Event ID: 863540
Event Started: 11/19/2007 8:19:28 AM ET
Please stand by for real-time relay captioning.

this is my introductory good morning. That was the attention getter. Now the official warm good morning. That was the real good morning.

Thank everyone for being here. I have a cold, but I'm okay, not infectious. It's a genomic thing with allergies. Where is the new cure, I am tired of this stuff that doesn't work crap.

Oh. First day. All right. Well, we do want to welcome everyone to the 14th meeting of the Secretary's Advisory Committee on Genetics, Health, and Society. The public was made aware through notices in the federal registry, as well as announces on the website and listserv. I welcome members of the public in attendance and the many viewers tuning in throughout the webcast. This is widely viewed on the webcast, so be on your best behavior.

We encourage those in attendance to comment, sign up at the desk. Extended period for public comment is tomorrow afternoon. On the draft report on oversight, released for public comment two weeks ago.

Secretary love Lovett made five new appointments. I will introduce them [ indiscernible ] providing diagnostic testing and genetic counseling services, MBA from Harvard business school. She's been serve as ad hoc member of the task force on gene patents and licensing practices the past year. We appreciate that work very much. Thank you very much.

Also welcome our good friend Paul Billings, a consult@lab Corp, works on special projects. He was lab Corp's vice-president, professor of anthropology at U C Berkeley, go golden bears. Member of the joint national NIH DNA advisory committee. Degrees from Harvard, and clinical training at University of Washington wash.

Paul Miller, we must say, where are you, welcome back?

I never left.

Paul is now the Henley M Jackson professor of law, director of disability studies at University of Washington wash. Commissioner of the EE C previously, serve as ex officio on this committee. White House liaison, and we recognize your service on our oversight task force. Two areas of expertise you bring to us, our legal eagle, you are also our consumer representative as well. We very much appreciate your involvement.

Paul wises. The Richard -- professor at Stanford, work focused on children's health, help outcome disparity by race, social status and the impact of technology on disparities in health outcomes. He received medical degree from Cornell, masters from children's hospital medical center in Boston.

The secretary appointed Rochelle dray fuss, long commitment at national academy, she's the Pauline new man professor of law, two national science committees, intellectual property issues, and the past chair of the American association of law schools, intellectual property committee. Before earning law degree she earned a masters in chemistry. I understand you are serving today as ad hoc members of the committee, pending completion of the wonderful appointment process. In that capacity you are not yet voting members of the committee. None None the less, we encourage you to comment. And we hope you have the courage to say I don't understand where you are in the discussion, please explain, because I haven't been here the 13 years everybody else has. That's a good thing. I hate it when I come to a committee new, or newly, or something. Everybody knows everything and I don't know diddley squat, so I urge you to ask as many questions as you want. Participate in everything but the vote. We will be happy. Welcome to the new members.

While the appointment is occasion to celebrate, often accompanied by departers. Tomorrow we will say good-bye to three retirees. Cindy Barry, and [ indiscernible ] Hunt Willard. Oh, there you are, she is here. Coming tomorrow. Sad about that, but we will be sad tomorrow. Not today.

I will welcome a new exfishio pb, Dr. E AE sop -- [ indiscernible ] I hope I got that right. I have never gotten it right. First time in history. Medical officer, clinical consultant with the office of population affairs, issues relating to family planning and adolescent family life. We appreciate Dr. [ indiscernible ]'s contributions, look forward to working with Dr. Aesop. Barry is a good valued colleague of mine, a chief medical officer at -- taking a much more direct involvement in our work on behalf of CMS. His presence today, know he can't stay the whole day, but Barry is making a conscious decision by his presence to really really emphasize how important this work is to CMS. I really appreciate your being here today.

I recognize ex officio's contribution, Dr. Robinson -- the director for the office of civil rights, responsible for overseeing program operations, policy development, received the secretary's highest award, distinguished service. Honored for commanding leadership in the work of civil rights. I congratulate you from the committee for your dedication to the citizens of this country. You dedicated your career to upholding civil rights employ after doing that, she's not here yet. That's fine, because it's in the record, and we will remind here we did this.

She's terrific, and great.

I will update you on the secretary's personalized healthcare initiative. In September a report, opportunities, pathways and resources. You may recall the secretary was kind enough to send each of us a copy. Identifies -- as well as the work that lies ahead to bring it to reality. We commend them for the work. Summary of an expert panel meeting in March. Assistant secretary office for planning and evaluation. Payers, representatives from industry and government, advocates. Five issues need to be addressed to represent personalized healthcare. Clinical -- validity, and utility. Value and cost effective fens, the need to build -- impact on health disparities and education of providers and patients. A copy of that workshop summary is in your table folder, and you can of course, download it from the HHS website.

There have been activities within the personalized healthcare group related to the second's personalized healthcare initiative. We are staying abreast through the participation of Andrea. There you are. Steve, as well, and Mark Williams. Thank you very much for your effort in this initiative. I have been tuning in by telephone, conference calls, and the work is very important, and key to what we are trying to do. At the beginning of each meeting I have established a tradition, will continue to take a moment to review our strategic plan, the status of our progress in fulfilling each of our study priorities. This gives an overview of what we accomplished to date and helps us stay focused.

New members of the committee, this was a plan that we as a collective team developed several years ago. It will be, before very long, time to revisit this again. This is not one of those government committees that just wanders around aimlessly and bumps into walls. We actually have a plan, have a set of priorities. We actually are implementing them and keep track of what we do. Hopefully we will continue in that vein. We may bump into a wall here and there, but we usually know what walls we are bumping into. The vision statement, how we reached them, in 2004, and continues to guide the group. The misuse of genetic information and discrimination has been our highest priority issue. We have written a number of letters to the secretary to enact laws to prohibit discrimination. Provided a legal analysis regarding the inadequacy of public law, documents showing public fairs about genetic discrimination. Interesting and compelling DVD of testimony received in the fall from the public in 2004. We also strongly supported the genetic information non-discrimination act of 2007, HR 253, commonly referred to as GINA, protects from discrimination based on genetic information. Supported on both sides of the political system. President -- will sign the bill in presented to him. Tom coul burn placed a hold on the bill in July, debate in the Senate. Supporters working hard to move the bill forward. Louise slaughter of New York set up a petition to ask senator Coul burn to drop the hold.

We developed a resolution about the importance of health education and training of professionals, how they could be advanced, genetics information and training for health professionals. Six speakers will report on the progressing of genetics education and training activities. These presentations will be followed by a one-hour discussion of critical needs in education and training and the best approaches to meet the needs. Four A decisional panellests will -- you will be deciding what if anything we need to do going forward on this topic. Whether we will continue to keep it as a priority or move it forward or let it go, say the world is safe, we may all return to our homes. That will be your task.

In 2006 we transmitted a report and recommendation to the secretary on coverage and reimbursement of genetic test and services, highlighting how problems in the system affect, and nine steps to overcome the barriers. These recommendations cover a range of topics, including evidence based -- Medicare coverage of preventive services, the procedural terminology codes, billing by non-physician genetic counseling provider and genetic education of health providers. And July CMS sent feedback on the recommendations. A shawl group of members led by -- has been reviewing. A copy was shared with you in October. We will take two CMS exfishio, Barry, in December. Our report. I will report back to you on the outcome of that discussion. Barry, you actually were at the meeting when presented to the head of CMS. It was a t was a terrific discussion. This is one of our successes, I am pleased about, led to enhanced collaboration between the FDA, CMS, and FTC, consumer alert issued to warn about using at-home genetic tests that have not been evaluated and be wary of claims. In it July we heard from CDC about their work with the potential to -- genetic testing. As part of the personalized care -- to coordinate activities and -- the office of secretary is leading this effort, will keep you updated on the progress. Greg is actually here. Would you wave? We have enjoyed such good close access to the secretary's office on a day by day basis, Greg is the person behind the curtain to make that happen. We are greatly dedicated to Greg for it. Concerning large population studies, the committee's report, cohort study of genes, environment and disease completed and transmitted to secretary Lovett. In August the secretary sent a letter acknowledging receipt of the report and the timeliness of our recommendations. You can find this letter in tab 6 of the briefing book and posted on the website. I point out an article about the LPS report published in the July issue of science and medicine, the development of report, letter to clarify the skoals goals and scope of the report. We have given them a what-for.

For more than two years we have been developing a reported on opportunities and challenges on genomic research, products, incorporation into public health practice. In March the draft report was released, comments carefully considered and in the fall a revised draft prepared. Most of our work today will focus on the recommendations is and the draft. Our goal is to come to closure on the recommendations and approve the report for submission to the secretary. No fooling around. We are going to close this out and make a report.

In June 2006 we decided to -- licensing practices on patient access it genetic technologies. The task force hosted a round table to discuss international perspectives on gene patenting and licensing strategies. Since then the task force has been working with Bob Cook began. We will continue to meet monthly to develop -- report and final product expected in 2009. Sprve issues related to the adequaciy of -- an extraordinary 33-member Task Force Chaired by Andrea. In response to the secretary's charge. It takes a village.

Now, for those now new members, the number one issue for us is genetic discrimination, always been. Number one historic issue of which is committee is successor of preexisting committee, was the issue of genetic testing. This is really in our -- don't get mad -- in our DNA. So, through dedicated effort, exceptional leadership the report was released for public comment on October 25, public deadline for comments on -- we will review, have presentations together, academic and public perspectives, brief on the analysis of genetic testing, learn about the conclusions of the summit meeting, topic in -- providing opportunity for interested stakeholders to share their perspective. I want to make sure this is absolutely clear: There is a considerable time period for people to comment. The public comment period does not end until December 21. I am say IT several times. We are having much opportunity for public input. At the end of this, I am trying to be as transparent as I can to every stakeholder in had this process. It is an open process, transparent process. If you are a member of the consumer, if you are general public, if it you are industry, if you are health professional, whatever your particular stakeholder view is, this is open process with lots of time to get your comments in.

I have reasons for being as emphatic as I am. To not be participated in the public comment, all the ideas gotten, so Andrea can duly deliberate over the best ideas. We have been pretty clear about that. In Mar much we added gene based applications. This effort combines two proposals, on the economic impact on genomic consideration and gene based applications. Steve Tor itch will be leading, including some of the same questions, issues involved in evaluating outcomes. I want to be clear the evaluation of outcomes based gene based applications, identified, hanging out there. Quite frankly, as you can tell from the long introduction, we have a lot on the plate, want to get this other stuff done, then will move on to that. The cross-cutting issues of access, public awareness and genetic exceptionalism, we have continued to integrate into the committee's other work you have heard.

With that, I hope you all get a sense, and for the new folk, I hope you don't get intimidated by the amount of work, but we are a very active, very committee. When all said and done, evaluated by committees, I want us to be not only the most prolific, but the most focused and intense. We are out front on all those scores.

Any questions from anyone before we get down to -- I will take a moment. We put a lot in front of you, let's take a minute and ask for questions.

That will give me a chance to drink my coffee, perfect.

Now for the serious highlight of the meeting, the ethics rules review by Sarah kier.

Good morning everyone, thank you Reid. You all have been A pointed as special government employees to the committee. Although in a special categorying you are subject to the rules of conduct that apply to regular government employees, outlined in a document called -- received when you were appointed to the committee. I will highlight two of the rules, as I usually do. First, conflick the of interest. Before every meeting you provide us with information about your personal, professional and financial interests. Information used to determine whether you have real, potential or apparent conflicts of interest -- while we waive conflicts of interest for general matters, we believe your ability to be objective will not effect your interest, we rely on you to be attentive to the possibility that an issue will arise that could effect or apeer to effect an interest in a specific way. We provided each of you with a list of your financial interests is and relationships that could become an issueif this happens, we ask you to recuse yourself from the discussion and leave the room.

Government employees are also prohibited from lobbying, and may not lobby as individuals or as a committee. If you lobby in your professional capacity or as a private citizen it's important for you to keep that activity separate from the activities associated with this committee. Keep in mind we are advisory to the committee of secretary of health and human services, we don't advise the Congress. I thank you for being very conscientious about these rules.

Reed V. Tuckson: The idea, also important, reminder to everybody, the idea of we are advisory to the Secretary. As you start to think about what we can do, you think about the multiple roles of the secretary of health. Those multiple roles are clearly, in terms of responsibility for the CEO of all those agencies, but also of course the Secretary [ indiscernible ] our recommendations are within that framework. We can't go tell the Congress what to do even though we thinking we know. Be careful there. I want to be shore as a committee we are attentive to each other of the hats we wear. The reason you are on this committee is because of your expertise, because of the places from which you arise. It is a very considerate process to get people from industry here, from academia, the genetic counseling community, from government, the payers. People from many different places. It is -- everyone knows who you are, they are following this discussion. So you are free to let people know what you think. Let them know where you are, where you are coming from. Conflicts of interest will be attempted to, monitoring, all kind of people monitoring those sort of things. At the end of the day you are who you are, you bring the expertise to bear, you shouldn't be shy about that. I want to make sure you are comfortable because of who you are.

One of the main goals of this meeting is to finish the important work we are doing on pharmacogenomics . We need to come to closure, be satisfied on the final content. The discussion in tab three in the briefing book, we will go through those. Before I turn to our leader, Kevin FitzGerald, I want to express the committee's appreciation, and Emily, chairing the task force during her appointment. You were instrumental in conceptualizing the approach and getting it off the ground. I thank the members of the task force, Kevin will name you. I thank -- for providing additional resources for the report's depment and the excellent services of Clint good man of the lo in group, and Susan goodwin of our staff for excellent work as staff lead on the project. Anybody who worked with Suzanne knows she's a tough tough task master, and intimidates all of us. We are grateful for you and your high standards, hard work and commitment to excellence.

We will go at this an orderly way, we will bring this thinking in on time. Kevin?

Kevin FitzGerald: Following up on what Sarah was telling us, I have to make an announcement that I have a significant personal interest in getting this done today. So I have a bit of conflict here. If this doesn't get finished today my personal well-being will probably be at stake. During the break if you want to see the psychological scars I have received sitting here between Reid and Suzanne, I will make those manifest.

Right now I would like to give you history, overview of the report, where we have been, what's gone on, to bring us to this day. As you can see on the first slide, indeed as we reiterate what Reid said, we are all about the finalization of this report.

The we of course is significantly dependent on the task force. Now, it's not exactly a village, more like an extended family. As extended family we were very open and frank with one another, that's how we got to where we are. As you can see, it's a great group, we had Jim Evans, Andrea, JULIA, Steve from the committee itself, and of course everything was begun by Emily. I too would like to thank her. She got the ball rolling, I just let it run me over and hang on. I would like to thank very much the input we have from our HHS representatives, Ger bin, Steve, Liz, Allen, Greg and Rochelle. Without their imput this report would be no where. We really did rely on their expertise and insight. At the end of today I will do a few more acknowledgments of people who were instrumental in getting us to where we are today.

How did we get here? Well, we began with some informational sessions which gave us the direction and the goal for the report. The first thing we had to do subsequent to that was a compilation of all the activities that were already ongoing. This is not something we initiated out of thin air, as the report from the secretary indicates, this has been building for some time and is really taking on a great deal of momentum.

To get a good sense of that momentum we did a review of the literature to see the different perspectives that are out there, particularly to try and pick up the concerns that different experts from different perspectives have about how to move ahead with the idea of pharmacogenomics. This led to revision says of a draft report, we came up with a certain number of recommendations, then sent that draft report out to be reviewed by some experts that had been identified as people who could give us a more comp comprehensive sense of where our report was sit waited at that time in the thinking about pharmacogenomics. In response we did a if you few more revision and sent out for public comment. I would like to give you now a sense of that public comment process.

The public comment period was from March 23 to June 3, ample time to get ahold of the report and give us responses. To facilitate that process there was a directed targeting of some people, as you can see. After the announcement it was put on the website and the listserv, totally 936 different addresses. There was a dear colleague mailing to A decisional 283 addresses, and finally, some specific requests to organization membership, that was about 31 different organizations. We really did attempt to get a broad and deep response from people because of the significance we feel of this report.

We tried to break down for you a sense of the terrain of the responses. Now, one thing I would like to point out, it says at the bottom the total is 57, that's not 57 individuals. That's 57 different compilation responses we received. If you look at the public responses, many came from multiple individuals or from entire institutions or organizations, as you can see, obviously representing the thought of multiple people within one response. As you break down those public comments you can see in our little pie chart four were from government, 10 came from companies, 18 from organizations, and the largest group from groups of individuals or individuals themselves. On the right, gives you some of the idea of the specifics of those subgroups. From the government, NIH, O CR, veterans administration, E EE lie lily, host of acronyms. This is wash Barb Washington D.C., you don't exist if you don't have an acronym. The individuals came from academia, healthcare providers, researchers, et cetera.

What was in the comment? It really ran the gamut, covered broad spectrum of concerns and suggestions, and some were fairly focused, looking at the text itself and offering corrections to inaccurate statements, data, or data we needed to update. Update of various activities that were ongoing about which we were not aware, and general ideas on how we might improve the report overall. Then there were also comments on the recommendations, that area that most people look at when they look at one of these reports. As far as modifications to existing recommendations, thoughts about which recommendations we should prioritize over others, and finally whole areas that we had not considered, so new recommendations that we thought about adding to the report. That was the sense of the overview of these public comments. Now, to give you some more specifics, just so you get a feel for some of the content itself. One of the comments that we heard more than once was that the report was somewhat overly optimistic about the long-term potential of pharmacogenomics. It doesn't do good to put something out that isn't -- we took that seriously. We wanted to in fact make sure that the report, as it goes out, is the best we can do to give people a sense of the terrain and the possibilities.

It was suggested that we needed greater discussion of the international efforts that are ongoing. Obviously we are advising the Secretary of the Department of Health and human services of the United States, however, when one looks to see what decisions one might make on a policy level, one wants to know what's going on elsewhere to get compare and contrast. That was beefed up, we looked more [ indiscernible ] at some of the collaborations that were going on internationally and in a public/private venue. This raises the question of whether our conceptualization, our definition of pharmacogenomics is adequate. I thinking it's a moving target. I certainly do not want to chaim what we will put out in the report will remain true for all time, we hope it provides a platform for the Secretary to move ahead.

I mentioned several times the desire for SACGHS to -- oversight of genetic tests. We are responding to that disiefer in desire in an entirely different report. There were more focused suggestions, call for federal government to call for collection of DNA samples to facilitate the report research. This is addressed in the report.

Need criteria to design what farm pharmacogenomics -- obviously another important aspect. More emphasis on the need more clinical effectiveness, payer reimbursement, approach to reimbursement for genomics products. Interestingly, a disagreement in the comments, whether pharmacogenomics will necessitate genetic counseling. Something we attempted to wrestle with, not necessarily saying it will come out one way or another, we can't predict how things will go in the future, but certainly an issue that needs to be continually revisited.

We received, as you saw from the timeline before, the full set of comments in June of 2007. Each of the task force members was assigned eight comments to review, so that we would get two people on each comment, and then hopefully get a little bit of variety of opinion from our own task force members, and then staff, IE Susan, reviewed all 57 public comments, and after the therapy she seems to be doing okay.

In our review of all the public comments, we tried to answer a series of direct questions. First of all, looking at the comments that one had to address, which should be in the next draft of the report. In In other words, should something be changed in response to a particular comment. Of the coms addressed, which would require the entire task force to discuss, or which could just be addressed directly by staff. Primarily, the updates were something that could be directly addressed by the staff, putting in new information. That was one of the examples for how we would take something, and not necessarily bring it to the entire task force. Of those that warranted discussion by the task force, how then did the task force think we should go ahead with those comments. How did we do this? Logistically? We had conference calls, long conference calls, two long conference calls, both TWO, and TOO. One was October 16, one September 10. If any of you have done these three-hour calls, after a while you are concerned about having to have the phone surgically removed from your ear. But in any case, a lot of was done. We reviewed the discussion compiled by staff, comments organized as you see, and primarily primarily focused by the task force and we discussed the items, flagged the ones that we had to discuss as a whole, ask then and then just made decisions about how or whether to incorporate the comments into the report.

I will mention this too, at the end, Reid already mentioned it. As with many of these things, there are people behind the scenes, without which nothing like this would get done. Again, the Lowen group has been fantastic, professional, also responded well to intense psychological pressure. Very handy thing to note for the future. So, in collaboration with them, the report was revised, recommendations were revised and then we went forward with that and the revised report is in the briefing books under tab three.

As we have heard several times, we wanted to reiterate that today's goal is to finalize the recommendations. We need to get even the wordsmithing done so we know what will move forward from here. This is what the committee needs to vote on. Now, if anyone again has specific editorial suggestions to the report itself, we would be very happy to hear those, receive those. Those we don't necessarily need to address today, those can be incorporated in a continual editing process that will go on after this meeting. I would recommend if you have anything specific in the report itself, body of the report, that you somehow indicate what that change would be, and please give that to Suzanne so we can compile those and look to see how they can be incorporated into the report. Our focus today is on the recommendation, we need to get the wording down for all of them so we can go forward with those.

Why do we need to do that today? Because after this we pull together everything so that in December the committee members can see the final report. What exactly is going to go to the Secretary. Then that report will be copy edited, made camera ready, and printed. Finally in February we target that time to send the report to the Secretary, so the secretary's office has a month to look over the report, respond, then release to the public, hopefully within a month. That is where we hope to be able to go in the immediate future. So now my understanding is everybody is to get a break before we get into the report or no? Keep going, get started? This is the way it is. Every time I suggested a break Reid would say no, go, go. It's just --

All right. Forward we go.

The organization of the report. As you noticed, mentioned before, the report is in tab 3 of your books. I believe, due to a specific recommendation from Andrea in one of our earlier meetings, the report, we all agreed, was organized into three overarching themes. These were areas where we thought important aspects of pharmacogenomics could be broken out into subgroups and addressed in a way that would allow us to keep contained within that subgroup our comments, and yet at the same time make them into an integrated whole, which the whole report is supposed to be. Research and development, the gatekeepers and implementation of pharmacogenomics, to improve out comes in clinical and public health practice.

It would be impossible for me to overstate that third piece, and the focus there, to improve outcomes in clinical and public health practice. This is something again and again to come which we returned. This is where we hope, think the good of pharmacogenomics can go.

There are 15 recommendations, but any of you that remember your college exams, one question, eight subparts. We have 15 recommendations and only 37 subparts. Not so bad.

This is the first significant section of the report, research and development. This broke down into further areas, basic research, translational research overall; raising the questions, how does one then build an infrastructure that will enable and facilitate this research. Finally the ethical, social and legal issues that come up in research and development. One thing you will notice going through the report, the L C issues are raised in each of the three sections. We could have had an L C session, thought it was better this way, thought it was better to address issues as they came along looking at the other subsections.

Looking at the second section, we talk about the gatekeepers, those who we identified and others helped us identify as the individuals critical to moving pharmacogenomics into the public sphere, of getting it to those improved clinical and public health out comes. The four groups identified: Industry, FDA, CMS, other party payers and clinical guideline developers, professionals in particular. If you notice one thing here. Before I said we well eight recommendations, here we only have one. That doesn't mean that this subsection somehow is of less importance. As I mentioned, these are the gatekeepers, the bottleneck. You are only talking about the bottleneck you need one recommendation; how to make it work better.

Finally we get to the third section, the section that focuses on where we hope pharmacogenomics can ultimately go, the implementation to improve outcomes in public heeling public health practice. This will address self, public health, guidance, economic implications of pharmacogenomics, ethical, legal and social issues in clinical implementation of fampl copharmacogenomics, and pharmacogenomics activities.

One of the difficulties in any of these reports is being able to draw clear lines of distinction. It's virtually impossible. However, I think what one can do is try to identify [ indiscernible ] from which one looks out then at the broader picture. Technology, economic implication, coordination of activities within HHS are going to be relevant to all kinds of different issues we address. Large population studies, oversight of genetic testing. What we tried to do here is to situate some of the broader issues within the context or focus of pharmacogenomics. The fact that, and we intentionally took this into consideration, parts of this report will in fact hopefully overlap well, or accord that coordinate with earlier studies and subsequent reports, like the oversight of genetic testing. We tried to in that way formulate this report so it is part of a continuum of the work of SACGHS. You will see in this section we have recommendations 10 through 15 with 16 subparts.

I hope that gives you a sense of how the report was structured and how we think, in any case, the report can best address the issue of pharmacogenomics. What are we going to do today? We are going to stop now and listen to Reid.

Reed V. Tuckson: Given we are getting ready to get into the discussion, report. We will take a break for a second, that way we won't interrupt the discussion, just plow right through it. This is the challenge, we [ indiscernible ] breaks. I don't. We start exactly when we say we are going to start. We do what we say we are going to do. You know that. By the way, Robin, we have read into the records all manner of incredible things about you. I want to say to you that we are very proud of the honor you received, highest award [ indiscernible ] ethic and great on this committee, we think you are wonderful. A round of applause for Robin.

Applause.

Now she will beat me up at the break. We will start at 20 of, that gives you 15 minutes, five, 15 -- 20 of, starting with the discussion. If you are late, oh my God, the woe that will befall you.

[BREAK until 9:40:00 a.m. eastern time. ]

we will now get to the discussion of the recommendations of the report. If you will all will take your seats, and we will now begin with going through the report itself, take it away Kevin.

Kevin FitzGerald: Let me begin by trying to focus our responses to the recommendations as we go through the report. For each section of the report we're going to review the key issues that we thought important to make clear, then we're going to look at the current language of draft recommendations. So the emphasize here is on current. Nothing is written in stone, however, if you wish to change the language you have to write the changes in blood. I want you to know it's going to cost you. No, we certainly are open, encourage all improvement to the language of the recommendations. Then we will work -- Suzanne is going to do this real-time. As we're making the recommendations you will see them up on the screen, and you will always have what's in your book to do compare/contrast as we move along. The idea is that we will get these recommendations to where we want them to be, then at the end, when we have done all the recommendations, and subparts, that's when we will vote on them as a group. Why don't we vote on them? Because we may do something later on, in a subgent recommendation that makes us re-think the wording we used previously. I want you to know that all remains flexible. If you believe to go back, revisit something, something pertinent, subsequently we can do that. At the end, the idea is to take them as a package, say this is what we want to put forward as recommendations. If we have time sub subsequent to that we can look at other recommendations. The key today is to get the recommendations well-structured and claved.

Recognize clarified.

As looking at recommendations, things we want to keep in mind. We are as advisory body to the secretary. The recommendations we want to make to the Secretary, these recommendations the best way to address the opportunities and challenges that we raise in the report? And of course, if you are not satisfied with the wording of the recommendations what wording do you suggest?

Subparts, clinical, translational, infrastructure, and again, we are in Washington D.C., so everything is acronyms, but sometimes it's good know what the acronyms stand for. Elsey is the short way of saying ESLI. The acronym for ethical, social and legal issues. It's not the name of my cow. Easily, easily L C, I'LL issues in legal and social ethics, however you put the acronym together, those are the issues to be addressed.

In the report what we identified is that more basic research is required. That needs to identify biochemical pathways, markers in drug response, to refine and improve sensitivity of high throughput methods for gene expression and drug response and look at gene -- in variability. As you see here in the basic research the focus is a great deal on what the response is going to be to particular drug therapy. Or drug intervention. One example of a group looking at this kind of thing is the genetic association information network. On page 24 of the report there's a small explanation of that, I don't want to go into that now. You can follow along in the report as we go through it.

Moving from basic to translational, team one translational research to validate basic research findings and apply to development of pharmacogenomics products. We are all familiar with the intent of that research. This has to be an important part of the entire pharmacogenomics project. Another example there is the pharmacogenomics research network. You can find that on page 25 of the report.

Moving from translational to clinical, one aspect discussed, also saw a great deal in the literature, the hope, at any rate, that pharmacogenomics can enable smaller, more efficient crinical trials. How? By using the test results to screen out subjects more likely to experience adverse drug reactions and conversely, identifying subjects more likely to respond well to a drug. The whole idea again is to use the basic science information and data that is gathered to bring it to clinical trials. A greater focus on avoiding harm and gaining the benefit.

Obviously in order to do that you have to have tests, how will people respond to the drugs? What incentives are there to develop these tests? One would be projected market utilization, return on investment, as mentioned obviously if you can avoid adverse events and improve benefits from any kind of drug therapy, that presumably would have a better return to your investment. This would lead to positive clinical impact because you would have the contribution, bringing in DNA sequence as a way of improving on overall healthcare, come includes non-genetic aspects. As mentioned already, hopefully reducing the prevalence of adverse drug reactions.

Licensing practice is something that needs to be addressed, very much a driver in the A A arena.

So if there is going to be a development of the pharmacogenomics test, how does one look to see this development working along side current drug development. Will there be a code development of pharmacogenomics drug and diagnostics?

It's not the resistance is a bad thing, it's a good thing, helps us focus on the issues, formulate good responses.

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Some of the areas that --[please hang up phone line so that new captioner can dial in ]

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So let me add, although I am not sure it tinges the recommendation, it may not necessarily be a very small piece of the population for which is the case. It could be one for which there is a dramatic negative effect on a small piece of the population where it is critical that does come out in that the report itself you talk about this, but it is important to link this to the comment on market segmentation is the idea that it could lead to a smaller market segmentation is one piece, but it could also lead to the creation of a market that otherwise did not exist. The two-part close, but directly comparable.

Thank you. The focus at least we were looking up today is on resistance. Obviously that would be an incentive. Thank you. It is worth the effort of getting you up the microphone. So he packed as we address these issues one of the questions that came up was, let's see how we can, perhaps, delineate these incentives or these resistances. This is one way in which we put to do it. So as you mentioned that testing does have the potential to improve the safety and efficacy of drugs on the market even in a Broadway. So what are the incentives for pursuing edification of these new indications? Well, obviously if one skill as a drug of the patent, that would create a greater financial incentive. Obviously less if it was off patent. Again, if that adverse reactions are severe than one has greater incentive to address rather thought mild. And if of course there are alternative treatments available care is less incentive because one can't just use an equally effective treatment. So we just wanted to clarify the spectrum on that issue. Looking at the small target populations and where pharmacogenomics might get a far from, it raises the issue of what if it is a very small target population? "we already have special provisions for orphan drugs and humanitarian use devices, and these could propel or could encourage the development of pharmacogenomics Christ Darden and test all populations. The difference is in this distinction we have the threshold for help these devices or drugs might be categorized so for an orphan drug, for something to be an orphan drug the target population must be an intuitive thousand people. Over something to categorize as an orphan diagnostic, aren't standing is and has to be under 4,000. One question is, if we are talking about the co development of diagnostics and drugs, is that different to have is that a to make a difference? So in other words the orphan drugs could be favored in its development over the companion diagnostic. Is that Greg to be a problem? This too was raised in the report. Moving from basic to a transitional, these were some of the issues that were raised in our investigation of pharmacogenomics. Obviously the adoption of technologies will hinge upon evidence in critical and public health practice which is as we mentioned at the beginning, the cold. Is this going to get us better clinical utility? , also and involved and this will be the idea of cost effectiveness. At what point does the cost of a particular to could begin to affect how it might actually be disseminated into the public in spite of the fact that it might have a significant clinical utility. One of the major issues we discovered which will run throughout the report, there just isn't sufficient evidence. In part, that is because we are early on and the pharmacogenomics process. In part it is also that there haven't necessarily been a lot of incentive to gather that evidence. That does not mean that some groups are to looking at it come up really one of the things that we found was copper hit we did not find sufficient incentive to produce this evidence which, of course, is absolutely necessary if we are trying to understand what that clinical utility is to be. Looking at the Research and Development infrastructure pharmacogenomics research and development could benefit from sharing and linking of research and clinical data bases, repositories, and records. When looking at live report that was cut output by the Secretary of personalized medicine you find the right treatment for the right person at the right time. Great. Nobody can argue with that. How does one get there? One of the things that had become clear is in order to do that you must have an inordinate amount of information and the ability to compare and contrast different datasets across different areas and an infrastructure. How can these be better linked so that that sharing of information can occur? There are significant challenges to this. There are IP concerns. There are variations and data format. Electronic health records are still in early stages of development, and there are different funding streams for all of these things. For the stakeholders, the adminstrative protocol and for organizational cultures -- different funding streams as well as different [ indiscernible ] different administer [ indiscernible ] and organizational cultures. They all lead to be addressed for us to get this sort of information sharing that we think is going to be absolutely necessary for moving ahead with the benefits of pharmacogenomics. As I mentioned, even the these challenges are very real there are areas and groups that are beginning to look at these challenges, and we have this list at the bottom here. They're is a daughter longer list in the report of projects that are already attempting to address these challenges. To the ESLI issues, all ethical, legal, and social, and the research and development of pharmacogenomics, here are some of the issues. Obviously many of these will be familiar to you, but it is important to bring these to the fore. Certainly privacy and confidentiality concerns are associated. If the only way that this does word is that researchers and clinicians have a great deal of access to personalize information, how well those persons be protected from any misuse of that information? And there will be trade-offs. The war has kept -- to access call the more risk. So how do we balance protection curses Abela sensitivity? This is one of the big issues that must be addressed. Another is that currently there are discrepancies between human subjects Research regulations, especially for coated specimens. One example is the comment rule versus that FDA regulation. If you what more specific secant look on pages of 51 and 52. That was another issue we flagged as something that the secretary could certainly help to have addressed. Another area that has come up, and this is not just in the pharmacogenomics arena, but one that must be addressed, is the concern that concepts like race and ethnicity might be involved in the development of pharmacogenomics in a way that is not beneficial. Instead it leads to greater health care disparity or even their confusion of exactly what the biological categories are being addressed versus some more socioeconomic categories that are often used in society. These issues also must be flags. Finally looking as we try to from a variety of different perspectives from the perspective of the industry, there are liability risks associated with questionable marketing cames -- claims were incorrect or misinterpreted test results. How will these areas of the to some confusion and potential conflicts be addressed in a way that everybody can move forward with the benefits of pharmacogenomics? Okay. So with that overview we get at the draft recommendations. This is a draft recommendation one on page 25 of your report. El at this point I need to let you know that the wording you will see on these slides does not always match the wording that is in the report before you. So some changes have already been undertaken. We are here to finalize. Would you see on the screen may vary from what is in your report. This recommendation is on pace 45. If you notice under number one on the slide you will not find two propositions that are in your report. Basically a search on the biochemical pathways as assistive but drop would double as an antidote pathways. In the report it says on the gene and gene creations. And on the function of the genes tested the safety and effectiveness. That is sub part one to a draft recommendation one. Take a look at it. Any comments, questions, suggestions? Our people happy with this? This is our first recommendation. NIH should put more research into, research on the bottom of the path is associated with drug metabolism and strike action, jeans and Jean variations involved in these pathways and the functions of the scenes with the to the safety and effectiveness of directory read.

By the way, can we is still caught Kevin, what is on the board is the newest?

Yes.

That is what we are working from?

We are right to work on what is on the screen and any wordsmith thing will be immediately placed on the screen. And in the end we will have all we have on the screen. For its point of clarification 43 When we say more resources do we mean a higher level than currently where do we simply been continue to put resources? And if it is a higher level can you tell me what that is?

Compared to what? Compared to.

But I to know whether it is compared to or something you continue to put resources and.

To be particularly precise I will just pull up what is in the report. First of all, the board that is there, if I believe this is accurate, it does indicate more in that sense of increased. I cannot give you the exact level of what is their right now, and I am --

Because NIH couldn't tell you.

Correct.

Suzanne knows, but she is not telling. So the idea here was to say that this the tip be an additional effort. That answers your question.

Yes, Paul?

The recommendation is asking for NIH to dedicate more resources. Is there a problem with asking Congress to sort of appropriate more resources as opposed to NIH basically taking from its limits upon the loss sort of moving the chairs around as if it were some day?

We can't recommend to Congress, right? If you what sets itself officially --

No got I guess that is sort of just -- I just want to fight that, that basically the reports is saying preference this immediate need and pressure on NIH over other immediate needs NIH we really the issue, I think, goes back to cars in terms of appropriating money. And given where we are and given the limitations on the advisory committee, that is just the way it has to be, is that correct?

I think what you are getting at is that be what the committee or the recommendation to the other call for the request for additional funding word you want us to specify whether we are asking for NIH to adjust it's current priorities.

My preference would be that it comes out of additional funding and it is hard for me to -- or it is hard personally for me or the committee to state pharmacogenomics deserves a higher price a priority than cancer research or never. That is an implicit issued within the recommendations.

Are you saying that NIH should have more resources available? How are we advocate the have more resources to put into?

That would be my preference. I don't know if NIH has a problem with more resources.

We can do it that way.

Okay. So NIH should be given more resources to put into.

What about the initial resources? Would that be --

You know, we recommended the secretaries seek more resources. The way to fudge it wold be to say the budget would be more resources be made available without exactly saying how.

Or maybe the way to identify the issue would be NIH is in need of additional resources, and those resources should -- additional resources to put into.

To increase its efforts and that areas of -- something like that.

It be appropriate to say something on the order of that NIH should develop funding initiatives? That is the process. You actually develop an initiative with defined goals.

I guess it is my understanding that NIH prepares a budget request each year to give to congress and so that is their opportunity to ask for what they need. So I think that is where we were trying to get to. They should define how much more resources they need and ask for those.

Yes, I guess this has not come up before. Our recommendation going to the agency's, we would all like to have extra. I am not sure that we need to massage as this one to death, but obviously what needs to happen is the integration of of economics into all of these activities from basic to a transitional, there could be a global statement at the beginning of the report rather than personal out each one of these recommendations because they all require additional resources.

And this one, it is that now it is pretty obvious that there is this time of very constrained resources. Even during the middle of the and desirable some estimates dissipated and the this did not so I think that it should be an area of importance with whatever budget you have. Even when new funds have been made available in large amounts, not everybody saw that need.

Would people be comfortable with NIH should receive and and put more resources into? That covers both.

I guess that would work.

Thank you. Bahrain?

Why do we have to say that? Everything will have to say the same date.

Roll-call why don't we just go through the rest of.

Okay.

We will put this down temporarily until the -- all right. Member to -- first of all, is a really happy with one?

The segment you have lifted out safety and effectiveness which is that the FDA said the Tory language. And it is and a victory of course. I would suggest that frees up to add to about reasonable and necessary is that term. Medical as a succeed in its present quite a bit. And what of the weakest we have had over the years is that the basic research.

At six and effectiveness but it is the look at medical necessity and gather evidence as much as it might to make the payments structure be able to respond. So I put suggest that this ought to include some mention of medical necessity are reasonable necessity. We will talk later on when we get to [ indiscernible ].

Elite?

At think we were trying to differentiate that basic research, understanding the underlying science from the kind of things you are talking about would come later in our recommendations as we get more into that a transitional aspects of it. At that point absolutely we want to look at those things, but if you don't understand the basic biology then it is hard to move to the next step. What we try to do is break this down into several subsets. The first you have to do is basic and then a transitional and clinical. At the end you obviously want to have all of those measures plus the health economics understood.

I understand the logic. I have a just suggesting that I can't tell you how many times we have many folks including around this table coming in and are asking for information that if it had been talk about way back and that basic science face could smooth the road. That is all.

So let me just get the sense of this. If at some point in one of these basic research recommendations put in that would it -- would you what it in every one?

No. I am did try to sensitize the committee.

The next one might have a slot work it would fit nicely.

Okay.

Just one question on number one of one. When it talks about drug treatments, but her aunt you to are correct diagnosis of as well. Does this one need to or can it brought an adjust to say safety factors effectiveness of treatments and diagnoses are with this just yet to be [ speaker unclear - audio low ]?

We would put in effectiveness of drug treatments and diagnostics.

Or diagnostics.

Anybody have any problem with that? It is just more inclusive. So then diagnostic is good. All right. Any others on this is to on a parade. Let's move on to the second one. If your hand is up and I miss you, just throw something blunt and heavy. None hypothesis based approaches to the understanding -- putting more resources into an on hypothesis based approaches to the destiny of the rest should between genetic variation in individual's response to drugs. Response to drugs. Yes? Please? How.

Could meet a little background. Give me a little about why this was included.

Recommendation one assisted with this approach. We also wanted to include the effect that we don't always know. So we wanted to open the possibility for non hypothesis this. So saying the drug is working to this particular genomic way and the only standard that, but to look at more whole genome approaches to things.

Good. Anybody else on this? We will keep that the way it is and will want to the next draft recommendation which is on pace 26. And this recommendation you will notice again a slight -- let me just make sure I have this right. Okay. So in this recommendation what you have in your text differs from what is on the screen, and I will point out where. As a loss of the of the line Pelletier cruise further research will be needed to translate this into clinically useful PGX test ends is not in your book, but it is on the screen. Test AND technologies to assess their critical validity and utility. This is where I thought maybe we could add something along. Be those that it is as should facilitate the development of currently useful pharmacogenomics Technologies by investing more resources into all components of transitional research including the transmission of a basic research findings into clinical trial. And that, I believe, right. It is not in that text. The as is missing as well as the translation of clinical research findings into critical and public health practice and policy. One of the emphases of this transitional research should be to foster -- and I believe that is also not end the text of the report, to foster the development of more rapid cost-effective to attack and technologies. Rather than just say to be the development, we have put into foster the development. Barry, does this get at more what you were --

It does somebody.

Could we make it stronger?

I and just wondering since he used the language here of critical and public health practices and policies it might Intel coverage, but you might want to put covered and they're also.

We could put into critical and public health practice and policy. Is everybody comfortable with that? Great.

I am going to exercise this one or time. The recommendation recommends gene mapping technologies when, in fact, phenotype and is probably in many cases closer to the clinical reality of changing practice. So what was the background for the final sentence for the?

Well, again. This is not a situation where this is being emphasized to the exclusion of the other. And so here the idea was -- up here are the slide it says can foster the development of more rapid than a stepping technologies. Phenotype and technologies would be incredibly broad and $0.1. That could involve all sorts of biochemical -- Jim? ARS this must have gone by me in one of the conference calls. I am -- that does kind of stick out. I am not sure why agree necessarily need to or should emphasize very specifically more rapid to detect and technologies. I think the first sentence really sums up what we want to get to. I'm not sure we should be that specific.

One way to address this but just be too in the last sentence strike and the typing and substitute diagnostic.

All right. That is what a way to go. This was a recommendation made specifically by one of our members who is not here at the so we can either get rid of the sentence were put in diagnostics. Diagnostics better? Yes?

You could just go back to the beginning of the paragraph where you say PGX technologies. Genotype would be more or less DNA and RNA. It is will make more specific.

Again, I think when one thinks about as a single research it is extraordinarily important at that level that think about a very broad range of things that include clinical validity and clinical utility. This it's far beyond diagnostics. I think diagnostics or even Technologies is too narrow. We should just walk out of licenses. There is much work category utility then technology.

What Jim is recommending is we got out that last sentence but the.

I just I will just counter that. If you only develop the collation -- that is what we were trying to achieve.

By singling out one aspect of technology one that loses the important general recommendation which is to encourage a neglected facets which is translation of research. I think that a specific recommendation that focuses on technologies and diagnostics runs the considerable risk of really putting it back. You need a surgeon at tapping but farms which is as traditional research. Eddie this will come to about 14 read of that last sentence.

Let me just do it this far. We have -- the two trusts it to be getting rid of that sentence and the other is about changing the last sentence. So looking at that, is there anyone here who is engaging read of the last sentence? Okay. We could all live with that and we have one person who does not want to live with tinging it even if it is changed. So for right now why don't we get rid of that last sentence. If we come back and say we need to be more specific, we can do that. It just did it for now. That solves that issue. Great. Next -- by the way, our tactics and will be calling around. He should do whatever he needs to do. Pay no attention to this person running around.

Okay.

This particular recommendation is the same in both the report and on the screen. Again on clinical research where study results will be used to test its safety and efficacy to report a pre-market review EDS application and sponsors and researchers should be encouraged to study with the FDA. This would help to insure that these have adequate critical study design and quality controls in place should to the research with their be submitted for regulatory review. I think this is the idea, you can pick out some of what he was talking about. Get down the road and see if we can't get these closely together.

I suggest you put in FDA and CMS. We are talking about parallel review. That gets people in earlier.

FDA and see CMS All right. Good. Any other suggestions? Great. All right. They are trying to move on. 3B. Okay. Again this is different than what is in your text. We have as appropriate at the beginning of this rendition. So as appropriate that NIH should consider making their standards a component of the scientific race of grants and contracts submissions. Everyone is comfortable with that? Fantastic. NIH should encourage grantees to end this participate in FDA if voluntary this submission Perkins to insure consistency in standards that may affect drug prescribing. Yes?

I had a question on this. I'm sure there was debate about the board increased purses require given that NIH does have the ability to supply funds it would be, as I understand it, within their purview to be able to require submission as part of the RFA. So tell me why it was to the why the word encourage was chosen as opposed to require.

You are absolutely right. That was discussed. My sense was that to leave it voluntary and not make it mandatory was something that was thought to be preferable.

I would just note that it does not change the program from being voluntary. But for people who want to do research using NIH funding there is nothing to say that the NIH couldn't require it.

That's true.

Whom exactly should be required? Every NIH grantee, I don't think so. As appropriate, I suspect.

So is that what you are saying, it should be of every NIH?

I guess I would need clarification or recall properly there are lots of DHHS groups that have nothing to do with this area. What would not require it to of those currencies.

So would you be comfortable if we said NIH required great cheese and contractors as appropriate?

I think you could put the as appropriate it.

That is the direction that I would favor unless there is compelling reasons from the task force discussion.

I would keep it as encourage because there are at the research done in a special groups that would not be able to do there research if it was required of them to participate in the FDA voluntary economic data collection.

Okay.

I this it is very important thing. If you make it optional few people would do it. But if you make it mandatory that it may affect some types of research. It is a difficult one.

And this is basically per our discussion was.

And that is where the as appropriate might work.

Okay. Let's get Paul and some others. Joe? Okay. Well, I would use both. You would encourage, but it should be as appropriate because he still have to designate who would be responsible for monitoring whether or not that occurred or not. And so as appropriate would go to the appropriate agency program, some program within the NIH and Abbas to me working with that. Because you wouldn't just leave that open. The same arguments being made for a mandatory should also be considered as to who then would be responsible for even moderate weather does that workers to carry it out actually carried it out.

Okay. Great. Paul?

Just as a matter of were expecting or sort of maybe just a style issue, and I am a those sort of -- I am uncomfortable with a throwing in the phrase as appropriate on both this -- because I am not quite sure what that means. And at the is a pretty when she what she termed. And to the extent that I want to limit this, this hour of the previous -- and I broke my tongue on the previous, then we should state exactly what we mean because as appropriate is so ambiguous it tends to confuse rather than clarify. That is my opinion.

I have marked and Steve.

Just to respond to the Soviet and Paul. From a Soviet perspective there could be an exception process for research that is considered -- where this would be a barrier to during research. And Paul's point, what we are really talking art is some language that would encourage -- and I don't know who this would be, to basically develop policy around what is meant -- who would be exempt from submission and under what circumstances that the exemption would be reviewed.

That is fair, if I could respond. It may be that you place some language in that text of the report explaining that rather than putting it in the -- or recommendation that that might be an appropriate -- as appropriate as anything for that phrase.

Mike, it was as we go further in this field are having a randomized trauma and I am assuming that the CDC would also grant grantees or contractors. So is it liable to think they'd hopefully fund research to be in this recommendation?

Mike? Go ahead.

Just to clarify, to Paul's point. It might be wise to include the statement, when it indicated is decorated in a study funded by a NIH then you can say required or encouraged. It is up to you guys.

Okay. That gives us our best the city.

Is this clinical research relevance to the research that is meeting for the pharmacogenomics application to be put as a test or as a tool? There's all kinds of research and we have reached the point where we are at this interface in translation between after gene discovery for pathways or whatever. And now you're trying to develop an application that could then be submitted to the FDA. So one could be a dishonest to appoint to say that that funded research that is designed to evaluate or develop applications to be used for practice of pharmacogenomics purchase the courage map would be for that kind of pressures to add to raise more with the FDA process is whether it is funded by NIH or wherever. I know we will be funding some, but most of it will come from NIH. It is probably a small fraction of Connecticut plants? Has reached a point in that pathway that is more selected. So there could be some words to thing that does a lot.

That is what we'd are supposed to do. smith away.

When sentiment data is [ indiscernible ] that is ridiculous because that involves hundreds and thousands of studies that will never read the light of day in terms of applications. So when a farmer could genetic data to a mistress for the purpose of developing a pharmacogenomics application are test for use in practice, that is when the trigger happens. I am stumbling over by onward because -- AB of this can help me.

That is not entirely right. They are actually posit to look at the use of the economic data earlier in the life and up the point about a diagnostic device is poised to enter the market as a companion products. When a diagnostic device is poised to the market the voluntary data submission process is that art process. You need to start thinking about CDRH protocol review process. So if you are asking me to play around with the language it is going to need to be parsed a little more cleverly and this. There is this stage when you are playing around with data in the context of the drug. The person did this submission hits the spot. And when you have a companion diagnostic that looks like it is on the way and you need to start thinking about a pre I T ER protocol review the need to be careful what we wish for. They don't actually have the resources to the in the pot out generous funding in this area is to start looking at dozens and thousands. Some kind of a disclaimer. Some kind of buffer. For one thing the data submission is an exploratory process. Could the doctor as. But he does not lead to keep reinventing the wheel. You don't need to submit back because that road has been established. I personally prefer a lulling some kind of flexibility. I thought it would have been a really nice to have a new diagnostic product that NIH was finding that they required that they at least read FDA regulatory documents so they understand the research has certain obligations about quality control and following protocol and doing things that may have a heightened [ indiscernible ].

So for the voluntary this submission program, do you have wording that would fit that program for this recommendation? The mic is not on.

It would be, should participate. And the submission prepared during the exploratory phase of drug development.

And Review Program is offering tax parts per -- note, it would be after voluntary to make data submission. The pre I T E process, when a dynastic is thought to be essential and the critical use of the truck.

It is thought to be essential.

That is the mark difference voluntary data submission and the pre IDE. You're not sure about the need for a drug or you may suddenly get the you need a drug -- you need a diagnostic when you know that you will need both the enter the marketplace as bright -- bride and groom. Then we are the winning all.

We are still some things here. When the pharmacogenomics data is generated for the purpose of -- that can be had. Hong okay. We have to clean desk. That would be down here, maybe.

So do we want to go back to HH as should encourage or require?

Let's try require grantees as appropriate to participate in the FT a voluntary state as well as the review process. So court comes after the pre IDE review process?

In situations were diagnostic is thought to be set so the truck used or clinical drug use.

Okay.

Scott, sorry. You have the like. Okay. We have of earth on trainee here.

This is the language of requiring participation in a voluntary activity is kind of -- is really not. As I pointed out before anybody can submit said that voluntary program, but what I'm saying is if you get money from the program they need you have to. That is completely consistent surgically and any other way that you want to look at it. But it you are giving money at somebody they can require you to do something that might otherwise be voluntary.

I have a point and a question. There are two Pauls here. I would be like to refered to as Paul the lesser. That is Paul the wiser. First of all, I am a little confused. Segmentation can occur very early on either in the pre critical phrase or and contemplation of the critical phase of that segmentation in this compilation of the collection of data may have nothing to do at the end with any labeling recommendation. So I've got little confused that this language as to how that is dealt with. I don't have a recommendation how to improve it. Maybe Steve just said in my year of minutes ago you put or in the pre IDE review process because that would then cover people contemplating a clinical trials but then not actually deciding that they want to submit with the segmentation data.

Okay. This is what we have currently. We should require grantees and contractors as appropriate to participate in the voluntary to know this is a mission program which major of the Pete. Renamed. During the exploratory phase of drug development or the pre IPE review process in situations where diagnostics are thought to be essential to critical IDEs. What a way to a wordsmith is it a little bit more would be to remove as the proper it says we are already saying what their conditions are at the end. Microphone please.

So notwithstanding the comments which are typically correct would be meeting requirement and voluntary. I don't think there is any problem getting rid of all Terri. It is still the program. If everyone feels it should be a requirement that they are required to participate in the that the number to Ted suppression program. So while you are right technically there would be a lot of confusion.

I have an a and then Steve.

I don't think we can change.

We can always use the acronym and to open have a clue what it is.

I think it would be very ought to take voluntary out.

I want to come back to the point that Paul Miller or whatever Paul was referring to. I just want to a reference with and that recommendation that the secretary will convene the relevant HHS agency to produce -- and I don't know whether these would be rules or regs our policies to address the specific circumstances under which this requirement would be active.

You want that in the recommendation? Assistive be expanded, but I think we are making a recommendation to the secretary. So it must be there.

That.

So convene the appropriate agency to address implementation. Parts and that got just reminds you that everyone, we are voting on these because there is recommendation 158 which is to say that an interdepartmental working group should be established to review all regulations. So it is sort of a grab bag trying to get at what you just said for all recommendations.

What you could then do is basically say that this recommendation will be addressed per recommendation 15 a.

Something like that.

Let's give send a moment here, get this together.

Change the or talk and work because there might be circumstances where both processes are appropriate.

A day.

And then and rather than or.

Okay. No, we did not take up voluntary. We will just use the acronym. HHS should require grantees and contractors to participate in FDA's VGES program during [ indiscernible ] phase of drug development or situations where pharmacogenomics diagnostics are about to be essential for clinical drug use. Implementation will be addressed in recommendation 15 a. All right.

Since you said the implications of all recommendations are "to be addressed it seems a bit redundant to have that. I mean apologies to you. Everything would have to be implemented in an orderly process. So just testing of this one out sends out a little odd.

Would it be adequate to have times when looking ahead to? We may have other recommendations we want to make sure that we make. We just want to emphasize. Don't need it? No? All right. All those who think we don't need this pick up your glasses and throw them out art. Nope, nope. Are you okay with that? Presumably this will. All right. How are we with the thing which right now? It should require grantees and contractors to participate in the voluntary economic data submission program. You know, if we just can't bring the public took greater clarity and the use of the English language, what good are we? Terri the exploratory phase of a truck development and/or they pre review process in situations where production alike diagnostics are taught that the -- it is changing again. They are thought to be essential technical drug use. What did you just change? It is grantees. Again. Wait a minute. It is you're right.

Test of a small part. In situations applies to both that too. So what if you began that recommendation with that phrase? Would that make it easier to follow?

Said the suggestion is to move that to the fraud because it applies to the pre and [ indiscernible ] bucket. Of that to the front. Thank you. All right.

Paul. During that discussion of this recommendation was there some consideration of what is part on and the drug industry and that non grantee population and how there might be some harmonization of what is part on and that non grantee and grantee world?

That was part of our discussion, why it was encouraged rather than required. Power at are accused suggesting --

I don't think it serves the purpose of this committee to set up two parallels. It does not serve the public interest either. Nergal I recognize that there are barriers, some important ones, but that does not mean that we can recommend better harmonization or sharing of data or ways of that.

We have that in their recommendations. At the it is brother on when we talk about the information. Go ahead.

It is just a matter of making sure that as we get each of these recommendations that we understand what our committee can do. We can only recommend to the secretary. The secretary has no ability outside of moneys that they control that they paid tribute to private entities to really compel them to do anything. And so and the text of the report there is a lot of verbiage as to why it is important that there be communication and consistency and that we have that as it that way. Beyond encouraging voluntary participation there is not what else that can be done in that context.

With a second.

I think that idea was that by taking the format that has already been vested with the side that note asking the federally funded researchers to use that same format, the idea was that those things would be more credible across was privately funded researchers as well as the public rather than having the public set up on a whole separate database structure and everything. So there was but the to the madness of choosing the FDA and voluntary data submission.

Certainly and the text of that it should be clear so that when the votes rate is they can get the idea of what we are getting at.

Do me a favor. Take a look at the text. Just to point out to you, we are trying to address this also so we have in situations where are cut to pound diagnostics of thought to be essential to critical Truckee's its rates as should require its grantees and contractors to participate in FDA voluntary genetic data submission program during the exploratory phase of a truck development and word the pre I T E review process. Going once, going twice, sold.

Paul the crater has something to say.

What do you mean by, are thought to be? Why not just diagnostics are essential?

You want diagnostics -- considered is the same thing. Diagnostics are essential.

I think you are still and the hypothesis States.

Not always. There is our problem. It may be essential. I know where Paul is current from. That can be used. We need to be adequately explicit about what we mean. The key to avoid the result words.

With a minute. We already have in situations where. So where pharmacogenomics diagnostics are essential, it is the situations that count. That needs to designated. That is part. Is that okay?

You may have resolved it with doing that, but I agreed with getting rid of are thought to be. I think the question is, at what point did you know they are essential?

That will have to be determined. That is recommendation 15-8.

And there.

A so now we have in situations where pharmacogenomics diagnostics are essential technical charts used. All right. I look around. Do it once, twice, three times, sold. Remember, we can come back and visit these if it thinks come on.

[ indiscernible ]

Until we vote and is truly kukri the final. Unless we don't get to a vote. This is just in here, this is for your information. This will not be in that recommendation. We just wanted to fly recommendations that came in from college. We should enable the investigation of markers associated with dirt response by encouraging sponsors of federally funded drug trials to request appropriate biological samples from Research participants.

The be it is implied but it seems to stop a little short. To request samples and get the relevant submissions --

They would have to be done with informed consent.

And be done with them as opposed to just getting the sample. Maybe that but is it is implied that and the text, but it seems to me it was missing the second half which is we are not just getting samples were samples but samples to be used.

By our markers associated response.

You could say to facilitate pharmacogenomics research.

I think the first part says we should enable the research of Bear markers associated with dark response. Is that not clear? We could rotate things around and put that in that and if you want to do it that way.

You can disabling things in the broadest way and request samples from research participants. I think is -- people get more concerned about requesting samples. I think it is important to connected with what we are -- for its part to be done.

Okay. So HSS should encourage sponsors to request -- in order to.

May be the other way. In the HHS should encourage sponsors across to request the samples -- I lost myself. I would add, get the appropriate permissions --

Informed consent.

That would be relevant.

Exactly.

I am just we are getting wrapped up on regularity. Comparing it, it is so broad you're facility all kinds of technologies. And in this recommendation we are to talk about access to some specimens in one situation on it. This is the larger issue. Their boss be a by a bank and other kinds of infrastructure issues here. This is just one part of this process we are focusing on. I'm not sure why we choose to focus on this part.

In part in response to public comment. And we thought this was reasonable in that response because when you talk about that need for the bill makes "plus some of that was already addressed in the report. So the question is, is this too granular? But this was in response to the public, at which we thought was our way of further specifying some of the things that had begun to be addressed in part population studies.

So what -- go ahead.

Can you look at recommendation five b. Does this get closer at what your talking about? It is 5-B, 5-c.

It could come and there also. Because as you are indeed you talked about the legacy which is really getting into specimens and using it.

And that would make it more profitable because this would just as a recommendation we are getting samples, but not enough connection. So this raises anxiety as opposed to reducing.

The reason this is in here is because in the public, but somebody said specifically it needs to be recommended. I had like and then again.

So if you are court to include this recommendation it is critical that we fall to the statement that right now there are no standards for either obtaining storage organization of any biological specimen that -- there are no national standards. And so if you are going to include this recommendation I would highly recommend that additional language be placed in that document to support the development of standardization for handling such specimens. Now, if your car to pull this out and put it in five be of just jump ahead. Maybe you should add to the laundry list of people that everyone should work with.

Okay.

But some are and this document it is a little anemic in this regard. You really need to emphasize the need for technology and sampling standards.

Let me make sure I got it right.

I was just trying to reiterate. When you were trying to point out why this was suggested -- I think there is some doubt rationale and having it, maybe with the modifications that Michael suggested. The point being that critical drug trials don't necessarily collect pertinent data, and really the entire promise of pharmacogenomics rests art collecting certain samples, namely DNA. That way they are available for study when we began to get a response data, a center. So I think it is a reasonable recommendation. I take something to that effect of what was just suggested about incorporating that into a I usable more comprehensive type structure.

Okay.

I definitely agree that we have to provide some additional context. The question on three or five or maybe both is, this is the clinical research section and five is in establishing the evidence. My assumption -- I am looking at the public the idea is we wanted to mention it in technical research session. It's sort of feels like it is missing. I encourage and I will try to spend a little tired -- I can't do this in real time, but we be to add some additional specificity on this. By Paul suggested what this means, how the samples would be used or are at least consistent with an appropriate guidelines on this type of work.

To enable the investigation of a player markers associated with stroke response within the development of national guidelines or something along those lines, just think about that. We have a few more cards to go to.

I just wanted to ask in terms of the standards and guidelines you are talking about technical issues rather than ethical and legal issues. I am sure you are aware that the guidelines -- yes, those are obviously focused on samples, but argues suggesting and other is suggesting that that is what is needed for this field, the way in which the samples are collected and stored. They're must be standardization along technical lines. So we take what in the CIA has done an oncology and focus on what is needed in this field.

Well even in NCI is involved in putting more money in is because there are no real standards yet for how to handle and collect and fix and stored tissue samples. So och --

So if we take a look at what is on this screen that sits at CS -- Suzanne did put up to enable by a marker assistive response HHS should encourage federalese sponsored to require research for participants HHS should have guidance on how these are collected, stored, and shared.

Fort previous reporting did we ever recommend development of these standards?

I don't have that on my computer. I would have to take that up. I am trying to remember.

There is certainly a call for the consideration of the ethical issues. It was focused more on societal implications and not so much the technical, as I recall. But Yvette has that report backwards and forwards.

We will check with her on that.

Just looking at the list of firms. The one that seems to be missing is used.

With your question of this development dinettes and standards on how samples should be collected, stored, used to likes the job. That was one of the recommendations.

In the body of this we can obviously clip of that. We will make a mark word that is a great idea. We wanted to add to rate these reports. I have Michael still on this. We have to move.

It is not just how the samples are collected and stores. It is held the clinical data associated with this, that we know if it is the same got to a condition or disease or some type. So the princess of critical data is a major impediment and not a technical issue.

We have here how these samples and they're associated critical data -- okay.

One quick one. I was hoping that maybe you could change request to obtain? It requesting is requesting.

Should -- or, you can encourage sponsors.

Requesting responses.

You encourage them to obtain because that does not require them to obtain. You could require the responses to requests. Right. But you cannot do both. We can encourage them to read quest or recant require them to obtain. And there is always work who is --

I will use the required work. I suggest that the recommendation especially reflect the recommendation from the population study report because a lot of times people don't read the whole report. If you bury it in the text it will be seen. That is consistent with what we have done in other reports we're recommendations preference that. So wherever that is and there I just say you should insert it there and the recommendation and not just a tax.

Are you what the words from the other reports put in here?

Not the words, but the specific records.

We are still all this would.

This is a the a bit of a choir.

When you collect the samples it is very important that the genetic data goes to the FDA or to regulatory agency who will have access. The patient has the right to withdraw the consent. But what this sense I don't know they can't take That away. I don't think it is even possible. It evokes the design of the study. I would add a word here saying that future studies should be designed in a way that would permit the submission of data with the FDA if appropriate. If the study wasn't designed for that you can't even have a sample and not do it.

That position if we are developing guidance and standards on how these should be collected, wouldn't that be part of those guidelines and standards? Obviously it would involve the informed consent but also which ones are appropriate.

Ahead. I think it does a little bit more than that. It is held the -- the intent of the study.

But if we -- it should also involve which should be collected, right? Okay. Maybe on how -- we need words here. Who had comments before?

Some costs because it to response and sometimes start prescribing which is, I think what meant to be the same.

Up there?

Not in this recommendation, but come bearing -- comparing recommendations. If folks think those are interchangeable I am fine with that.

Which term is preferred?

I'd like a drug prescribing which is broader than draw response. That is how we did it on the last one. So I suggest we be consistent

Do you know which produce recommendation?

3-seat.

The development?

Maybe it got out of there.

Well we agree driving is the term we can stick with? Note. That was a mistake. Okay.

I don't think we need to parse it. The concept is a reasonable one that we need to be consistent with our use of rather than try and fix that here which may be well impossible, to target the task force to say, you must look at drugs and use the same language consistently unless there are specific reasons in a recommendation to make it different.

This -- we don't have a chance for their on from here. It's --

It is called lunch, Kevin.

Obviously there is no preferred term.

Why don't we need it as is, and maybe as we look at the recommendations over the last --

I just want to agree with her because prescribing takes into account of response as well as 80 art. Whereas if you just say response then you sort of let the other side of the whole thing out.

Okay. Steve?

I disagree. Prescribing gets you into the hall utilization, and this is about clinical research and finding out what relates to the response. I would keep it the way that it was.

All right. Let's put it this way we started with response. Let's use that as a default. Are you okay with response? Do you need prescribing? This is critical translation.

Probably leave it as response now. I would like to as we get back to it but to see if it needs to be consistent.

Either we can leave it at response our response / 80 art.

Okay.

If you think it covers that, it is fine. I was trying to get the concept that it wasn't just initial response.

Everybody is good? One more time through this. To enable the investigation of Bias' markers associated with the response HHS should encourage sponsors of a federally funded clinical drug trials to obtain appropriate chemical biological thralls. HHS should develop guidance and standards on how these samples and they're associated data should be collected, stored, shared, and he used. We could put in parentheses here or a footnote whatever recommendation from the large population study report. Okay? Okay? Okay. Great. Next. It

[ speaker unclear - audio low ]

What? This is why the NFL has that new problem with that rule. Okay.

We want critical data. What does that mean? This is drug use. Do you want other data? IBM when you are trying to make records and you are the key at outcomes, there is other data related to team environment and action.

What did you have in mind with clinical data?

Okay. There we go.

I just want to add to that step that the initial recommendation was phrased to focus on the biological sample. Not, depending upon the context of how it is right to be used it could be purely political or have more of a team environment. So that I'd be up to the committee has how broad you want to make it.

How about if we have associated patients day? Is that better?

Not all participants are patients. They could be healthy individuals.

Participant to eject Iraq that keeps it great, but there is some clinical data. There is also a cartel that.

Okay. We have art and Paul.

This is and the context of developing guidance and standards. The point being brought up is something that be addressed in developing guidance and Sanders. We don't need to parse it out anymore. And my comment is, there are too should in the second birth. Maybe you should turn the second one into on will.

So in developing the guidance and standards, would that be part of what sort of data will be involved? Okay. Other data will be collected and stored and used. Okay. Try it again. To enable the investigation of by a work associated with response to the top should encourage sponsors to obtain appropriate biological samples from research participants. HHS should develop guidance and standards on how these samples and other participants did will be collected, stored, shared and used and also see recommendation was never from the earlier parts population study. I am calling to get -- house samples and -- you have to push your buttons.

I think this will help with the earlier discussion. How these samples and that debt associated with them will be collected. Then you have all of that debt associated.

[ speaker unclear - audio low ]

But the samples, for all participants, don't they? We are not talking about anything but simple participants treated participants samples.

Wait a minute. This is starting up again. I agree. I think participant data is socially but importantly different from just accompanying --

All right. That could be concentration of the sample.

I hear people leaning toward participant. Is everybody -- during was? Note. All right. So what was your comment?

How about participants sample?

None out. The samples, the Czech of tissue, the syrup, that he and a. What we are getting at --

I would bet on this in our party. I don't I will throw [ indiscernible ] in front of you. Okay. I think we are good. No? Y? I have to ask. Next. Page 35. Here we go HHS should -- by the way, nobody these until we are done. If we are here until three and the order to buy isn't that how it works you back

HHS should ensure sufficient resources are available to build on an employment agencies' efforts to develop guidance on the code development of pharmacogenomics drugs and diagnostics. FDA guidance should clarify the review process work of developed pharmacogenomics products word that chart is subject to FDA review but the average rate developed companion diagnostic test may not be. It also should promote cooperation between drug and tight plastic manufacturers. Steve? Where? Down there.

Well, again could somebody clarify why diagnostic manufacturers are specifically noted and why not the laboratory and industry which is the major provider of these tests?

[ indiscernible ].

At the what we are asking for was guns on both aspects. That is where there are just available for service laboratories as well as tests that would be put in a box.

But we want cooperation amongst all entities in the provision of these, but we? In the last sentence it's as promote, but in fact report collaboration across the whole spectrum of providers and this field.

That way we get back into combat does FTA have purview? This recommendation was a third to specifically to develop guidance.

Can I make a suggestion? I am the stand that is a bigger issue. But I you wonder if we just want to say diagnostic companies? That way that will encompass both manufacturers come on about service companies. It is broader and the FTA has some draft guidance now with some a as our that oversees things at the laboratory service companies to.

We have run as well.

I want to go back to the point that when [ indiscernible ]. That is the use of the board resources. This recommendation is calling for us to ensure sufficient resources are available. Recommendation one ask for NIH to put more resources and. We see recommendation 58 HHS should provide resources. Why in this recommendation there is a need to emphasize resources. I agree that we should just have an omnibus recommendation at the end, perhaps expanding when we get to a recommendation 15 p to talk glibly about looking at needed resources to carry out their recommendations.

So in changing this one how would you --

I would just --

[OVERLAPPING SPEAKERS]

Okay. And then refer to a 15-be.

I am just wondering if this recommendation covers when a truck company develops its own diagnostic. Is this language includes a of that?

That was trying to get back to a your point.

No, but was a different point. I actually think the way it is written now by diagnostic developer's does include that because it would not matter what kind of company.

Update. All right. So we have diagnostic developer's. Good.

So should we say diagnostics or development of drugs and be to extract the six?

Drugs and --

Code development, you are talking about a specific target a specific diagnostic. It does not need any additional explanation.

Mark, what are you saying? Should we go back to the way it was art just say drugs and diagnostics?

Note, I think the key Texas, the that is part.

I agree.

Doesn't that limits you because then by definition it has to be cut developed with that drug? There will be other diagnostic tax --

Those are addressed and other recommendations. This is specific to cut development. Let's read what we have no. Wait a minute. Emily?

Somehow we got to the diagnostic developer's -- part of this guidance has to take into account for the battle sentence its seats to take into account both processes where the diagnostic is developed by a manufacturer and bird the diagnostic is a separate for developed test. Somehow when we changed the last sentence we lost the whole manufacturing part of the industry.

So what would you recommend?

How about and instead of but? I am just trying to see where the right place to put this is

And the note leopard for developed --

Yes. So the little sentence is just one case where the drug is subject to refute, but the diagnostic might not be. We need the contents of that for when the drug and that diagnostic are subject to review.

Could it be brought her and just say the guidance should clarify the review process? Do we need to clarify it?

Wait.

Take the laboratory out.

Wait a minute. One more time.

Take the part about the laboratory developed companion out.

Stop the sentence after review and get rid --

Some of these issues will be further down.

Exactly.

So to the that part.

You don't need the including? And so get rid of including.

Start at parks. Okay. Try it again. We are into brevity if we can do it. All right. Let's see what we have. FT Asia develop and implement guidance on the coat development. The guidance should clarify the review process for code developed pharmacogenomics products. It also should promote collaboration between drug and diagnostic. First to weigh in?

What do we mean by broad collaboration?

Beat them about the head and shoulders

The text talks about some ideas where they could work together where they have meetings together and the voluntary separation data. In my mind that is one of those examples.

Her cat. So we have examples. That is good enough? Okay. Anybody else? It is living. This looks good for the moment. FDA Office of combination products should coordinate their review of Farquhar genetic tests and drugs among the various FTA centers / offices to minimize delays and approvals of car developed pharmacogenomics products and to insure timely access to such products. Great. So far, yes? All right. Excellent. Everyone is happy.

Once used as a private parts is needed to do that job you can to be the third line. It seems redundant to have that third fund.

Okay. Shorter is always better. The Office of commission price should coordinate the review of our good to know it's just

To minimize delays and the approval and to ensure timely access. Yes? Yes. Excellent. The key.

I think by taking out among the various centers offices the sentence may be too broad. So I suggest the qualifier should coordinate that have be a preview. And we are addressing all the FDA, is that correct?

Yes.

Does that bring into account the fact that some tests are produced by that at the a that wouldn't test become review? Because I was going to have a slightly different comment, but that may broaden it enough to get to that because some of the tests are not under the FTA.

But we are talking just the FDA review, read?

All, I think with the addition it helps clarify that.

Okay. Going once? Going twice? Salt. Grade. This is on page 39 in your book. And there is a distinction between the way we have it on the screen and the way it is in your book. We will have to discuss that because they're up could be a significant difference treated HHS said the gates all stakeholders in provided incentives and the development of pharmacogenomics products especially for smaller -- of the screen it says markets and in your pocket says patient populations. Arquette was our the tradition. Why markets? Hi think people wanted it to be proper that a patient population?

So we need to go beyond orphan drug possession and create a new think based on market instead of number of patients?

I am trying to recall -- I think it was -- we certainly can't do patient populations. If people want patient populations we can do that. Is that okay?

I have a question on that.

There are very large patient populations that represent small markets. And that should be captured in some way. What do I mean? The development of drugs that would be extremely useful for useful people, but considered small markets. And incentives should be developed in accord with those considerations as well.

I think that may have been one of the points behind the market thing. Yes?

This may be a question, but it gets to what Paul was getting too. And the summary there was to doesn't possess or below for trucks. Where does the 4,000 come from? Is there a visit to the humanitarian crisis exception? That brings in another of -- a number of other regulations that you can -- that have to get through approval. They cannot profit off of it. It seems to set up a very different standard. It is also subject to a steep. It seems to have a whole other hurdle of unnecessary regulations, approvals and profit restrictions that the orphan Drug piece does not permit that was have a statement, but for the a question.

I think the point we were trying to break was to point that out those two numbers are out of sync with one another. If you have this system it is an orphan on the trucks' side. And I think we provided the committee with some insight that really this is that all the diagnostic mechanism that is available in a "world and status. There is an equivalent. Correct me if I'm wrong.

No, that's right.

I'd think the comment is a very important want to read it was the driving force. Why not include both an say for smaller patient populations.

I think this gets to it and that way. The patient population is a market. But to be get to a recommendation that goes to analyze point about the differential here? This is one that may not be effective.

There is no recommendation that is specific for that, but we discussed that and whether or not there need to be. And the thought was a way that would be working that was what we should recommend to the Secretary and not necessarily for something on that specific issue of the understanding is that issue would be addressed as part of the process of following up on these recommendations that left it open to how it might be resolved

I understand how. I wonder if it should be -- I guess I'm recommending it should be more explicit because I don't think you did it.

And the question that relates to the explicit this is whether it is under the secretaries per view. Is it able to be done under a rule making or is this something that would require of the assistive change? If it is the lesser we can't make an explicit recommendation. If it is the former, the weekend.

I think you could recommend to the Secretary that he seek a assistive change if it did require a stop the story changed. Does it?

I don't actually know.

Okay. Why?

Just sort of it's just a question. If I were looking at this recommendation, if it were published in a list of recommendations, I think the way your point to present this is your right to have a separate sheet with the list of recommendations along with part of an executive summary.

This would be part of the this is not a specialist.

Is there enough information in here that somebody would know what you are talking about with this recommendation?

I would agree with Michael I think in and of itself this is a piece of that, but to serve the or to -- I don't think it gets too, as in late described it, that differential and that need so we look at the be at a minimum the small patient market issue around diagnostics. I don't think the uneducated -- most people --

Again, there is always this tension between how much should go in that recommendation as far as a story materials and how much goes into text. There is obviously more in-depth report on this because we already saw that. So I guess the question is, says it is a recommendation to the Secretary then as you say, if the public is seeking more information about what is explicitly involved in this they cancer and they look at the larger report. Even in the assistive summary there is material. Even if you want to work to get this to make -- how would you give it to ` extra Santos would you want to put in to back Suzanne is doing it right now. If you have something -- maybe what we could do is --

I have a suggestion. I think the issue that we have heard is -- it would be aware as. Given the inconsistency between the numbers of patients for orphan drugs versus the numbers of patients that would qualify for orphaned devices and that inconsistencies between those two sets of rules, it is recommended -- that would at least give it some context.

I don't know. I think that having the parts to recommendations brief and to the point makes a sense. And an MTV hundred you can say those kinds of things and put it in context. I tend to think that brevity is probably -- I think party should be something we speak and there is expired for inflation. Even and the executive summary they don't have to dig through it.

Okay. He likes that too. Whit.

I think you have to be careful. It is very much because of the cost of these things that needs to needing different kinds of economic incentives to bid I think that is in here. Schroeder is better.

All right. Is this short enough? Let's take a look.

With a minute. HHS should engage all stakeholders in the to the buying and providing incentives to the development of pharmacogenomics products specific incentives should be identified for a smaller patient populations in the world markets to address inconsistencies between prevalence, thresholds' for orphan drugs and devices. We're worried back we definitely want markets.

We are back to a HHS should engage all stakeholders and identifying and providing incentives to encourage the development of products especially for smaller patient populations and work markets and make sure that that is explicated clearly and the materials. Yes?

I may have a simpler art. The fundamental problem for me is for orphan drugs the system works as an incentive. For orphaned devices are test the system currently works. I think it is a disincentive with more restrictions than incentives. So I wonder if be in as simple way to do it. I appreciate that comment, but we have content and a lot more of the other recommendations. I don't think we are having too much. At 81 multistate the development of these products and diagnostics, if you think about products as drugs or drugs and stuff agnostics --

Rather than products.

Because some people will consider price being drugs, not everyone I've wanted to highlight diagnostics because the process today works as a disincentive.

Okay.

There are two concerns here. One is the technical conversation about the different types of pharmacogenomics development and there is a great sensitivity that is generated the conversation around this recommendation. Very large populations that are small part markets. In other words, a large populations of people who can't pay. If it would require credit the six -- it has to be balanced by a strong statement that also elevates this issue of small patient populations and markets. If they are right to put an extra bag which to clarify that it might require moving into a 4-The that explicitly elevates or addresses the sensitivity around small patient populations and small markets.

Look at what we have now. Is that sufficient to sufficient emphasis?

Work language was born to be placed to clarify the issues that you are racing. My concern is that it is completely lost.

Let's look at what we have now. HHS should ingates all stakeholders in providing descant incentives for the development of drugs and diagnostics especially for smaller patient populations as or markets. Does that get to where we want to go? Yes? Yes? Yes? Excellent. Very good. Next. All right. We are supposed to break at noon. If we can get one or two were done, page 43 is right you will find a draft recommendation 458. They should provide resources and the analytic validity, critical validity and utility and cost effectiveness. Progress would require high quality Data Resources. Improved methodologies and design, conduct an analysis of a series of studies and empirical research arm of the evidence and standards necessary for making decisions for various purposes. For example covered a lot performance that tricks and different political context. This is getting at establishing an evidence base.

Again, this is a bad crowd question. The this report is surprisingly to avoid on the current use of testing. There isn't a table that shows the frequency of use or P450 testing or anything. We are advocating for the established brands. I am curious about why that occurs.

Was flat because the data is out there.

Well got the people who provided that tests are keeping data, is that what you are trying to tell me?

There are a number of different issues. If any outside agency that wants to review that can't because of the coating deficiencies. You can't collect the information or tell based on generic goes with it this was a task or an and the year as a or b RCA. So the third party payers cannot develop data as, as these tests are being done. Manufacturers are variable in terms of their willingness to put their data out for public review in terms of numbers, results, except for. So there are no sources of data and the available to the chair that can give any sort of an estimate about utilization.

Can I just -- so does that mean that the committee or somebody asked the providers of tasks and the sector to voluntarily provide that data and they've refused?

No, we did not do that.

This is actually an issue that is addressed and the oversight report because we talk about what or of the transitional process and the critical decision support.

It is worth while making sure that we cross our friends said.

That will come out what's letter.

Steve, actually we can't. My understanding for what I have implanted in my brain is, we cannot anticipate because nothing has been voted on yet for that report. But that report could certainly respect to this one which will --

You can do that. But we did not attempt to do that because our idea was to look at what the current trend is. And that is currently that that information

I am aware of the whiteboard or unevenness of the public data. But that doesn't mean that there aren't ways of voluntarily providing some of the predators of this data. Because some of these tests upbeat and the public domain for of all time.

Was there something you wanted to then address?

It is a striking deficiency of this report that there is no compilation or at least comment about the compilation of data in this area.

So can we make sure we go back into that narrative of the report and reference the fact that there is stuff going on and the keyboard and this recommendation is the word progress and be deal with it that way.

I had Jim. Barbara?

I wondered if we could remove some of the methodology and just make it say something like using acceptable methodologies are using explanations to explain them. Aren't those standard methods for critical validity and cost effectiveness?

Well, we had a discussion on that and some people thought it was important but we can still have that discussion. Steve?

I will be the way. The methods are developed and they aren't accepted and the use of service or other things. Whether you want to include them is another question, but there is a general problem. This isn't unique. How do you incorporate them in and accepted manner is still a subject of considerable debate

Empirical research on the evidence and standards necessary for making decisions for various purposes whether it is coverage, a clinical guidelines, performance the tricks from your point of view is research that supplies the evidence? I mean you know what the evidence and standards are.

I am wondering, is the operative thing here research arm -- are you suggesting we do more research on what evidence and research are necessary or research that answer is the basis, the evidence basis of making these decisions? Because the people making critical coverage decisions and bad decisions pretty much know what those are. They don't need more research. They need answers. "swell is primarily for coverage purposes. I would agree with you. I was quick to suggest that in fact and the parentheses we put critical guidelines and performance of tricks, something that will set well with the Secretary committee he usually talks about this. It goes beyond those categories and gets into improving quality and improving efficiency

So to add value health care after performance, tricks.

Okay. Credit -- did I miss somebody over here?

Just to respond, the issue relating to your specific question is that the key issue in the first sentence is a that by evidence that. We don't necessarily know what those are. Some of them 80 relating to equality of evidence and some be related to critical data. So I think it captures the point that she made.

There were two living variables and the equation and I wanted to block when and. The evidence gap necessary to answer the paradigm of decision making as it exists and the real world today. We want to figure out what the Perot type of decision making research is and figure out what the caps are at the same time. Basically let live it along. You know what it takes to answer these questions. We know how the people think of it every day. Now let's provide the data and information.

So did you want to recommend a change in wording?

Its research that supplies the evidence

It has been my experience that the evidenciary requirements differ from all walks different agencies, private, public so unless your car to offer some harmonization of what the evidence Santos are and have some bite across the public and private sector, I don't know quite decently how you are part to resolve that.

I would advocate giving it the way it is. I don't think it is a no brainer as to what evidence really is important and what should drop Shantay acceptance. So I think he might want to play in. He would want to run out of the throne. And I would advocate giving it the way it is.

Can be said of? That we sit research only evidence and standards necessary to back that is fund. If you want to keep it there, I don't want to prolong it. I'll withdraw the suggestion

That is a marvelous template by the chair to the does forward into the afternoon. Yes.

I'll -- if you're talking about an "analytical validity or talking about standards. I want to bring up the point that there are only a handful of actual physical standards for diagnostic tests available. And if part of your evidence cap is the reliability of the essay then you really should put some additional language in here regarding the actual physical standards in standardizing the technology and platforms.

So would you recommend?

I have to think about it.

You have to have answers.

Hold on. Go ahead?

We will deal with that in that next report.

Right.

But we can -- can we say in this report that and other reports is under way? That is going to attempt to address it or something like that? We will make sure that is in the text. That question is being addressed more complete in a later report. I don't think we can say exactly what we are cord to say.

A quick edit for consistency. Should we take action to provide resources? It should read instead HHS should as a to buy and address of its caps?

HHS should identify HHS should identify evidence gaps and the critical let's see come critical utility and cost effectiveness of pharmacogenomics. Progress will require high progress Data Resources, approved methodologies and the desire to my conduct an analysis and empirical research on that evidence and standards necessary for making decisions for various purposes. Coverage color critical guidelines, performance records to what I you driven health-care and different critical cantrips. Okay. We have been told we are done. Let's do a quick process check. If we sort of think about this we now have to talk when we come back at 12:45 p.m. We have to go through all the rest. We are about okay. Of a little nervous, but will push through. What do you think?

This is maybe just a point of order some other work that we have done in other groups, we sort of set a time, on progress related to certain activities given how you break it up. And I realize that there may be that need for process on some of these things, but I think that if we set a time limit that will accelerate our thinking and sort of really make this come to a decision or quicker. If the plan is to try to pin and get through a are several conditions before the end of the day, I would recommend that we said summit set up time and it was the amount of dialogue that we have either buy recommendation or by -- by block a recommendation or some perimeter of Thai.

Thank you for that. We are quick to do their quanta calculus and to our last so that we don't have any recommendations. That is great. One way or another broken through it. Those of you who are appointed to enter to cut there at the fabulous in its growth need to inform if you already haven't had the. You tell her that you are going to -- their will be no food. And then there is the food court. And it is not our fault. You did nothing. You walk like a pretty else walks of the weight to the food court about 18 miles down the street. And the same building on this floor and you just walking. But it takes about 10p. The thing is somehow you have to get your food and get back here part of 45. So he should go right now. Leave anything you want here. [Session on lunch untill 12:45]Please stand by for real-time relay captioning.

busy signal on audio line.

Just perfect. Everyone came back exactly on time, knew when we were going to start.

It's coming to my attention from mean people like Mark, that apparently I once again, instead of recalling gur ven eat, I called him gur ven at. Everybody snickering at it. For the people who don't know, I mangle everyone's name regularly, that's my responsibility. Of all the people I mangle, it's gur ven it, man dale a.

I will find somebody else to -- we have the Paul wise and Paul the less esh.

Take it away, Red.

Okay, we are on. 5 B. So gearing up again, after lunch, get the synapses firing. Tab three, and it reads, HHS should initiate and facilitate collaborations between public, for example that long list of acronyms, and private entities. For example, private health insurance plans, healthcare facilities with electronic medical records, research genetic databases and repositories to advance generation and sharing of knowledge on the Ann lytic validity, and cost effectiveness of genomics.

Can you add NE SS to the list?

It's up there. We try to -- okay, I love this, this is good. No, wait wait oh.

Back to what I was saying on the prior one, the first sentence of 5 A, very research focused but the term value, cost effectiveness is in there, but if you insert value into the first sentence of 5 A and also 5 B. Quality and cost.

We have, not underclinical utility?

No.

Not really.

We need value, put the word --

I would add it because cost effectiveness is way too narrow. We are looking for a bigger picture here.

Analytic validity, and value?

Just the word value? Everything comfortable with that?

And value.

In the same phrase, present in 5 A, may want to change that to be consistent.

Great. Okay, excellent. All right. We have made a couple of changes. HHS should indicate, facilitate collaborations, including -- including the whole list to advance the generation in sharing of knowledge on the analytic validity, clinical utility, cost effectiveness and value of pharmacogenomics. Fantastic, next.

5 C, same page in the report. HHS should encourage and facilitate studies on the clinical utility -- we will see about value -- dissemination of stud I findings, including negative findings where appropriate through publications, meetings and information clearinghouse.

Mark?

Do we need "where appropriate?"

The question here was, since obviously you are going to get lots of negative findings, right, some come may or may not be relevant, would relevant be better? Doesn't do more specificity than appropriate. The just say including negative findings.

Right. Reflects, there's a reasonable amount of literature saying this is a major issue. Saying negative findings is sufficient.

Not too draconian for anyone? All right. Anything else on this Great. HHS should encourage, and facilitate studies on the clinal -- dissemination of study findings, including negative findings, through publications, findings --

Great.

Now, NIH should provide mechanism that's promote interactions between basic, translational and outcomes researchers for the identification of end point and -- the goal of these would be to maximize the value and utility of basic and translational research data for down stream assessments of -- and clinical utility of pharmacogenomics tests. What's in the report has another sentence. We are recommending deleting that sentence and stopping here.

Yes?

Should it read NIH or HHS?

Good, thank you. Anyone else? This is good, we should have lunch more often. Going once, twice, three times, fantastic, sold. Next.

Six A, is on page 47 of your report. Again this, is slightly different on the slide than in your text. HHS should encourage private sector entities, including academic institutions, here's where the difference is -- voluntarily to share -- doing a little word submitting ahead of time, proprietary data to advance the development and codevelopment of pharmacogenomics products. Manufacturers should be encouraged to make their data publicly available to allow others to do research and publish such studies. Decided not to split the inif I havative and make English professors across the nation unhappy with us.

Voluntarily may be in the wrong place, sounds like you are voluntarily encouraging, might want to put it after --

To share voluntarily?

Or -- data voluntarily.

To share proprietary data voluntarily. Okay.

Is that -- to share proprietary data voluntarily. Okay, anything else now that we finally decided where we are going to volunteer. Trust me, we had long discussions about this. The final is SS H should encourage -- voluntarily. To advance the development of, codevelopment of pharmacogenomics products, publicly available to allow others to conduct research and publish such -- this will make Red very happy.

Six B. I am getting 10-dollars every time I say that, from gur -- to develop solutions to overcome the obstacles. For example, legal and data confidentiality assurances, intellectual property protections. Okay, ruminations, suggestions? Yes?

Have we been working on this extensively over the last year or two in terms of Medicare data, claims data in particular. I suggest you put in parenthesis funding. You focused on legal issues, but who will pay to collect data -- share it.

Funding of the data collection.

Yes.

Funding data collection rather than just funding.

Specifical