural right. If somebody comes up with something they deserve a degree of rewards for that. Recognizing a number of distinct types, one is a trademark, something like the MacDonald's arches, the way -- is written in script, to communicate to the public what that product is, and foster the advance of that company's idea. Copyright is protection of idea, song, can be under copyright.
One thing patents are specifically designed to circum ven the is a 30 way, the trade secret. Trade secrets are a viable way of protecting one's intellectual property. In fact, the recipe for Coca-Cola is probably the most famous example of that. They would have been advised early on by most people, including most patent attorneys, to patent the recipe for Coca-Cola, would have given them a limited time on that. They chose to make it a secret. They said you won't be able, bad move, hard to keep upon a secret. They have been successful, many people aren't. Patents are designed to disinupon centivize the idea of trade secrets. Back to the the Constitution, it's important to look at what the Constitution has to say about why we want peacht patents, to secure for limited times the exclusive right to writings and discoveries. It's the granting of a limited time monopoly. I point out the purpose of this, expressed in the Constitution, to promote the progress of science and useful arts.
So, patents are a trade-off. The government grants a right of limited duration. In this country it's 20 years from filing, to prevent others from makes, using, selling, importing, the claimed entity. In return, the patentee discloses to the public and this presumably fosters further research and development. To be granted a patent, one has to fulfill certain requirements. That invention has to be useful. There has to be some defined use for it. It also has to be novel, and non-obvious, has to be new, non-obvious to somebody who is practiced in the art.
If we now zero in on the issue of patenting in biology, specifically patenting, say, human material, there's a long activity of that, back almost a century. Adrenalin was patented, and the courts ruled this was a legitimate application of patent law because adrenalin has been purified, taken out of natural environment, that intellectual expertise had been applied to do that, et cetera. So this was patented in 1923, pros that gland ins, in 19 a 28, a bacteria was patented that was genetically engineered to eat oil. Never used because of concerns about the environmental impact of releasing this into the environment.
Isolated genes, considered compositions of -- by the court, most of the world, including Europe, China, Japan, allow patenting of genes, although there are significant differences in the threshold for awarding genetic patents and the criteria met in different jurisdictions. What's the problem then? Why is there controversy, why did we take this up?
I think there's two reasons. This is seen by many, on both sides of the issue and all points in between, clearly not a dichotomous issue, there are many stakeholders with many different opinions and incentives. There's the public, patients, clinicians, industry, researchers and academia, researchers in itself. There's small innovators, ethics-based groups. All of these people and groups have some vested interest, position relating to patent and licensing of biological material and our purpose especially when it comes to genes. They have distinct interests, they overlap to an extent but sometimes are mutually exclusive. We belong to more than one group of stakeholders with regard to this issue. We are all potentially patients, and unless we die before we get to the hospital we will all be patients at some point. Even those with no direct financial stake have an interest in commercial vaigz if such specialization enhances the medical innovations, in this case for our purposes, genetic tests.
So, as an overview of the types of things brought up on both sides of this issue about ends of that spectrum -- it is a spectrum, there are many nuanced physicians, in one camp, cannot agree with another camp in certain instances, and disagree in others. The perceived problems that are brought up when one begins to talk about gene patent and licensing are, and we will get into them: Moral arguments, inhibition of research, inhibition of patient access through pricing, limitations on volume due to a sole provider of a genetic test, improvements due to sole provider and lack of competition, inhibition of test verification, detriment to quality, more incentives to quality control, and in the future, concerns about the creation of patents. Many benefits as well to benefits in the patenting of genes. More on this in the spectrum as well. There is also the strong argument of induced investment; the idea that patents are designed to prevent what's called the free-rider problem, that somebody else does all the work and you benefit because copying costs are low. It compensates on the need for post-invention investment, especially important in a realm where there are regulatory burdens to be met. The idea of simulating commercialization, the idea that test ag disbaigz ag gazing ag regazing tb a benefit. Enhancing innovation and the ever present issue that gene patents and licensing cannot be thought of in complete vacuum. Gene patents, patents in general work pretty well in this country, simulated a lot of innovation and there's concern we don't want to throw the baby out with the bath water by tinkering with one aspect that has unexpected results.
Boiling down to a couple of physicians, the moral objections are often [indiscernible] context, that is, there's an inherent value issue at stake here, there's something inherently special about our genes, they define us in a special way. The epinephrine and INS insulin upon do not. No one should own your genes, and as we get into it the two things are dissectible from one another. Oftentimes rely in genetic exceptionalism, we all agree when going overboards doesn't make sense, but genes are special, it's a balance to grapple with, the very existence of this committee, the acronym implies special nuances, not irrelevant to this discussion. Clearly utilitarian arguments that, it might inhibit research instead of promote, [indiscernible] patient and clinicians to genetic tests. The arguments for are, usually utilitarian, benefits accrue by harnessing self interest and encourage innovation. There are value-driven arguments that reward should accrue to the inventor, the natural rights argument for patenting.
One of the things that deserve one slide of discussion, the issue of ownership. The argument that argue against the patenting of genes shouldn't necessarily be conflated with the idea of ownership this is a slide from Jorges Goldsscene, who owns your genes? Answered if they are in your body you do, and if they are in the lab -- you own the tangible personal property, but intellectual property is divers divorceable and someone else can own the IT. That makes sense to me.
The effects of the current system of gene patenting and licensing on research is a focus of this MRC report I mentioned, we spent some time discussing at a prior meeting. It addressed patent, licensing and -- ended up with 13 recommendations and 12 of those had to do exclusively with research issues. It concluded that for the time being it appears access to patented inventions or information, inputs to biological -- rarely -- they have a caveat, felt there were several reasons to be cautious about the future, including the increasing complexity of the gene licensing landscape, thickets due to multiplex technologies, and the impact on patients and access to genetic technologies and testing.
Final recommendations in recommendation 13 had to do with concerns or independently verification over sole provider offered tests, limiting such verification. As we go on, I think you will see, I find that a bit of a distraction from the main issues here, and I think that it's a great report. Again, all the more reason that this committee took it up, because their choice of what to focus on from the clinical aspect, as a clinician, seemed a bit odd to many of us, and certainly that wasn't their main goal.
So, a major function of the patent system is to inDeuce investment, this is especially vital when development costs are high and copying costs are low. You don't want somebody to invest lots of money some something and everybody else can copy it. You need some kind of protection in that setting. I would emphasize specific use to which genetic knowledge is supply, effects the need for patent protection. Follows from the first bullet, and that can be summed up by saying all gene applications are not created equal. There are applications in genetic technology that may have very high development cost and very low copying costs, others have low development cost and thus hard to argue one might need patents intentivization and protection. We need to look at gene patents not as a monolithic entity, there may be a variety of uses for such patents, some very logically be afforded patent protection; others one could legitimately argue about. The positive and negative effects of current gene licensing and patent was a focus of this task force.
We focused on gene patents for health related tests, diagnostic tests, predictive tests for other clinical purposes. I will get to the definition of terms in a moment. We wanted to look at clinical access and patient access. While we went over all those at a previous meeting, I occasionally forget minor points that were at meetings two years ago. We will go over those again. We wanted to consider the effects of this on translational are research, that's, for very good reasons translational research, doesn't do good if you have advances that never make it to the bed side. We specifically excluded drug or other therapeutic development, that's a very different application of genetic technology, one not in our purview.
So here's the study plan. Those things in black we have essentially done. We have undergone literature review, case studies, commissioned further research, gathered international perspectives, and the data, input from experts, international approaches, and tried to incentivize all that to develop the range of recommendations for further comment by the public.
We are now at the threshold of eliciting some kind of formal public perspective. Obviously, this is something that at any SACGHS meeting the public can and is encouraged to come make comments about, but of course now with the release of a draft report we will solicit in a formal way their comments. We will then need to compile and summarize those comments and we will need to analyze those and eventually, then, come up with a set of actual recommendations for the second. Today is in yellow, what we want to do, approve if we can get that approval the draft report for public comment. A couple things about terminology.
We could spend days talking about what a genetic test is, a family history could be a genetic test. We obviously need tractable, facile type of definition for our purposes, and what we settled on was the income genetic test for the purposes of this study, any test performed using [indiscernible] biorigin method to deft DNA or RNA -- this would include things like microarray technology, sequencing, [indiscernible] identification of a particular allele, et cetera. We use the term clinical access to mean the access by healthcare professional to obtain the test they feel is required or of benefit to patients. This involves, necessarily, the issue of reimbursement and cost issues in addition to the medical use of geek genetic information. Can the patient get a needed genetic test?
A number of study questions, some answered in more detail than others for a variety of reasons. What is the role of U.S. patent policy in patent and -- should be patient and clinical access to existing and developing genetic tests? How does -- genetic information effect the patient in clinical access? How does legal interpretation of the patentability and boundaries effect patient access to search technologies?
I think all through this we should keep very firmly in mind the impact, relationship between patents and licensing, because how one handles patents in the realm of licensing is absolutely critical to things related to access by patients. So we will be talking a lot about licensing practices, how are licensing practices effecting patient and clinical access to genetic information and tests? How are licensing practices effecting the ability of industry to develop such tests? What role to transtear fer technology play -- what evidence have we founds, can we find if -- genetic tests where in the healthcare system do the barriers exist? And relate to the healthcare system? With regard to development, translation of this type of research, in what ways do gene patent licensing and enforcement create or prevent -- genetic tests?
Costs, what are the economic data, studies that analyze the contribution of gene patents to the cost of genetic test and ultimately to patient access and treatment outcomes? The positive and negative effects on the cost and pricing of genetic tests?
Quality is often brought up in this context as well. How is the quality of genetic testing affected by the current landscape of gene patents and licensing practices and how is such practice impacting the ability to perform multiple gene tests, panel and arrays? One thing I want to emphasize as a clinical geneticist, it's clear to many of us the future of genetic tests likely lies in multiplexing and the increasingly robust technologies we have for genomic characterization and scrutiny. I think it's very important as we go forward thinking about gene patent and licensing, to think about how these policies will play out in a new era where, for example, the $1000 genome will be a reality.
There have been a lot of models, alternative models proposed to try to handle these type of things. Are some of those feasible perhaps those developed by other countries, innovations that can be applied to the patent and licensing system to enhance the benefits of the system, to enhance benefits that exist to help A Meliorate problems identified. Software comes to mind, software has dealt in many ways with issues, restricted access to a technology or information.
Coning down on the huge busy slide, the stiedy plan consisted in literature review, expert consultations, case studies and some additional research. There have been a number of previous policy studies. This is not a field there's any paucity of studies and opinions on. Something which makes it all the more daunting for our group. Can we say anything new about this? My view is yes, we can, because we crafted the moons amongst the committee to look at something, the major change, access to technology and the previous studies have had much broader aims. The council released a report on the ethics of patenting, and the proper balance of law and policy. The Australia law commission delved deeply into the issues in 2004, the guidelines for licensing of genetic inventions and the report I mentioned before, from the national research council in 2006.
We felt that a very productive way of trying to learn about where we stand, where we are going in the realm of gene patent and licensing would be through commissioning case studies that we'll describe in some detail. These case studies were commissioned by us, conducted by Bob Duggan and [indiscernible] butchering your name -- I butchered Bob's name. Sorry.
Trying to stay Reed's footsteps. It's an extraordinarily talented group. Not good at baf basketball, but they are great. They have done a tremendous job of really, I think as best as possible, distilling lessons from the current landscape, looking at natural exper experiments in gene patenting and licensing, a number of case studies, instruct thive each for their own peculiar and particular reasons we am go into. They looked at breast and [indiscernible] cancer, always Alzheimer's disease -- and [indiscernible], not picked at random, but for very specific purposes. They provide a nice, broad analysis of patenting and licensing formats, the disease genes, include most of the most clinically pursued tests in the clinical realm, and because of their juxtapositions, with breast and colon cancer the [indiscernible] they provide natural experiments for trying to tease out the role of patents and licensing. We can learn some general lessons, communications, marketing, the adoption by clinical providers, testing labs, how influenced by the patenting and licensing landscape, whether adoption by third-party payers is -- parameters of access are multi-fold.
One is whether a diagnostic test is even available, whether improvements are available. Just having a test available isn't necessarily what you want. You want a test to be able to be improved by technological advances. You want a test reasonable to the provider and the patient. You want to see how quickly a test is available following discovery of a connection between a particular geno time and phenotype and how rapidly that test improves as future discoveries are made. Finally, another parameter of that is simply the number of distinct test provider that's exist. There are many factors that effect access.
Some of these are directly influenced by intellectual property rights, the availability of the test following the discovery or -- the landscape, the number of providers offering a test is directly influenced by how licensing is carried out, et cetera, how infringement claims are enforced by a patent-holder. The test price directly influences access in the sense if it's exorbitantly priced very few people will be available to avail themselves of that test.
There are a number of indirect factors, as well. Coverage and reimbursement in our -- to use the term loosely -- medical system, is very important. If a test is not covered and if that effects access in a profound manner, the utility of the test for clinical decision making is important, and evidence for whether it has utility or not is an important -- has important impact on access. Quality of testing service is important, not good enough just to have a test; you need a test of high quality. There's logistical issues, factors if a test is very difficult to get, that will indirectly effect access, as well as the fear of genetic [indiscernible], it's amazing to me, even in some way, raised awareness of genetic discrimination in the public's mind. It's rare for me to go a single day in clinic without being asked about fears of genetic discrimination by a patient undergoing testing. It's amazing the impact that has, and again, it adds to the importance of what this committee did in trying to promote the passage of GINA.
Before I start talking about the case studies, any comments? I hope people will -- such a shy and retiring group, a few people who are literally retiring, but -- I don't think anybody here is figuratively retiring, so please hop in and comment. I don't want to make it an unbearable monologue.
Let's look first at breast cancer and colon cancer from a hereditary point, no particular test has gotten more attention. I think it's safe to say than the RCA 1 and 2. Interestingly, I would add that RBCA 1 and 2 are the most-sequenced genes in the history of biology. Hundreds of thousands of individuals have had their BRCA genes 1 and 2 sequenced. It's aive experiment. They have been sequenced so many times because they offer clinical utility, there's value to a patient and provider in knowing someone's status.
BRC 1 and 2, mutated, increased risk of breast and ovarian cancer, broad patents, held by -- in Salt Lake City, the sole -- in the U.S. Hereditary -- HMPCC or Lynch syndrome, as well as, both colon cancer syndromes that differ clinically, but both result in a high risk of colon cancer in one's lifetime. The lynch associated genes, primarily NSMH -- as well as the APC or the -- gene, very strongly associated with the risk of developing colon cancer, predominantly held by nonprofit it entities, [indiscernible] stark contrast to the situation with the RCA 1 and 2. Multiple test providers for full sequence analysis of genes associated with -- exist. One can immediately see that a natural experiment here, you have similar types of predictive -- genetic tests, one for breast/ovarian, the other coul own, in one you have a sole provider, exclusive patent, license, and on the other hand the colon cancer situation with multiple nonexclusive right and -- of that testing. It's by any means a sole source type of test.
Looking at test price, a good case by which to try to tease out the impact of gene patents and licensing on cost. This is something that surprised many of us, surprised me. Full sequence analysis of the RCA 1 and 2 costs 3100, up to about 3300 now. [indiscernible] is from 4760 to -- of the three major genes. I should mention the BRCA 1 and 2 analysis includes largely -- if a patient needs a certain threshold of risk, also another technique good to look for smaller types of insertions and deletions. If -- from 12 to 1,800-dollars. Rearrangement, dosing testing services vary in availability and cost. Myriad, not only offers BRCA 1 and 2 and -- but they also offer their colon cancer testing and [indiscernible] sequencing and's arrangement analysis. Probably the best way to try to compare costs in the -- of this type of diagnostic is the cost per am pli tron, segment of the gene that needs to be amplified by the chain reaction. That cost per am pli conis $38. The APC gene, which is not exclusively licensing, is costed at the same price, $38, includes insertion/deletion testing and a couple of [indiscernible] for --
Because the testing through the nonprofit it competitor ranges from 12 to $1600, and rearrangement test suggest not included. You see relative equity in the cost of these tests.
Quick question. I can understand why you picked a.m. asm lie con, for one reason, reason, what about [indiscernible]
If you have classic FAP, 100% chance of getting colon cancer, if you compare -- syndrome, a are amazingly similar, about an 85% chance of colon cancer and 85% chance of breast cancer if you have a BRC -- a very nice natural experiment.
I was going to say, if you throw in the attenuated FAP studies -- sort of washes out.
Scott's -- condition called attenuated FAP, the risk is not 100%, you lump them together it's a beautiful natural experiment.
Question: Are these the advertised --
This is if you send the box to Myriad or -- does not impact on -- that's a bit of arcane ya, you send the lab test out there's additional costs tap odd tapped on to that.
All right, so trying to [indiscernible] patent premiums, Lynch syndrome, multiple providers, including Mir rad, not exclusively -- testing through Myriad is $3000, includes -- analysis, compared to $38 for -- an in-laboratory comparison. On one hand the exclusive and self-licensed, BRC attest versus the nonexclusive Lynch syndrome test. The non-profit, competitive -- so there are concerns regarding Myriad's sole provider status. Analyzing Myriad and -- has become a cottage industry, like a Cuban missile crisis, a study comes out every six months on BRCA 1 and 2, gets to be tedious reading after a while. Include what constitutes infringement, what actually is infringement.
concerns this pole provider status limits strategies for testing and there was a furor a couple years ago about the possibility of incomplete testing, we can talk about if you want to. Basically, the idea when you have a sole provider there's less incentive for that provider to offer innovative new tests that could increase sensitivity, increase specificity, brought into focus W4 an article was published by [indiscernible] group in JAMA, that showed a certain percentage of BRCA mutations were not detectable by the current procedure that Myriad used and shortly after that, Myriad came out with that more extensive analysis that could pick up the deletions and insertions.
There are concerns regarding myriad's patent, a survey found nine instances of enforcement of patents by Myriad. The same study found -- and no instances of Lynch or -- enforcement. Enforcement actions basically serve to clear the market and drive users to Myriad's services. The question arises, did the prospect of patents encourage the search for gene disease association in the first place. The prospect of a patent on a gene is a major driver in the discovery of that gene's association with the disease, then that's arguably an important benefit. In the case studies, the precise -- was unclear, access to data, exclusive rights to therapeutics to genes attracted industry funding for the search. I would point out therapeutics and genetic testing are very different things. The development, commercialization of the test for MPCC gene, did play a role in simulating research in this area and the patents have been noncluesively licensed once discovered.
How did the role of patents -- yes?
Question: I was wondering if you had looked into the issue of having access to patents and protection it affords into incentives for investing in other genetic testing companies. Well, I mean, you know, the fact Myriad made a lot of money with this --
[indiscernible] I lost my -- very interesting.
Well, more on [indiscernible] than in revenue. That's an important thing to consider.
Right, and actually, keep in mind because some of the other case studies -- better than this one does. Yes?
Question: One thing that's interesting to think about, that's a large proportion of gene patents are held by academic institutions, which I think basically, the drive there for invention is the fact you have patients who are sick, need diagnostic or therapeutic interventions don't exist, as well as the academic promotion system that requires physicians and researchers to invent and create and do research to be promoted and succeed in their own careers; so while academic institutions certainly benefit from patents that bring financial gain to the academic institution in the currently nebulous academic/economic environment, that is not really the driving force for these inventions. The vast majority are held by academic institutions, we can talk about their misuse in the licensing of these, but it doesn't seem to mean the patent system drives these inventions.
I think that's absolutely true, important as we march through these keep in mind what Deborah says. I completely agree. The incentive for discovery in this realm, arguablily has not been dependent on the aspect of patents. We address that in each of the case studies. Where were we?
Okay, the role of patents in test commercialization. Again, it's important not only to make discoveries, but important to commercialize those or at least get those tests out there so people can get them. It's not enough just to discover them. That was the Genesis of the [indiscernible] act. Myriad enforces its patents, serves as sole provider. Has there been a difference in the commercial vaigz, doesn't appear so. You can get lynch syndrome test nothing a variety of venues.
How did patent and licensing practices effect price? As sole provider, the patent comes down to testing volume, presumably the business plan Myriad is pursuing is that they are able to get a higher volume. Therefore, they are content with the lower price in getting that higher number of users, versus charging a higher price and fewer users. There's another externality in this whole economic equation in genetic testing that hinges on the bizarre aspects of our medical care system, the issue of third-party payers. If you own a patent on a gene, exclusive, say I am the sole provider, there's a limit on what you can charge because nobody is -- people are, except for the 47 million people without insurance, used to having insurance pay for the test. You have to keep that in mind as you price the test. Another externality to consider here.
Question: The other point to consider relating to this is that part of the Myriad business model was that the full sequencing test was going to be an entry for what they anticipated would be a large number of family members, generating revenue, that's a low price test you could argue, higher than the original sequencing. Part the of the issues relating to the current business and profit relates to how many family members they thought would avail themselves of follow-up testing. That is an issue, but impacts the top price.
Sure does. Yes. What's the potential the patent might cause some future harm? I think that, as Yogi Berra said, predicting the future you is difficult. That was Neal -- obviously you won't be able to know the landscape in the future, but I think we have to try hard to not anticipate problems that loom large.
I think that we have to think hard about genome sequencing and how it will have an effect to this landscape. We are able to do whole genome typing [indiscernible] and I think most people realistically feel in the next few years whole genome sequencing at some feasible realistic price. How is that going to interact with the fact that by some estimates 20% of your genome is staked out in patents?
Alzheimer's. Four -- high penetrant low-frequency genes, these are genes that mutated, result in extraordinarily high risk of -- Alzheimer's. In contrast the [indiscernible] gene is polymorphic in the general population and various allele -- the 4 allele is predisposing to run of the mill garden variety Alzheimer's disease. So, if you have an -- allele or two -- your riff risk is higher than otherwise, but no deterministic aspect like in -- you test the first three genes if your patient is in a family with early-on set Alzheimer's, very high prevalence in the family. E 4 is an allele that is shared by many of us in this room, and it is generally considered that it's pointless at this point, perhaps harmful to engage in screening of the population for the APOE gene. That could change, for example, preventive measures came to the fore come could be applied in individuals with higher risk. Screening the general population -- used on the other hand, not often, but recommended use to confirm diagnosis in individuals with dementia. Not clinically useful, but theoretically could have increased confidence in the dtionzis in an individual patient. Test suggest ing is available in card cardiovascular -- relative to testing for all four genes, and Duke University holds three methods patents on -- testing, the price for testing is that -- ATHENA charges $475 and you can see the range of prices there among other labs. I would point out, just so people don't get confused, that the way this test is done, for PPOE, a different test than -- what underlies how much cheaper this test is than those other tests.
Health insurance companies differ over whether to cover Alzheimer's disease testing or deny on the grounds it's still --
The search, case study indicates the prospeck the of patent was not needed to simulate the research. How about the role of patents in test commercialization. Patents provided a mechanism -- disparate academic groups, testing, whether that's a plus or minus depends on which side of the fence you are talking about. I think you can argue aggregation just in and of itself is not necessarily a good thing. In certain circumstances it can be useful and be a good thing. It was intended, according to the patent holders to exclusive licensing, to limit the testing to patients already diagnosed with dementia. Could help ensure proper use of this test clinically. I am not sure how well that has worked.
So how does price effect it? It's unclear how Athena's exclusivity effect the prize. The University of Pennsylvania, before prohibited from testing, as well as Canadian providers are significantly lower. Price wasn't available for the [indiscernible]
The patented helpful in aggregating the test -- no patents, any one company could have given all the tests, so I can't understand -- what -- means.
That's a fair statement, Bob, do you care to --
The argument is that it prevents others from entering the market if you make the investment and interest the market first. You aggregate patents and prevent other competitors from entering the market.
It's an argument about free riders, or economy of scale, but not about the patent -- [indiscernible]
A lot of counter examples, like Lynch syndrome, aggregation --
Business reasons to do it, the aggregate market might be larger than if it's fragmented.
Yes.
So, how about the role of -- licensing, availability of the test. It's unclear whether the monopoly will harm the -- in and of themselves. Athena offers two programs that -- patient protection program, limits the cost a patient will have out of pocket to 20% of the test. Now, for this test, that's arguably not a huge amount of money, but keep in mind as we go on, they always have ATHENA access, low cost testing to some patients.
You as a clinician, have you ever been able to access this program with ATHENA?
Let's hold off, I will answer that question. If I don't -- I will remember, don't worry. It's an important point. The potential the patent may cause future harm? It isn't clear whether milt plex tests infringe in this case, or clear whether direct consumer tests like naff agenics would infringe. I e-mailed Bob and -- about this, just a few days ago and it looks like in the can have naffgenics test, it's a 14 KB from the APO -- tight linkage to disequilibrium. My thinking is that particular application may not infringe, but certainly sequencing of that region, I would think you would have a clear case of infringement.
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You really can't tell except in rare circumstances which one of those genes are sequenced. There are population differences in the prevalence of mutation. It counts for only 5% of the Ataxia concentration. When you have ataxia, you do this; you can't walk, you don't have a balance. You do this. It is part of the syndromes representing the ediologies. It constitutes 60% of the cases in which there looks like there is a genetic under licensing. There has been aggressive in the enforcement of this license. It is widely assumed that they are the sole distributer of these tests. For the individual gene, they can order -- this is your question --
No. Can we go back to the previous slide? While they may be the sole provider, there wass a con -- was a consortium of providers.
So testing for the individual genes, it can be 400 to $380. I saw a patient last week who clearly had SCA. There was no particular genes that allowed me to sequence these particular genes to figure it out. We had to complete a ataxia panel and it is $7300. That an expensive blood test. There are programs that help pay for the tests. I would just point out that 20% of $7000 is $1400. That is a significant -- for the population of the patients that I see, that is a great amount of money. I have never had personal success in getting this done. It'sIt's laborious procedure.
Scott?
That's a practice of medicine if you chose to do that being forced in to doing the package deal, it is part of, in a sense, your strategy. I wouldn't recommend it.
I have done this --
Right.
You don't have to do them all at once.
Yeah, if you guess right, you save money. But if you guess wrong, you end up spending more money by doing the tests one at a time.
If you added to the panel things that you didn't indicate on the clinical side of the tests, then that wouldn't be enforced then.
Right. That would be the menu of picking and choosing. In the military health care solutions, they will not picking that out of the panel, but --
Right, but obviously --
No, but I am representing them and I want to speak up.
Absolutely. That is a solution and we should all speak up.
For the ATHENA and the Broad access program, I have tried to manage that program. With the kick-back roles where you need to have open and equal access, it is extremely difficult to have the ability to have the tests open. There are some where you have been -- where they have been interpreted where you need to get the tax return --
Oh, yeah, the W-2, is required.
-- yeah, for the patient to overcome --
Sure. Absolutely.
-- some of the patient's testify to that, and they will talk about the procedure that is not so burdensome to the company, but, more importantly, less burdensome on the patient for tax purposes.
Exactly. Your point is well taken. The access is difficult with this program. I don't know why. There could be all kinds of reasons.
Yeah, the statute there, I didn't want to imply that it was their program or one specific program. You have to go through these roles and the tax return hurdle ask one I have -- is one I have experienced.
Yes, I am sure there are reasons why they are cut across from company to company.
Now, how about the patents and the participators. They provide a testing panel such as ATHENA.
Yes?
While, the patent is encouraging the search, I think all of these are from academic institutions.
Yeah, they all are.
Right. I don't think they are saying, let's do the research so we can get the patent.
I will agree with you. I think we need to stress the other symptoms that exist in the ATHENA.
I hate to be corny, but most of us become physicians because we cared about patients and health care and we wanted to make the patients better. It means we have to do other ways of diagnosing and doing further research.
Right. I know those with the non-academic persons don't have an interest in these goals as well.
Yeah, but they have more of a business side of those activities.
I want to show you how complicated these are. Her numbers are 78% of the DNA patents which were owned by 4 profited companies, and in the non-profited companies, only half were designated for the government funding. Her study shows there is not a good correlation between the DNA patents and the DNA diagnostics.
Yeah.
Okay. I think we have covered that. This aggregation point, and I think Michelle brought that up. I think it is true that ATHENA's aggregation on it's prima facia case. We have to figure out what licensing is necessary. I think it makes sense. I don't want to send six different tests to six different labs to do the testing. Think it is -- I think it is a way of getting the licensing. If you look at the standards, you can see the precedents of the aggregations of tests for the licensing for such clinical aggregation. Every laboratory that was doing the testing as the new genes were being discussed were bringing online the new tests and they were going back and testing all of the patients that were negative for the previous ones. If they were negative, the planet they would -- they would perform a new test on the patient. It was being done in aggregate any way, one new gene at a time.
Right. That is why I added the bullet any way.
What is the potential for harm? It is the effected monopoly. There enforcement rights have been aggressive. They are leading the labs for offer the services. The lab of concentrated testing was to work towards and consume the new tests. I am hopeful that the public will flesh this out as we release this report. Is this part of the major third-party payer that doesn't have a contract for whatever reason with a sole provider of the genetic tests. They don't have a contract with ATHENA. Therefore, they can't get the SCA testing done, period. It's as simple as that. There is no testing available because ATHENA has limited the graphing of the offered tests. This is a clear example of hindrance and one that is a problem.
Can we change that word "several labs"? In my understanding it was "many," so I believe that is the word that needs to be used.
So the next study is hearly -- hearing loss. It is a profound problem for toddlers and babies. There are five genes that comprise significant bulk of hearing loss cases. We have connect 26, Connect 30, Connect 34, and it is available through the multiple providers for the gene that are listed above. Three of the five genes are not patented. Connected 26, MTTS-1, are not patented. GJBB testing is offered through ATHENA. R-10-R-1-A testing is available through a list of providers. Clearly there is a list of problems there for those providers to be a part of the testing.
For the Connect 26 genes, there are other labs for the ATHENA diagnostics. We are able to offer the tests because of the Fairway Technology. They were able to give us a way to protect it by specific mutation. They provide an alternative message for the protection. So I think the lab --
Will not be able to provide.
Yeah, okay. So now we will not be able to address the --
[ Overlapping/Multiple Speakers ]
-- yeah, why is that France pirred?
pir -- transpired?
We have developed the test and developed the insight or the knowledge on why the testing is not developed in the mutations. We are able to talk to the providers about that. They may change rapidly in the more recent development.
It would be great -- I don't know if that is distillable in a program, but it would be great to provide that.
It is available.
Okay.
And maybe Steve can talk about the new ways. It is not just this test, but there are several tests that are being stopped, not offered, by Third Way. I am trying to figure out how this is interacted with the patented licensing issue? Is there a reason to believe that this is a mesh?
No, I think your oversight of genetic testing and documents are having an affect.
Okay.
I don't know if it is the affect that you want.
Right.
Okay.
[ Laughter ]
I think the Connect 26 and the 35 gene mutation is a way here -- first, they are not able to offer these in a specific region anymore.
So what I am interested in when you summarize this, if you could, we are focusing on the patents and the licensing, right? So what you can shed light on from that standpoint, which is an overlap, it is important, but it is not our focus.
Right.
Okay.
Now, there is another issue, where we are starting to provide the genetic testing and the services. You learn a lot about the genes and the mutation and the advantages. You are able to do and provide more tests on those and how you would implement those tests across the board. I haven't seen any of those on the studies was the impact on the genetic knowledge. A lot of the providers know how to implement the testing, but it is not transmitted into the local level where the primary care physician may have a question about the testing.
You are saying there is an inherit value in the local testing?
Yes.
I haven't seen in any of the case studies that you are checking have here where you are able to look at the impact of the genetic knowledge.
Yeah, we haven't looked at that.
I think that is important to look at. Not only looking at the genetic testing and knowledge, but also how that would impact the --
Yeah.
One of the things they have done is actively contributed and implemented it into the database. This is largely because of their willingness and their protection. There are other parts on the other side that can provide the value of each labs and what not, right?
Right. The fairly highly implemented tests get lost, if you will. I think they get lost. How you work with the clinician or the health care provider who has specific questions about the test, you will walk off after you get the tests results back and we are unable to approach that because we don't have the knowledge of those tests.
Right.
I want to bring up some points here by someone who is not living this day after day after day. It seems to me that there was a broad patent that provided the genetics and the testing. They were licensed to ATHENA and they were not comprehensive to cover all of the possibilities, so it was able to be prom yule gaited -- promulgated, because the safe harbor will be disappear, not logistically, but just because you will no longer be able to do it, correct?
Yeah.
There's a reason to promote in order to get the value out of that. It does happen in other industries. What do we have in this personal knowledge as opposed to the other knowledge out there to make everybody aware of what is going on out there. Obviously, not everyone has the knowledge of the --
Right, it is a double-edged sword right? I don't see most of the information put out by the commercial labs as necessary for me to decide what tests to have done. Now, that said, I think that our -- I happen to be emersioned in the -- emersed in the knowledge and education of people. Let's say it is kind of a slippery slope and I don't know -- in general, I would maintain that physicians adopt typically the things they need to adopt as they practice, and I am skeptical of an excessive alliance of the profit motivated education, if that make senses.
Again, since we are picking on one particular provider here, you know, the issue that you have brought forward with the SCA testing and the fact that it is clinically challenging by specific types, there is a great ability to be able to distinguish the type of tools on the findings. This is the genes that need to be tested. This is the different scenario.
Yeah, that is an interesting point.
I appreciate your opinion, but I guess I would take issue with the idea --
Naaa ...
[ Laughter ]
The idea is to get the information out.
Hmm.
The drug companies may or may not be a good example, but there are 85% of these companies that are dedicated to cancer. And there are many persons who don't have access. You know, you have the community, and they don't have access like many other people have. In terms of the judgment calls, where do you draw the line? You have sales, educationers, and what about the -- educators, and what about the websites? Those out there talking to the physicians are relatively small. You can see that doctor's quite frankly, are impacted whether it is directly or indirectly through their patients. It is an effective way to get the message out to their patients.
Well, I --
[ Overlapping/Multiple Speakers ]
It is certainly out there to apply the impacts to the patients, but --
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I don't want to say that it is not in detail, but I think it is clearly evident that it is abused. It is not the best way to educate the physicians, but it not saying that it is not one we can use.
Well, maybe we can talk offline.
Yeah.
I want to agree with Mark that the bundling of the tests are clinically inappropriate.
Yeah, okay.
So if you look at the price here, the genes in yellow, are the genes that are not patented. The two in white are the ones that are patented in the exclusive licenses. I would point out, again, that the current gene of hearing loss is clearly a part of that and we at this point can't tell what the genes are for infants and their hearing loss.
Can we go through that material?
Yeah, it could be possible to do that, because we are unable to tell --
Well, that should be the connection of --
[ Speaker/Audio Faint & Unclear ]
Yeah, if you would come up to the microphone.
The last slide?
The last slide, I would like to point out that not all of the costs are implemented in there.
[ Overlapping/Multiple Speakers ]
In Connection 30?
It's full sequence.
No, it should not be.
It is a deletion of the Connection 30.
Oh, so --
[ Overlapping/Multiple Speakers ]
You have to look at the method of testing.
Right.
That would be helpful.
[ Overlapping/Multiple Speakers ]
We can do that. We do have that ability.
Okay. Great. Thank you.
Yeah?
One of the things that are going to be interesting given what they say, we could do a -- we shouldn't do Connect 30 unless we find information under the Connect 26. It won't matter from the convenience perspective that you raised earlier.
Uh-huh.
That will be reflected in another patent.
That is reflected in the future and that is, in a way, a hold-out issue. Say you have a gene that has no reasonable percentage of the other cases, then your inability to do that renders your panel worthless.
Yes?
Hey, Ryan.
Sorry I am late.
That's fine.
I was in my own private lounge chair.
Yeah.
We have discussed what is the issue of the term appropriate measure. We need to come up with at some point some comparative index. I have worked on the mathematical models or abilities, and I have ran out of tasks. But on the issue of population, I think that needs to be balanced. Debra's points are telling. In the area where a specific patient needs some sort of service versus a large scale of tests that are needed by a lot of patients. They are not always going to be consistent or comparable unless we normalize the tests.
Right.
They didn't begin to hinder the research as a patent in these genes and studies. The role of patents and the testing configuration, the patented and the unpatented genes are developed and offered clinically for all of the providers. In the interest of hearing loss institutes were really for a diagnostic patent and services. I think the caveat that Sheila will address are worth looking into. I think probably that conclusion will remain, but we will see. How about availability? You have the lack of utilization of patent, skills, information, and data. We really don't have the data on that. So there could be some harm in this area. The -- it's unclear how the patents will affect the geneship and the microarray of diagnostics. How aggressive the license es will present those diagnostics.
I think we have for the hearing loss is 10 providers for now. How that compares are is different for the sole provider with the different issues and accesses, when some of these are non-profit organizations that actually do some of the tests, so I don't know if we have looked into the particular issues there in regards to the issues with hearing loss.
Not per se in those terms.
I think we need to bring in Mark's points and Andrea's. We need to bring those points in. Connect 30 should not be done unless you have done Connect 26. If that is a sole-provider and has that type of status, then that is when it, the testing, should be done.
Right.
Now, moving on to hereditary human ptosis, this results from mutation in the EFG gene, which is disorder where they keep too much iron. It's an important inreal. It doesn't allow us to get rid of the iron. Those in the mutation of the EFG genes has a shift in the balance, and that can cause a variety of the disorders, like the diabetes, heart failure, and probably, most importantly, the liver failure. There has been an exceedingly complicated history of business transactions with who owns the patents and licensing o. A single provider model was ruled for a time in the EFG history. The human chromotosis testing will -- yes?
Having the EFG mutation is similar to the --
It's not determinative?
Right.
So it is part of the exclusive broad testing. It is what we feel is really important medically. It is exclusive to a singular provider or model.
It intercepts the whole human utility. It really hasn't turned out to be the case. There was a call about three or four months ago to do a case finding approach. To do the limited, yet still screening, of the populations, so we still do see recurrent calls for that type of thing. There has been a complex scientific history and it turns out that knowing the mutation is existing, is inherent, but it is not applicable at this point. There are two alter area -- alter area areas there -- ulterior areas there.
[ Speaker/Audio Faint & Unclear ]
There is another whole-grouped patents which are believed to be separately. It is an individual patent and they are separated, but they do own a few or more mutations. It is a way to offer the NSR, so I think there are some additional Pat in patents out there.
Thank you. Got ya.
So these are based on the technology use and from the sub-set providers there can be a cost range there.
I don't mean to be too detailed, but there is a company providing a test kit, and you had to use the test kit, and they were doing the F 65 D, and they were creating a bad situation for the laboratories.
Right.
I don't know remember how the public comments work, but you remember those too, right? But if you could summarize some of those things so we can get those in the report, that would be great.
Do you mind?
Can someone remind me?
[ Laughter ]
Yeah, I am writing it down.
Also, my talk back on the --
Right. But what I am getting at though is --
[ Overlapping/Multiple Speakers ]
What I am getting at though --
[ Overlapping/Multiple Speakers ]
There is a whole mass --
[ Overlapping/Multiple Speakers ]
We are forced to use specific tests for the patented holders, and there is a questionable quality of the testing that we use. We are not able to use those for the diagnostic purposes.
Yeah, that is an important point that we don't have in there. I want to be sure we include that.
This is a complex question when it comes to he Moe toe sis -- hematosis. It might call for a population-wide screening. This could be an extraordinarily high volume test. Once the association was found and was published, they were sprung by many laboratories where they were developing the tests for the mutations based on the article. As soon as that association was discovered there were many labs offering this testing because it was a fairly simple test.
How did it effect the price? It is unclear how much of that can be attributed to the licensing issues. Patent enforcement clearly removed the -- in other words, substantial clearing of the market was engaged at that point. At the moment the genetic genetic testing for the he MA chrome mitoses sis -- he Moe chrome Moe toe sis -- he Moe -- hemochromatosis, I think, with the blemished and the things that we find in the future, it is important that we come to conclusions here.
Bryan? I didn't hear you or see you back there.
Isn't that subject to a patent, Debra?
The third one?
Yeah, I couldn't hear that.
We don't know.
We don't know, okay, so my question is if the license requires you to use a test kit, I am trying to understand why that would preclude you from doing a separate test.
Well, you don't do a 65-C by itself.
Well, it is a logistic issue, right?
Well, it is not relevant.
So it is much more important and much less penetrated.
So you are not precluding -- precluding it, right?
You have to add in the cost.
Okay.
I have a question on all of the genetic testing genetic sequencing.
Okay.
[ Overlapping/Multiple Speakers ]
I am not a patent turn, but my -- I find it extraordinarily hard to image in this -- imagine in this situation where if an licensees, we sequence the tests and that's how we do it. We don't take the measures and the average with all of the sequences with the gene that they have their whole lab based upon.
There is precedent in the microarray area where the microarray companies have been asked to remove the sequence of the information that they have with the muscular-distrophy issues. They are saying you have to pull this off of your micro-array ship. I think that is extremely important to the whole gene issue.
Yeah, I agree with you.
It will become a nightmare.
Yeah?
Well, I asked the 23 people and me-type of people, how they feel. They have to go to another location to do the test everybody though the tests are not required. This is a real problem.
Yeah.
I would just add that the 23 and me-main genetic testing genetic codes, is going to be a real problem. When it gets to the future with this type of analysis, it will be a type of slam dunk. Since is there is a -- since there is a discussion on this part, I think it is unlikely to have a $1000 geno for all of the genes that are needed --
Yeah.
I think there needs to be a royalty configuration for the 1000-geno -- gee gnome -- $1000 genome.
Okay. For any of you who have had a hobby of following the gene patents and that type of arena, you are probably salivating right now. A, we have the operative gene, and the other is the gene that is giving you rise to the candid-man disease. There is a highly effective enzyme test that was developed in the 1980s, and it is still in use because it is extraordinarily practical test to use and it is superior to the genetic testing. ASPA gene was patented by the children's hospital that was determined by the confidential out-of-court settlement, which brings up the opacity of this case. There is similar targeted mutation tests, and the analysis tests are also, again, almost identical. Did the research team do the proper configuration. The case study doesn't address whether Canavan researchers developed that tasks, but the family groups were also involved in the Canavan researchers and development groups, but they were not developed in those tasks. The impact is ultimately unclear in part because of the out-of-court settlement. For the Canavan testing, it imposed the high fees and the characteristics or the tasks needed within the laboratories. This was a focus or target as a good deal for the Canavan community. An out-of-court settlement provided for a more throw thorough testing. Genetic testing for this was widely available, but the chemical testing was preferred. The genetic testing is not always the best way for testing for something; in fact, we usually do the genetic testing when we don't know enough -- about the tests themselves.
There are important patents that are being specifically patented in ways that no health care providers would do. This is basically banning the University of Pennsylvania for testing on the patients.
They shut out the patients, right?
Well, we, of course, didn't sign the contracts, but it shows the situations that can arise.
Can arise, right.
And actually, they have --
Arisen?
-- arisen.
Right.
And it shows what is not typically being patented in the situation where this should not be allowed.
Right. One counter-argument, and this will be the public's decision, but it is the way it is ultimately resolved. One argument will be, Well, that is why we have the Courts, et cetera and those types of things. This is a way in the example of how this system is ultimately working. I will leave it at that because there is a real -- you know, different people have different takes on that, per se.
Well, these are not worked out in a systematic way.
Right.
There were inventors of the patent, the question is: Is the patent valid?
Right.
There is a typo in the application, you know, --
Right.
There is not a legal document saying, here are the arguments and this is how they are being resolved.
Yeah, they are very ad hoc.
Yeah, so it is not necessarily saying they are completely ad hoc.
Right. But I think we need to try to represent the range of arguments that are brought to bear on this.
What are the issues that constitute the organization? The effective of the Canavan disease is hard to access due to this development. This is a research statement where they are not subjected to the liability of infringement. Let's stop here. It's 10:30 and we will be resuming in 15 minutes, 10:45, and we will continue with the last two case studies and from there move on.
(The -- Secretary's Advisory Committee on Genetics, Health, and Society is now on a 15-minute recess. The time is 10:30 Eastern Time Zone. The Committee will reconvene their session at 10:45 Eastern Time Zone).
(Captioner on hold with music while the Committee takes a recess; please stand by).
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(At this time, the Captioners will be transitioning; please hang up your telephone line and reanswer the telephone. Thank you).
captioner standing by.
Paul, are you on the phone? I hope, he will join later, be on the phone. Heard if not seen.
We keep plowing through, have this session prior to lunch, then we have two hours after lunch in which I would like to devote that entire two hours to going over the range of policy options one by one. We are finishing up the case studies with two interesting cases. One is cystic fibrosis, the other is -- syndrome.
A disorder that effects 30,000 Americans 1 in 20 of us are a carrier. It means there's an overwhelming likelihood somebody in this room carries a heterozygous mutation for CF -- the early detection and screening for CF does arguably allow better disease management, although there is no cure for CF. The carrier and new born testing and screen suggest is available and endorsed by medical professional societies, 35 states or 37 states at last count engage in CF testing as one of the newborn screening panels.
Patents for the CF [indiscernible] gene mutation are held by three entities, University of Michigan, Johns Hopkins and -- all of these patents are nonexclusively licensed. This case study gives us a way to look at the landscape of a [indiscernible] by genetic terms, relatively -- disease and exclusive lights. rights. The testing price variouses over the laboratories that offer CF testing. The full gene sequence range from $1200 to $2500. Looking for the -- in half the cases will be there in two copies, one can employ targeted analysis, [indiscernible] those target -- the range is influenced by the fact there are a number of different panels one can order. One can orders a panel of seven or nine mutations that are fairly common all the way up to a panel of several dozen and then the most exhaustive would be full gene sequencing. With regard to whether the prospect of the search for gene -- does not appear gene patents were an important incentive for C FT R gene discovery, research ires and funders agreed to pursue protection so broad protection could be encouraged through nonexclusive licensing strategies in a way that, my understanding is, the history of the CF patent issue is that these were in a way preemptive patents taken up by the discoverers so that they could control matter and make sure broad access was available. There's no evidence patent process affected the speed of test development, there were -- not resolved until fairly recently, 2002.
How did patents and licensing practices affect price? Lab to lab comparisons are difficult because of this range in services. You can get whole genome sequencing, a variety of different panels that look at different mutations. You could, for example, if you wanted, get precise targeted mutation analysis as well.
Question: These are practices of pricing on diagnosis for 55 -- have you looked at the pricing for carrier screening, see specific panel recommended to see --
No, that's not included in the [indiscernible]
The role of patents and licensing practices and the availability of this testing is pretty clear, that it's offered by 64 laboratories nation-wide and there's no evidence to suggest the CFTR patents have limited consumer utilization.
With regard to fiewlt future harm, development and commercialization have continued to pace as techniques for genomic analysis from progress the, regularly and rapidly applied in the context of siftic fibrosis. Licensing practices have been compatible with competition as well as innovation, as evidenced by the fact there are 64 labs offering a variety of products. It's clear to say patents and licensing practices of the CFTR gene will not contribute to future harm in testing.
The last case is one still in flux, hence the disclaimer. Longs QT syndrome is a shifting and changing landscape. The authors of this case study continue to update the report and I don't want to my the conclusions or interpretations in the slides are final. We do not know the whole story when it comes to QT and the surprises that regularly pop up with this situation .d
From a genetic standpoint this is interesting and from a clinical, a tragic condition. It is inherited in a [indiscernible] type of pattern. It effects about 1 in 3000 new 3000 borns, not rare. There are mutations in 12 12 susceptibility genes. Mutation ins three of those genes account for the vast majority of cases. It's called long QT, you look at the -- of somebody with the syndrome, under certain circumstances and at times one of the intervals between the little blip system prolonged between the Q and T. Unfortunately, the EKG is not sufficient to make the diagnosis in many circumstances. You can't just do an EKG and determine whether the sibling of this child who died suddenly, turned out to have Long QT syndrome is 56BG9 affected. It matters, they may need a defibrillator, close follow-up. If they did not inherit this Congress condition from the parents they can forego screening. The ability to diagnose long QT is a matter of life and death with no --
There are particular genes that have a more malignant phenotype than others, necessitate the implantation of a defibrillator than others. Testing offered through clinical data corporation, subsidiary of PGX health, and the Fame I will yon services, prior to launch of the Fame I will Familion services -- the story is difficult to unravel, still being unraveled, discovered at the University of Utah gnaw in the 90s, exclusively licensed the patents to DNA sciences for several years, from ' 99 to 20082003, then purchased by Geno science, they were required by Clinical Data, Inc -- if you are not lost, let me know. Rapid growth in commercial testing for this disorder. Testing is offered by clinical data corporation, $5400 per patent, and per test, additional family members, $74, a bit of an ought liar compared to $38 for amplitron RBCA.
The patents encouraged the search for gene disease associations. That prospect did the appear to simulate a race. Because of the rarity, presumed small market for such genetic testing. With regard to the role of the patents and test commercialization, there was perceived value in the Long QT -- and appear to have made testing for Long QT part of the genetic testing business plan. Both -- and Boston U, offers testing from to 2002, suggesting it wasn't the only incentive, getting back to a recurrent team -- by no means the only reason or even a reason many labs pursue such anal analyses.
How does patenting affect price? $5400 per -- and $90 900 to confirm in other family members. You want to discover if the siblings have it, it's $900, it is more expensive than most testing. On a per preliminary per amplitron -- enforcement actions, DNA sciences, perhaps those of Geno Science, may have adversely affected consumer access. There was a period of time during which testing was not available at all due to the -- serious issue with a condition that can result in sudden cardiac death for which there is an intervention available if you know it. Moreover, for which it's difficult to diagnose, if not impossible to diagnose without DNA analysis. Clinical data doesn't offer prenatal genetic testing for longs QT. This gets to the more general issue of concerns about exclusive licensing offering one being genetic test, but not another type of related test that many individuals may want. So the issue of prenatal genetic testing diagnosis is complex, controversial issue in the country, but certainly there are people who i intellect elect to pursue and [indiscernible] if they are the sole licensee that can obviously create problems. That takes us into the realm of potential future harms. Today there's no evidence the virtual longs QT monopoly has had a -- oftentimes noted, the exception -- one second Andrea, this is a problem inherent with PCR tests, not sure how unique to this situation. Andrea?
I was curious to see if the company has a program that allows individuals to pay for that test, to have access to the test.
I don't know, do you?
I don't know, we may have representatives here that can talk to that. But if you want to offer tests, offer tax returns, most patients are not willing to -- able or willing to share that level of information.
Right.
Those who elect to do, do they have that --
I don't knowledge why that's understand why that's the case.
It's a great story. It's actually different for testing than for drugs, and in many examples, we can look at drugs in this instance, in terms of patents, but it is an area where there's n on[indiscernibleability in terms of antikick-back and rule about providing services for which the requirements are actually higher, so there's no sampling technique. It may go back to a point about 10 years ago, but the challenges are great.
I would go on record personally saying I don't think the answer to our cost issues and affordability of genetic testing, other types of things matters so much, will be solved by those kinds of programs. So clinical health has been criticized for processing -- samples from deceased individuals. I am not sure how relevant that is personally, because that is not routinely done in many situations. It's hard to get payment, who will pay for analysis of a dead person's tissue. It's not something that clinically is done very often.
Questionment. Wouldn't this be done in the setting of VACR testing? You have to have the --
I would say it's almost never done. So, what's the potential that the patent situation may cause some harm in the future? Clinical health declined to add gene QT to its panel, to other companies, due to the rarity of the mutation in other genes. The [indiscernible] in five genes, rarer in seven other genes, known to predispose to this oftentimes clinically undifferentiatable syndrome. I would add this is not unique to Long QT and is unlike unlikely to be lynchinged directly, and this is common in clinical genetic testing. When an assay for a gene that plays a very rare role in the disorder. So, to some extent this is a natural, this dynamic is a general result of the nature of genetic hetero heterogeneity.
Question: Does --
I think Utah holds all the patents involved in this. What happened, and that gets to the next point, there's been exclusive licensing at different -- licensees, there's note been, that I can make out, a really broad coherent policy with regard to this. So I think Utah holds the patents to all these chains.
The harm would then result from holding a patent, not developing the test, not making it easy for somebody else to, and people literally don't have access to testing because the test is not available or being developed.
That's precisely where harm could come up, when you've got a patent holder who has refused to license, even though it is for a rare sub-set of the disease, might be willing to test for.
We might invite comments from the audience, but --
Oh --
Bob?
You an in an airport?
Happily know. I was. But I had two quick questions, on your slide is clinical -- and clinical data the same thing? I think it's a mistake.
It's clinical data.
You may want to correct that.
Yes, we need to.
Second, these disorders, the Long's QT syndrome is caused by mutations in ion channels and as you say there are quite a number of them, no evidence we have found them all, by the way. So, these patents, some of which are owned by the University of Utah, there may be others that are out there, yet -- or [indiscernible]
Great.
I will make a technical point. What we can and cannot say about the intellectual property situation, it's not too hard to find the patents and who was originally assigned the patent. The crucial information we don't have in this case, and we know we don't have the full story, is the exclusive licensing status of some of the key common mutation patents and it's brought to our attention there may be a mutual blocking situation here.
Right.
This is such a great example of where diligence might be the fix I wanted to jump in and suggest it; it has been proposed very broad and non-exclusive licensing would be the best fix, aggregating all 11, potential six, but incentivize their adding the additional mutations, that if they don't add they lose rights. So add or lose rights.
That's a good preview in the range of policy options we present. You will see a progression, a range from lower and less nuanced fixes.
In terms of the comment Mark made about technologies not being developed, if there were government funding, that would be something appropriate to consider. If technology had government funding, is not being developed.
You caught me with a macadamia nut in my mouth.
I'll save you. One other thing to note with this particular case study, unique to this, this is the single case study you presented where there is a strong financial incentive from two other stakeholders, the ordering physician, usually a cardiologist, who will presumably be able to able generate revenue relating to implantation of devices, and the device manufacturer will benefit from that. There's still a wide variety of opinions about who should get the defibrillator ranging from everybody carrying the gene, just in case, to more of a selective issue. But the amount of money associated with these devices and inserpgz insertion --
Very interesting point.
Two comments. One, to Mark's, I am not familiar with the medical history there, but the sense of financial incentive, doesn't mean people do the wrong thing, the implication of how that works through the system.
I understand that, but I am saying in terms of -- one thing we frequently argued to payers about is for the vast just of genetic test there's no personal financial incentive for ordering the test or not, it really is the patient. This is not the case with this particular test, and that is something that could, in fact, promote a broader use of testing than might be defined as --
It's an interesting issue.
I think more broadly, testing is probably the one area that there is no financial incentive -- so when drugs, incentive on developer, to go back, the fundamental basis of our system. So virtually all of the other interactions have some financial incentive for the ordering institution or physician. Point 1.
Point 2, let me say thank you for your presentation, giving it in such a brought, open-minded way, looking at the areas, questions, and the way it was put together was very helpful. One of the things I would add, and I know we talked about a little in the committee, but suggest as we move forward for the case studies, that last question, patents have the potential for future harm, we should also have does the patent have future potential benefit. We talked at one point, seem to have gotten lost in that. The Long QT one upon is where we earlier spoke about the role of the people -- you talk about the fact that without aggressive, or nonaggressive education of physicians, many are not even aware of this, much less have an interest in doing it. We need, right now laying out the situation, some work now -- need to ask the question both ways.
That's a point very well taken.
I think the example of the [indiscernible] long QT syndrome is very illustrative and important. For other testing there may be a financial implication, and that is people tend to like and refer to -- perceive as doing something. It's the reason why people write scripts at the end of an exam, to make people feel like you have done something. Many folks in genetics, particularly, perhaps, ordering a test is doing something. I think there may be a less-overt, more subtle interest in doing something.
Good point, even CRT 1 and 2, you need -- talking about a major financial incentive in that respect to a report
Doesn't that -- the test, send it out, speak to the patient about it, without genetic counseling, none of that is being paid for, that incentive may be to do something, but the actual time it take 20S go through that is a loss rather than a gain.
Medical genetics is based on losing [indiscernible] volume --
I actually wrote a commentary, catch-22, I use money on every sale, it's just the volume that keeps me in business. I never understood that until -- it's right. We lose money on every sale, it's that we're perceived as being needed, demanded, we survive.
The vast majority are done by non-geneticists.
We will try to march through preliminary conclusions that we have made. I would emphasize what we have tried to do here is, among the task force, the grueling conference calls, come up with some of the lessons learned, and the -- I do not want to imply these are the only lessons one could learn, and we are trying to present a balanced type of set of conclusions. So, I would start by saying not patented or unpatented, but now the patent is used. A good example is something like CF. CF has broad access, patented, it's been how the patent is used that allowed for such broad access. The findings in the case studies suggested it's this use and enforcement of IP right that's ultimately effect access.
Common [indiscernible] most likely to occur when the interests of medical practitioners and patients are not taken into consideration and exclusive licenses are issued that's pretty clear, in the realm of exclusive licensing we run into progresses, a disconnect between the patients, families and individuals who were setting policy with regard to the use of those patents.
I think it is surprising, demon straibl there's no clear relationship between patents, license, exclusivity and the price of the test. The evidence in the case studies don't reveal any exorbitant patent premium for most of these genetic tests patented and exclusively licensed relative to tests either unpatented or non-exclusively licensed. This is a surprise, but relatively uncontrovertible. Why is that? I don't know. It could be because of third-party payers, because of the quest for volume in lieu of price per test.
I think some of the -- looked at comparison to price, sequencing, not that many providers. Not a significant amount of competition among laboratories to be looking at the changes, and the third is third-party payers, kind of a regulator.
That's probably what --
If you have, for example, more laboratories competing for -- maybe the problem might go down. We see testing from 76 to 48.
Those aren't clearly related to the patent.
But I think you might need to see the number of laboratories --
We see a lot of laboratories that offer testing. HMPCC and --
[indiscernible]
So, I think you are right, the id yolg of this of this most likely --
One of the nuances of third-party payers, you may see differences in laboratories, whether they will accept specimens from Medicare, Medicaid. A laboratory that takes all comers will charge a higher per charge test because they know they will lose money on those payers because of the current payment structure which we will go into ad nauseam, if some don't accept those payers, or you say we're going to build the individual laboratory -- the referring laboratory, institution, and not bill a third-party payer, you can afford to charge less if you are getting dollar for dollar oz opposed to a discount. Looking at the test price has so many variables associated, I don't disagree with your conclusion. I think we should -- [indiscernible]
To be honest with you, it's hard to disagree with this conclusion, the facts are the facts. There doesn't seem to be a relationship. The reason for that is complex.
Patent holders range from for-profit, not-for-profit, universities, individuals. There's no "they" one type. To me it's not surprising. You look at drugs, services, the relative prices, margins, vary. All right, so there's no strong evidence within the current gene patenting pricing landscape. Documents show various -- not offering a test a period of time, certainly a problem, test costs, royalty payments, inability to combine for multiple mutations and the problem arises when there isn't a contract between a sole provider and major payer. By making this statement, pay attention to the nuanced nature of the statement. We are trying to say there's not strong large-scale, long-term barriers that have arisen due to the patent landscape. At this point, while there have been problems and there are problems, I think it is also fair to say that in most cases genetic test suggest available at what appear to be reasonable prices for most things. But, I think -- yes?
I I think it's a very strong statement here. It might be that we are lacking some of the information. Some of the case studies -- nature --
We get to that.
We have to be careful with that, statement. Strong evidence -- I don't think we have enough data. The annual meeting of the association for -- there was a very nice -- where a patient, indigent patient, university, not able to get access to -- mutations even though there is strong clinical, positive --
But again, it's difficult -- two things. Where do you lay the blame for that lack of access, is important. And B, I completely agree, the field is opaque, the absence of evidence is not evidence of absence. Bear with me, because I think we address some of that.
And I think in this case, sorry to keep coming back to -- if you have more providers that can offer --
That isn't borne out by what is probably one of the strongest case studies when you compare colon cancer and BMCA --
Nonprofit its --
But they cost the same.
Yes e.
Not talking about the cost, the access to -- who cannot afford --
Bear with me, these are nuances, I am not trying to say there are no problems. I am saying there's not a pervasive huge problem that people aren't getting the test, but countered by the following slide, your hard copy doesn't reflect this very important change, the no -- I said that last night -- wait a minute.
At the same time there's no evidence that gene patents and exclusive licensing practices provide powerful incentive for the availability of genetic tests. In contrast to the situation of the development of therapeutics, clinical lead, academic
Serve as predominant drivers. In most cases diagnostic tests are quickly offered without the need for patents or exclusive license. You can go on and on, the structure can change as the regular regulatory environment changes. The proliferation of -- this is a very important point. One has to think about what the purpose of patents and licensing are. People can differ about what those purposes are. If the purpose is to have tests available, and to promote innovation, it's arguable that we have uncovered no evidence that suggests that exclusive licenses and patents are necessary. So -- yes?
Just, if you go back, changes to conclusion, but threshold for developing diagnostic system low. It's important to, as a minimum, say relative -- lower than therapeutics, but increasingly changing, several companies spent in the tens of millions, one a hundred million, the relative benefit is not A, like it once was, and B, like it's portrayed.
The third subbullet we can get into more as we get into policy options. The incentive structure could change with regulatory -- I think that it's phenomena on clearing the market, occurred so many times in the history of gene patents and licensing, empirically instructive to us, what it tells us in no uncertain terms, we find a situation, entities that do not have deep pockets, clinical labs in academic environments quickly fill the gap and start off in testing; then what exclusive licenses there is, they clear the market. When that happens over and over it's telling you something important. Telling you that you not only need incentivization to get the -- out there.
A different point, regardless, the incentives don't change today. In the future, the first statement about the cost for developing diagnostics is rapidly changing.
That's like subbullet three.
No, what I am saying, not related, the incentive instruct the you are never changes, the hurdle to make a diagnostic clinically accepted today --
May change.
Has already changed. If you look at the IBBMIAs on the market.
Yeah, that's a good point.
To do that. The third point --
Separate issue.
Right.
The incentive is --
That makes sense.
I think that's a strong statement in that there hasn't been a look at the null set, what's the negative? What's not being developed adequately because it's not being licensed, patented, licensed this way, selecting products developed, it's a set, not the null set. There may not be a powerful incentive, but there are those who would agree there's an incentive. I know of companies saying we will not spend several million dollars on studies if there's note some exclusivity.
It's a spectrum, and I think that there's been disagreement with both slides, exactly what we want, sending a stronger statement. The realties are nuanced.
The point I would make to John's reference to the null set, were there not issues relating to that, particularly in the rare disease area, or ultra rare disease area, we wouldn't invest in something like the CD crerks, in the ultra rare disease, there are definitely? Places where incentives would be ins necessary to bring that in and just because of the volume.
The question about Myriad, I thought there was some suggestion in some of the phone calls that what has become desirable behavior of Myriad, they correlate phenotype to phenotype, disiewng that do you think that was in any way [indiscernible] further incentivize -- utility.
What are we [indiscernible]
Tom?
Interesting question, I don't know, Bob, do you have insight?
I don't know how to answer the question about whether patents are related to that. It's clear Myriad did that, but not a universal finding for all of our case studies. It's cool that they do it, and is it related to the fact that they are the sole provider? I think it probably is some ways and various other --
All right.
I think it's instructive to think for yourself about what you feel the purpose of patent and licensing is. I think this is arguably a question that reasonable people will differ on. But to answer the question is incredibly important in how we go forward and in crafting policy. It gets to this: . Are patents, and exclusive licenses, they an inherent right? Should we be able to have patents, exclusive licenses, in and of themselves, or do they exist as a tool to achieve some other goal? Some positive goal? So, I think that's important because it alters the threshold of action. If one says they need to accomplish a goal, then that second slide that says look, doesn't seem there's a lot of need for these things, weigh very heavily. If one feels patents and exclusive licenses are an inherent right, then that first slide that says oh, there are huge problems, rises to a greater significance.
I didn't chime in earlier when you talked about the goals of patent law, you did put in the notion that people have a moral or inherent right to patent. I would say that's an odd statement about American law. I don't think American law recognizes a moral right to intellectual property. In fact you --
The natural right argument, mostly for copyright, personalities, but even that is more a statement of European civil law, intellectual property, not American law, intellectual property. I would say it's quite the opposite. Thomas Jefferson, the founder of the patent system in some ways was skeptical to the need of property rights at all. He talks about the fact, I have a candle, light yours, have not given my own fire, only added more to the world. Anything that moral claim goes the other way in American law, that ideas are things that should be shared if there's no special U utilitarian right. The clause on the board is purely utilitarian.
Exactly. The U.S. Constitution is totally utilitarian in the contract, to promote the advance of arts and sciences. It says nothing about inherent right.
The notion the states create own patent rights -- completely --
Taking it, I want to jux that juxtapose, doesn't have to be either/or, doesn't need exclusive natural rights, but in the larger framework, like European --
Your own -- type of -- Mara --
On this fill toff philosophical issue, the balance in patents, where you call it a right or a privilege, you have it a certain period of time, it's broadly open. That time period was put in place, recently revised in U.S. and internationally to be able to say rewards, but then step away and ensure broad access.
So the second bullet, how does patenting and healthcare differ, this is also germane to what kinds of policy recommendations we ultimately come up with. Yet, is healthcare the same as a widget to use the economic jargon. I maintain no, it isn't. There are other important considerations in healthcare. I think that's demon straibl, that we hold different views about healthcare. In examples like the Gas key-Frisk bill, we separate healthcare issues when it comes to patenting and licensing than in more purely commercial arenas. Important to think about going forward with possible policy range. Is the patenting of diagnostics inherently different, something about an individual, relevant to ask whether discovering that information through a diagnostic test should be treated differently, controlled in some manner. Those are reasonable things to take into account. People will differ on those, maybe Rochelle this is a time for you to -- we a conversation at the break about my statement at the start that patents are a fact in every jurisdiction, patents of genes. Rochelle countered really instructively, why don't you --
Rochelle: I think the notion that genes are patentable is very heavily dependent on the idea that what you are doing is isolating something from nature and purifying it. Those are the cases you cite, great deal of human intervention required, something different in kind than what was in nature. All of those cases are about therapeutics, purifying something, then you have a nice little liver pill you then swallow, and it is the isolated substance which is the thing that is commercialablily valuable and the thing the patent protects.
When you talk about DNA you are sometimes talking about the same things perhaps, there may be therapeutics with DNA, but the isolation and -- it's the information content that is commercially available. Diagnostics, utilizing the information content, not utilizing the purified version of the DNA sequence or whatever. We really haven't had good -- any cases on the question whether that itself is patentable. The Supreme Court has recently, in two cases, about things quite different, hipted that pure information may be something not patentable. One question is whether or not the information content is patentable, or just the actual substance, way of thinking about it, even if you get a patent on the DNA, what will be considered infringement is use of the knowledge considered infringement. There's real questions at this point based on a couple of Supreme Court cases, federal circuit case, about how far the patents on this stuff actually goes.
That's the an interesting issue. One thing that we need to keep in mind is that our power as an advisory committee to the Secretary lies in making concrete recommendations. Those issues will be decided by the courts and they are kind of out of our control.
But I also think Rochelle makes a good point. The metabolites case indicated the opposite.
[indiscernible] on the metabolites case, we will talk about that.
Oh, okay.
I guess I disagree about that. How the courts decide things, they are not -- you like evidence-based medicine, I like to be treated that way as a patient. Law doesn't work that way always. The potential harm greater this way or this way? This kind of data, case studies Bob worked on, and conclusions of this committee could weigh heavily on a court. It's an issue that is very much at the forefront right now, seems to me to be a mistake.
okay. There are a lot of other patents one could imagine around diagnostics, not just DNA. You mentioned biological chemical assays as well. The formats to other kinds of things. We are also in a time period of a bolus of DNA patents that will expire, perhaps the number of new issuing DNA patents is diminishing and will ultimately come to an end and we will deal with a different set of patents in relation to diagnostic and interpretation of judicial, and other cases. It's a period in time looking at DNA, patents that issued long ago, licensed in the past, and looking at the consequences today. What happens today will be different.
Deborah: The committee looked at international perspectives, Bob and I were talking this morning, bull Belgium and France have -- the Gaskey-Frisk type of -- includes diagnostic --
In other countries.
Right. Where we excluded those. There's precedent internationally for including diagnostic in --
Right. So U moving on with preliminary conclusions, a regulation of IP rights may not necessarily be the optimal primary point of action for resolving actions relating to qualitative testing. We put this in because frequently as you read about the controversies regarding gene patents and licensing, the perceived and potential detriment to quality is brought up. The argument is made, reasonably, that well, perhaps with the sole source provider one is unable to have the kinds of quality control that are inherent when there's competition. This was touched upon by recommendation 13 in the NRC report regarding verification.
What I would argue, what I think came out of our task force discussions is that intellectual property rights and their application are in some ways a peripheral matter with regard to quality. Perhaps they are not the best place to focus if one is concerned about quality. The issues related to quality are perhaps bet assessed through mechanisms that assess quality, instead of trying to do it in a round-about way. This committee has weighed in on it. It's a complex issue. I am not sure, and I think the sense of the task force was that quality perhaps takes our eye off the ball and isn't so much an IP issue. What do people have to --
I think the other way of stating that would be to say if we had a robust oversight of genetic testing quality and practice, I don't think this issue would arise within the context of a patent discussion, and I agree, I think the quality issue is a very poor lever to say we shouldn't have patents. It's reflective of another problem in the system, we addressed it, and you are right on.
Two different issues where you have external proficiency, external assessments for quality. What I am concerned, something we discussed for hemochromatosis, the patents done --
That's not a quality issue. That's an exclusion of --
The ability to identify the disorder --
I am talking about quality in does this test do what it says it does, is it robust enough to detect, et cetera. That's a different issue than, oh, we can't test for this because it's underexclusive rights.
If you are not allowed to -- allow you to detect the disorder it's an issue of quality.
I disagree. I don't think for these purposes we want to broaden quality in that way. I think that is an issue of can you test for this allele? Right. It's not -- when we talk -- maybe we need to define quality in a more precise way.
I am going back to the specifications because there's -- quality of -- [multiple speakers]
Right.
I am getting here to mainly analytic validity issues. That's a great way to think about it. Thank you. The field of genetic testing is rapidly evolving and the land scam landscape of licenses and patents may cause confusion in the future. We can agree on some things, imagine that. Most of -- these heterogenous, not up for argument. Right. Technology is rapidly moving to the ability to engage genomic analysis. Here's where the interpretation -- I think patent thicket it is may be a more logistic problems, rather obvious to me, maybe other people want to argue with me on. But it seems to me as you test more and more genes, some of those are exclusively -- patents, you have a problem. The issue of full genome analysis, sequence analysis, will materialize.
You can argue about whether it will be three years or 10, but most of us agree it will happen. It's very hard for me to envision this not being a serious challenge to current system of patents on individual gene and rights. I knew Bryan would raise his hand, then Kevin.
Two questions. The question of patent thickets, the examples of the 802.1 and the new network standard, that's been preliminary forever, could be considered a patent thicket. The DVD standards could be considered a patent thicket. My question is, I don't know if there's evidence of patent thicket it is occurring, and if it is, the community, commercial community doesn't know how to deal with them. I think there's a potential issue, not sure the solutions are not in the tool box of at least --
Right. That's very fair. This is a concern that I think may arise in the future. Now, whether the remedies currently exist to get around them or not, I don't know. I am skeptical, but there are people who know a lot more about the patent system than I do. I would love to hear how they are getting around that, but Kevin is next.
On that note, if I remember correctly, somebody brought up the similar example, talking about the HD TV, 1100 different patents, and everybody gets their little piece. The question is -- example of --
Software, I think. Software development is an example of where there's been great potential for this, and I think as we get into the policy recommendations that we have to look closely at other models. Who is next? Cheryl?
I wouldn't direct too much happiness from these other examples. Think about the DVD, or HD TV, you have a patent on a tiny piece, you have no product unless you agree with everybody else. If you have a patent on a gene you can still market your test, there's no need to agree with everybody else. You can still go market. There might be good reasons to want to agree, but they are not driven to it in the way you are in the other examples. That has been the problem in agriculture, where there are some places where you are seeing some of the these pools, but the pools are much harder to create because of the fact people can make money even if they are outside the pool. You don't need everybody else to market a -- it's completely different.
Who is next?
On that note, I agree, that is an issue we have to look at. However, I wonder about the fact as you talk about moving ahead to the $1000 genome, we are keeping personalized medicine as the horizon to which we are moving. When we get a greater sense of what's out there in the healthy "population," my guess is the relative simplicity with which we look at some of the supposed deterministic genetic conditions will be a lot less deterministic. If somebody has a patent on the CAG repeats in Huntingtons. We may discover there are people sitting there with 42 --
We already know most of them -- vast majority --
Things will become less determinist being rather than more. You engage with other people in order to pull together the information in an in inintegrated fashion.
Hard for me to see how that will solve what Rochelle brings up. Mara?
[indiscernible]
Okay.
To Kevin's point, clearly, even though the association studies are showing genes of relatively low level of effect, the reality is the market for those is enormous compared to any of the case studies we --
Perhaps. I would still say perhaps. We have no idea clinically how assessing somebody at a 1.3 1 point relative risk for dx will ever be valuable.
I would argue in the protein realm, CRP, HP little A, those are --
Those prove my point, of minimal clinical utility. For the most part.
The guidelines suggest they will be important in terms of what LDL level you treat for, evidence around that, the issue is not necessarily the science, but it's the convincing and the uptake. We know the adoption curve for physicians in terms of new testings is relatively slow. It may take 10 to 20 years -- yeah, basically. Once it takes off, it takes off strongly. I wouldn't necessarily say because we haven't seen high adoption of biomarkers at the present time it doesn't mean within five years we won't.
Absolutely, but I don't think that takes us out of the realm where we should be sanguine about the prospect of patent thickets and hold-outs. I think this is a looming problem, my impression. Allen?
I think it's a very good slide because it helps prevent us from being federalists fighting the last war. The case examples this morning are very useful, informative, but by definition they examine the past. A point Mark made, [indiscernible] made to me eloquently, of course, that many of the patents we talked about will expire very soon. When we look forward, we do need to think about the time of being able to sequence the entire genome, the larger issue in terms of patent issuing is the genome analysis, how is that patented, licensed? We have a opportunity now to look forward to that, make recommendations on other kinds of things, recommendations that look forward, esm siedz emphasize dealing with that, perceivable world instead of fixing the past.
Good point. Laurie?
I wanted to make those points; around the technique, physical sciences, there is a lot of competition which I woarch won't get into. If on the slide, you had information patent thickets, one concern is that to be mindful of creating instentive -- incentives for people to disclose --
Association --
Maybe they will --
[indiscernible]
Databases, seems lirk something really not good because those don't expire.
Right. Bryan?
I was going to advise the committee that in March of next year, when the new contact net comes in, the new patent bill will be coming up again. One thing they will be considering, somebody mentioned metabolite, the [indiscernible] case which deals with the simple correlation with the standard, that will be on the table or is supposed to be, leadership is saying send it, they want to bring it up in the next Congress. I wanted you to be aware of that. What happens in the next meeting, February, right. There might be some chance to bring [indiscernible] to the center.
Mark, then Deborah.
This relates to the pint Allen made about looking to the future. We have clearly been promulgating that in order to make any of this work, at least for common diseases it will require robust clinical support, combining information. In some sense that is being treated as a device in and of itself. It's an area where whether or not that information, combining information is in some sense going to be a device in patent, will also dramatically impact how we are able to use this information.
Deborah?
He said what I --
All right. Perfect. Let's move on. Preliminary conclusions. It's difficult to access the current landscape for diagnostic purposes, associated licenses and whether the IP rights access the effect on patients to diagnostic -- tests. The lack of transparency has implications for the future. When it comes to multiplex testing, how does the provider know if the test infringes on another -- we might have infringement problems. How will you know, as you develop the program, questions begin to rise quickly because of this opacity.
Now, after lunch -- 12:15, we will get started because 12:15 is lunch, I am not giving you extra time.
I want to explain something. Unless we frame this correctly there could be considerable misunderstanding about what we are trying to do with the range of potential policy options. We are not saying, as a task force, if we approve such a range as a committee, this is what we are telling the Secretary. This is a very complex landscape. We are trying to frame the issues, some are virtually mom and apple pie. I can sign -- to that. Others have vo sieve vociferous reactions -- some will depart considerable from what I think and you think, but I think it's reasonable to get them out there, have public comment, and then next time we can have a really friendly conversation about what should go into the final recommendation. I thought I would beat that horse into submission.
We divided this range of options into eight categories. The categories, by the nature of the action, how the change would be affected, and the entity to whom they would be directed. The categories of, E is noun, A is --
The categories of potential policy options include advocacy efforts by key stakeholders to ensure access; enhancing transparency in patents and licensing, filling gaps, licensing policies governing federally funded research to facilitate access, study federal implementation of IP laws, related to that. Improving, clarifying, PTO policy and recommending statutory changes be sought.
So again, why present this range? To present a number of options to the public to help frame the issues. The public perspectives will help guide formulation of final recommendations to the Secretary. Yes?
Procedure question. My sense is from this you are saying, you are looking at this issue, at the same time complex and yet opaque, you want to get this feedback without necessarily indicating the next meeting is going to be the meeting where this report is -- but may not be --
Not so much that. It's that we feel like just putting out an unstructured call for comments would be far less productive than putting out a framework of possible options people can then comment on. The other side of the spectrum would be to just have come up with a task force of "here's the recommendations." that wouldn't be fair to the committee or the public. This is a nice amalgam of this, but we do very much, hope to move along quickly. There's 60 days for public comment, then we will have really fun conference call and come up with something and at a full meeting iron out our recommendations.
So we are having public comment live today?
Not on this.
Some people may comment, but the main comment will be in the 60-day period.
And will be written.
Yes.
We will do all that laborious.
May have live comment at the next meeting.
We always center live comment.
And looking towards finalizing.
We really want the public comment in writing before then, to have as much as we can to make recommendations.
What I am asking, after this meeting, the documentation talked about today will be available for public comment.
Yes.
Actually approve the draft -- that's right.
Okay. Let me keep moving. It will be -- we need all the time we can get.
I would just make a plea for balance at the start. I remind people, I don't think this is a particularly controversial statement, that the [indiscernible] works pretty well. We should be mindful of unintended -- -- we don't want to muck up the whole system by trying to fix things. On the other hand, if there are problems, we can recommend policy changes. We need to identify problem and potential problems. That would be my plea.
So, the questions for the following draft options are the following. Are there policy options that should be added? We have heard suggestions. Remove, modify, prior to releasing draft. I can't imagine there would be changes, but --
Is the range supported by preliminary findings? Are there other issues before released for public comment? Overall, further editing may be needed, ready to release in early 2009 for that 60-day period?
With those kinds of instructions in mind let's tackle the first. Some are mom and apple pie type things. With regards to advocacy efforts with key stakeholders, in order to optimize patient access to and the quality of genetic testings, stakeholders, for example, industry, academic institutions, researchers, patients, should work together to develop a code of conduct to encourage broad access to technologies through licensing agreements for the diagnostic use of gene patents. Comments?
Given the discussion of --
As I read it, I thought, why do I want quality here?
Why don't we leave that out. Patient access.
Right.
I have some issues with a number of these, but I wonder whether it takes sense to edit, but read them, have comments on them.
That's a good point.
Presumes a lot of thing. Never get through it.
I don't want to do too much wordsmithing here, the whole purpose of the subsequent phases is to get people's input. If there are reasons not to have, substantive, or ones to add, I think your point is good. Unless there are huge issues, we should proceed.
The only issues I will say, that implies as a result of the patent system we don't have broad access, for which some of the case studies we do --
Says in order to optimize. Not necessarily implying bad, we want the most access possible.
The other point I want to make, the quality thing, maybe recharacterize, restate, the point before Andrea brought up, some of us within the general term of quality, the idea that if you are not operating certain parts of the test that effects your actual, what might be considered to be the utility of that test. You might want to characterize that as utility, opposed to quality, leaving out the analytic validity piece of it.
How would you phrase that?
In order to optimize -- and
Good, I like it.
Can I ask, does that include the issue that sometimes having very many people, companies or labs doing one test who may have lesser quality because there is variable standards and not a clarified ability to show one reference standard --
Talking about analytic or --
Not what --
No, I am saying it --
If you want to include that.
No. [Multiple speakers]
Analytical validity from --
Talking about adding different mutations here, different clinical utility to the test, will cover that portion of being only -- not able to add that mutation to the --
Kevin?
Might be helpful for our own reflection if you add into A that HHS should bring together she's stakeholders to develop a code. We find out from the public they think HHS is the place to do that or some other group.
Say work together (perhaps --
Whether we are the place it's supposed to happen or not.
When different stakeholders, for example academic stakeholders -- work together -- mom and apple pie, work together to develop identification of gene mutation and tests -- whether to seek patent protection and how many resulting patents should be licensed. Does that seem controversial in any way?
Action steps on this, who is enforcing this or --
Why I am saying, believe me, we get to ones with big teeth. Have no fear this, is not one. This is a recommendation, a statement, we should all get along.
This is a statement, not really a recommendation. The recommendation could be that DHHS provide a role or forum by which the stakeholders could actually get together and discuss issues.
Maybe C, interesting, maybe something like to facilitate this, HHS, we could consider another option to put out there on the table.
What I don't understand about this, I thought patents were held in some level of secrecy until filed or -- so how will we have these discussions within the context of how that information is handled?
I think this is saying that when you got people already working together, right? Different stakeholders work together to identify a gene, develop a test, the owner of resulting invention should consult, right? I think it doesn't preclude not consulting. It's a recommendation or suggestion that this is the most beneficial way of proceeding.
When? After the firing, before, when exactly?
I think that -- I don't know. We didn't approach it with that.
It's not whether, it's how it gets implemented.
Something to do with marketing, not so much --
Paul, this is Bob. I think this is trying to get at, I think, let's use the Huntingtons disease and cystic phi bro Film fibrosis example, in contrast with the -- don't screw up your relationships with the constituencies that contributed to your invention.
Maybe Paul's objections can be overturned by saying, instead of owner, those stakeholders should coven consult with one another whether to seek patent -- gets over some of the ambiguity.
There may be patents in process that people may not choose to check.
Absolutely.
You could phrase it either way, but as a live entity under today's system, very well may be things people do -- maybe part, some would say I don't want to sit here, don't want to learn things that will impinge upon this. This is meant to be draft, then to have more substantive comments on it later. I think Paul's point is a good one as to how logistically this will work. It may or may not -- may want to do it, but unable to.
What about substituting, instead of owner, if we said those stakeholders should consult with one another. That make its -- why don't we change that.
This is more of a general add mon igz add mon igz in monition in the field.
Patient recommendation, to proactively, when beginning, interact to -- development of diagnostic tests, they proactively make their input a condition of their involvement.
That's a little different. This is an admonition to all those stakeholders, right? You are right. St it's instructed by the [indiscernible] this didn't happen. Saying you should play well together, I don't want to dwell too much on this, these are mom and apple pie, we want people to get along. It's useful for the committee to mention this, but when we have things that have no enforcement we shouldn't spend that much time. We do have to break for lunch.
I want to say to the extent this is to the Secretary of health and human services, what is an actionable statement we can make to get to this point, that the Secretary can either set up a commission or -- set up a forum --
That's a good point. Maybe at the lunch break we can do that.
Something like that may be necessary, post-granting of patents. There's afternoon an A sfekt of as sfekt aspect of this, may be most practical -- you have how do we make the world better for our healthcare -- post-granting as opposed to pre-granting.
At the lunch break, we will have to finish up, lunch.
My question is more for clarification. Feasibility question. I agree with the statement about what's actionable, but back up and ask the question, how realistic is this? Is this process, can be answered here maybe, is there an adequate -- do we have adequate information about how often this actually occurs in the development process such that we can spend a reasonable time getting this done? Team seems to me if we are making a recommendation, should be strong enough on accessible data, information that we can actually say, do something about. If it's not done often enough to even be something reasonable --
I think the case studies clearly demonstrate there are times when this didn't happen there were problems. I don't think it's unreasonable to --
Sorry -- not what I am saying. Then I recognize from the case study it happens sometimes. I am worried Mr. worry about when [indiscernible] occurs.
I think my guess is that it's not going to happen that many more times for individual genes. It might, but when you start multiplexing this test, trying to put them together on one platform, the issues are going to become very, very complex. That's something we may want to consider, looking in the future.
Can I just recommend that become the focus? More, actually become something considered when we talk about more actionable steps, what to do, this projection. That would actually help focus, more, whatever recommendations we make, very concrete --
We can focus on this, during the break, come back with wording. One more.
The thing about actionability, is there a role, speaking to someone really naive in how the agencies work together. Would there been a role for the Secretary to convene something involving the patent office, commerce, et cetera, different people at the governmental level would have the stakeholder's interest, the issues teed up, we think it impacts you, can we get together and discuss your perspective on this? I don't know if that's reasonable or not.
Again, what we need to do now is break, anybody interested come on over and we will talk a little about adjusting this. We start back at what time? 1:00.
And 1:30 to 3:13 :15 we will -- soldier -- and if we aren't the done we will take the break away.
[Lunch break until 1:00 p.m.]
[Captioners will transition during the lunch break; current captioner hanging up phone line.]
Please stand by for real-time captioned text.
(Captioner placed on hold with music until the Secretary's Advisory Committee on Genetics, Health, and Society is on a lunch break. The Committee is scheduled to return from lunch at a 1:00 Eastern Time Zone).
Okay. Now we will try to continue. Welcome back, everyone. Before we get on with our discussion on patents, we will be turning to public comments which is one of our critical functions. We do public forums, as you know. This is the important way to get the input. In the interest of time here, I will ask the commenters to keep their remarks to five minutes or less, and I am going to adhere to that because we really do have a full schedule.
Let's begin. Our next presenter is sitting in the back, Mike Watson and he is representing the American College on Genetic testing nettics. Welcome, Michael.
Thank you. I have the luxury to listening to the webcast from my office this morning. I will try not to repeat things already mentioned this morning, but who knows. I am from the American College of genetics. We offer genetic genetic labs throughout the unit, and as far as I know we are the only college throughout the United States.
Now, I do want to say in sort of preface, that I wouldn't want to encourage anyone to infringe on a patent. I hope what you take -- that you take what I say is just preference. I will say that there is little evidence that patents have led to products. There are few products in the genetic testing. Most of the licensings were done and the products were acrude throughout individual laboratory-developed tests. There are very few evidence that the patents have been proved over time. In a few examples that I would agree to, there are few evidences that patents have been proved through the licensings.
Before you project a patent or license test, it is processed through a gene. It was shortly after two organizations where the carrier screening began that the enforcement of the patents came into play. It's an important phenomena that they used in the genetic testing nettics and -- genetics and researching. I think the research is different in the clinical practice arena. There was a researcher in the science who made arguments on the gene patenting and testing that there was very little evidence, but, however, there is very few limitations on the patents on gene. I disagree, I believe it very limited. At that time, it was 1 and a half or $2 million to engage in these cases and get to the merits in court. We never ended up getting to the merits of the case. And they ended up giving the ability to Sue -- Sue -- sue. What the lawyers determined was they would not have to take them off of the array, but they would not be able to point out the deletion or the duplication of itself. When that laboratory identifies the [ indiscernible ] in the array of GCH. Another focus has been brought up recently. Bob spoke this morning about the hearing loss and the longing PQ syndrome. This is identify kids in the newborn screening molecularly. We would like a molecular test to allow us to identify the multitude abnormalities. When one is doing this with a child who has hearing loss, you are not able to test for that particular gene on the particular arrays, because it is on the Long TQ patents. This is arising around particular genes and patents which is going to require us to think outside the box. We are going to have to separate the gene patents from the protection of the gene patents to develop the therapeutics. This is going to lead to the investment of the therapeutics and that is quite thin. The only other area that I can -- I better not go on with that, but the other case is the [ indiscernible ] labs versus the [ indiscernible ] labs.
Thank you, Michael. We appreciate that. The next speaker, Debra Lenard is changing her presentation here. It says here you are representing the Association of molecular Pathology. You are going to change the hats instantly, I assume.
We have two kids in college last year and three this year, so I am here representing the Association of Molecular Pathology. We have recently redesigned our AMP. Clinical laboratories in both the public and the private sectors translate and develop the discoveries in the molecular diagnostics for the tests that are available for the public goods. They are available when they have access of the broadest based of genomic discoveries. The patent holders and the license es are monopolizing the patent packages. The education of physicians and researchers and the health care professionals and the continued improvement of quality and medical care. While attaching the rights to the inventions of the therapeutics and diagnostics. The genome is a product of nature and should not be patentable. H this is a -- this is part of the molecular testing because they provide access to the baseline of genomic invention, it is a threat of the patent holder and the costs which is a chilling effect. In the gene patents the exclusive licenses and the single provider is detrimental l to the public interest. This is impeding the advance of the medical knowledge and the enhancement of the public's health. No governing standards currently exist that prohibit the granting of those licenses. Human genes or pathogens can be provided on the molecular tests and the licenses are obtainable in the financial and the practical terms. AMP provides the following: The biological states shall be discontinued through a Judicial review or an act of Congress. The whole gene patents should not provide the grants to these patents. To ensure they are widely available and affordable to patients the financial terms to the test licenses should be reasonable. License agreements should be offered at limited terms that can be performed by a laboratory or elaborate the technical uses performed during the tests. This is limited to the researching and testing or limited to the research testing and findings. This allows all of the stakeholders to work together in the gene pathogens and the licenses. This is going to provide the access to the health care and achieve the benefit of the current knowledge of the genome.
Thank you, Debra. I'm going to move along because we are pressed for time.
The next speaker is Mr. Brink.
Thank you.
I think Dr. Goodman can agree with me when we talk about the genetics and the tests that the details are provided in the definition. What we have seen in the [ indiscernible ], the industry has taken a lot of time and effort to define the [ indiscernible ] and to try to exclude certain tasks from the [ indiscernible ] definition.
When I look at the definition currently as stated by the committee, it is performed by this committee in order to test the DNA or RNA. We have a gene expert profile. We access the expression of the multiple genes and put that into an algorithm. The gene profiling tests would be a genetic test and when I look at the case studies and the investigations that were performed none of the expression profiles are investigated. It's a part of looking back after what has been investigated to define what has been investigated and to also clearly state what has been used in this study.
Great. Thank you. That is helpful information that we can look at as we revise the graph.
The last one I have on my list is Carol Reed. Welcome.
Hello. I am the chief medical officer of clinical data. We are the parent company of which PGX Health is a sub syed airy -- subacid rare rei -- subsidiary. We have been identified and one of the reasons for h this is the success of our commercial tests. The burden of testing for the five genes have in fact caused us to sequence those for a more common syndrome and to identify the research to identify more rare causes of the genes. I would like to address the issue with the patient access. Patents are a major topic of discussion in this area, we should not ignore reimbursement and paying the policies and cover these tests. To use the [ indiscernible ] testing as an example, we have made a significant investment in the customer services. Our prior authorization and acquiring the authorization takes more time than it does to perform the tests and return the results to the patients. We have Medicaid coverage in 38 states and we have pending coverage in 12 other states. Now with the private and the government insurance, we have exceeded in the coverage of 160 places within United States.
I don't think we should underemphasize of the mutational and analysis tests. We should have a reflect on the mutation and the structural relationship of the protein and the database and access identified during the testing. With the option to provide the normal and the research tests results to our patients. We are going to have the variance identified in the appropriate background in order to interpret and analyze the results and the patients may be put in endanger including the implantation of the defib laters. -- defib laters.
Thank you very much. These are helpful comments to us as we deliberate. Is Ms. [ indiscernible ] here? [No Response]
If not, we will move back to the primary topic today. This will be reflecting the perspectives as provided by our presenters.
If you want a break, we are able to provide you with that, but we have been leading this through during a complex area this morning, but we have to get through the recommendations. We have to get to the approval and the draft of the public comment. We don't need it perfect it, we need it in a way where we are able to get it out and minimize it. We are working our way through the accounting period afternoon.
These are draft proposals that are to go out. They can be amended and adjusted later as part of the whole process. The second one has to do with the advocacy efforts by the stakeholders. The associations and organizations should embrace and promote the principals reflected in the best practices as well as the nine points to consider that are well known in patent circles. That are supposed to -- they are supposed to be relevant to the genetic testing where it is appropriate. It should work cooperatively with the gene patent and lance licensing -- licensing technology. This has more granular recommendations in articulating more specific accommodations for the licensing and the exclusive licensings.
Comments?
[No Response]
Steve, you must have --
No, I think that lunch was our friend.
[ Laughter ]
Holders on the patentsover the genes and -- patents that are related to the genes and the patent technology should be including the factors on the patents that are publicly available.
Explain what that means. Does that mean there may be a patent, but they are still letting the patent information be aware to everyone?
No, I think it is focusing primarily on the licensing issues. It is developing the scope and making it publicly available. There is a difficult in this process in trying to figure out what the licensing parameters are with the specific licenses.
This means -- you mean the financial factors?
No.
Just with who you would go to and who has the licenses? Beyond gene tests?
Yeah, the test itself.
I'm trying to understand the validity of that.
Yeah, the public and advanced records, you can find that, but it is hard to get your hands on the licenses. That is a problem. It can be difficult to assess the various agents and how they are acting with regard to the exclusivity and the non-exclusivity, and then it creates a problem with the developers in terms who they are developing the licensing agreements on that, et cetera. Trying to include general licensing across the board will facilitate and access the field for the problems that are occurring for the best guidelines, best practices, and et cetera and that would help in developing the and adhering to the tests to which we know are out there. So for the patent holder, they would list everyone they have licensed it to, in theory, and then it would be transparent for the ones who are not licensed are put in the field among the licensees.
Yeah. I think it is a desirable thing. I think there are a lot of values to that.
Right.
What ability does the secretary have to be able to do this. What is the legal landscape there and what are the barriers within the industries and --
Yeah, and that we will get to. We are looking at the subsequent information in a general nature as far as what are the developers initiatives.
We are in the where/and issues. Here is the principals of belief, where as, where as, where as, and if you give them the recommendations at that point and time it will read as --
No, that is a point well-taken and we discussed that at lunch. We need to revamp and say, here are our basic principals. Here they are, but where and how do they and HHS work with those barriers or those principals.
Okay. In relation to the diagnostics we need to encourage the licensers and the licensees, to allow the parties to include the information about their relationship as it concludes to the licenses and the scope of it. This is again -- this is more directive or recommendation that says, Okay, the best practices, which was presumably released for a reason, right, should be amended in order to address those specific things which we find are, perhaps, lacking. Okay?
The secretary of HHS should seek statutory amenities for the in-vitro when offered as a laboratory or diagnostic test. This is the issue to patent and the patent number to provide the control and reasonably believes the information to the provider or to marketing. In other words, Labeling. This is to shed the light about the particular field and to ensure that the information and the licenses are readily available.
Is this in specific to the licenses that are in effect today?
I believe so.
Go ahead.
Why is the -- what is the background for such a disclosure?
Right. The background is that -- it is evidenced by the case studies. It is proven I difficult given a specific gene and test what the licensings surrounded around that. You are looking for the adherence of best practices and test development, et cetera, we were attempting to come to -- to come to mechanisms that shed some light on this. We were making it approachable and easy for the individuals to figure out what the patents and the licenses, et cetera, that are given to a particular test.
Currently, not only is labeling the blind is the issue, and also the best practices of the labeling is a blind issue in terms of the best practices.
[ Laughter ]
Right.
They are not suggesting that we do this under the existing law, but they are also suggesting the statutory authority. If you want to make it less erroneous, you may want to suggest that we search for the statutory or the erroneous issues that are out there. It is part of the law. That is not part of the package right now.
Is it administered within the law and the drug label as well?
I don't remember seeing it administered on the drug label.
Me either.
Okay.
I guess the majority of the committee thought it was a recommendation to [ indiscernible ], but I don't know this as a genetic testing on the report. It is not part of the diagnostic testing so that in a way it puts a burden today and traditionally and the preventions in the health care arena and then, again, I am not clear how you would provide the access.
This is not the forum to provide the better -- the pros and the cons of the access. It would enable the developers to do a a efficacous. It is putting a burden on one portion of the industry and then not the others, that will not help the innovation.
Right, and I think that will come out as our public comments. We have to be cognizant to the discussion that the multi-flex testing -- multi. Lex test thing.
It is -- I think we should -- if people are okay in putting this out for comment, we can waive the various types of the arguments.
So if the object is to make it more transparent, then why put the burden on the company? If you have a multi-thousand dollar gene complex, the package would be available. You can do it on the website. But if the object is to be more transparent that we then maybe suggest to the secretary within HHS and make it more centrally available.
Well, somebody will have to put that in there.
Somebody is going to have to put it in there and maintain it.
Right.
That's going to be more difficult too.
Right. That will come up as we discuss them.
Filling the data gaps. Where the licensing arrangements and the agreements, they should encourage the researchers and the medical pact tis' nevers who -- practitioners that they are to be reported and evaluated in order to ensure they are able to perform the gene testing as it becomes available. It may be required to do a pilot testing on this before they are able to conduct or perform it. We are trying to corral what the perceived problems are and then trying to figure out whether the perceptions are accurate. By having such a resource, there could be an ongoing forum that is centralized in order to bring to light things that people thought rose to the level of problems. It sounds uncontroversial, right?
[ Speaker/Audio Faint & Unclear ]
[ Laughter ]
I guess -- I'm not sure I can rephrase it in real-time, because I like the first sentence, but again, Presume the access problems as opposed to the problems within the patient's access.
I think it needs to be --
Yeah, that's fine.
It needs to be more neutral.
That's fine.
You are not going to measure the access, you are going to measure the problems. You may have good conflicts or consequences that you didn't anticipate, so you may have missed it.
Yeah, I don't envision this as tackling the whole problem, but I see it as part of the transparency and filling the gaps. If you go to the enhanced access, people tend to report the problems and not the successes.
[ Laughter ]
I am trying to figure out what that means in the practical terms.
In terms of doing the report in a broad way, I want to encourage people to represent the enhanced access.
I think that part is clear, but how does one capture that? I agree, you want to do that. When you are talking about the voluntary reporting system, it is like a safety system. It is not that they say, gee, I had a really good safety system, and I was pleased with that, you need to have it where it asks for a more proactive approach.
[ Speaker/Audio Faint & Unclear ]
Please come up to the microphone.
I'm sorry.
The people who are able to disclose and are willing to provide the information on the access, and it will ensure that the data is part of the aggregate to ensure confidentiality throughout the companies and people. First of all, it's is not part of the companies only, it is also through the universities and throughout the people within the public. I think it should be --
[ Overlapping/Multiple Speakers ]
You can't get it because of the CPT system:
Currently.
And that is, perhaps something we should consider as a separate policy.
I guess in answer to your question, and I am not sure I have the perfect wording, but I think the wording should be more neutral to say, filling the data gaps and accesses. It should not be only focused on locating the problems and then as part of what the challenge is during the comment period, what to get out during that, and how they would access it during the beginning.
I would say during the recommendations of the coding issues, I wouldn't say to make a recommendation, I would just say, we would support the previous reports that the coding would fix this recommendation.
That's a good idea.
Okay.
On the theme of filling the data gaps. Recipients of the federal grants, agreements, and requirements are required to -- contracts are required to provide reports which are there I-Edison. That will include whether and how many licenses that were provided if any. They were to provide the data as a tool to help to provide the extent of the licensings and the patents that may prevent a roll role in the -- role in the diagnostic testing and data. They should assume that the licensing of genomic testing and licensing is used in accordance of the best practices.
Straightforward with the word inhibiting may provide a role in the patient's access.
Sure.
Positive or negative.
Sure. We can do that.
Do you have any specific research agencies in mind?
No, I was hoping you might.
[ Laughter ]
I think that that is something that needs to be explored. Most applicable ones, you know, and the efficious ones should be. We didn't want to get to granular at this point.
I was thinking what Rita was saying. The more specific recommendations we can make to the Secretary, the more enhanced we will be. We should probably say something like that.
Right.
There wasn't any consensus on the task force about that. I think it is something we can add in here and we can specifically ask for comments about that. That might be reasonable to solicit that time of guidance.
The easiest thing to do is put it in parentheses.
NIH.
Right, that is what most was thinking here. We may want to put that information in the parentheses, NIH, and others as recommended.
[ Speaker/Audio Faint & Unclear ]
I like it.
We have an end there.
I would note, Jim, that it is not required by the I-Edison, they can submit it by the I-Edison and others.
We can put that as -- it's the most commonly used?
Yes.
Okay. We can put I-Edison and others.
Yeah.
Okay.
We can include the data structure an the terminology or enhance the I-Edison function to submit more data at the time of the licensing they are able to submit and review specific tests. One, whether the grant provided the licensee were allowed to continue with the testing; two, that the information about the grants and the licensing rights; and whether or not the licensing has the non-essential diligence and performance. The date of the first reported sale during the testing service and the periodic services and whether it was on the market. And five, whether the number of sales and the kits were sold even if they were not part of the royalty sale. It should be designed at the time of the database and they are reporting on such data.
I will go to the first one. It's a rather long one.
Is I-Edison under HHS? Or is it under --
Will you help please stand help me.
It is an encrypted web-based system that is optional. Many parties use it. Many universities use it and it has been adopted by many other agencies. Most of the agencies within the government use it for the inventions and the annual --
So my question is, administratively, is it to provide the standardized I-Edison and is that under the Secretary's purview and I don't know the answer to that question.
It sounds like it, yes.
Are there other types of data elements or are there types of that provided in the I-Edison or the annual?
Is it in there now?
I believe so.
Well, none of us have never seen it.
Well, that's what I thought.
I thought the licensing data was in there.
To this extent?
Not to this detail. This part would be right. Well, actually, not the genetic testing part. It's the licensee and who the licensee is from the data standpoint.
So this is not a public database?
This is not, no.
So do we want that to be a part of -- Sara is shaking her head no. If it is all in there, this information, who is using it?
Well, we --
No, do we want to make a recommendation as to who should have access to this. Is it by NIH and the approvers and the grants or who is that going to be provided to?
The reports are not publicly available, so they can't be publicly available; that's my understanding.
[ Speaker/Audio Faint & Unclear ]
I think that is from the NIH, the secretary, and I presume the information that you gather is something that you are doing and how you are doing it and then that is something that the public would be able to find out.
Right. Then these types of data are able to be collected during the purview of the HHS as far as what is correct in order to find the information available for the annual reviews, et cetera.
This is provided so that HHS has the reports on the data and then they can report back to the public in a public forum, is that what you are saying?
It is saying that I-Edison should be able to access stable forms and function licensing and do that at that type of assessment.
They should be able to explore and use it to access it during the testing functioning.
The analysis should be able to be done out of there as part of that.
Okay.
All right. So no other elements that people think would be good use?
Are you really just trying to get to the point where somebody is overseeing this and making -- you know, getting enough data to make it --
Well, some kind of --
Some make it some type of compilation of the reports to --
Yeah, to collapse the data in a centralized way in which the problems are able to be --
In a way to provide the data that is not necessarily provided to the public.
There has to be a fire wall here; it can't be all provided to the public.
Can't you put this under one standard here? The Secretary can do this and then you can outline the things that are critical to that?
Yeah, I think we could. We could put things in there that are critical to I-Edison. And then you could go into detail of all of the things that need to be done.
Right.
The gist of it would be to create the reporting system and provide it to the public without the harm being done.
It's not just the harm being done, it's an understanding of the extent of uses and the granting and the office programs are able to get that information out and use it parallel to the guidances that are out there.
Right.
Essentially when we go out to the multicomplex testing, et cetera.
So basically, you do want to get the information out there.
So you need a pre-preamble, right?
Yeah.
[ Laughter ]
It should be providing an advisory board on the impact of the gene licensing and the impacts of the best practices. It should access the extent to the enforcement of the property rights. It can provide inputs on the future policy changes including any that may emerge from the come flexty of -- complexity of this report.
That's it.
Yeah, maybe we should make that the start and change the wording there.
Yeah. That's good.
We can change the order of that.
Federal grants to promote the broad licensing and access. They should promote the wider accessover the principals and the licensing of the genomic inventions and the OCD licensing of the genomic inventions and I would anticipate that would say, there is no teeth to this. But as we go on, I think you will see, the emerging potentialing to this. This is considered teasing.
When you say there is no teeth, there is actually huge teeth implied there where the federal agencies reimburse a huge fraction of the health -- fraction of health care in this country. If there is a causation of the best practices, then --
Right, but we will not be going there I didn't do do -- yet.
Right. That's fine.
It's not the reimbursement of the federal agencies and how they provide the grabs, it's --
Right and that will come out in just a bit.
It is part of how we highlight the grants and the --
Let me go on to the next one.
This is part of the encouragement of the licensing and the researching technology. These are relevant to the genetic testing. This should be incurring the diagnostics developments and tests. This should be part of the drafts included in the needs and giving the particular intentions on improving the testing and diagnostics. This is to request the nine points.
It is either controversial or everybody is completely confused. All right.
Now on the patent pooling, this could provide developments of different technologies referring to the tests. This works into every type of commission or committee that looks at this that usually isn't brought forth here. There is at least a nod on that or throwing it out there.
Federal agencies should consider providing more detailed guidance for the gene-based diagnostic conventions to use the terms and the licensing agreements, such as the due diligence to provide the quality of the diagnostic testing associated with the license to include the reversed aspects. Improve the specificity and the requirements of the test in order to meet, earn, or maintain the license rights.
Lori may want to expand on this. The idea is: Licenses are a lever which can be used and the conditions of licenses are -- can be manipulated presumably to create more benefits.
Lori?
[ Speaker/Audio Faint & Unclear ]
I understand the principals, but why in the third line, D, does it include the academic institutions.
The main reason that is in there is because we have had discussion about the academic institutions that own the patents. It doesn't have to look like it is made exclusively for those academic institutions.
Yeah, but in the --
They are academic holders.
Yeah, they are academic institutions, and some of them are not.
Yeah, it may be best to narrow it down to academically.
Right.
And I can't recall the exact discussion that reinvolved around this this -- revolved around this.
Yeah.
We need to keep it broad. If it is meant to be an NIH granting, then we should say that.
I think the patent holders would be a better term.
I think the origin is by --
Oh, yeah.
The preamble is talking about the protection of patient's and their use.
Would it make sense to say patent use?
Right.
It is just by Dole who would represent them.
[ Overlapping/Multiple Speakers ]
They are not academic institutions.
I think the patent holders would be a good place to wire that mark.
I think that we could use the qualities just to ensure they are consistent.
Sure.
I this I would be reluctant to add the insurance reimbursement here.
I can say this, I work in the insurance industry, okay?
This is not related to the contracts and the decisions made by the publics and their employers, in order to make that decision of --
Couldn't that be a leverage?
For whom?
For the individuals seeking to maintain a license?
I don't understand how it is a eleven.
Wouldn't it make sense to --
I don't understand how that would be a lever. This would add more leverage or more pressure. You can say, there is a reason for this. Why isn't there a reimbursement party, et cetera.
I understand you are sake they are generally align -- sake they are generally assigned.
Where the insurance decisions are not resting solely on an evidenced-based test or product, it is not --
Well, --
-- it is not, if they are not paying for a genetic test, it doesn't matter whether it is good, bad, or whatever, they will not pay for it.
It is by in this way an essential exclusive or non-exclusive, then you have the four or five players that have that code, and then I think that would be good for the public.
I think we are mixing apples and oranges here. I think you are trying to get to the fact that we want to accumulate the evidence, and that is a good thing, and making it stronger is a good thing, and a lot of people will come along saying, yeah, we want to pay for this because it is a good thing; but, I don't know, but I don't think I understand the mechanism of this --
Yeah, I understand. We can put one or two in there for a type of "for example," but I think the question is: Many aspects where the criteria where the licensings is are not required to, for example, spes facety and sensitivity, and that is something that is bio logical and it may not be able to be improved. That is pegged to the parameters where the licensing is pegged to. I am not sure that that is different from the other --
[ Speaker/Audio Faint & Unclear ]
If you are making a suggestion -- well, heres a suggestion take the steps to improve --
[ Overlapping/Multiple Speakers ]
[ Speaker/Audio Faint & Unclear ]
Where are you? Show us what you are saying.
Well, you are just doing what Mark wanted you to do.
[ Laughter ]
That is one option, yes. But I really think we need to have that in there and then has this in the meeting we have on the outside. Then we can go around the table there and see how everyone feels about it. Mara?
I would agree.
You have made your case for now, but then we can go ahead --
Yeah, but I want before we make that meeting available, I would like to know the reason --
Can we move on?
Can we just say we will address the specific retorte from Utah who is going to write about this?
[ Laughter ]
I don't think we should be quite that detailed.
[ Laughter ]
[ Speaker/Audio Faint & Unclear ]
So, now, licensing policies, government funded practices in NIH. They should make compliance with the best practices and genomic conventions with the future grants or awards. This is where you get into some explicitty.
What they would be saying, the guidelines and best practices are there, so in sense of that, let's use them. This would be part of the best practices and the genomic conventions.
This is part of the authority under the Dole act to require a grantee or licensee they should say that all of the licenses should be exclusive, so --
Well, we can do that if you want.
Well, I mean we can change the range of options, but --
[ Overlapping/Multiple Speakers ]
We have a system where we are free to engage in the exclusive licensings, right? So I guess do we need to put in there -- is it more than a restory call -- restory kl -- -- rhetorical question?
If the public would like that, then we should but it in there.
Yeah, I think the public should be able to comment on that.
Is there a regulation or comparable otherwise where --
Well, it is within Dole.
Right. But to the extent where it is requiring the non-exclusive examples of --
Well, there are more dramatic examples here. It is part of the --
Michelle?
Yeah, Michelle?
Well, I understand the range of options of what the case studies show. What they show is the exclusive problems within the licensing. They don't show the non-exclusive problems within the licensing.
Right.
Maybe we should submit that and be more explicit in the guidelines. It is not picked up explicitly in the studies, but implicitly in the guidelines. They have existed for a while. And the nine points have been in existence for a while. There is no problem with that, but there is small universities where you don't have the backbone where you have to go up against the companies with the exclusive licensing. This will give the companies to say and have an option to say, well, we are going to lose our grants if we don't follow through.
I think that is something the case studies need.
I will not go back through and clarify the small, large, or no backbones, there are some that have no backbones, small or large, that have the --
[ Overlapping/Multiple Speakers ]
No, I agree with that.
But I think in general --
No, I agree with that.
Right.
[ Overlapping/Multiple Speakers ]
I think as you describe it in there, we should generalize on how they do it. HHS can do it for the grantees and the contractors, but I think the issue is to provide access not necessarily on how they provide the access, but I would be more comfortable, one step back, on the last one where that is a key issue, not that we are telling them how to do their business.
That's fine. That is why we are putting these out there, people are going to have different opinions and feelings about this and how they want to do their business; again, that is why we are putting these out there. This is another possibility that we can engage in. It's on the table, right? We don't have to do anything, right? Everything is working find, we understand it, and we don't have to do anything.
But the nature of the case study is that sometimes there is problems and sometimes there are no problems.
Yeah, but we didn't see any evidence saying, Boy, this is the way to go.
Well, I saw it in the Bracka -- [Phonetic] -- versus MPH HCC, I saw that.
Well, we need to move on.
It may be an issue where the costs of the tests would be high.
That is a good point.
Well, it may be a presumption, but --
[ Overlapping/Multiple Speakers ]
Would it help, not just for this one, but where you have the list of the different points, sometimes I get the impression where you would like to do 1, 2, 3, 4, or 5, and the others you say, we would like to do A, B, C, --
Right, but.
Well, I am trying to --
Right, but --
[ Overlapping/Multiple Speakers ]
There will be different points where you have recommendations in 2 that are not compatible with C or h.
Right.
We are bicycle to take great pains in in -- great -- going to take great pains in illustrating this at the start. Some of these are mutually compatible and we recognize that. All of our jobs will be after we meet again after the public comment is to reconcile and make sure that are internally consistent. I want to point out for B and C here we have asked for clarify in the statute as far as what falls under the purview in the HHS and what doesn't. I think these are appropriate and I don't think they are necessarily loaded. I think the clarification of the authority is as a result of the --
Right.
We need to understand where the HHS can operate within the scope and when it can operate out of scope.
I agree.
I think these are important recommendations from my perspective.
Jim, I would like to point out, my concern in C it doesn't say, never exclusive licenses, it says it should be tailored.
Right.
It should be a propriority format that the company has and it would not then be an objection.
I think Michelle's issue on the presumption may lead to that, but I couldn't agree more there are situations where --
And for all of the diseases and --
Right. That is a perfect example.
This should provide a commissionable study on how the diagnostic reviews are advancing. This is to look at how they are used.
This is to commission a study and how they are interpreted and applied by the Dole Act in terms to and in relation to the acquisitions and studies and negotiations. Okay? So this focuses on the U.S. PTO policy, and this is trying to clarify the issues in that. It recommends that the Secretary of Commerce -- that means we are recommending that one other secretary recommends to the other. We can't say anything to the Secretary of Commerce, but we have to reflect in another approach, and I don't know if there is a more stream lined way to do that.
We have to establish a committee related to the genetic tests and the technology that may form a patent of locations and specification; B, to have the non-obvious guidelines in assisting the personnel and the diagnostic the -- purposes that were established in 2001. I am going to wait for C and talk about that in a second.
Comments on A and B. In other words, we are trying to offer help on -- yeah?
We am going to comment on B. We want to wait for [ indiscernible ] to come out. We probably don't have enough information to crack guidelines specifically in how to tell our examiners what is or is not obvious in how the [ indiscernible ] comes out. It is a about a gene, a broad claim of the gene, where the board of appeals says it is not patentable, it is not obvious, it is using a KSR stipe and language -- style and language in other words to make -- in order to make that decision. We need to wait to see if it is obvious.
You are saying we really wouldn't need anything like that, right?
We would need a recommendation on the -- the obvious would be to crack the new guidelines after we get the decision rendered.
Right.
So after the decision is rendered?
Yes.
Oral arguments are coming up this month, and I don't know what the --
Is that going to be in the Polly Newman reports?
I don't know.
You have Claussen which is a die die diagnostic survey, and we haven't heard anything about that and it has been out for a year.
There is really three cases: There is [ indiscernible ], [ indiscernible ], and Claussen. While there are three comments in the [ indiscernible ], where they talk about the essays and the diagnostics, there are only really three cases that are pending in the Federal Circuit that have not yet been decided, Claussen being the oldest, and they are waiting on Billski being the -- to be decided.
Billski addresses the issues of associated patents. Remember, for example, the me -- metabolite case where the vitamin B12 deficiency in that patent. A decision written by Briar said that the court should have granted that because there were implications on the required best practices. Billski was requiring that it -- the associated patents are not going to be looked upon favorably, but there are other cases reflected upon that. I think there is a significant feeling in the medical community as a whole and the genetics medical field in which they talk about the associations of the medical patents have an effect. What I would say the next recommendation or draft is is to prohibit -- is to prohibit the associated patenting. That is the background information on that, if that makes sense. Are people generally okay with having these out there in the draft proposal? And with those, which are especially mentioned in the last ones.
I want to make a comment on the last slide where you talk about the diagnostic talk about the assays, those are the bio-medical technology part of the industry. That is depending on whether they are enforced or not and that needs to go out before it can be considered a recommendation or not.
Yeah, we are getting into those to which are more controversial and which ones have the most inherently proposed opinion.
I think the language that we use is something where the secretary can change that.
Okay.
It's a matter of legal --
Well, I think there are a couple of mechanisms to do that.
So, you are just saying it is clear to --
One would be the statutory recommendation, right?
We can do everything in this slide, and we are going to. We are keen on what the certificates are and we are -- circuits are and we are obligated to follow the law. We will have to develop the guidelines and examine the trainers once that comes out.
Exactly.
Now, we will get into the ones that are more controversial.
[ Speaker/Audio Faint & Unclear ]
Yeah, we will get that.
You shall work within the administration to encourage support. You need to follow these options:
This is an operational question for the next time we get together for the public comments. We can predict the public comments. We will get a lot on one side and a lot on the other side and then we have to adjudicate those. When we don't have a sense of whether this is a good thing or a bad thing --
Oh, I think we have a sense.
Yes, I agree, but we need to predict which side it is going to be on.
Well, this is the start of the topic where I see is the most difficult and the contentionous that the Secretary has to address. You know, on certain aspects of the genetic discrimination, that is apple pie. That is an easy decision. People have different reviews on these things, but --
Yeah.
I don't know how we are going to do it, but we are have to -- will have to try and make it easier.
If we know that the public comments are going to be polarized, would it make more sense to pull this out or --
No, not at all.
I think the public --
No, I don't think the public will weigh in on that or help us to solve the problems here.
Well, just because --
Well, I think we need to provide those options to the public.
Well, it's not part of the way we can operation -- operate.
We should put something out --
[ Overlapping/Multiple Speakers ]
It looks like it.
It looks like it.
That is the issue.
Options that you are giving are punitive options. They are not balanced.
How would you remedy that?
We need to decide that before we go out there before the public and decide it as a group.
[ Speaker/Audio Not Clear ]
[ Overlapping/Multiple Speakers ]
The secretary needs to look into the issue and provide that as a propriority --
Well, we can't.
-- right, we don't have the points to make the decision, but we should --
Again, I think I am missing -- I think part of this is getting across to the public that this is an option. It has been an option. We are not the first to raise this option. We need to bring it forward and raise it as an option.
I think one of the concerns here with this section, why is it distinct?
I did -- it is distinct because it is controversial and what have you, but it is a level of concern where they flow from the case studies and they are potential remedies to that. Can the same be said to all of the options that are proposed in this section. I don't feel like that about the most severe ones where they are -- they may be right or wrong, but in either case they do not flow from what the task force has develop d in the case -- developed in the case studies and that raises a level of concern with the elements contained in this section.
I agree with you. The one that flows the least is 7A.
Let's come back to that.
Yeah, just hold on one second.
I think this is something that we see as an operational flow that we have seen. Whether there are patents on the basic association or the -- or are not the basic associations, I think this is raised very much by if case stud -- by the case studies and I think it would be odd not to put it in here and let the public comment on this particular one.
Yeah, well --
Whether it is part of the gene patenting.
Yeah, and as we discussed this and we talked with the task force conference calls, should we have that, add it in or not add it in, but one of the things that are out there is that it would be remiss of us to not include these recommendations. We are supposed to look at the whole land scope.
Joseph?
I would agree with the last statement and the admonishment that we need to consider it in advance if we can. It seems that this section is begging for a preamble; if nothing else, it is asking for a clarification. By the time you get to this in the review and public comment, you may not necessarily have that level of recollection or considerations. For practical reasons, I think it is important to have it here. You should have the options that allow you to run that in a bulk for those provisions. You don't want people to react to this, you want them to give you thoughtful and recommendations that we can truly consider.
I like the idea where a preamble would encroach this.
I think it is wrong to pre-suppose that.
We are thinking only about the genetic testing, but this would majorly screw up Pharma. There are ways you can do that without messing up Pharma. You can do this through the HHS-A in order to develop the technologies that people are needing.
I think the issue we have here is clearly at one exstream. Is the intent -- extreme. Is the intent to be provocative?
No.
Maybe there is --
Well, --
Let me finish.
Maybe there is an emotional finish there?
This is no different than the republican committee sends me a survey. It is all about the way the question is asked. We have to at least say we are putting these out as intentionally exteam solutions to -- extreme solutions to the public comments.
As I have said six times, these are ranges of options. I would urgently tell you that we are not trying to be provocative. You may find this provocative, and others may find that in an exceptional and reasonable policy option. I think to ignore the policy options that are discussed and that people people perceive as problems -- I mean, if you look at the policy issues, these are patented allot. I wouldn't take it as we are trying to be provocative, we have been provocative a lot. But I would make it clear to people that we are not wedded to these and we want to get people's comments. Who is next?
I think we can put in a preamble as it was recommended earlier on these issues. I think we can also provide the list of options and provide that to the community.
Two comments, I still have a problem with the broad range of options. If we want to have that, we should reinforce the options in the at enterprise systems and --
I think that would be reasonable.
Same with me.
I think that is reasonable.
[ Overlapping/Multiple Speakers ]
I agree with Mark, and the way it sounds is the issue. The way it sounds -- I think the survey example is a good one, but it passively implies that this is the -- what the [ indiscernible ] that we are putting out. It is only --
[ Overlapping/Multiple Speakers ]
I am not ready or comfortable in doing that.
Would they be okay in putting in the option of doing that? Maintain the status quo where the exclusive licenses are --
[ Overlapping/Multiple Speakers ]
That's the --
Okay.
[ Overlapping/Multiple Speakers ]
Are we here to represent that we heard 90% of the views on one side, and then we say, well I feel 10% of the side is here to say, I agreed.
I don't think we are here to try and guess the publics feelings or comments. We are looking at the range of options and listening to them. We are trying to provide our best advice on thorny issues. We think our -- we should provide that our best intent of the Os are included -- options are included for the public. After that, we will have another enriched discussion. We need to decide today what are the kind of things we want to lay on the table because they are within the reasonable realm of possibility where we are going to elicit comments on. I am fine with having something in here if that is the consensus, that is more ardent about maintaining the status quo. I don't want to be seen as provocative, I want to be seen as seeing all options.
Can I be heard?
Sure.
I think the preamble that we are talking about is to say: Looking at the results clean from the case studies with the goal of making the technologies available to patients, right?
Right.
Right.
The best option for the statutory change is ... and then you put in your list of availabilities and options. You are saying this is the list, and I don't know in this is the -- if this is the whole list that you want, but you can say we are proactive in this area.
Right.
Yeah.
Right.
You still have the status quo or something on --
Yeah, that's right.
Yeah.
Yeah.
Right.
Yeah, I agree with this too.
[ Overlapping/Multiple Speakers ]
I think there are profound economic issues in this that have not been taken into consideration. Our affiliates said there are going to be a chilling effect on the economic. We need to look at this as a more perspective grouch -- group we are not economist. We have to look at what is the global aspects and what reflects our -- what recommendations on the reflection of the diagnostics are going to reflect on the health care industries. I think there are many other things that need to be taken into consideration, and then we need to put a stake in the ground rather than saying this is the come option.
I think that is a key part of the ring. We have to face some hard decisions as to whether or not we come out with specific representations or not. That will way into it. Did we have sufficient expertises and did we take the sufficient accounts into consideration?
We must move on.
Just one more.
There are aspects offense the associations that are -- aspects of the associations that are part of the institutional studies. You wouldn't necessarily come to say, this is where we should be.
We can talk about this all day. I think your points are well-taken. I think they are well-taken, but they do relate to patentable subject matters. We need to clarify in the preamble or in the text or the reports that are going out, why are we picking this out? Why are we relating to this in negotiations or associations within the case studies.
It has to do with what is the patentable case studies.
Yeah, but for those of us who were not involved in that case study, you need to explain, where that went.
Wow, they are dropping like flies.
Yeah, I have a quick comment. With respect to the preamble that was commented on, we would like to have specific comments with the specific requirements so it is very targeted no matter what we get back. It will be very targeted and very clear as to what our goals are.
Right.
I would add that part of the recommendation up to this point is is that the -- is that a committee is there to conform this committee and I am trying to address those issues.
Okay. In the vain of trying not to be provocative, we are impeding the designation of the diagnostic tests. I think this is in relation to the subsequent ones and then we will go back. Now this is in support of the legislative change with the following options: Infringement on the liability that are ordered to use the clinical care and diagnostic tests and they should be held liable for those tests. This is part of the issue within the diagnostics. This is part of the landscapes and this is what CE-2 is trying to represent. This is in the pursuit of research. The only reason they are underlined is to make clear of their differences. The health care industries should also be covered by this exemption. Again, we are talking about the 7-B, and 7 D. I think it is important to craft a preamble that states that this is arranged. We are not wedded to this. We want people's specific comments and I think that in the -- in the -- in the spirit of trying to adapt or adopt what Mara and Mark said, Do you feel there are other recommendations -- are these unbalanced in your minds and could be balanced with the other recommendations that are on a different end of the spectrum? What are your thoughts about these? Well, sense it was addressed to me, I will say: These are much less reflected on here. This is just to add the ignorance on my part. This is opened up to the landscape that could or would damage the industry in relation to things -- you know, in terms of the clinical provisions of the tests as opposed to a researcher's test to do research and gain knowledge. I as a practitioner, when I write the order form, am I dealing with reliability?
Yes.
I have to go back to disagreeing with Mark --
[ Laughter ]
That's the moral of the story.
Yeah.
Are you speaking in terms of a recurring event in terms of --
No.
Well, if it's in the pursuit of research at least until the patent is granted, there is no ability to enforces the patents --
Well, --
I mean, towards what someone is doing.
[ Overlapping/Multiple Speakers ]
Yeah, if it is -- granted.
Yeah.
I don't mind being provocative, but the only way we can be that way is throwing this out there to the group. I don't mind being provocative, but I think --
[ Overlapping/Multiple Speakers ]
I think this is to see how it is flowing from our case studies to our --
Yeah, that is from the fundamental part of the case studies; for instance, C-1, and also C-2, it is the one that is essentially undercutting the --
No more than the --
Well, for the referencing of the diagnostics.
Will, it could be in a way that there is a con estimation of the -- consumption of the --
Yeah, but in the way of --
[ Overlapping/Multiple Speakers ]
It is part of the clinical care for all of the patient's uses.
There is some confusion in the rooms. A lot of the option we should -- have so far -- that we have so far is the way we know it. It is not necessarily possible right now under the law. Some of the judges in the Billski case says they don't believe that the law is patentable. They used to think that there was a research convention. The Supreme Court indicates that the Federal Circuit should rethink that. And the Federal Circuit has also admitted that they should go back through and research that. So all of the things -- as Mark pointed out, the clinical care one is the extension of the Gangsty -- [Phonetic] -- rules. This is a national progression of where the various judges have reflected what their thoughts are and what the law is. And the question is: Should we create a statute to this? It is also a question of: What do you think the study is? I think that is helpful to the judges.
I agree with that.
To me that is not the point.
I agree with you Rochelle. I feel that I --
Right, but that is not what we are discussing here.
[ Overlapping/Multiple Speakers ]
But if we go back to -- a few minutes ago, we were trying to make the decision, should we go through these in detail? Kevin suggested that these are strawmen -- [Phonetic], and should be reflected as the strawmen -- [Phonetic] and I just want to know for sure.
Yeah, what we are doing here is to decide whether they make sense? And the other thing we are trying to figure out is: How do we go about it? How do we grapple with these? In the vain of not being provocative.
Yeah, now we hear that.
We are encouraged to hear the legislative change. We will recraft the preamble ast try to make this -- preamble to try and make this a little more clear.
Let me just read these as a unit. We require that the patents are limited to the utilities specified in the patents, use them for diagnostic purposes, or prohibit the patents on those surfaces. We have a lot of discussion as to whether or not exhibit 3 should be in here. It has been introduced in legislation in the House, right? This is not something we can conduct, we have to discuss this. We need to make differences as to whether or not that is a blunt instrument or not. I think it would be a glaring omission not have that in there.
When you say the DNH issues, do you mean a clinical decision?
Oh, I forgot --
Well, that's why you pay me.
Yeah, that's where you dry the big black truck and the big black rig.
[ Laughter ]
That's a comment that I picked up.
Somewhere in the draft, somewhere in the comments we were going to address that. As I was looking through the draft, I was looking at that and I think, perhaps, we didn't get that in there. We were look agent the DNA and the sequences and as to whether or not they relate to health. This is a messy issue in the corner and we have 18 minutes to resolve it. Should it include SARs? Should it include the human pathogens?
What is different here is the development of human patenting. I think it is dealing with the natural DNA and not man-made DNA.
I think what Kevin was eluding to was the human pathogens.
[ Overlapping/Multiple Speakers ]
John?
Well, firstoff, I don't like the recommendations for the same reasons that I don't like the previous ones, I think it was quite chilling.
I think you should include the pathogens or the other DNAs that are associated with the diseases. I think you want to be careful when you crack this so you include the industrially useful proactive pathogens.
Right. Steve's suggestion is to clarify it as health-related issues.
Well, does that include the nutrition?
Medically relevant.
Precisely.
Plants are being used to genetic genetically grow and use that as part of the vaccine.
Right.
[ CAPTIONERS TRANSITIONING ]
(At this time, the Captioners will be transitioning, please hang up your phone line and reanswer. Thank you).
DNA--
That just reminded me of something on a coven freeness call that addressed this, by having diagnostic purposes in there, in many ways this solves much of this problem. Talking about diagnostic purposes would include SARS, the human genome factor --
But if you are putting -- you have to put the third one, the idea of diagnostic and that's therapeutic.
That is the most extreme, because it's --
Much preferred B 3 than B 2, separate one part of --
That's your opinion.
Of course. But the idea of looking at broadly, I think, having a line between a therapeutic vaccine and what's a diagnostic, what's a therapeutic, somebody made the point before, we will be thinking forward in the future, the lines will continue to blur as to how we use a drug as a tracer.
That's -- right.
Discussion [indiscernible] Andrea, we -- okay, all right.
I want to -- I think once you make these rules for DNA and RNA, there's not a big leap to go to proteins, metabolites and these other --
I am just bringing it up, okay.
I assume this would include that.
It says DNA.
If we use Rochelle's definition, I assume -- do we assume it's the broad ire definition of naturally occurring substances, so RNA --
I think one could further consider nucleic acid, but to talk about proteins --
How would it be different if the next wave of technology --
Look at our initial definitions at the start. Talking about diagnostic tests that are pled predicated upon the analysis -- I actually do think, you have a point, this should be nucleic acid sequences, not RNA, RNA is a major player.
Jim, I think it might be good to get some sort of legal opinion on how difficult it would be to take the language, trajz translate that into --
The point --
Everybody might get upset protein patentings are getting --
That's not on our scope. Somebody needs to take a look at what, how big a leap --
That could be something we could talk about whether the committee should discuss, but I don't think it's in the purview of the scope --
Except in the oversight of genetic testing.
But now we are talking about --
We defined genetic test in that document.
We did.
But for very good reasons, I think.
Okay, so, now, discussion questions, we have been hammering this out. Here's the big question. Disiewng DoDo you think there should be anything added that isn't here?
We talked about the preamble and --
Right.
Yes, so that assumes we are going to include the broader range, including status quo. I don't think we came to a definitive decision on whether there should be an action we should encourage exclusive licenses. That seems nuts to me. Is there strong feeling we should encourage that? So, status quo would be appropriate.
So with the changes we have discussed, should we release this for public comment with the understanding it's a draft and we will make that clear, and we will get the public comment, going to be quite a conversation.
Just to be clear, though, taking the comments we got today, making the revision and as you stay, the task force will look once more.
Right. And in December, if approved, we will send it out, February April will be comment period, April-May analysis, so clear your calendars for those delightful calls. In June we all meet again and discuss preliminary findings, it's the summer of 2009 we will revise the draft report and it will be the October 2009 meeting we hope to have final recommendations. That will also give time for some of these decisions to --
I think you started to say, if we get crystalline recommendations to give to Jim, that would be great. But -- leave ourselves open to October.
So, with the public comment indication, how is that going to be worded because you could say, just comment on what we have written, or is it open to bring other ideas, can people say what their own experiences are?
Sure.
I think that request for public comment is really critical.
Right. And Yvette is pulling that out. not just confining your comments to these particular.
I think we should encourage people --
The Roman numeral 5, briefing book, tabs in the beginning, the note that goes along to the public.
Tab 3, Roman numeral 5.
Having gone through the process from the patent office point of view, I can guarantee you they will not be afraid to let you know what they think.
Actually, on that note, building on past experience, up have to ask Andrea, I think you will get a huge amount of --
I completely agree.
That will take you --
All right, thank you. It will be very interesting. That's right.
Question, in the vaip of vein of the large questions, there other organization we want to ask that need to be notified, or does the notification process --
I think you guys have basically a large list of -- right, of whom to target with regards to soliciting comment.
Maybe the committee, given this is a more legal view, than some of our other, maybe the committee could give recommendations on other people to --
Absolutely.
We want a this widely disseminated for comment, anyone, please let us know so we can target.
Great, when would this, after the committee reviews, go out, that would count for 60 days -- back to the slides -- okay, so, again, February to April will be the comment period. April to May will be analysis, meeting we will discuss preliminary findings and [indiscernible]
We will be mid-course.
So with emphasis on the word preliminary, data revision of the draft report, taking place in the summer and we hope to have the final [indiscernible]
Well done.
Controversy well done.
Sure. Okay. All right. So Jim and colleagues, tremendous to get us through this. [Applause] many thanks to all of you. That was a very rich discussion, appropriate one. We will take a break. Since, most of the folks here, why don't the we begin at 25 past and will hear comments from NIST, other agencies about standards.
Thank you all very much.
[Recess until 3:25:00 p.m.]
If you can join us, we'll get going again.
We're going to begin the next session, but a couple of housekeeping notes first. Those joining for dinner, you can meet us at 6:00:30, or if you would like to walk or, meet in the lobby at 6:00:15.
I would like to bring to your attention there's a draft letter to the incoming Secretary, secretary Daschle, that talks about the work we have done and some of the priorities we think he should have early on in his tenure. This is presuming he, I think it's not officially announced he's the incoming secretary, but the papers seem to say he is. Anyway, that's the presumption and needs to be approved. If you have comment on the letter, we will be discussing that tomorrow.
Now we are going to turn our attention to standards development, initiatives to enhance oversight and -- technologies. As many of you know, who worked so diligently on the over sight report, reference materials play a critical role in genetic test results, use ed in performance test and oversight report we identified a number of significant gaps in the oversight of clinical lab quality and called for stronger [indiscernible] requirementless, proficiency testing and development of reference materials, methods for assay analyzing and platform validation. Quality control, assessment and standardization. The National Institute of standard and technology, and CDC, the federal agencies most involved in addressing the quality control and reference material needs. Currently reference materials are available from only six of the more than 1300 -- amazing. Giving importance to this area, we thought it would be useful to spend time exploring how the -- and innovations in the field, biomarker analysis into crinical practice, larging about the opportunities and initiatives urent way.
We want to explore the impediments to greater private sector involvement and incentivizing commercial efforts. I would like to thank someone, Michael Amos, for helping organize that.
We will start with a presentation from Dr. Dr. Willie May, Dr. John John Butler, metabolomic and -- to round out the presentation, Steve Gutman will discuss measurement and standard challenges facing FDA and Dr. Jeff Cossman of the critical path institute, Dr. Ams on will discuss -- and diagnostic testing, based on the multiplex determination of complex biomarker signatures rather than single markers of biological activity.
While the focus of today's presentations will be on NIST's efforts, we also want to remain cognizant of CDC's work in this area, the newborn screening program and the reference materials coordination program. We showcased these efforts in the oversight report, and Dr. [indiscernible] from CDC is joining to represent GET RM, the program's current initiatives to develop materials and array base, genomic hybridization, hi resolution analysis of chrome somal analysis.
Kenny Keller is here for the CLEA program. Tab 4, biosketches in tab 2. We don't have all the presentations in the notebook, but the remainder will be available tomorrow.
So thank you Dr., may for being here.
Dr. Willie May: I would like to talk about our organization, basic mission and some of the new initiatives we have, specifically talk about why we would be involved in -- since we are not in CDC, FDA or NIH, talk about current activities in the area of bioscience and health. I will say now that standard genetic testing is a very small part of that portfolio, but perhaps one we can convince us to increase and talk about how we are connected to the international measurements standards community. Our organization was born a little more than a 100 years ago, to support manufacturing, commerce, makers of scientific apparatus, support the a.academic sector, it's like the charge was given to us last year, the focus of a lot of our activities. Early drivers, and excuse me if I talk fast, I have lots of slides and I want to get through them in 15 minutes.
We were in the midst of the industrial revolution, and people noticed construction materials were not of uniform quality. Also, there were eight different values for a gallon, if you drove from the East Coast to Chicago. They needed standards for the electrical industry, scales were note standardized and often biased in the favor of the seller, as you might imagine. The metrology standards to support the railway system. Lots of trains were jumping lots of tracks. The thing most alarming, we being who we are, we didn't like sending our instruments abroad to be calibrated. This led to the national bureau of standards. We don't have the lead agency for health, environment, food, safety, nutrition, we found having this ar cane mission of being responsible for nation's measurement system, we had to change the focus of our activities continually to focus on major problems of society.
Today our organization has four major components, the NIST laboratory, remnant of the national bureau of standards and we manage the Malcolm -- quality award, the Manufacturing partnership and the technology innovation prsm, used to be the advanced technology program, perhaps after the session if anyone has questions on any of these programs I can share those with you.
Our mission is to promote U.S. innovation and industrial competitiveness by advancing measurement science and technology in way that's enhance economic security and improve quality of life. If you were to look closely, this part and that part changes, the words change, almost every administration, but these three bullets have not changed to any substantive effect over the last 100 years.
The NIST laboratories are responsible for maintaining the expertise and facilities for providing this measurement standards infrastructure to support the U.S., that work is carried out by what we call the laboratories, the chemical, science and technology laboratory being one of 10. We are organized pretty much like aity cam us, university campus. Primarily, lots of work goes into the realization of seven basic units of measurement; things like improving our realization of time. Right now the NIST atomic clock is accurate to 1 second and 30 million years. We are working on clocks now we think will improve this by three orders of magnitude. You might think why would you do this? My watch works fine. Things like GPS, you don't think about, interstellar travel, very depend I want on time , time dependent.
The -- in Paris, if you look at editorials in the popular press, up find the kilogram is set to be losing weight, about one part in 10 to the eighth per year. We don't really know that's happening. All we know is that the mass of the kilogram relative to the mass of about 30 other prototypes based on that seem to be changing over time, so the relationship between them are changing, and that's a practical reason for changing but there are also pure scientific reasons, to try to establish the electronic kilogram. There's an approach, something called the watt balance, new definition based on Plank's constant most likely, then to lock that time will take this kilogram and then have a device called the watt balance, different countries have different realizations of this, to balance electrical force and mechanical force to try to transfer this, and again that realization has to agree to about 1 part in 10 to the eighth, and right now about one to two orders of magnitude off from that. That has to be completed z in 2011.
So this is traditionally focused on -- on the physical science and engineering. Identified as area for significant emphasis and growth at NIST. In the biosciences, leadership looked at our mission, we feel it is congruent with our mission and our mandate to support U.S. industry and other stakeholders overcoming measurement standards related to challenges in the biosciences; to provide confidence in results from measurements and enable and facilitate realization of the maximum economic and broad society benefits of new innovation. We have this discussion all the time, NIST should be involved, no, not at all, innovation will take place whether NIST exists at all whether we maintain the infrastructure to support comparable measurements over space and time, will provide the infrastructure to allow society to gain maximum benefit out of new realizations, at least, new innovations. The other reason we are doing it, emphasis of the administration, better understanding of complex biological systems and I think this will continue into the next administration, the executive branch, let's say.
All the agencies come to us, this is one quote from the Deputy director of NCI. There is an oversight committee that NIST has, the visiting committee on advanced technology, we heard from two of its members that NIST should also expand activities to support the biosciences.
Well, actually, we have been involved in bioscience activities for quite some time. In the ' 20s between nifert nift NIST and American dental association, things we take for granted like amalgam fillings, drilling, [indiscernible] developed by a number of employees of the American Dental Association who work at NIST full time, about 30 people, who many people don't know the know they are NIST employees, work their full time. We started a program in radiation and physics, x-ray calibration and [indiscernible] form suiticals, started in clinical diagnostics in the 70s with support from NIH, primary -- for electro light and metabolites, glucose and so forth are, if you will, an E eke E electro light, and then serum based -- and biomarkers for proteins, peptides and DNA.
This is an example of some of those small molecules, primarily electro lights and metabolites we had standards for a number of years, reference measurement procedures and standard reference materials. Then, about 10 to 15 years ago we began to focus on more challenging biomarkers, and these are some of the things we worked on. As you see, two of these might be considered genetic standards, but my colleagues will talk to you about some of the more in-depth details of expansion in this area.
NIST spends a little more than 10% of its appropriated funds on bioscience activities by or own self-declaration. Of this, around $39 million, focus on the biosciences, 10 is a result of that, the other by individual laboratory directors to reprogram fund intuse this. Right now we are in the process of developing a strategic plan to support growth of the program in biosciences and to do a better job of directing some of the funds we already have. Right now, to be quite honest, each laboratory has its own program and to get maximum impact out of the resources we have, we are going to try to coordinate this in a much better manner
To go through some of the activities we have, projects we have that support healthcare, what is the typical role of an organization like NIST?
We see all the national institutes around the world have scientifically sound, metro logically based measurement science, not weather, based competencies and measurement capabilities that are vetted internationally. That depends on the delivery of a number of measurement services, one is certified reference materials and standard reference materials is the NIST brand name for the certified reference materials we produce.
Now i the Treaty of the meter was developed, this collegial group of national standards institutes around the world, those that existed, before NIST existed, and then NIST joined in the early 1900s. In 1999 there was a mutual recognition arrangement that required three things. All national standards institutes declare and document the measurement capabilities we use to deliver the services provided. They were also, by signing this, you said you would agree to participate in very formal international comparisons, so you have evidence to support the claims you are making, and further maintain a quality system to underpin your dissemination of services you deliver using these techniques you vetted and prepared. Now based on over 200 nationally designated institutes around the world.
This is the European union laboratory, Korea, the U.K., NIST, of course, and the German laboratories. This basically shows how well our cape abilities for providing reference -- agree with each other. This is a more recent one, completed this year, and this is court swrol, serum, projest roll and serum, I think that's China, U.S., Germany, Korea, and then progesterone, same laboratories, Australia's. andnd Mexico.
In this example, certainly, if there was a -- developed by Mexico, based on this analysis that might be -- to question, if you will.
So the MRA is about documenting measurement capabilities that national institutes maintain, and looking at how well those measurement capabilities compare with each other. Also, around 1999, there was this European directive that said the traceability of values of scientific calibrators to reference material must be available through available reference materials, materials of a higher order, and that the U.S. IBD manufacturers and metrology community, said we need help with this, without that we won't be able to fill out products in the European union. At NIST, among all the stakeholders, establishment of a global consortium, professional societies, metrology institutes and regulatory bodies, this organization became named the Joint Committee on Traceability and Laboratory Medicine. The committee, international committee on weights and measures, the national metrology community, for pharmaco[indiscernible] and the accreditation community.
The product from this is a database of higher orders reference measurement procedures, certified reference materials, and laboratories that provide reference measurement services to the clinical chemistry community. Another work product other than this database is the comparison of standards in the database to see how they compare with each other. The standards, say three years ago, for cholesterol, came from two places, NIST and a Japanese laboratory, how they compared. Any of the certified reference materials in the database, they agree to within less than 1% from each other.
This shows the two reference measurement procedures for cholesterol that are identified in the database, and there are only two. This is how well they agree with each other.
The world is changing, and we realize we have to change at NIST. [indiscernible] will talk about this, I will just say one of the future thrusts for us is to look at tools for visualization of disease signatures and the new program that we are putting, Nigh initiative new initiative for 2010, beyond we will have two years of focus, medical imaging and protein measurement science. At this point we don't have standards for genetic diseases, but after discussing with you, if the general capabilities we have won't support that, then there's a opportunity to amend our current plans. So, thank you for your attention.
[ applause]
Happy to entertain questions.
Sure.
Question: 40U How do you -- first, very impressive history. How, in brief, how does the process work, how do you get the communication and time frame to do that?
Right now we are developing a strategic plan, putting together in the strategic plan, have cataloged a number of workshops, conferences, visits to stakeholder communities, captured conversations we have had when we had official visits from stakeholder communities to NIST to develop some cohernlt plan for NIST. What we have done in the past is, individual divisions would conduct their own needs assessment, and lots of the standards we have now were developed because of input, most often from the American association for clinical chemistry. We would have workshops at ACC meetings often, and try to interact with -- say what are the X number, top priorities, if you could give us priorities, what would the top five be, for example. Basically, yes, to answer the question quickly, we get input from lots of sources, distill that, look at the highest priority and then match that with the capabilities we have, because if there's something that's a high priority, but we don't have the skill set to address the problem, say within the next two or three years, we tend not to do that, address that, won't do us any good to have an answer 10 years later when probably the priorities have changed.
Do you use the same societies to disseminate the information after you created your --
I guess we disseminate information probably poorly. We have our website. The standards are in our standard reference materials catalog. Right now NIST has about 1400 standard reference materials, about 1000 of those have values assigned for chemical, biological an owe light, a lot of customers, old customers know to go to that catalog to search for what they need. What we have not done as effectively as we should, provide avenues for new customers who don't know what we do, one of the reasons we are down here today.
Question: [indiscernible] wonderful presentation, I had a question that on that cortisol measurement you had, because it is true the same sample, different measures -- genetic labs, sometimes you get disparate results, would you be willing to do the same thing with genetic companies, see what is the divergency rate?
We could, but normally we look to the CAP and other accreditation bodies to see what the -- the laboratories that are supposed to be providing traceability to the private, the companies within their region. So, obviously that's not perfect because many right now, more than half of the standard reference materials we sell at NIST are sold internationally, not within the U.S., people are free to get their reference materials from wherever they want. But this, basically, is information to the national institute as to how they should stack up relative to others. You may ask how we know the true answers, these are not spike samples, we use naturally incurred samples. A lot of intentional, at least a lot of intellectual debates, have each participant go through their methodology, shoot holes at it, try to discern from the arguments which laboratories will be used to assign the reference value. It's not just if you happen to luckily get an answer. We look at the materials, for example, LGC, their information can't used to define this. Turns out, they were right on, but in the description of their methodology there were issues. Same here, only three laboratories we agreed, consensus E had a sound approach. These are not -- so everybody develops the approach in their laboratory. This is not using one published method. Methods of the highest metrological order, defined by that individual institution, and then we try to get from that to discern what we think the truth is, and then compare things against that.
As you bring the information back to NIST, assign a -- before you commercialize, the end users again to see if the value changed and do you periodically send surveys out to some of the laboratories to re-check the values?
Okay, it's within our policy system to do a stability check on all of our reearns materials. Some of them we might take a year, two years to make a measurement now. And make another set of measurements in our laboratories, say, a year, year and a half later to assure ourselves that the matrix is stable. So it's not until we have addressed all of the issues, and every certification company is different, depends on what the material is, how stable we think it is, other measurements to try to assure ourselves that in fact the values are correct and the material is stable. We do all of that before the customer ever gets the material.
In your opinion, the different anolytes for materials, different types, conception to distribution, but a meantime from actual formal distribution --
I guess back when I worked in the laboratory I could give you that answer, but -- it varies so much. I would say for a clinical material I would probably say two years. David, do you think that's about right? And for a sort of genetic standard, how long would that be, John?
[indiscernible]
A year?
Year minimum, probably maximum, two to three years from the time we begin working on the project. From the time we get input from the stakeholder community, that could be three to four years, getting input, deciding this is going to be our priority, that might take 8 years time, we get lots of input from lots of people. Part of that is deciding internalally, making sure we have resources for a successful campaign, development of the reference materials.
Thank you very much. We are going to take the next three presentations in a row and take questions after that.
I will turn it over to Dr. butler.
Dr. John Butler: Thank you for the opportunity to address the community today. You will notice the slides, two new ones, should some will be hidden, but I want to show some of the things done in the past, some from now, new genetics group formed within the bioscience division the at NIST and thoughts for the future. Most of our experience in the past came from forensic testing, materials, assays, new technologies for improving forensic testing, something that has been well-noted in the press in terms of the need for good standards and quality measurements.
In terms of the present, the two months ago, developing reference materials, now applying to clinical genetics and agricultural biotechnology, genetically -- improve being nomenclature, testing compatible with things and a few thoughts on plans of genetic testing, things we would like to work with, CDC, collaborate with them on things.
So in terms of our initial efforts, interests in getting into forensic DNA, Congress passed the DNA identification act in 1994, gave the FBI authority to establish a national database for DNA testing. As part of that, there was a DNA advisory board formed. One member was from NIST, from that came a qawltd assurance standard, determines how all testing is done in the U.S., standards adopted for testing around the world. Standard 9.5 says specific allege laboratory shall -- changes made in procedure, standard reference material, traceable to a standard. This is what's driven most of our standards in DNA testing, trying to provide information that can help with the pinnings, auto the highest level, community level, quality assurance standards to make sure there's laboratory studies to make sure everybody can talk to each other. Within a laboratory there is the American Society of Crime Lab -- accreditation, audits performed annually to make sure they are compliant with the specifications there.
Each individual DNA analyst must perform two proficiency tests per year on any type of testing they are doing, plus required to have continuing education to keep up with new technologies. The method level where we have valet validation of procedures, you have a traceable reference material to make sure your instrument and method is working properly.
The standard operating procedures, to consistently, from analyst to analyst, each data set has standards, positive/negative controls, mixture of DNA samples to show you can get all the possible alleles that would be seen. Individual samples have internal size standards run with them, and interpretation results, finally when you go to court vu defense attorney generals, to examine data as part of discovery request, check and balance on how forensic DNA results are done from the community level to -- checks and balances, provides a small piece of the validation of the analytical validation of something.
Over the years a number of 2EBG technologies has been used, we try to have NIST reference material available to help with this. Developed in the late 80s, the initial Dan dpan fingerprinting or typing, the poll I poll I polymerase -- phased out, added to the same samples, certified on the same samples. This is to illustrate some of what we do on the genetic tests, a picture on the top right of DNA samples themselves, 12 different samples provided for this particular test and a certificate of analysis that provides income data for each of those samples and will characterize in this case, characterize for 22 [indiscernible] short tandem repeat markers used in testing around the world. We added 26 new STR markers to the same value added to the reference materials. Haven't changed, added more certified information to them. We also tried to encourage the slowing down of consumption, expensive to make, certify, laboratories make traceable materials instead of just using straight off the shelf reference materials themselves.
The basic steps, you collect a sample, extract DNA, quantify how much is present, multiplex PCR, look at short tandem repeat markers and interpret the results, put in a the database, alleles to determine how common the profile is, presented in court if -- the reference materials only focus on the typing results that are produced, many other aspects of the process that could have reference materials, now we are focusing on the separation of the DNA itself. We are looking at short tandz em repeats, forensics, targeting a repeat reason, the number of repeats is converted to overall size of product as measured, number of repeats, what is actually considered in the final analysis. In this case eleven GAT repeats in the database is and that DNA profile. That is made against -- mixture of alleles, you can see this case two samples, one a 16/17 and another -- compared against -- manufacturer produces, checking the -- against the reference material.
There are different sites for forensic testing. The FBI identified 13 core loci and a sex typing called -- and overlap in Europe, reference materials are used in Europe, slightly different markers, genetic markers for testing there. Within the U.S. we have 6 and a half million profiles on the database, a profile cannot -- to make sure results are accurate and so on.
More on the FT Rs, measuring the base pair size, repeat, being stored. This is also used for paternity testing, reference materials to help with making sure paternity testing is done properly within the American Association of Blood Banks oversee how paternity testing is done. This is what a full DNA profile looks like, to illustrate the process, internal, and sample, and individual samples compared to -- ladder, getting the geno types for each individual site. The measurements performed by the allele size. The other thing, different genetic tests use different PCR primers, because of -- mutations may produce different results because of drop-out of alleles. One example around 23 2391 B, Krome 2391 chromosome 16, we do a lot of work to calibrate sequence, regions, why a particular assay or kit doesn't work properly.
We are funded by the national [indiscernible] of just, reference materials, standard information, conduct a lot of laboratory studies. On technology side, constantly developing new assays and training materials. You can go on the website,STR, star base website, download to help people learn more about this.
Where we are now, up hear some work going on in the chemistry division in a moment. We are within the biochemical science division, we recently, two months ago formed to a genetic group doing genetic testing. Marcia Holden and Ross Aims are new additions to the forensics group. We are expanding in this area. Our mission is to advance technology, traceability with quality genetics, biotech and DNA pi owe metrics, tremendous interest in this, speeding up the process of -- making sure it's accurately used by the intelligence community.
Group expertise, funding sources, primarily, reference material, construction of new assays, sequencing SNPs, NIJ, internal funding from NIST, and strengthening the portfolio in the clinical genetics portfolio.
We need to wrap up --
These are materials available now, and some RNA work, trying to help with nomenclature, genetic genealogy, consistent results across laboratories. One of the new ones, the Huntington's disease, alleles to define each of the characteristics you expect to see.
One thing to point out, we have to decide, welcome input in terms of what kinds of materials we should certify, for a sequence, specific genotype, the quantity of DNA present. We want to continue making information available to the public as we have with our forensic stuff, and make that available for clinical diagnostics as well. Feel free to contact me if you have questions, and thanks again for your attention.
[Applause].
Thank you, hate to rush you through all of that, but I want to give everybody else a fair chance. We will move to Dr. Bunk. Who will talk about pro --
A new effort in terms of standardizing measurement in prote mick proteomic research, mostly -- high quality, moving in the right direction. A quick definition in case you are not familiar with proteomics, the identification of all protein, whatever sample, human protium or specific tissue. The interesting thing about proteomics, very little research in proteomics measures intact proteins. You can divide proteomics into two distinct approaches, the top-down where intact proteins are measured, but the vast majority uses approach called bottom-up, proteins are degraded to peptides and peptides are measured, relating that information back to figure out what's going on at the protein level. That's important in terms of standardizing the measurement techniques. We need to know what's going on, if things aren't done at the protein level we don't need reference materials, we can do work on peptide based reference materials.
Clinical proteomics is a kind of subcommunity of all proteomics. The goal of clinical proteomics is to discover new diagnostic biomarkers. So it's both looking at the change in the structure, the concentration and interactions with different proteins in order to improve clinical diagnostics.
If you look at the clinical biomarker pipeline, the first phase of biomarker work is the discovery phase, where we identify candidate biomarkers, then that moves into the verification of these candidate protein biomarkers and then clinical validation. In the discovery phase and verification phase, clinical validation is large-scale, large cohort studies in which most of the work is done using traditional techniques like A A amino assays, but technologies are being developed in order to -- but importantly proteomics is focused on the discovery and verification.
The distinction, in the discovery phase we are talking about a small number of samples, maybe one healthy, one disease state samples. As we move verification we want to reduce the number, patients to be sure we have a true -- diagnostic or -- utility.
Still . Proteomics is in its infancy, we want to bring higher level measurement quality to proteomics. Basically, one of the fundamental problems in proteomics now is there are no metrics, performance, studies, published, looking at inter laboratory, and much of the results are not positive, very little comparability. Obviously if you want to develop technologies for doing clinical diagnostics, the fields of proteomics had to be improved to get more reliability, comparability of measurements.
The other issue, it's difficult to assess truth, no one knows what the human protium is. It's difficult to access agreements, it's why here at NIST, all this led to the potential diminishing opportunities for research funding. So on that note, a few years back we partnered with the National Cancer Institute on one of their initiatives. It's one of the fundamental approaches we take in developing reference materials, procedures for clinical diagnostics. We are not clinical chemists. We have to partner with professional organization like the ACC, FCC, and the national cancer sfiewt in National Cancer Institute in in case, we have knowledge of the fundamentals of measurement, bring their application knowledge to solve problems relevant to them.
The National Cancer Institute developed a program to assess prote I proteomic technologies, they were told not much future research, not much pay-off, needed to initiate a program to evaluate the technology, it's not about bhi biomarker discovery, it's about clinical [indiscernible] the program, advising on interlaboratory study design, materials used in interlaboratory studies. We are working with them to help assess the technology ourselves. In the meantime we are learning a lot about proteomics, getting technology from the community by working with partners, an important aspect. Through this initiative we are working on interlaboratory studies, also developing the information we need to develop our own reference materials to support proteomics.
Let me go back to the biomarker pipeline once again to draw some distinctions. In biomarker discovery that's mostly a quantitative measurement, work mostly done in tissues, the sources of disease like cancer, tumors. The verification stage is doing more of an absolute quantification, signature peptides from the candidate biomarkers, being done in mostly plasma, diagnostic platform, instruments used are much more qualitative.
Realizing proteomics is playing a role in both fields, discovery and verification, using reference materials to support both efforts. Not supporting the entire pipeline you run into problems, we need reference materials, standardard operating procedures and tools for the entire pipeline
Let me just mention terminology we use in terms of reference materials. Vertical standards or reference materials. Talking about a very complicated measurement technique or measurement pipeline with proteomics, sample processing, instrumental analysis, data analysis, a lot of places problems can come in. One is horizontal standards, standards which support measurement quality in individual steps along the way. The other thing we developed is vertical standards, very application specific. A horizontal standard might be a [indiscernible] used to evaluate analysis. Vertical would be a more complex, like cholesterol and serum, geared towards a more specific measurement problem, where the standardard is to the entire measurement process. Proteomics, that's the approach we are taking, developing horizontal standards and vertical, in order to support the measurements.
In most cases, new measurement area it would be impossible to develop just vertical standards, the application where proteomics is being used is very significant, we would have to develop vertical for a specific app application. wewe have [indiscernible] and that approach for proteomics just wouldn't work, too many areas in which it's -- a horizontal standard is how we apply resources to improve measure. As best we can. We have two reference materials in production, the horizontal, mixture of synthetic peptide, not application specific, designed to improve quality in mass spectrometer -- could benefit from reference material, common points in the pipeline, making that a standard -- the other is a yeast Proteum, designed for proteomic investigators to take a complex mixture through the pipeline, validate procedures used and more complex, plasma based for quantitative measurements.
In addition to those new reference materials and additional one mentioned, complex matrix horizontal standards, vertical standards, we are also looking at developing higher order measurement tools, proteomic -- agents of arrayings, multiplex arrays, as well as developing a [indiscernible] agents. Both technologies, improving technologies, developing standard operating procedures for people doing proteomics, as well as the [indiscernible] throughout the materials which people can use to validate the technologies and their techniques in proteomics. We hope that by having these different areas we can support the measurements going on in the clinical community, improve the outcome of clinical proteomic research. Thank you.
[Applause].
Dr. Phinney: Thank you, I am happy to be here today, appreciate the invitation. For those of you who are unfamiliar with metabolomics, this is something going on a long time, measuring small molecules, cholesterol, as part of diagnosing disease. It's a fancy name for something going on a long time.
So metabolomics, the endpoints of genomics, proteomics, what you really get when you look at a sample of plasma, urine, reflecting the exact -- at that time. Advantages to looking at the metabolomic -- by stress, exercise, disease, health, you name it. Instead of looking at genome, you look at what might happen, you are looking at the phenotype of what really did happen. To a great extent this could be the ultimate in [indiscernible] disease diagnosis. Other things to know about the met an lum is it's simpler simpler than -- hundred s of thousands of proteins and genes.
[Captioner transition.]
Please hang up and reanswer telephone.
You can use the patterns and try to segment that into different groups. That is part of the diagnosis. That is part of the anmar -- [Phonetic] -- analysis or critiques there and there are some differences in how those appear. The goal in the meto -- metabolomic issues for the particular issues for the population boxes. You can see these metabolites at different levels. If you can do that -- use that with reliability, you can use that as a specific tool. You can try to also identify places where you can intervene in an identified and diseased state. In those particular elevated or decreased areas, you can intervene the pathways through a pharmaceutical or pathway. One of the mechanisms to identify therapies -- and there are other areas in this industry, but the dug industry is look -- drug industry is looking at this mechanism to identify the toxicity. You can measure those in a multiplexed way. You can predict whether a particular pharmaceutical is going to have adversed effects. We hear a lot of things today about products making it into the market only for it to be taken off or withdrawn.
On the first slide there, the only things that are related is that the metabolum goes all the way back to the genome, and the fergienome -- [Phonetic] -- and other things you must capture. That is an ideal way to do that.
So some of the issues that do come in, what are those? Well, if you think of the metabolisms that come in specifically, you can look at the data sets in which they come in. You can look at the data collection, sampling, handling; but, how do you get to the point where you can say with some certainty that they are within these particular issues. There are form variations, software, and that is just in dealing with the large data sets. So once you get to the data crashed , how do figure out the relevance of the particular figure that you are -- product that you studying. Of course, there is room for error and clinical diagnostic studies. We need to get to the metabolites and what they are. You have to look for the diagnostics based on the metabolites and their signature. About two years ago NIH came to us and they have been funding a number of investigators for the metabolites and genomics. And for some common mechanisms for them to use was developed. They approached it and a reference material for the me tab loamics and we have been going through this material for the past 10 years and it should be introduced in early 2009.
This came from the African Americans and, of course, both female and male individuals. When we have to prepare the material again in 10 years we want to be able to prepare it in a similar way. This is whey we set the criteria up this way in order to design the material. We have a lot of experience in measuring the individual metabolites. We have reference materials on the individual metabolites like serum and key tin. If there are other things like that, people like to know what other metabolites are present. We want to see what techniques we have available through collaborators to provide additional metabolites and other additional information. We can use this material in a variety of different ways. If you are looking at the glucose or the Guinea disease, we are trying to provide as much information as we can.
Now, clearly, this is a starting point in terms of providing the standards for this particular area. It is an evolving field and we recognize that. We see potential for the different reference materials and standards here. Also, tools in the area of bioinformattics. How do you provide that from the laboratories and different forms that are available. We realize there is a need for the reference materials to focus on specific population. It by a group of individuals with heart disease, female, males, and the list goes on and on. There is some reflection in the area of data reporting and we are working with the organizations to offer our insight in the [ indiscernible ] and also to learn from them in areas where we can contribute it. With that I will close and I know we will have discussion here at the end. I appreciate your time.
[ Applause ]
Great. Thank you. I think we will continue on. We will be able to take questions at the very end.
Steve, let me welcome you. Again, thank you for all of your services; certainly, the FDA, and the other committees along the way. Thank you so much. Let me talk a little bit about the regulatory perspective.
This is what you use for the devices in calling the university decision. In the late 80s -- early 80s, rather, which provided perspectives of the he Moe globen -- he hemoglobin, and none of these acts recall or require for standards traceability or performance against the standards. That is a weakness in our regulatory tool box. That is not to deter our renegade work group, we continue to rail for the standards. UTA is a founding standard for U.S. CI, and we have the active members in the subgroups, the globen task force. We reference the standards and the more with it companies in our submissions in our discoveries, those will reference the standards. We also have an interest in the material standards that NIST is developing. We have always attempted to identify the usable standards whether they are NIST, CVC, HHO, or other sources, and we have pre-and-post-market programs. We have a formal market process. About two dozen of individuals in my office present it actively. They are all present and announced on our web page. Is there is a formal process once the standards are recognized and can be used, there is an abbreviated 510-K, where the companies can conform to the standards in agreeing with the FDA with regards to that particular standard. There is usually partial rather than complete performance. The standards are hybrid towards a practice, and the 510-K is not a perfect program. The informal standards are infrequent and the pedigree materials from the sources may carry the company over the threshold in terms of the pre-market review. While the pre-market review has weak regulatory tools, the regs in that the come compliance program does have portions of the regs that might speak to that if the FDA were aggressive in those regs and standards. There are tools out there for the future in qualifying those standard products.
I would argue that the issues and the other standardized issues will only have a compatibility of the other standards and issues as well. That being said we have [ indiscernible ], [ indiscernible ], [ indiscernible ], around arrays is come -- and some of the arrays are some of my favorites. You are able to look at the laboratory differences. You can get a heart attack from moving from one area to the other.
[ Laughter ]
Frs
There are mountains of new assays and some of them are protected by IP which may make it difficult to create the cross-lab standard standards. This is furthering the fact that in 2009, we have a complexity of the procurement and the analytical standards and the systems in terms of reacting the results within the systems and what they may generate. At the end of the rainbow, I believe there is a pot of gold. Mike spoke in -- about this in detail. This is an evaluation in the medical field, thank God. There is no free lunch and this will take a lot of work. There is free literature about the standards and literature written by dark bow ets -- poets.
Thank you.
[ Applause ]
The last slide is going to give us a lot to think about.
[ Laughter ]
I guess we will go to Dr. Dr. Crossman. Thank you for being here and thank you for discussing the clinical path -- critical path institute.
Thank you. Steve is a tough guy to follow. Thank you for your work and I wish you look for what you are planning to do in the future.
I want to talk to you about the Critical Path Institute. I want to explain what the concept is. In the development of diagnostics, we can expect delays. It is delays, not just because the FDA regulates it, but delays in the regulatory path and the diagnostics. We see enterprises throughout the applications of the FDA and then it is returned because the date is not prepared in the way we need to see it. There may be surprises on the part of the FDA where you are receiving information that is shoddy and not consistent. So on the other side we have -- on the other side, we were able to create standards to help the diagnostics standards and to help the FDA communicate with each other. We are a non-profit agency that is not part of the FDA or the industry; in fact, we are not part of the government at all, but we are a neutral party that helps in the communication between the FDA, regional groups, advocacy groups, and researcher groups to bring those persons to the public and the consumers. We have a number of consortium in the critical path institute. We have assignment groups working with the FDA, in Sweden and Europe. This can be in the case of Alzheimer disease and Park Parkinson's disease. This is to verify the quality and the accuracy across the groups. What is the best way to predict the safety and the efficacy. What is the best class method? Have the FDA accept the mission. And we will know when they come to them, they will already know what they are talking about and accept them as part of the application for the new drug. What we have seen in running these consortium is that there is a role in the identity to understand the means of standardizing and testing the diagnostics before they are submitted to the FDA. We have seen many bottlenecks along the way. There are problems in the developmental data that goes to the FDA. So companies may have -- so 10 companies may have that available, but they may not be comparable. If they are looking for a 510-K, we can't always know or prove that the test is equivalent, because it is not tested under the same material. We are trying to reduce the number of surprises that the FDA is giving to the industry and how they are making them redo the study. We want to improve the efficiency and the requirements for the highest -- for the highest approvals within the FDA and how you can improve the efficiency for the high bar. What is the evidence-based medicine. How does the payer know that the tests are performed as the insurance is required? What evidence do they have of the test that is valuable and it is actually performing the correct performance in the way that the test is done. We have to look for real proof and evidence of the rea layerability and the -- reliability. We have to have -- we have multiple companies submitting the data now and we need to standard that to make -- standardize that to make it easier to have diagnostic information. Diagnostic measures go into a test, and then we come up with different information. They can be done as an independent body and put the seal of approval on it and you can say, Yes, it was run as claimed and we ran it on the standardized manufacturers, and we can say that it was provided. This is provided in many industries, many other industries, it's for consumers for the food industries; so it is not a new ideas, it is just a new idea for this particular industry. We see that the FDA is interested. You heard Steve say that, and they are interested in the diagnostics and they are talking about the targets and the therapy. They were specifically focused on the target therapy and cancer industry. They would like to see the service provided and available for any clinical diagnostics. What you see there, Steve told us, and it is mentioned here in this template, but this is targeted through the cancer therapies, but these are a way diagnose this in a accurate way. Does it tell you the correct total? The second one is the outcome come which is attached to the clinical samples and you could determine the relative value in this diagnostics such as the therapy and the clinical submissions.
That will then be put in there to a point of the test. What does this meet? One of the goals here is that -- this is what the session is all about and that is having a standard sample of repository where it can be used, modified, and recreated, and remade as it is used so the tests can be ameliased on the -- analyzed on the same samples repeatedly. It can be a neutral site and you can test whether it is equal to the red cat so the researchers would know that it did what it said it would do. This is for the FDA, and they hope to improve the diagnostic factors to have the data intercepted and then it does provide a format for the other companies and if they wanted to they could run a bake-off. You could have multiple companies competing and being tested on a neutral site and with the same analysis. You need to know whether or not the test is performed as it is claimed.
We have talked about this and we are starting to develop the laboratory and we have a seed funding in Arizona where they are developing an economic package. We have a couple of people here stating this where we are looking to take on the first demonstration case whether it is in genetics or cancer, we are not sure yet, but we are looking in the area where this would fit in the certain diagnostic areas. We have asked several questions, number one, diagnostic performance area. I think the last thing I need is someone coming into my laboratory to inspect it, regulate it, and find something else that is wrong. That is not what this is about. There is no regulatory body. This is to be helpful to the manufacturer and the developer in order to diagnose. How did this lab relate to the federal agencies and other agencies that are involved? We are looking at ways to becoming synergistic and compliment reimbursement, and we are are -- complimentary. We don't have use this data. It is their data. We don't have to use it. If they don't want to use it, they don't have to use it. How is the IP protected? Everything that is run is confidential within the standards laboratory, so if there is any intellectual properties, it will not be run unless the manufacturer wants it to. How will the methods be maintained? You know how do that and we do that as we need to do it in this area. That is the end of the story and thank you for your time in licensing.
Thank you.
[ Applause ]
Why don't we take a couple of questions at this point before we go to the final presentation.
In some sense, if you tie this to data that is used by payers and reimbursers, the people who control those strings, you know, depending on what they decide to do, you know, they may say, we are not going to reimburse the process here in these tests so you have the de facto issues issue. Iowa think this is important, and I think -- I think it is important and it is the direction in which we need to be going, but I would ask you to respond to that issue.
Yeah. I don't know if everybody heard the question, but maybe I can paraphrase it. If this -- this has become too successful in the sense that even though this is not a regulatory body and there is no federal mandate to go through this process, but it is something that everybody maybe wants to have the recertification process in order for that to be made. That is a real problem. I don't have -- I can't tell you that I have an answer on how to solve something like that. We would like to start small with single bites and look at one area and see what the pattern is and the emersions in terms of the reflects of the payers. First of all, we have to start small, because you can't start with the diagnostics and do them all at once. We are 2.5 FTEs and it would be hard to open up all of the diagnostics as we just open the door. We would like to just try one. And once we try one we believe that the exact criteria would be the issue. We would be swamp and we wouldn't have the band width and we would be the second FDA. We don't want to be the second FDA. We don't want that. If that is a starter, though, we will continue with this and that will happen. I am open to people who have ideas and who are creative and innovative here and who are problem solving, but we don't want to create for of a problem than what already exists.
I agree.
So if your goal is not to be a de facto regulator, how do you envision going down that route?
You see --
I can see the consumers and the other payers where you have to control the laboratory to go to another place in order for it to be reimbursed by third-party payers.
Yeah, I think that is a similar issue. How do we not become a regulatory body. That is in terms of payers. Is that what you are asking?
If the payers are required to pay it, then you are saying it part of the de facto. What eare saying is we -- what we are saying is we would start small and then we would see the emersion process coming and starting out -- coming out of and from the starting payers. What we have seen, which is from a very large insurance company, but we as the insurance don't have the band width to determine which tests are ran. We just pay the CPC code. We don't know if they ran the test that worked well, or works pretty well, or not at all, and we don't have the information and the inspection in order to do that. So as of now, they wouldn't be able to use that information.
So they don't have the means today?
Right.
But they can ask if you are submitting the claims to the third-party payers that you submit the information.
Right.
We have the regulatory body to investigate the qualified testing and I think in the future this is another hurdle that we may have to look at then.
Right. If this is another hurdle, that is a deal-stopper. We want to be innovative and creative here and find solutions so we can find a way to complete this process. If you have ideas, we are open for suggestions and I am happy to talk with people in the insurance industry, CMS, and we can see in what ways we can do this so we are not flooding the problems, but we can solve the problems.
Thank you.
Our final speaker is Michael Amos as we all know. Mike, because we are -- we are going to hold you to your 10 minutes so we have time for discussion at the end.
Thank you for your attention. I hope you appreciate the level of detail and precision that the NIST colleagues go through to provide these decisions. I think we have talked about the standards and who uses them and then we also have the vertical standards. I will bring my other hat up here because my boss told me to put this disclaimer on here. I am going to talk about things we have learned over the last couple of years through many talks with many different people. This is what they consider the future of diagnostics and where those things are going. These are not official programs or ideas, but it is a food for thought if you will. We will talk about the changes and the lessons learned. The fact that the laboratory medicine will drive the change, and then we will talk about the measurements and the challenges and what those will display and then the plan to enable that and make it change.
Really, the future, where we are is kind of scary if you think about it. 80% of health care goes to cover the chronic health care diseases and the rest is only 17%. That is like -- 43% of that is spent on hospitalizations. The scarest part is the -- scariest part is one of the most expensive is the one we are using most. There is very little known about the genomic basics. We have a growing number of children taking drugs for chronic diseases. Diabetes is running rapidly and growing. Kids under the age of 5 are now taking drugs for type-2 diabetes. Things are not going that well in the medical research. The gap is really wide -- the weddenning. There is -- there is one or more manufacturers reported in terms of events to the FDA all of the time. There are billion dollars of drugs coming off of the market due toxicity. This is the best as we can tell the complete list of single bioproteen -- bioprotein. We have learned that the human body is complex. It is not only made up of individual components, but it is really diseased calmed by protoevasions and there is no such things as a met to bollic, only 17% is a good indicater. Medicine will focus on keeping people healthier. We got to keep people out of the hospitals. That is possible and the laboratory medicine will lead the way. Complex procedures that are comprised of hundreds and thousands of data points will be the biomarket of the future. This will be developed around the therapeutic treatments. It is the same model and it is based around the complex procedures and measures. This is developed by chemical net works. You get the abnormal a layerties and you can -- abnormalities. We have no idea what the disease signatures will look like. It will probably be a risk score. There will be a number, 1 to 100, this is how many is going to get to disease or not. We won't know what the number will be, but it will help the scientists make the decisions and discovery and recovery of the health lines, so to speak. We want to help people. Not just through the diagnose agnostics and testing but to really help people. We have to place the focus where we are looking at the markers that occurred years before these symptoms occur. They often occur long before people realize they are sick. They are unique biomarkers and they are going to identify the person who is sick. And one of the rules of the clinical trials will have to change because each person will serve as their own control. There is going to be parameters and blood. These signatures are kind of like a good radar signature. A good radar can give you blip on the screen radarring the good and the bad guys. One of the potential concepts the by Dr. Leigh Hood, which is fingerprinting and it is an integrative measurement and computers where you are taking the develop of blood and putting it on -- drop of blood, and putting it on the analytical platform and then printing the data out and receive the analytical measurements and such to find out what is going on in your body. That is the dream.
Today the health care markets are based on the number of sick people. They are based on the number of people they can treat. That is based on the number of people they project will come down with a disease based on the data. The outcome come is people die and suffer with chronic diseases. It's not changing. We see $4 trillion in health care costs by 2015. That is not sustainable. The health care markets could be based on the number of people with preventable diseases. If that is the case, the metric for the causes will be a valid and predictive biomarker. Most people die in their own sleep than they spend the last two years of their life in terminal care. For diabetes alone that is 50 billion, at least. Diabetes is more expensive to treat than cancer, we all know that.
So what happens? What type of standards are needed for these types of things? We are really talking about a different perspective and approach. We have to take into account all of the things you heard today from my colleagues. You know, the horizontal and vertical standards and which one do you go after? That is where we felt the protein sciences was one of the biggest challenges. That is one of the big things we have to do. But we have to prompt the signatures, and then on the backend, we have to promote the signatures. I have to disagree with my boss; although, I love my boss, but if there was a set of standards where I didn't have to purely figure out what my assays were and what they were doing, I could have sped up things a lot. I think what Dave is doing with the protoomics is the platform standards which is going to drive the future. You have the transitions states and medicine, developing the procedures, they were pew -- therapeutics, and enhancing the quality of life.
What is preventing us from getting there? Well, basically it is the capabilities of doing one of many things, but this is one of the major issues here and that is providing the analytics in order to do those measurements. This is a way to stimulating the advent of the new technology. We are within our ability to measure the proteins. That's a real issue. I think we are in the beginning of the genomic project. I think one way of sustaining that is to have a mission to the moon. Here is the idea. Maybe we can put the stake in the ground and say we can identify and develop the procedures by 2020. The numbers, of course, are subject to debate, but this is some of the -- these are some of the things we need to do. Maybe we can come to new approaches and a way to stop the diseases and allow people to live healthier. Without the new technology, this is not going to happen.
One thing I can say is, When I came to NIST, I was pretty ignorant of all of this, but I hope the presentation today helps you to better understand what me and my colleagues do. I am one of the scientists that focused on the nitty-gritty nuts and bolts of the measurement and I think that is why we are here and I appreciate your attention.
Thank you, Mike.
[ Applause ]
Thank you to all of our speakers.
We have had a great tour of the measurements and what they will read and accurately read, and what the future will look like.
I will now open the floor for a couple of questions.
Do you have any additional comments that you would like to make from the CDC perspective?
We would like to -- we think that having the reference material is key during the quality of these tests and not only for the day-to-day QC of the tests but also for the sufficiency testing which is a big deal and is a large part of the oversight report that this group did a few months back. We served as an accountant and we are -- there are six different diseases that were on NIST or FDA approved. There is a real small fraction of the current tests that are available. The CDC through the program is trying to address this gap by -- we are just simply organizing a volunteering effort throughout the genetic company and we are trying to compare the [ indiscernible ], and the [ indiscernible ], throughout the industry. We can use these for the quality control and then the proficiency testing and needs. All of the requests are addressed by the CAPs and those materials. We are doing pharmacology-co-sites and their material. We are going to do a prompt for the array and the CGH. We were trying to do a project for the muscular distrophy. All of the labs stopping because of the patent issue.
[ Laughter ]
It's coming from a full circle.
I have my opinion.
[ Laughter ]
I want to thank Teresa for her role in the CDC. I think she needs to have an applause from all of us.
[ Applause ]
With that said, there is a lot more work that needs to be done. I think it is interesting that you have already identified through the collaboration through the professional organizations and within the use of the different laboratories, what are the needs in the current laboratories not only to provide proficiency, but the materials we need to identify and qualify the control. What is the integration between the programs and in order to initiate those programs.
I talk to NIST on a regular basis and we have a yearly advisory committee meeting and I also talk with them then. There are also people within the molecular oncoulology -- onology. If that is if vision in where we are going then are the samples worth it in where we are going there. The perspective that I have would be, you know, what is your real vision on where you are going to need to invest your limited funds in terms of standards in the biomedical grounds? Is it going to focus on genomics, protonomics, samples or are you going to try to do it all? I think in the short interim, we have a lot of living to do between 2020 -- now and 2020.
[ Laughter ]
The new implements are going to be on medical imaging and protein science, for sure. We may do some things beyond that, but for the near future, two or five years, I think NIST is going to improve the capabilities of medical imaging and develop more competencies within the protein science and also with the biologics. We are trying to address the tool kits and provide those things. We are not going to stop the other things, but in the area of NIST we will expand on those specific two. In the science lab and commission, there is going to be a greater emphasis on the genetic testing and diagnostic phases.
Just a follow up to that, the oversight report, the PT issue and having stamps is a -- samples; it's a huge issue, we have plus or minus 5000 things to address out there. I think it is unrealistic that NIST is going to be the Savior on the stallion at this point.
Well, that is true. If that is a major issue that your committee has identified sending me a note with that effect perhaps to the CC director may not be a bad idea.
I think discovering the technology for the future is going to be dependent on the environmental effect on the genome. You have to have good genomic data in order to do that. You have to look at that and the other things that are sequencing and moving forward. We have genomic studies and situations and we are going to be looking at that and the next genomic formation.
I have to agree with Mark again.
[ Laughter ]
I think this is a great perspective. I know tomorrow we are going to jump into the priorities moving forward. Where do you see this going? Can we -- I love the idea of taking the action and seconding letters to NIST because as Mark said -- [ Laughter ] -- this is entirely consistent with the recommendations not only in the last report but also in the last two. This is needing for insurance standards and quality.
Absolutely.
We not only the requirements -- we not only need the requirements per se, but we need to take the corrective actions.
Letters we can certainly write. We did get a lot of reinforcements from that and we are able to submit the measurements going forward and we are able to identify that. We need to monitor the implementations and what is required for that. We can have some discussion tomorrow in terms of the short and long term interim actions and it has come up in similar places throughout the this process. -- this process. I think we need to talk about and think about what needs to be done. Maybe a letter of support or something similar, but somewhere a lot of actions and oversight that we need to move forward on.
One quick comment and invitation. We certainly -- well, NIST is going to have a new director in the next 6 months or so. Bioscience has been identified as a priority. I am pretty sure that the new director will be sponsoring that. Having said that -- bioscience health is a priority. We are looking at the protein sciences and medical imaging, and I would extend that you have your next meeting at our campus if you will. It is not as convenient to the Air Forces out here, but the Metro does run out there and I would invite you to meet there, perhaps, and perhaps -- I don't know if we will is a new director at that time, but you can speak to the leadership and you can influence us more in the future directions.
Great. Thank you, again, to all of our speakers. I want to also provide information on the genetic arrays conference that is going to be held a couple of weeks from now on the NIH campus and that is to conduct conferences on the standardized quality control and the clinical database for the research push purposes -- purposes. I want to thank the speakers for their presentations today. I want to thank everyone who has worked so hard on the patents. We have come a long way and we have a long way to go, but we will move forward in accomplishing that. There is a bus heading back to the hotel leaving on the third street side, when you go out the door, it is on the left. We will be reconvening form morning at 8:00 a.m. Paul will be leading us through our discussions and our priorities.
I think you can leave the non-valuables here, but your valuables, you should take with you.
Thank you.
[ Event Concluded ]