Event ID: 1552516
Event Started: 6/16/2010 7:50:26 AM ET
Please standby for realtime caption text.

Good Morning everyone.

Good morning.

Is that Mara on the phone? Mike yeah.

I am glad you could join a.

We have a lot to cover today. I want to Thank Paul and Kara for helping organize the session yesterday. I heard from many of you that it was one of the processions that we have had and we clearly had some terrific speakers. We had some very productive discussions so thank you to Kara and Paul and for those of you who do not know, Kathy was the staff person who put it all together so thanks to all of the.

This is the second day of our meeting and did today we have an update from FDA and issues related to carry your screen, residual dried blood spots. One just housekeeping matter, we have a slightly different format for lunch today so you did not have to pre Order. There will be a buffet line set up outside and those who want to partake in that you will pay at that time and the menu is in front of you otherwise you can go wherever you wish.

And Kara we just thanked you, terrific sectioned the Lexus and yesterday.

We wanted to start this morning with an update from the Food and Drug Administration and Liz Mansfield who we all know and love and I think after this presentation we will know we love her more and she has some really exciting things to share with us.

Liz?

While we wait, let me ask if there are items it that anybody wants to raise cash if there are items that anybody wants to raise.

You know, we were talking about the database and he is actually doing some of the work related to that some he has been tied up for the less than two days so he sent his regrets.

All rates be we will proceed, are you good, Liz?

Yes.

Liz, take it away.

Thanks for having the FDA here to address the secretaries and buys the committee. I do have some -- advisory committee I do have some exciting things but I do have to leave at 930 to go to the BA meeting.

If you read the newspaper comic Internet, any of that you will know now that there has been in large discussion going on for several years now about oversight of the direct consumer genetic testing. They have been trying to implement or increase oversight of direct to consumer genetic testing because there are medical claims.

Made and many believe that the clinical value is quite poorly established. Many people are concerned that it does not provide intervention of a health-care provider. I think we heard a lot of this already in the direct to consumer discussion. Unless you were asleep you probably heard about the Pathway Walgreens story in which they said they intended to market direct to consumers genetic tests that included pharmacogenetic tests and were going to do this directly to the public the Walgreen's and a device would be sent to Pathway.

FDA became very concerned about this particular method of marketing and it has since come to our attention and we sent a letter to pathway to said they are not -- to sit there are not allowed. Walgreen's has since abandoned their marketing plan. We asked Pathway to come in and talk to us because it is an ongoing complaint issued and I cannot tell you anymore about it.

There has been a lot of progress no interest lately and they have sent a number of letters requesting information about their tests specifically their analytical in critical for validity and other information and I am aware that they sent an additional letter to 23andMe following on the news that there had been a sample mixup in which patients received results that were not their own and Congress is interested and there's a possibility for a hearing this summer on the subject.

We got the hint and we sent out on the 10th and five untype -- untitled letters to these five companies and we have previously spoken to them about what they were doing. We had spoken to these companies and we knew what they were offering and are letters request to the firm to work with us. We believe there may be some claims in their test that do not require oversight because they are not medical claims and certainly some of them as the tests are currently configured are medical claims and we would like to work with them on how they will submit the information to get all of these approved.

So that was directed to consumer. There is upside a printout of the Federal Register notice and we are holding an open public meeting on array based copy number testing which has been a standard laboratory procedure. The meeting will be on June 30th pick it is a very short time line and we have done much had to work it best to -- We had to work it fast and is open to the public what you need to register. You can make five minute presentations and we are requesting that the presentations are designed to into the questions asked in the Federal Register notice.

Our intent is to gather information on regulatory approaches to non targeted testing. We talked about this a little bit yesterday with the whole genome sequencing were you can see everything without having asked to see everything and we realize that our record Tory approach will have to beat a little bit different.

We will have a panel that will address the six questions in the FR notice and the docket stays open all the time and we are requesting comment by July 30th and that is the docket site if you're interested and I think Cathy has a printout right now.

I think this'll be an interest for the array community as well as the whole genome sequencing community because many of the issue is are the same and we don't that array testing four copy number has supplanted said a -- cytogenetic testing in most slabs so we hope to get a handle on this and make sure public health is served.

This committee, I am not sure how much we talked about this in the past but I did want to let you know that FDA is working on companion diagnostic draft guidance that will define what a companion diagnostic is and that is a diagnostic that is required for C and effective administration of the drug. We intend to explain when regulation is required in order to assure that the treatment plus diagnostic companies and is safe and effective. Hopefully it will be out in 2010. In addition we are preparing a much more complex document which addresses the issue of code development of a treatment and diagnostic. This has been requested by many, many different people. We intend to make it aberrational and not directed and you know every situation is different from every other situation so we did not think we can build a path that says do this and this and this because everybody is going to have a different way of approaching it but we will address differences in the regulatory strategy that are different from normal drug development, normal the cost of development and plan to be published this year so I hope that happens.

I think that Alberto told you last time that we had developed after a meeting after a patient advocate made a complaint we did develop a new product code for laboratory develop tests that enables anybody who wants to report an adverse event, making medical device report to FDA bid previously there was no way to do that and we realize that was probably not a very good idea so we put a product code in there and we have actually received several MDRs from the public on this so we think it may help us keep tabs on people who feel they have been harmed. We investigate them and so on.

So that was another success coming out of the SACGHS meeting but there has been a call for a review of the 501 process at FDA and people said it was being used incorrectly and so on and FDA is conducting an internal review and IOM is also independent of FDA and we expect any changes to our recommendations the summer. Interestingly many of the issues that people have complained about in the office that regulates in vitro diagnostics we already did it the way that may be recommended so I would not expect Major changes but until we see the report and recommendations we will not really know.

This is the biggie. We are announcing today that FDA intends to implement oversight of lavatory develops test. That is the docket number and the display will be available at age 45:00 a.m., in a about a half hour -- at age 45:00 -- 8:45 a.m.

Our intent is to establish a framework for all tests not just a commercially to civitas and our general expectations at this time is that we will require in registration and listing period in order to find out who is out there and we will do a risk based phase in looking at the highest risk first and take health precautions to avoid disruption to access to tests that are currently on the market and that we would probably provide a lobar ordinal bar for some tests such as rare diseases Korea not sure that additional oversight beyond CLIA would be beneficial.

The meeting is open to the public but you do have to register. We are allowing the public to make five minute presentations and are requesting them to be subject matter presentations not complained about this is not legal or something like that. What we're looking for is help in the public in putting the correct for Merck in place. To do that we will have four different sessions addressing four different issues. Patient needs, the clinician needs and how this affects patients and clinicians and we will have a separate session on direct to consumer testing and educational issues. How FDA can help educate labs and help labs get started on this process. We will also have panels in each of these sessions to discuss the issues that will be laid out on the Web site that will be -- I guess go live today or tomorrow because today is just the fans to -- the advanced notice. The panel can proposed approaches in Salon.

Our intent is to implement a 0% of laboratory developed tests but we are cognizant of the need to work -- our intent is to implement oversight of laboratory tests. We are also cognizant of the needs to minimize disruption to the current paradigm of medical care. We want to provide as much access to FDA and education as possible to labs on how to do this and how this whole system works and we are looking forward to on going public engagement as the story unfolds. You should not expect a draconian wall to go up for today you are not regulated and tomorrow you are. This will be a gradual process. It should be interesting.

Well, that was pretty quick [ laughter ]

I started early and I will stop there and I can actually take questions if you want now, Steve, since I'm going to be leaving.

This is really exciting and these are issues that have been a fixture in the interest to this committee.

The secretary actually, we did have a meeting with the secretary where she says that they have recommended for years.

So we really do appreciate your responsiveness to all of this bid let's open it up for questions. Let's start with the senior person on our oversight report, Andrea?

Thanks so much for the presentation and when you say you will regulate LDTs you are talking about all LDTs?

The frame work will encompass all LDTs and the level of regulation will be scaled to the risk of the test and other factors such as rare disease.

If you start regulating the LDTs will you put that information on your Web site accessible to individuals that you have actually registered that will have to be out there?

I actually do not know any of the mechanisms at this point except for it will beat -- we will work with the public to build the right framework.

I am dressed concerned with the registry at NIH and work here.

It is highly probable that we will try to work with that registry to avoid duplication but again, we have no predetermined detail.

Right 31 were questioned. When you had the Walgreen and pathway tests you said that the test was not a LDT.

In laboratory developed test is a test that is to collect and offered by a laboratory in the reusing arrays that they purchased from someone else in the whole system including the instructions for use that came with that system and all of the reagents, they were merely providing those results with an interpretation and we do not consider those to be laboratory results.

Jim?

I am just wondering, risk-based -- is that risk of an inaccurate results due to complexity, due to critical stakes?

Yeah, this will be a very important one for us to cover. At our risk assessment is based of possible harm to the patient based on an undetected incorrect results.

Going to the array meeting that you're happy I am just curious on FDA's thoughts. Of this -- I am just curious on FDA's thought and there has not been any enthusiasm at least up to the present time for a standard set of genetics to be under this type of regulation. Could you talk a little bit about what the FDA procedure is the difference between the arrays to say this is something we think the needs more research.

For one thing we have had about five different companies approached us with an intent to file. [ laughter ] so we need to be able to give them answers. In addition, the normal cytogenetics mostly people could use ASRs and cariotyping in general is something that we regulate to bits and pieces but it is primarily a judgment that the laboratory person makes by looking at something using regular the pieces . We're as the array copy numbers using someone else's system that is not a result of judgment and somebody needs to use judgment after that but we have always regulated the parts that go into the testing and that is what we are intending to do at this .1 company's common but we're not going out and oversight of LDT come yes otherwise we're not going out and saying this is a special problem and everybody really everything so it was based on people coming to less.

Liz, how is this going to interact and interplay with the CLIA oversight of Laboratories?

CLIA as everybody on this committee has tried to commit the long conversation on the oversight, CLIA regulates lab and Lebed to these and has a certain -- lab activities and the FDA and regulates products in bits and pieces and if you run a lab you know that FDA cleared and approved tests are somewhat regulated by CLIA. But it will probably be something like that however clever truce would be considered the manufacturers -- the laboratories would be considered the manufacturers and CLIA does not require design control which we do. We are going to publish a guidance that tells you where CLIA and FDA quality systems correspond and will be providing lots of help on getting people up to speed on this. We know basically what level the labs Arnelle and we will take that into account.

I think that is a real serious concern.

It is.

The FDA controlled labs are a completely different kettle of fish. So that will be a large transition with an enormous amount of expense involved.

We are aware of the big transition and we actually think the quality systems are one of our best regulatory tools because it tells you to do whatever you need to do to make sure that your test is designed properly, manufactured properly and spaced the same over time. So it is very not directed, flexible and you can implement how you needed to be in order to fit your situation.

Can you give us some sense of what we could anticipate of the oversight of LDTs in terms of process and time frames until you have the guidance or remark?

I think that is still to be determined. The expectation is, I guess that we will make calls for certain tests overtime and we did not expect this to happen very fast. It is actually hard to figure out what to do in the first place and we have to give people time to get their ducks in a row so probably overtime for the highest risk and then depending to the level where we think we can cut it off pretty we probably will actually have to make some changes as well to the kinds of tests that we really did as commercially distributed because, you know, there is a resource dependency here. There are certainly a lot of tests that we regulate now that may not benefit from our oversight anymore. Because they are old technology, old tests, low risk. It is tenable has given proposals on some that we could possibly do.

I just want to follow up what Paul brought up on the quality piece because of some of the laboratory tests are very important for patient management and the still need to be available for patient care and there are certain laboratories that, you know, might have extremely high quality but not necessarily the Quality System for FDA. So that is a very high concern that I have the some of these testings there will never be an IVD because commercially it is not feasible and still has a huge, critical impact in patient access.

Great Right.

Even some infectious diseases like herpes or CSF that actually are critical that this completely disrupt --

We are not intending to do that so those will be the kind of comments that we need to hear at this public meeting. So I invite you all to register it if you'd like to make a presentation --

This goes beyond the genomics and infectious disease and everything.

Yeah.

I mean, very different issue.

This is the kind of commentary that we're looking for. What tests are release sensitive if they were to disappear from the market or something like that.

Any other comments? This was great. Thanks been there was a lot and what he presented today in terms of looking for work for some of the oversight and not only lever to develop test of our concerns about DTCs and it's good to see Kevin in the back of the room so thanks so much to you and all of your colleagues for moving these agendas foreign.

I look for wood to seeing a lot of input from the individuals here on the process -- I look forward.

Look for the FR notice to go on event display in about 15 minutes.

For those of you who did not notice there was a copy of one of the notices that one-to-one of the manufacturer's --

They were all very similar questions.

Terrific kid thinks back so much, Liz. It was great.

[ applause ]

So next is our session on genomic data sharing and Charmaine has been moving this addendum -- agenda forward and we welcome Kevin in the back of the room as part of our planning process to put this on the agenda. So, Charmaine?

I am trying to move this agenda forward [ laughter ]

I am hoping that our session today will be a productive foreign and I will talk about some of the things that we have been doing since our last meeting and some of our thoughts about where we should go and looking forward to your perspective arm that.

We look at the issue statements which has been the same since our last couple of means and that's genomic did the shooting is increasing over time and this a viable tool for a financing research but this can result in a lot of questions and concerns of the issues related to consent and privacy and discrimination and some other issues that we are going to talk about and, of course, the issue statement is what brings us here in terms of thinking that this is an important topic for us to address. So what have we done so far? Into a dozen eight, genomic data sharing was identified as eight important topic of -- as the important process and they contacted with the little group and this is expected to guide our deliberations and The Lewin Group has completed their review and we have gone ahead with doing some backed by Indians in terms of the committee itself and our work will overlap I am sure with the years when their report comes to us and we will see where the overlap is -- with there is when their report comes to us and we will see with the overlap is in the NDP differences in how we approach the issues.

Last October we formed a steering group to begin to look at these issues and in February we had a number of people come to talk to us about different models of genomic data sharing. Our sense is that there is an informational overload and hopefully we have come some of that and will be able to pull something out that we can focus on.

So the steering group as far comprises current members Sheila and Dave and to ad hoc members Kevin, Sylvia and Julio and the cabin -- Kevin is here and our backs of issues and Symma has been the staff lead.

I cannot think them enough for moving us forward -- thank them in the for moving this forward.

We will go through what we found and identified with the central issues are and what we think they may be and we are going to talk about those in the policy implications and, of course, the policy implications is where we might coming in terms of what we recommend and decide to do and our next steps, do we continue to pursue this and how?

So the fact finding consists of lit review a and for the most part is focused on the blurring of that line between the research and clinical care and samples collected from them being used for research. Also in terms of samples that beats back into the clinical setting so really a circle and how this information gets moved around. So the blurring has been a major issue I think from the onset of this discussion and leading issues of literacy and provider and researched attitudes.

The blurring of the line is just one aspect of the genomic data sharing that many are probably not looking at and a big aspect is gesturing between researchers and the blurring of that line. Researchers at the lecture samples and data with researchers of that really is the big picture.

And then in addition to the lit review which was conducted from consultations with program directors from two different types of programs were data is shared a government model and the consumer Disease registry. We also talked with three secondary data users and also interviewed eight ethics researcher. So in terms of looking at the indications of the blurring it revealed a number of topics or issues. The timing and nature of informed consent. How many times to you need to give consent and the process. Or is it just one consent that we need, a broad consent? And articulation of risks and benefits some of which remain not know at the time at the generation of the data or collection of the samples. And then the communication between the provider and the patient and the ability of the provider -- we talked yesterday about the limited knowledge of providers and genetics and that also comes into play here in terms of genomic data to participants and to patients.

The whole issue of incidental findings and return of research results returns those findings? Is it the condition, is it the researcher? And, of course, the whole issue of how that is done. And allocation of resources. In many cases time constraints. Physicians often do not have time to do this. And the resources to communicate the information. Additional staff that might be needed to move these events for word.

The issue of privacy and security keeps coming up did not just in genomic data sharing. A lot of other groups are looking at privacy and security. One of the questions that are lit review braced is reasonable expectations. Do we promise anonymity and keep things private and secure? Most would realize that we can not promise that so what is reasonable to tell participants in the patience in terms of what we will be able to do in securing their data.

And the issue of group harms. This is one that comes up not just here in the issue of health disparities, public health activities and the whole issue of Public Health has I know but the major issue for SACGHS and questions about whether it needs to be a separate topic I think is in my mind probably no longer a question in that it cuts across just about every topic that we will address and we talk about whole genome sequencing and the issues of health disparities and public health issues. So eerily is something related to groups and identity -- it really is something related to groups and the identity and group rights cuts across every topic that you may catch on as the committee.

I will talk about some of the things that we've found in terms of our fact finding food and our consultation -- and in our consultation with the to program directors, the government model and the patient consumer controlled model. We learned that there are mechanisms in the consumer control and the government also to provide for patient input into the policies in the program goals and the authorization of data. When asked about returning of results and how that is done, both models, of both persons to be consulted with talked about it being done through websites and newsletters and patient education conferences.

We asked about the perception of risks and problems in the greatest challenge that was wrist was that the data breach and the potential for did -- for data breach and they talked about publications that had been generated by the data appeared we asked about data on environmental exposures and how that is handled. The response is that it is included in genomic and family history is taught and we asked about the ability to link EHRs with this data and that for both programs is currently under development.

In talking with secondary data users, many -- they talked a lot about the potential value in using this information but they also talked about the lack of dragons in terms of power this done and who is responsible for communicating incidental findings. We asked about the challenges the secondary data users experience. We talked about the application process and how difficult it was to get through to get the samples were the data -- or the data.

And the preparing of data sets for their use in some challenges there. We asked about the biggest barriers for data sharing and again they talked about the lack of standards concerning the note -- phenotypic data and blackened incentives to make it easier for secondary research use.

We talked with a bioethics researcher at that has been looking at the participants perspective and she found that patients have the desire about their information and the sharing of their genomic data. The current study that was done between 2008 in 2009 looked at six GWAS studies that are ongoing at Baylor and participants in those studies and looking at the participant perspective. It involved 229 people from those studies and the -- they did a randomized trial of three models with no options for sharing. By Neary informed consent included the traditional and sent come asking people to participate by giving them two options in terms of full sharing, full relief of their data.

And then the tiered informed consent gave them three options. With the additional consent and also for relief, restrictive relief and no relief.

The research and her project has generated some rather interesting findings and Dr. McGuire has allowed us to submit this unpublished data and she found there was a gap between what people understood between the study goes and examples in what was actually told to them and what actually is the case.

I have to -- what she found is that 40% of the participants did not know that they were participating in research and 28% never heard of Genetics cites. I am talking about people who are in GWAS studies at Baylor. 28% never heard of genetic studies and 15% did not know that they had given DNA to their doctor. 26% did not know that their DNA was stored as part of the study and 26% -- get this -- 26% did not remember finding -- signing the consent form.

So the whole question about what people really understand. That is not new to any of us in terms of what people were told and what they come away with or what they believe there were told. Other studies show the disparities in the differences there and in research in general principle that really raises an issue about communication and, you know, the communication may be time for the people -- maybe find but it's the people's understanding.

The study also found that the traditional. I think this is probably a no-brainer. That traditional and binary consent did not provide as much information as a tiered model.

Of participants gave equal importance to privacy protection and the audience in scientific research. We thought that people would get higher prelude to privacy. But in this case people are acids as interested in the bands in scientific research so it creates a delicate balance.

The majority of the purpose of this bill that it is important to be involved in sharing decisions and 65% want to see all of the data sharing options.

Some of the recommendations that Amy has, some of her preliminary recommendations is that we may want to think about really the about a paradigm shift in terms of how we think about privacy. And being more concerned about trust and respect that we are about this whole issue of privacy that we cannot guarantee any way. And then one of the other things that she had suggested and we talked about this, too in terms of a stratified or tiered consent process. Not just a certified or tiered form, but a tiered process. When that occurs over time so that people understanding of the study is the value we did at different points in the study and with new studies, but we evaluate whether we need to do a different consent. It is a process that we talk about the most cases it is not treated as a process, it is treated as a onetime thing so this whole thing in terms of process and consent.

So and are backed by means we identified three major areas that we might focus on for three major areas that keep coming up in the literature and what is the implications of that blurring of the lines between research and clinical practice. How do we deal with issues that research reasons and its connections to clinical practice? How to participants and patience -- do participants and patients understand that. And the potential for group harms and I think at one earlier stage we talked about for -- vulnerable groups we could talk about prisoners, and children and most of the work we focus on "racial, ethnical, cultural, diverse" groups in most of this -- and most of this has the cultural ethnic groups in the whole question of privacy and what might be the reasonable expectations. And what role could that have in informing? There is a general sense that privacy, what we can do in terms of security and privacy is limited and how do we deal with communicating those limitations and doing the best we can to protect insecure people stayed at a while moving research forward.

So in terms of the blurring, some of the major issues are the informed consent process in the adequacy of that consent. In clinical studies but also during public health activities. Screenings, newborn screening, the general population screenings where data is generated and shared.

The provisions for return of results. Return of results is a major issue now in genetics and genomics and who is responsible for communicating that? And how is that Don? And then the education that is needed to providers pay the sum of our earlier work, our educational reports, the ones that we can build on in terms of how we address and to what extent we deal with education as it is covered already in one of our earlier reports. And even in a group harms some of the issues have been dealt with in the report from the perspective cohort study and you may want to go back and see where you can pull things out and emphasize certain things as we think about group arms so some of this we have already done work in some of these areas.

And informed consent the way we think about it generally do not address issues of group harms. And it varies with the particular group and how do we tailor a consent form for that that they might be inclusive in terms of the potential harm to the identified group.

Community engagement has been talking about a lot, written about a lot and implemented a lot as a means of addressing some of the issues related to a group harm. I know of one study that is actual looking at -- I do not think I have seen a publication yet of respected news of community engagement and what it accomplishes and how useful is it. In general I think many of us think it is sacred thing, but useful thing and I have done it here in the U.S. and a couple of African countries and it is helpful in terms of how people understand the research and researchers connecting but we also need to revisit that. And are there other approaches that we might use to address this issue?

In general, the general sense is that guidance is needed to help us in picking about how we -- in how we can appropriately in bulk commodities.

Some of the central issues. These are just some examples of cases involving group harms. Most of these did not even have to do with genomic data. Some of them have to do with genetic data or samples which is also an issue that we may want to talk about later. Our topic has been genomic data sharing but we also know that samples are shared with the data is a part of you're talking about or just the actual data. Many of us are familiar with this case at Arizona State University and the span was trusted by the committee and they approached him about doing research for diabetes which is of concern to this group and so he started this work which you later collaborated with Mark Hoe who started doing the work are in schizophrenia and between 1993 and 2004, the daybed, the samples were shared with researchers -- the data, the samples were share with researchers which raised a lot of issues in in April of this year a case was killed in that case has been ongoing. I think it was filed maybe 67 years ago and has been ongoing and was recently settled. The Havasupai received $700,000 under their original request for $45 billion -- was it 45475? Forty-five, I think and they got some $700,000 so that shows the impact of the different groups.

The second there, this is a paper by Rebecca Isosie and the fact that we collect the debt in samples from groups it is not just the participants and is not just for Native Americans. Whenever we think about and to identify groups is not just that group but the whole tribe, the whole group as a whole. And she talked about cultural harm and values and culture need to be factored into decision-making about how groups are engaged in genetic research and hounding of American tribes specifically she talked about that is more than just, you know, a study that is related to some particular goal of a researcher. But the value of those materials to the tribe transcends the physical harm that we might think about.

Research in Mexico with different types and above the genomic medicine program in Mexico developing guidelines about involving groups in Mexico in genomics and research in general.

The paper there about the tribe is about the tribe in British Columbia that I think over 25 years ago provided samples to researchers to look at rheumatoid arthritis which has been a major issue with them and over the last 25 years samples have been shared privately with researchers in Canada and elsewhere. Since then institutes of Health research in Canada have develop some guidelines about involving indigenous group and help research and then the last case here really has to do with a case I am sure many of you are familiar with. They got samples from about 200,000 farmers in central China, some genomic research looking at a former -- pharmacogenomics work and all kinds of inappropriate behavior by the researchers and as I said before many of these cases do not deal with genomic data sharing and research in general but the involvement of the group and some of these things we may talk about. We do not have a lot of examples in terms of problems with being involved in genomic research because many have not been and as we do more with to no Research and whole genome sequencing and more groups become involved -- do more with genomic Research and whole genome sequencing.

The issue of privacy and security. So much talked about the tension between uncertainty and trusting versus protecting your privacy and not trusting that it will be protected and the informed consent in data sharing is different than typical informed consent because the concern is about inappropriate use of did it and people argue, what is the problem there? In many cases it depends on who the subject is and what is actually done with that data store Mexico increasing our discussions that we're going to have hopefully in a few bits -- So in framing our discussions that we are hopefully going to have a few minutes, how do we decide informed consent with information that produce bins want most or see that they need to make informed decisions about the sharing of their data.

How do we decide informed consent. It is a onetime consent adequate? Are there times that we need to think about waiving consent? Was the best person to obtain the participants' consent and how should incidental findings and data be reported cracks group parlous. One of the questions that has been raised is what is lost when researchers do not identify groups. There has been some literature in the past that talked about not needing groups as a means of protecting them. From exploitation, identification. There was some push back in terms of we would not gain by any means groups and.

Able to identify what group we need to look at particular outcomes and that is an issue that keeps coming up did I do not think it is as big an issue now but I think in many people's minds it is valid to identify and name but we need to figure how to do its so that group harm is minimized.

Are their best practices for raising awareness among researchers and the whole issue of best practices as I mentioned. At the Canadian Institute of Health corollary to our NIH has come up with guidelines and Mexico and other places have done it. Is it is time for us to do something like that? And how we approach Research. Whose responsibility is it to think about addressing group harm? Is it the group, the researchers, the clinician's? Are there additional concerns and privacy again. The consent forms and how we talk about privacy and how we will be able to protect people's data is something that we need to address.

To existing policies have provisions for the revocation of breaches of security? There have not been a lot of I think documentation of breaches that have occurred so in some people's mind a lot of this is hypothetical this is perspective in terms of the potential breaches. But how do we document actual peaches and should privacy be emphasized -- breaches and should privacy be emphasized? On to our next steps British should we continue to do this? -- on to our next step, should we continue to do this? And if so what should our focus be. There we have the three topics that we identified, the Prairie, a group harms, and privacy -- blurring, group harms and privacy.

We know that international issues transcend group harms. There are issues about whether there needs to be regulations or if it's possible to reconcile across the globe, across the country in terms of data being shared and how do we think of the international issues related Data sharing and are there other issues that we have not touched on? I am going to stop there and then we will move on --

Thinks that, for Charmaine did we really appreciate it. Those are the questions that we need answered today and I did not know that you have seen all of these slides but you raised the original issue. Do you have some thoughts, are these the request since? And are they trained off -- are these the right questions and are they framed as well as they might be? Cuts to the microphone, would you -- come to the microphone, would you?

I think that Charmaine has done an excellent job and I think one of the things that this committee has to wrestle with is the organization or the structure that needs to be driving this. I think as we discussed, there are a lot of people looking at this from a variety of angles and one of the questions is, does this fit with the initiative of SACGHS to pursue or is someone else within HHS, I think it definitely has to be within HHS somewhere.

Okay, market and then Jim -- Marc and then Jim.

Just to follow on what Kevin said the two questions that I have, you know, there are a lot of people who were working a lot of different aspects of this and in some since we have to say where are the potential gaps that we could potentially be targeting and if we could identify some of those gaps then the next question is are those gaps that could be addressed by the secretary in a charge? It would be hard for me to wait in on this without a pretty good sense of those two issues.

I think that is what we need to figure out today. Where are those important gaps.

Right. The idea of addressing the broader front of the genomics data sharing and all of its manifestations seems quixotic and impossible. That is my view. I think, however, there are perhaps a discreet subsets, some questions that this committee may be very well positioned to weigh in on it in an informed way and that was a great presentation and you covered a lot of ground. The things that I think we might be able to dress in some tangible, productive matter of getting into what Sheila reminds US of Israel recommendations and the two things were we would be well positioned is tangible aspects of informed consent and the second is the return of results because that gets into the coal clinical issue that I think we have some expertise on -- the whole clinical issue that I think we have some expertise on.

But I think getting into things like group harm's etc. maybe so nebulous that be at best may come up with extraordinarily unproductive broad platitudes. I would be really interested in what Charmaine thinks. She has been very careful to kind of present everything in a kind of nice way and frame all of the issues really nicely but you are the person in the committee who has been deeply immersed in this. I would love to know what you think whether we can contribute something, whether we should and if so should we take a subset.

Thank you, Jim.

You're welcome.

[ laughter ]

I must state. And this may be obvious and one it may not have been and I struggle where to go with this since it was dumped on me by Kevin [ laughter ] so I have been trying to find my way as well. There are so many issues and others are destined them and I think particular informed consent issues and personally I think that the area of the group harm, and that may be because it is one of my personal interests. I do not think that that is an issue that is being addressed at a high enough level where it makes a difference so I think there may be a place for us to do something with that. But informed consent and privacy those two areas I struggle with a lot more than I do group harm. To me, group harm is a given it an area that needs some attention and I am not sure yet we go with this. But the issue of the brain of the line has been one -- blurring of the line has been on the table since this came up. Bad as opposed to genomic data sharing broadly among researchers. I agree with Kevin it raises some issues that may not be at the floor in terms of how the informed consent issues are being dealt with. And I think we could probably take some things out there to look at in terms of how we engage patients and research and how their data is shared. I talked about the data being shared from the clinic to the research it back to the clinic and how we look at that model.

Those are probably the two areas, some aspect of the blurring and I am not quite sure of the informed consent aspect of it. That and the group harms issue for me.

Just to make the committee aware of some of our cities I think I have mentioned before the secretaries advisory committee has to spend well over a year now exploring issues related to research developing biospecimens for genomic Research is a subset of the type of things that they're looking at with in that topic and one of the big things they are focusing on is the adequacy of informed consent when it is informed consent sufficient for when the future research is designed and for specific use like research involving diabetes under what circumstances could you then shared those specimens with other researchers who would do it with a different purpose and with is that appropriate , if ever.

Our office relies there is a for the credits needed for researching biospecimens and many of these issues related to informed consent and we're looking for to the guidance that we expect to receive from the SACGHS did so some of the issues are on going and the issues to be aware of. They're focusing on the informed consent issue. Not necessarily on the specifics.

Can you help us identify what you see as gaps or issues that may be a very specific to the genomics, Genetics arena that are not going to be address here so we can get in a little bit of a sense when -- get a little bit of a sense of what we might be addressing.

I think the group harms issue is one that they have not spent much if any time on but at their meeting in July they're going to have a session involving the University of Arizona research involving members of the Havasupai tribe and invited to that is the principal investigators and members of the tribe half. Whether they will turn their attention to the group harm issue it will open the door to that. That is certainly one area where this group may have more expertise to address in the genomic with group harm.

It was interesting to me to hear this concept of group harm and social harm because in my world [ inaudible ] and there is a huge amount of work going on in terms of who owns their genes and holds the information and it and that theory as well and that kind of recognition of a property right. So I think there is just a huge amount of work going on on this and as you say the international issues are very much at the forefront and biological diversity has provisioned who owns rights to genes that were done at usually applies to plant and a number of protocols and the United States has been a little bit back in terms of intersected with the international group's -- intersecting with the international groups. That is an area where our government can be doing something. And I think for people who do genetic research this notion of reconceptualizing things or the rights of people to control their genes is something that is very important. And just one other thing of terminology, when you say reasonable expectations of privacy they are very cynical about that because they use that phrase to say they have no right to privacy so if we do something on that and the privacy expectations that we should have.

I appreciate your comments, Rochelle, I have gone back and forth with this group harm thing and I think group rights, ownership are those things that we think about.

And the international literature.

Barbara?

Charmaine, this is great did you guys did a lot of work in a short period of time and I just know that you've struggled with the boundary limits but I think I am kind of seconding what other people are saying is seems to me like informed consent is covered by a lot of people and this is definitely were lots of people are looking, that is specific to genomics but the two areas that I think would be really useful if we could come up with models to report to the Secretary. I am kind of interested whether the consumer Disease registry do things differently because they start from a different etiology so I wonder if we would have anything to learn from that as well as international for me the two issues are return of research results and group rights. I think that return of research results does crossover to nongenetic, nongenomic Research and people read about research on social networking in the Internet and knowing that their family who has a condition and calling the researcher directly and giving those kinds of important results back so I think that is an interesting way. About how could that be done. In the other one is the group rates or group harm issue and I really like your comments of traditionally put it into the category for there is some ethnic minorities or vulnerable populations and the like expanding it to other groups that we do not tradition think of as vulnernable.

Paul?

I want to speak in favor of this topic of the blurring between clinical and research uses and that want to draw on a comment that Paul made yesterday about the social network striping more and more people to have extensive knowledge about their genomes in a non medical or social setting. And those becoming very valuable for research discovery and allele frequency and all sorts of things. So having a good process for resolving the blur, if you like is important and may take place as head of the medical office and may impact your research results also.

Glenn and Marc, I know you have been dealing with a lot of these issues so you have some comments to share?

Suggests to build on what Barbara said I think that is a really interesting place to start, please to look -- place to look at what groups have been doing because it was to control the destiny of their samples and what they were given and one of the groups is the inflammatory breast Cancer Research Foundation which has a alliance with the Duke Cancer Center and they have allied with other groups. That is something to look at and there is also the tissue bank at Indiana university. There are a bunch of groups that started so they could sing who owns their genes and who owned their samples. We could talk about it and I could give you some ideas of people I know just to talk to.

Marc?

It seems like we are in need of an analogous situation and will be talked about in February of around before the screening and I have not heard that there are two Secretary advisory committees working on the same types of issues so I wonder if it would be practical to again try and coordinate between what Michael has told us what is going on in between what we're doing. I think if there is coordination there that could result in a more effective for vacation to the Secretary about areas of interest -- effective communication to the Secretary about areas of interest.

Of course, we can involve Mike's office directly and if we can form a task force we can ask them to, you know, to have some of them from our organization if.

I do not want to call you out of properly but I know this is what you deal with a lot.

Thank you. I'm struggling with what is the issue of what is our strategic contribution? We have heard quite a bit this morning the words, "a lot of people working on this" which is usually the signal for us to be cautious however, it is also perhaps in this case and other times for this committee a signal that, indeed, we do have a potential role. It in that often I have been impressed with some of the greatest contributions this committee has made has actually been contributions of coherence in a field where a lot of work is being done and there is no conceptual clarity as to what the challenges this department really are. There are technical issues, legal issues, political issues proceed in operation here and maybe so much work is being done is actually a good reason for this committee to take a step back and bring the field in terms of policy for the Department paid and identified a particularly -- and identify funding priorities that may make sense for the field it.

I'd just want to bring it -- I'm sure most of you are already aware but I heard breach and privacy a couple times in the presentation and HHS did issue an interim final rule, sort of a national framework for the edification in the case of breach and it does only required to HIPAA required entities and certain other entities and we do not pose, we are required by HITECH to post a certain level of these beaches on our website. So in terms of I think in terms of breach and privacy and whether or not all of these entities would be covered is another question but we have been doing quite a lot of work.

Mike?

So does to give you an idea to sort of stock are timeline they have been working on the issues of consent and virus specimens for over a year now and they are entering the final stage of. What will be their major work product from that. They developed a series of questions and answers. Real-life questions about the use of the biospecimen and how you can form consent or would you waive it. If the intent to probably finalize the work product at their meeting in July and then it would be afforded to the secretary and back to us with hope that we would develop our guidance on this topic.

So they may finish their first work product on this topic and we have -- they have a subcommittee of boat policies across -- about policies across biospecimen and biospecimens so that may lead to of the work products in this area which are in their stages but a burst with a product is likely to be finalized in July.

That is very helpful. We will clearly have the benefit of seeing that and not falling over. That committee would be helpful. It might think I am hearing is that there's a lot of interest. We have some general issues about framing and some general interest in Group and there are clearly a set of issues here and genomics is probably particularly relevant more broadly than some other types of specimens in terms of the group issues and then on sort of blurring between clinical research there are some issues here and probably informed consent is not the place that we want to peak but how the information gets communicated back-and-forth, areas that we might have a specific niche.

I did not hear anybody speaking directly to the National Data sharing issues. Mike, do you see that as a space been field?

They are looking at that very broadly across human research in general not specifically research in genomics are virus specimens.

Are you looking at the turn of results to research subjects.

We have not focused on that a great deal could we did have one panel session on incidental findings and reporting that but they have not taken that anywhere. It is not clear that they will.

Clearly as to talk about yesterday there is a lot of potential for challenges with shearing information that may or may not be useful or actionable. Marc?

You mentioned international and under what circumstances would the Secretary be able to impeach around issues of international --

The groups of harmonization of standards and things like that. Very much we talked about and you will be talking about with, you know, coding and phenotyping.

I was just going to reaffirm that, that there is a lot of interaction and direct involvement internationally in the scope of the HHS.

Well, it sounds like -- in terms of your first question is probably yes. Should we continue to pursue this topic. Does anybody want to suggest that we not do that? Hearing none, I do not know if that is enough guidance be set when I said in terms of allowing you to move forward did are you good?

To you actually have -- that is what I worry about. Do you actually have a kind of concrete charge?

Well, we need to for a charge could we have a task force and probably need to come back with a specific charge.

We will need to form a task force and we can talk about that. Do you want to share a, do you have your charge covered Charmaine? Do you want to share that with us?

Yes. Which relates by the to the topic that I covered -- broadly to the topic that I covered and I think we can refine it a bit in terms of taking something to cell. Still not sure what the boundaries are going to be paid it might be for the task force to decide that once we get together. I think right now Sheila and Dave -- I am sorry, David is not here. They are the current members on SACGHS who are members of the task force and other officios and then our agency folks. So I would imagine that we would probably need some of their bodies of the task force, if it's a buddy else is interested in helping us think through where we go from here.

Just looking quickly at this speed I have not read this before it sounds like at the first one -- time just looking at the bullet points right now. The primary focus of the first bullet will probably be reframed on some of the returned results. The group harms and securities would be a primary focus. I am hearing that the privacy and understanding would probably be off the list. Asked at the back actual risks bareback perceived --versus perceived risks and the last two would be potential things depending on whether we after in the exploration find the there is a real role for us are on International Data sharing issues that we can entice the secretary on.

And then I am not sure what to do with the phenotypic information.

Am I missing return the results were we said not to?

I thought that would be a topic.

Mike sort of said that was not a primary focus of his.

Right.

Nor have they focused actual risk of the genomic data sharing that is not a topic that they had explored at all. Just to note that.

Thank you.

[ Captioners Transitioning ] Please hang up the phone so a new captioner can dial in. Thanks!

[ Relief captioner standing by waiting for hosting party to hang up the phone line so that I may dial into event ]

-- really, um, that will really resonate. The other way is the idea of return of results, um, in a more -- in a separate but more broad way. Looking at it from a research and a clinical perspective, um, and then focusing this task force in on group harms and the international flavor, as Maureen said.

Wayne, you are shaking your head.

I think we are probably not saying the same thing, but -- I mean, I think the -- um -- well, I think I need to think about this.

I'm going to -- go back to square one and ask a question of the group. Because it seems, this has been our third session on this topic, I think. And I really am going back to the first question there on that slide: Whether we should -- because there's so much overlap with things that we're doing, and others are do. Do we feel there's a place for us to say something about genomic data sharing? Or we'll address it in comparative effectiveness and other things? Do we need to single it out as an area of focus? I want an answer. I really do.

Maybe a reminder of the other task forces that are ongoing so we can look at this question and the list of ongoing task forces.

I can't remember --

As you said, Charmaine, we've been down this road. Maybe there's a lot going on and we need an umbrella framing of all of this as it relates to genomic.

Barbara?

I think this task force is different than the others, the perspective of the consumer or the patient or the participant. A lot of the other ways -- some of those are more technical aspects of information and things. But if this group took the perspective of the participants, that is a different lens than the other ones. That might be a small enough and unique enough and actionable sort of approach.

That's a good point, Barbara. It could be individuals, as well as groups. Right. Good point.

Jim?

I have the same trouble that you are articulating. I see you trying to chair this nebulous beast, right. It's frustrating. I'm actually skeptical that we are going to have something at the end of the day tangible to say. I think it's very worth while to go through the list of these points and say, "okay, is informed consent being worked on"? If so, can we add something to is? Return of results issue. Those are things that people could come up with tangible recommendations for. But I'm not sure that it's needed because of other work. The thing I have trouble with "group harms" is not lack of importance, but I am having trouble envisioning tangible kinds of product from that. So all I would say is we should go down the bullets, we should answer yes or no. Perspective of tangible result, would this be redundant, and decide whether we move on. This vague charge has to be very frustrating. I think you need a very concrete charge.

So I actually -- I actually agree with Barbara. That could be interesting. Going from the point of view of participants. Maybe one of the reasons is there's trouble is we don't know where the redundancies are, that's the next thing to look at. Where they are being done in over places and how they overlap. I think that's what Phyllis was asking for, you know, I think it's very difficult to say whether we're being redundant if we don't know exactly where the redundancies potential lay.

Sharon and Charmaine have been going through that. It's maybe a matter of depth. Rochelle?

I think if we did the groups harms one the thing we could bring to this is the question on the other side, not only the impact to the group, bull also the -- but also the importance of [ Indiscernible ] research. Those kinds of issues are looking at it ogee from the point of from view of the impact on the group. I think we could bring a much more balanced look at it, because you guys know a lot about how this information will be used, what the potential is of it, you don't see a lot of that in the legal literature. It will be a more controversial study. Because I think is quite different from the things that I see in the legal literature on this question of who owns the gene.

Gwen?

Um, I think that's an excellent point. I think that you will see when you look at some of the advocacy groups that many of them are research advocates. Their own whole point of view is to make sure that the research happens. They're not talking to each other. I think that could be really interesting.

[ Indiscernible ]?

I just wanted to add about the idea of group harm and risk. One think that could be contributed is saying where in the process and who should oversee that. Right now it's not clear to me that IRBs are really charged with that. You may even -- the data is aggregated into the biorepository, an IRB oversees that. They may oversee the release of the data. Let's say that the data is deidentified. An IRB is going to no real look at whether a large body of deidentified data will harm a particular group or not, because it's either exempt or not even human subjects research. I think at the very least we could say who and where in the process this would be overseen and suggest ideas about how one would look at it ethically to approve a project. That would be something fairly tangible that could be added.

We are getting a little more concrete. I'm hearing let's participant signs, looking at the balance of benefits and harms -- so we get both sides of this.

I will retract my criticism of the nebulousness of the group harms. Rochelle, great comment.

There's institutional issues regarding oversight. Which is really different than how we've looked at it before.

Right. Rochelle's point gets to the broader public health implications.

That's a fairly discreet thing. This would bring it down to the group-related issues and rights and ownership. It seems to me if we use that as the starting point for this there still can be more exploration about whether there's important gaps, I'm not sure there are, that could be explored, but wouldn't be part of the immediate charge. Is that where you all would like to see this go?

[ Speaker/Audio Faint or Unclear ]

Jim is affirmative. Are the people that think that's too narrow or missing some real opportunities that we need to make sure are part of this?

The return of results is that off now?

That would not be included in this. We can go back and revisit that.

I thought what you said is you were going to -- you still were going to look for gaps. I would advocate if nobody is looking at return of results in some kind of formal way I think this is an exceedingly important issue.

Yes, but not part of the direct charge right now.

Right, right, right.

I'm sorry, yeah --

If you follow through with Rochelle's framing, then we'll be able to touch on return of results there. Obviously, what is the group benefit? [ Speaker/Audio Faint or Unclear ] the NCI is going to look into return of results [ Speaker/Audio Faint or Unclear ] but remember that [ Speaker/Audio Faint or Unclear ] as well as germ line. I'm chairing one of these sessions apparently. This was good, Charmaine. This is one of the specific things that is troubling them. I suspect this is a high level look.

Just to be clear, when we talk about return of results, I thought we were talking about return of results to individuals of general things. As opposed to research --

Correct.

[ Overlapping Speakers ]

I think would be part of all of -- would learn something --

These are individuals, try to grapple that.

All right. So if people are good with that we need to form a task force. Among the drafties are Charmaine, because no good deed goes unpunished in this group, if you are willing to continue the leadership role. And we need some volunteers -- Mike, I think the task force we have should continue unless people have -- want to move off of it. Mike, if there are others from your group who could help with making sure that we state coordinated -- stay coordinated and knowledgeable. Maybe you could work with Sarah. Then we need other volunteers. Rochelle, Gwen, great. Barbara. Others? Charmaine, are there other issues that we need to cover?

No, I just wanted to be clear. Steve, part of our work would be looking to see where these gaps are. Would that be part of our -- I guess another discussion -- I don't know if that's for the task force -- [ Speaker/Audio Faint or Unclear ] that's probably we talk about later.

Right. I think you can bring a recommendation back to us as to what this looks like. What I'm hearing is these group validity issues will be the primary focus. As you can explore a number of these others, international, return of results -- see if there's really a need that, where we can make some recommendations that are meaningful, if so they can be added to the charge and brought back to us. Whether this is a letter or a larger report depends on what you find as you get into it a little bit further, and how much of that is -- yep, that's what we know and we can move ahead, or whether we need to do more research. Is that all right? Cool.

Thanks everyone.

Thank you very much, that's terrific. We're a few minutes ahead. But we also have a few extra things. I would suggest we take our break now and come back at 5 minutes after 10:00. Then we have public comments. Marc, can you share with us some of the issues you brought up yesterday?

Yes.

We'll do that as soon as we get back from the break. Yeah, actually, one thing that would be helpful now. We have not heard that anybody wishes to make public comments. Are there individuals? Okay. That's good.

[ SACGHS on morning break until approximately 10:05 Eastern Time Zone ]What we would like to do is revisit the issues that Marc raised yesterday in terms of the ARRA money available for the comparative effectiveness. How the resources can be well utilized this fiscal year with specific recommendations.

Marc, you had some ideas that you wanted to share with us, that would get crafted into a letter to get to the secretary. Marc, take it away.

The first thing to say is that the letter that I was reading from yesterday that is behind Tab 10 is dated March. There are still funds that are under the secretary's control that are not designated. That's the assumption that we're working under. That may not be accurate. What I wanted to do is Steve asked me to talk about the issues of phenotyping. I wanted to give more context to that. Again, I'm not sure if all of you read that paper or not. Let me make a brief case for phenotyping. Phenotypes result from the expression of the genes and environmental factors and interactions between the two. I went to the definitive source, Wikipedia, you may have some quibbles with that. But I think it's fairly reasonable. In the article they say there is a big elephant in the room. We have a deficiency of phenotypic data. It requires more samples to achieve more stat stickal power. I think this has applications in terms of some of the things we heard yesterday in the afternoon session about doing ground/up systems biology. The commitment to better phenotyping makes scientific and financial sense, because we're not wasting money trying to do genomic studies with poor phenotypes.

But phenotyping is hard. I think we saw that in that document about how do we do the phenotype of cigarette smoking and environmental exposure. We do collect lots of data in health encounters. Height, weight, BMI, blood pressures, et cetera, et cetera. But the problems that we have are these are not collected in standard fashion, most of them are text-based. Even those represented electronically are frequently collected in different systems that don't talk to one another. Unfortunately we have a heavy reliance on diagnostic codes that are not up to the task. When we talk about all payer databases we're relying on ICD-9 codes. Every genetic syndrome has the same ICD-9 code. It's a little bit useless if that's the only code you can pull on.

There have been some other approaches. There are some consumer-focused approaches. Such as patients like me, it is self-reported data. There's no adjudication taking place. It has basketball shown to have an important role, it provides the evidence and feasibility. We've heard about DB gaps in a number of presentations here. That is a collection of deidentified data. The limitations here is that the information is study specific. The data collection is not ongoing for submitted cases. And because of the deidentification there's really no way to go back and enrich phenotypes to answer questions that have been raised. We heard briefly about Geneva yesterday, and also the emerge, which are also looking at ways to aggregate phenotypic data using different models. There are project-specific issues like the U.K. biobank and others. These are all done under recon tact consent. They're beginning to develop standardization of information collected, although the information is still not readily consumable across all inform attic platforms.

There's an effort in the world of [ Indiscernible ] and metabolism that Rob has alluded about being able to collect fiend tippic information around inborn errors that can lead to better care.We've only been treating [ Indiscernible ] for 50 years. We should be able to answer the question about what is the target [ Indiscernible ] level? But we can't. We're not collecting the data. Again, you are looking at neurocognitive outcomes. That's hard to collect. But if we don't invest in trying to collect it we won't get anywhere. There's been very intense phenotyping that has led to some interesting discoveries. I think there's the potential for how the ARRA funds could be used in this space. Highlighting the issue would not be a bad use of funds. But I think funding opportunities that -- that should be convene not convey -- to develop a long-term phenotyping strategy. Defining a minimal data set. This is not work that has to be redone and redone and redone. If you have one project that says we will define standardized collection of phenotype around blood pressure, once that's accepted you could then use that in any other project that wanted to do work around blood pressure. There would be issues relating to how to store and access this information, what are the issues relating to collection of phenotype? Are there sensitive issues such as mental illness? What are the roles of the various DHHS agencies? And evaluation of DB gap. We could also fund opportunities related to currently funded projects. We have disease-related projects. Among all of those projects funded by the various groups we do analysis of gaps in phenotype collection. There could be project specific standardization of data collection. There's also a lot related to infrastructure. Funding for training for dedicated phenotypers.We need a human fee Nome project has been suggested, that might be a bit much, there maybe others that I wasn't able to come up with this the half hour that I put this together.It may be that the group decides that train has left the station, we will just look at opportunities going forward. I can certainty understand if the committee does not feel this is germane or interesting. Hopefully that clarifies to some degree the issues that were raised yesterday about what we're talking about in terms of this phenotype gap. Maybe before we discuss the letter I could entertain questions.

Thanks, Marc. Thanks for the summary of a broad ranging issue. You pointed to a couple of programs, there's a third one that I called PMENIX.-- PHENIX. It gets together experts and comes up with measures. There's a core of how you might do this that is already in place.

You need money?

How can you possibly -- we think it's a great place -- where additional resources could expand the scope of this project.

Okay. That would be meet the ARRA definition of shovel ready.

Yeah. They are shoveling.

Other questions? David?

Marc, I think this is really important. I think there's a great likelihood we will have information about samples where we don't know anything about the person, trying to create a platform and also dealing with the ethical issues is a top priority issue.

Steve, let me turn it back to you. You had some significant questions about this. Does this clarify the role that we may play in this?

Yeah. In terms of advising the secretary --

Yes.

There's the immediate ARRA issue and what can be done that, and what falls within the scope. Some of it we probably can't answer today. There's a number of issues here that bear attention. And the money may be able to be used for it. Even if it can't, these are still issues that we think need to be addressed, whether it's through some of the other activities of HHS or otherwise. So I think you've clarified phenotyping. But now we need to talk about the letter, which I think all of you have in front of you. It's fairly sweeping in some ways. We should talk -- how do we frame the letter? I would probably do it a little bit differently. And then see if we are comfortable with the three main bullet points that you had there. I don't know if you want to walk us -- unless there's more discussion on the phenotyping. We should probably give people a minute to read this.

Right. I think this would be appropriate.

Let's give everybody just a minute to read it.

Before you start walking us through this, we do hope to take up the issue of comparative effectiveness in October. This is not our only shot at this. This is the short-term stuff that we want to get to the secretary now, because there's immediate potential. A lot of this looks like long-term infrastructure building.

Which is under the purview of particularly the FCCER recommendations for ARRA funding. The intent to get people off of the ground --

Exactly. Fair enough. The ARRA money is short-term money. But there needs to be longer term support.

For the people that are responding to those grands, they also have to provide information relating to sustainability. There's onus on the people responding to the RFAs to talk about how to keep this going beyond the infusion of funds.

Realizing we will not have the opportunity to really wordsmith right now, why don't you walk us through each of the bullets.

Right. The first bullet point relates to a center, a research center sphoa cussed on -- focused on comparative genomic information. One of the things they would be tasked to do is defining standards for utility, it keeps coming back in a number of different contexts. We heard it this morning in the FDA comments, we heard about it a lot yesterday. And then also developing the abilities to disseminate these findings to appropriate audiences and stakeholders. This is consistent with what the FCCER recommended relating to strategic framework, building human and scientific capital for CER, and we have previously recommended creation of an entity.

Let me just start by asking a couple of things. One thing you didn't mention is the sentence that reads "-- work that would enhance the applicability of genomic technologies." That's a fairly sweeping statement.

Right. I must admit this has gone through several iterations, including once just in the last ten minutes or so. I'm not sure I would suggest -- I don't think it could be done in a year, to have collection. I think it would be more addressing issues relating to collection of data from underrepresent -- I would see it more studying the issue than collecting --

It relates to the discussion we just had, regarding genomic data sharing. Maybe something that would be better deferred to that.

I think that would be fine.

The other it talks about building the human and scientific capital. That's fine. That's about workforce development.

Which is what ARRA is about. Any funds must talk about what is the investment in human capital, along with the sustainability. This is language that is directly extracted from the documents that are guiding the dispersement.

It's about jobs am it's about jobs. This is really about developing training and that sort of thing. At least as I read it.

I would agree that the term "capital" is not explicit. This is the language that is in the documents we just [ Indiscernible ed it.

It needs wordsmithing.

That was the language that was put out in the proposals. We could choose to use that.

All right. Sheila?

I just wanted to follow-up on how this would relate to the [ Indiscernible ] that was established in health reform that will have a separate committee to come up with national standards. I'm wondering if this might be something that could be created as a standing subcommittee of that methodologies committee, or advisory group. It does seem to be pulling all of the standards and evidencary discussions.

Maybe a way to deal with that, since this is targeted to funds that are available through ARRA, you are talking about a different funding source. We could add a sentence to say part of the group's task in the year of funding is to look at the feasibility of adding this as a standing subcommittee to the patient centered for outcomes -- would that be reasonable?

I think that's closer. How they're going to fit together will be important.

We could probably word -- if that's acceptable, we could indicate that in a sentence.

By the same token, we have the centers that are similar to this, that are doing this for cancer, right.

Correct.

This is now centers that will deal with genomics more generally.

Yes.

In addition to the ones that NCI has been sponsoring. Somehow we need to put the context. There's this part of a larger --

Right. It's so new --

[ Overlapping Speakers ]

It's really building on this dialogue. Do we know whether any ARRA funding has been used to create centers? When you look at the sustainability of the Corey, I understand it's a $2 tax on many Americans. Once you are creating major new centers that's pretty expensive. It may be a nonstarter to focus on a center. However, that said, I think there's a need for this. Where should this be housed? Part of PCRI? Do we know if ARRA funding has been used for this?

Yes. It's been used to create centers. Cancer Jen is one. There's a number of other centers that have been created through use of the funds. Again, with the implications that you had to say how you would sustain it beyond the initial start-up funding.

Okay. Is there a general sense as to whether -- clearly there needs to be some wordsmithing. Is there a sense that if we go forward with a letter at all that this is an appropriate kind of thing with the broader context that Sheila and Sam are talking about? Seeing some nods.

The second bullet relates to inform mattics infrastructure. It was a specific far get of the recommendations of the FCCCER document. We've communicated in a number of different venues to the secretary the concern that we have about the current structure being able to accommodate genetic and genomic information and this bullet articulates, again, those concerns and talks about actually looking at building on the work that had been done by the American health information committees work group, which articulate add lot of these issues and offered recommendations going forward. So this would be funding that would allow continued evaluation with renales to -- recommendations to the offices under the secretary, such as the ONC of HIT, certification, et cetera, et cetera. This is what we think is needed to really adequately support genetic and genomic collection and to address the disconnect where the IOM report and the FCCER report indicated it's critically important to examine subpopulations. Currently we don't have the ability to collect that information in a standard healthcare processes.

Comments?

I think the an important consideration and support it. Just have a question: It's my understanding the national quality forum has been asked to look at measurement performance and what elements would be in meaningful use medical record, as are the regs that will be finalized soon. I just am trying to understand where the intersection of this is with those two.

That's an interesting question. The reality is at the present time there is no intersection. There's no one -- despite our comments through meaningful use, and certainly not at the quality forum, there's no reference to genetics and genomics. The disconnect that I would look to this bullet to bridge is there's a bunch of things going on relating to EHRs and outcome measures and comparativive research completely ignoring the importance of these markers. The idea of this is to say how to bridge that gap, how to fix that problem.

It makes it even more important to be boulder in saying that no one is looking at something that is critical.

The reason I specifically referenced the AHIC on this is because they were charged to address this issue. They did a tremendous amount of work in two years under John Glasser. That work is laying fallo.

As is other AHIC work?

They were sunset. There were ten work groups under there. I chose to focus on this one, because it's relevant to our committee.

Sounds like a little more context here as to how it fits in here broadly. Otherwise, this is very consistent with what we've already said.

Yes.

I don't hear any policy change here.

The third one relates to phenotyping. I was talking about using funding to convene, I think we could also make recommendations to fund -- to provide funding to existing efforts like Phoenix, emerge, Geneva. Groups that are currently constituted to address these issues. I think that could be a pretty concise recommendation with a very targeted focus of funding.

Comments?

This is the one that is really new.

Correct.The one thing I might, as I look at this one more time, the other thing that I think -- I would move out of the second bullet, which is where I referenced the IOM top 100 [ Indiscernible ] studies. Many of those have been funded. In our analysis of those projects, which we presented to the group back in February, we identified certain of those projects that seemed to have more relevance to the ideas of genomics and personalized medicine. If we move that to bullet three and say analysis of those specific projects with attention to whether or not the phenotyping associated is adequate and specific enough to move this forward would be a reasonable investment of some funds, as well. I don't know if we would -- if that is within the purview. I assume there's ongoing review of the projects where there could be midcourse corrections as needed. I would propose moving that down and adding that to the third bullet. Does that make sense?

It just provides a concrete example.

Yes. We could take that previous document that we presented here. Here are the ones that seem to have direct relevance, here are the ones that have reasonable relevance, and use those as the exemplars.

David?

Steve, if the secretary says this is great, who would get the money?

I think what would happen is there would have to be funding announcements that would be developed around each of those that would be put out for applications. Then whoever, you know, whatever applications went through the review process aawarded they would have the --

That's not the problem. It has to be obligated by September 30. There's no opportunitying for new funding announcements.

There are still nearly $100 million of the secretary's money that's not announced.

Right. I'm not privy to know --

We haven't been able to confirm that. This discussion it may be that the window of opportunity for the ARRA funds has closed.

Two things. One, I don't know what is in the funding opportunities. I assume they're out and they have applications in or on the way. This would be encourage to fund that type of work. Or these are things that need to be done, you know, if they're not under ARRA that they be done in the future. There is going to be comparative effectiveness money.

I know that Sarah and Darren have been working within the office to determine whether or not there is still the opportunity to use --

You are shaking your head no. Do we know for sure?

We know that the money has to be alKated by the 30th. I didn't think there would be time to do a new announcement. Because people, you know, you have to get it out. I was assuming there were applications that have come in -- with any remaining funds -- here are the priorities we think you should target.

What I'm saying is we don't know if all of the announcements have written. I thought we were taking time today to say if there are still some opportunities to put out aknownsment it's here's what we recommend. What I would say is if they say we've written them. This becomes the starting place for the bigger discussion in October about how to look at other funding opportunities. There might be something available within ARRA that could be gotten out of the door quickly. That's why we were taking time.

We need to couch it somewhat in that --

David?

Whether it's worth writing to her right now about this, given our inability to influence the funding opportunity announcements, that probably is not likely. Whether there are things coming in that we think -- that they should be given priority.

There could be some prioritization.

Or at least to help set the agenda going forward.

Right.

I think that's the context with which this needs to be written. Staff needs to explore if they could still get a funding announcement out this year. Based on my understanding of civics and watching the government in action is --

Almost every deadline relating to the secretary's discretionary money --

We can find that out. Two questions, if we were to write to the secretary, are these the right things to write about? If they are, given the fact that this committee will not have a chance to do much review of them, we would need to get this out really fast. Do we want to send something? I will entertain either. Are these the right things to say?

Are these the not right things to say?

How many people think that -- let me switch -- that we should try and write to the secretary about this issue. Should. Let's do that first. How many think that we actually should? How many people think we should not? If we are going to do so, then do we have -- do you want to take them one at a time? Or take them in the aggregate?

Aggregate.

All right. How many people think these three things should be part of what we communicate to her? I'm seeing about six hands, and some ambivalence. How many thing these are not the right things? Are there other things that you all would like to see put in that letter? If so, what are they? Okay, Janice?

I just have one comment on that first bullet. I would be interested in lieu of recommending creating a new research center, whether to explore the potential for integrating the genomic component within other existing centers.

I think it's fair to say that we have had no exploration of anything. What we're trying to do is say here are some potential ways that you could choose to use these funds. And creation of a center is consistent of what has been done with other funds. I think it would be intrinsic there would have to be collaboration with other centers. But the sense that I've had from what we have sent to the secretary before is that the integration into other centers always seems to get short shrift. That's why we thought it might be the best way to go.

Other thoughts? Seeing none, I would say we will have to work on the general framing so it gets the right context. We don't know what flexibility there will be. These are important things that need to be done with these, or other funds. Then we will tailor these bullet points.

I think it would be helpful -- this will be on short turn around. It would be helpful to have a couple of people in addition to Marc and myself who work with staff to get this crafted.

I would semi-volunteer David and Sam.

That would be great. Anybody else? Dr. Corey, okay.

Do I have veto power?

No, no, no. You will have to discuss --

I just don't want to see no figure represented in all -- no fig represented in all of these letters.

We will go forward with it. We will need to get it out within a week.

Thanks. This may be a record of sorts for this committee.

We will find out if that's a good thing.

Let me ask one last time, are there any public comments? I'm unaware of any. All right. Hearing no public comments, we will move forward to a topic we began addressing at our last meeting. We have the pleasure again of hearing from Rod and his colleagues.In February Rod said that his committee would be interested in forming a joint task force to introduce carrier screening. There's been discussions about whether a task force or activity will be the most appropriate way to move this agenda forward. We've asked Rod to come back and talk about what emerged from his committee, so we can have a discussion about how we would like to proceed. Rod, welcome. I gather Sarah will present with you.

Thank you very much, Steve. The last time I was here we were hurrying away from the snow storm. We may all die of a heat wave today, that's interesting. As you remember, we've been identifying carriers for decades. When we screen for sickle cell disease we identify carriers, that information has been handled in a variety of ways. We've recently added CF, we now identify carriers for CF. Our work in newborn screening has moved us into the area of carrier detection. Our committee has been work on this a lot. Sarah has been working with the work group on carrier screening. The reason we had spoken to you before is we thought there might well be some issues of interest to this committee, you might be interested in participating in the work groups. I will ask Sarah, who is the department directer to tell you what the committee has been up to. Sarah?

Thank you. It's my pleasure to present to you today. To say that I already have a work group formed is kind of ambitious. I would say we've talked about it. Today the main reason to speak with you is to get your input, insight, and help us to address this topic and how to go forward. I am here representing the secretary's advisory committee for heritable disorders and what their -- what they said was something to go forward with. I also want to say that a lot of these slides I have taken from previous meetings. They are not my own original work. I'm not trying to take credit for them. They are referenced in the notes.

Here's the agenda for what I want to say here today. So what do we mean by carrier screening? This has been detection of asymptomatic people who carry one mutation of a recessive disorder. We're starting to question whether or not the carriers are really asymptomatic. We are looking at not necessarily detection of effected offspring. Carrier screening at this point can be deliberate, we're looking for carriers, such as some of the prenatal testing that can be done. Some of the examples would be cystic fibrosis screening, muscular dystrophy. These are groups that have very common [ Indiscernible ] mutations. We could look at disorders that have very decreased penetrants with high mutation rates. So looking at things like [ [ Indiscernible ] muscular dystrophy and looking at carrier status there.

Some considerations for carrier screening is that the disorder should impair the health of the affected offspring. It should not be a benign condition. There should be a high frequent of carriers in the screening population in order for it to be useful. They have to be efficacious. There have to be options of ways to deal with this information. Consent needs to be informed, involuntary, and protected. And here's the big one, knowledges of benefits and harms is transmitted pre and posttesting. That's very difficult to do, as we all know.

Privacy is very important, as we discussed today. It needs to be protected. There is a dearth of genetic professionals out there, so the professional resources are another issue. Some perspectives to consider when looking at screening are the public health impact, are we decreasing the impact of disease on society? Look at the burden to the subspecialists and to the primary care physicians. How current screening programming impact carrier screening. Looking at the findings that we have as part of newborn screening, and also look at family and individual perspectives, the stakeholder perspectives.

So I went through this. I'm thinking who, what, why, and how. Who do we screen? The whole population? Or do we do high-risk populations? Do we do targeted screening? If you know that someone is of a decent has a silent mutation in a certain gene, cystic fibrosis is an example. How do you screen it? Do you do the family history? If there's no family history you don't do the screening? Or do you look for impacts of decreased protein efficiency in biochemical markers?

When? Do you do it at the newborn timeframe? Childhood at the time of other mandatory testing such as lead levels? This is the age of consent, age 18. Do you do it prior to pregnancy? Or when they're already pregnant?

What is the purpose of the screening? Is it to inform people prior to pregnancy?

[ Overlapping Speakers ]

Who end up with acute --

[ Overlapping Speakers ]

SC trait and some of the [ Indiscernible ] -- and when there are no other interventions, detection is important to onset of symptoms. Are are there other reasons? We need to weigh the pros and cons.

Rescreening has been an issue. For the most part athletes that are college age are all screened for [ Indiscernible ]. Who do we do this on? Do we -- how do we ensure that it stays with them? Who is responsible for this counseling? When should the counseling be done? Who should be targeted for rescreening?

Direct to consumer testing, I think this might be a very dead horse for this group today. We've talked about it a lot. There are commercial panels being offered to consumers, as you know. We're concerned, as are you, about who is making sure that testing is done per professional guidelines, that the counseling is done, and is adequate. And keeping the information for reproductive choices.

So if you look in the literature there's been some previous experiences discussing carrier screening. California did a study. Less than 50% of OBs offered screening to the parents. 17% of couples were offered that. Only 50% would even suggest it. As we introduced CF on newborn screening this has been improved, but it's still not full populations. The panel of the screen is also growing. This is going to be an impact throughout all of these disorders. Because ethnic background makes it important that you choose the right panel. There's the discrepancy between prenatal and newborn screening results.

[ Indiscernible ] Jewish population has the best history in preconceptional screening. They started in 1973 for stay sacks. We've had some very negative experiences. Sickle cell disease in the 1970s the Air Force developed a policy portrait carriers, there were some problems with you are a provision. There's also been the stigma related to being a carrier am.

There have been three recent big meetings discussing this issue. In '06 there was one held in the Bronx. In '80 there was a meeting in rockville. At the NIEH in '09 there was a meeting for spinal mustily atrophy. The rockville meeting in '08 the high priorities for what to screen for, and when to screen is that you need to know the carrier frequency, the disease burden, and the cost, as well as the rationale for screening. And then balancing the screening interests for individuals, communities, and societies. What we found with sickle criminal disease is you need to engage the communities, the community-based organizations are huge in these kind of decision making situations. You also need to identify the correct gatekeeper. Maybe we could look at other screening models where maybe we bypass individual interests and just say this is a mandatory screen.

Or maybe we make it standard of care, and not necessarily mandated but everybody should get a cholesterol, blood pressure check, et cetera. And then do we target certain subpopulations? If so, on what basis? We need to know when targeting these are we doing it prior to screening, or after screening?

[ Captioner Transition ] [ Please hang up the phone line so that the relief captioner is able to obtain audio line into conference, thank you ]

They may be candidates for ethnic specific mutations. And they concluded that a child can be [ inaudible ] and they suggested care. And that the trait result becomes part of the help record. Looking at the mandatory nature of newborn screening can put certain populations at a disadvantage and customized counseling is very important. There is case law that has said precedent for anti-discrimination in relationship to genetic testing but there are some areas that are not clear-cut said Dennis Doody to -- such as duty to disclose.

And we need to get input from professionals in committee members. And this last fall, they came up with the recommendation that pan ethnic carrier screening is technically feasible and that the specific study of implementing a program raises broader issues and that the consensus was to effect of the it just the broader issues. A federal process such as that by the SACHDNC will be needed to balance stakeholder interest and technical concerns so we need and evidence based kind of model and to recommend that we pursue carrier screening issues more broadly.

So in summary some work has been done previously by others and some populations have been very successful. There is no model for population based carrier screening. There are many issues and probably no right answers and deciding which conditions should be screened and when is difficult at best storax of the plant for this work group. I have taken care of the main presentation and this is the June presentation. And the next step is to discuss the options of doing a work group looking at the purview, possible activities and how to go about that.

One thing that I did want to mention is I do not see as or anyone coming up with the suggested panel for rescreens, but more ways to evaluate the role of carrier screening. So I am done and I want to take time to ask questions.

So what is the actual recommendation of your committee?

The recommendations from our committee is that we go forward with forming a workgroup and task force in order to further develop carrier screening recommendations.

We actually have a theory interesting discussion yesterday on the whole genome sequencing and what do we need before we do screening in a general population and the need for real outcomes data supported the design I am not quite sure where we are but I would be very interested in people's sense of what the evidence base is, if there is enough to warrant go forward -- coated board and what that might look like in terms of what we might really add.

Can I get one point of clarification? What was the upshot? Maybe I missed it -- but was a proposal to develop the task force from the other Secretary's committee or you have agreed to be are going to form a task force.

If we can do it in conjunction with your advisory committee.

But we are going to have a work group and the question is, with this group participate as a joint effort? Because we clearly are going to go ahead and do some additional work on a carrier screening.

So if you are going to do some additional work on it and you think it would be good for us to participate so the question is not do we or do we not.

It was thought that it would be helpful to have this committee -- let me elaborate on one thing that Sarah mentioned briefly with sickle cell disease and you might all be aware of that but to our surprise actually the NCAA made a recommendation that all level one athletes in the devastates -- in the United States these screen and rework with a variety of a constituent groups and actually sent a letter -- ended up sending a letter saying that we did not think this is inappropriate thing to do because there is considerable evidence that if you appropriately handled carriers for sickle cell disease than other people look alike you abolish the increase risk seen with sickle cell disease.

So we're going to have a workgroup and work on sickle cell disease and we would invite this group to participate, if you would find that resemble in working together -- that reasonable and working together.

Could you repeat what you said about your question about evidence?

I looked very much at what is your and I think it is a continual challenge with all of these rare disorders to show that there is a real outcome difference. That there is evidence, if you will. I think it is an evidentiary question.

I am not so sure. I think it is apples and oranges. Correct me if I am wrong but carrier screening has a whole different set of utilities associated with it. And I am just going to go ahead and say it here but abortion is a major reason people do carrier screening.

And if that is an option to couples to have positive carrier screening you now suddenly removed from all of the necessity for showing that clinical utility and even knowing about it, etc., etc. Do you see what I've seen? I think it is a much easier when events it is independence of that whole -- independent of that whole raft of evidence issues.

Bursting have to figure out what the outcome is and if the scene -- burst you have to figure out what the outcome is and from the patient's perspective. You can argue with the zero come should be.

We know what the outcome is.

We know what the outcome is for most carriers screening and I would argue that this reproductive decision-making and therefore since -- therefore I think that the evidence bar is much, much lower for carrier screening. Does that make any sense to you guys to know more about carrier screening of them than I do?

The main difference I can see between this and genome wide sequencing is it is for no disorders and depending on how this done in this target as a mutation than you know that impact of that significant mutation and otherwise you run into similar problems but there's definitely some good evidence for outcomes in the affected individuals and what parents choose to do, there has been some good research in the Jewish population and some Eastern European countries and the screen and there choices and the known carrier frequency and known carrier status.

I would draw an analogy to the work the committee has done where what was really lacking was are methods to determine what should be on the panel and it was processed that the committee put in place where a realm where it was -- were there was no decision-making or no clear way to go forward. So we were very involved in the SMA meeting and what came out was a similar deal was that there was stated that comes out and there is also individual screening programs that no comprehensive method in which to make decisions about which conditions should be screened for in terms of carrier screening appeared and there is really kind of aid guess, if you will, the methodology on where to go and not just for newborn screening but after having soared to become more involved in these issues that have participated and, there seems to be a need. It seems like a very good fit and a very worthwhile endeavor.

I did it is an extremely worthwhile endeavor. I think we should be involved and I think it's really important. I just want to how late I think there are big differences between this and the other things we have been grappling with doing the carrier screening for SMA has different implications whether diagnosing SMA as a newborn is worthwhile. And I would argue that the decisions are much easier in the realm of carrier screening if one accepts a certain -- Well, that gets into values but from an evidence based procedure.

What is interesting to me is that the Jewish population, because they are very much -- they are not proponent of abortion. They do the panel and your results come back as a good match or a bad match.

I think that is an utterly unrealistic model to apply to the general population and I think if you look at least the data that I am aware of you see a different use for that information. And that use for that information is the law of the land and, you know, is acceptable by most in our society.

I want to clarify I was actually in an Islamic population in Israel.

There is actually one in New York as well.

Lots of similarities.

Yes, okay.

So to answer the question of whether this committee should be involved the answer is yes and I second Jim although I do not share Jim's sweeping generalization that this is easier than all the other stuff. Actually this is much more complicated because of the values issues and up comes and we are all carriers for one or more of diseases whether it is borderline. I mean, this is much more complicated.

Had a very different and it's easier to think about evidence for held up comes in preventing mortality in the person.

Tested but when you explode this to everybody in the population we know that our carriers with one or more rare genetic disease is so as an aggregate this is all of us and where do you draw the line and we need to engage the other committee for a very fruitful discussion along the lines that you have put out there including sort of the discussion of are the outcomes and values and, you know, the whole discussion of whole genome sequencing will make that a reality whether we like it or not. It is going to happen so I think we have to be involved rather than not being involved.

As to not misinterpret what you say from what I understand in terms of carrier screening, what is wanted is the choice being given the option and done on babies largely and given the option of whether you want carrier screening or not. One of the mechanisms that is implemented.

I'd think all of them would benefit for relief from consumer and puts and the disability community as well really has an important role.

Our committee has a very active consumer rules.

And if you guys to the side I am looking for volunteers for this -- do decide I am looking for volunteers for this.

I have been part of this and we had a meeting a couple weeks ago and it is a very interesting how the very little we know about the street. We thought about it being benign in the N.C.A.A. rule liens and athletics and the need for research and what it brings in terms of some of the medical and clinical implications of people with traits that we do not know a whole lot of information about so I think the issue of traits is a complex issue and there's never enough knowledge about what traits actually means and whether it should be defined as a disease. You know, that is taking it far but some people with traits to have symptoms -- do have symptoms.

That is different than what Jim is talking about preview are talking about clinical submission the Mexicans of the traits themselves.

I will provide kayeight Steve -- I will provide Steve with the letter that was said earlier this week.

And the trait workgroup is the kernel of redwood tree trying to build the carrier screening group. And the implications in that group to discuss the pros and cons of screening. Should it be done, should you be re-screened, how do you make sure your status remains reduce so it does address some of these issues.

So, David, go ahead.

I would just raise a question when you're talking about carriers usually talking about recessive disorders but there is this whole range of mosaicism and the dynamism that you do not necessarily detect speed are you interested in those more subtle areas of genetics? Personally yes but I believe that would be a beyond the purview of this work group.

If you do a carrier screening program lets say, you will detect persons who are affected with the disease to have not yet manifest conditions. That is also an issue you will be dealing with when you do a carrier screening you will pick up the carriers but the person might will be affected. It is an extremely interesting area the more you think about it you find all these little interest -- interesting subsets.

So we have the application in front of us.

I am hearing general interest that there is enough meat here that we can have some engagement so may be the focal point of our discussion should be what that engagement should be. Realizing what is on our plate and we can take this on and still say, you know, be equal partners. We can also have members participate, bring it back, or other variants of that.

It seems to me it does not make a tremendous amount of sense to do a to head its leadership of this. Clearly that is something the other committee is going to be taking on whether or not we participate is seems more appropriate that we do participate and select summer% this from our group to participate as part of this group -- select some of our participants from this group to the dissipate as part of this group and not co leadership -- we may have to adjudicate how the final product will be moved whiteboard. And whether both committees would have input on it I think that would be desirable.

And that is consistent with how we have worked with other groups in the past. Jim?

What would be most useful?

It would be helpful to have a group from this committee that has taken some considerable interest in it, a group of persons that would be interested in participating in an ongoing work group. So I think that Steve and you should decide what that will be and then we can coordinate how that will come together and how that will actual function.

I've got to say, I like the idea that Marc endorsed that we agenda-fy a small group of people that will work with you under the leadership of your committee and as all of this evolves bring back the nature of the work. And we can, you know, recommendations and other kinds of things that might be prepared for us to review as we see what emerges.

Vilas was very articulate and selling of some issues that came out of the SMA meeting about gaps that have not been systematically luck that and I think that can be very helpful.

-- systematically looked at and I think that can be helpful.

Is that the report of the work group or a NIH position?

It is the result of a multistate Cold War group that we helped -- work group that we hope and a lot of people had a lot of different opinions that we and and then the question was well, it would be a shame to have to do this for every condition that comes up for being included in the screening panel.

So this is a general comment. I know we have two advisory committees with the two different mandates and this one is more genetics and the other one is more focused on newborns and children. But increasingly I think we have a few examples of residual newborn blood spots. I think with the evolving technology that two committees will have a lot of joint endeavors and may be similar things to look at speed and sometimes the interest marriage and eight from one committee or the other -- may originate from one committee or another but we will be increasingly working with the other group or person for separate we can explore this as a model about how to go about doing this. Depending on where the issue originates may be that committee can lead the effort and then we can have this represented from the other committee. But I see it's unavoidable that the two committees will increasingly converge overtime and the efforts and put the -- they look at.

One of the things that has been discussed in the newborn screening committee is genome wide screening and that is something we will certainly need leadership from this group.

It is reasonable to talk about this group might be the leader depending on what the topic is. So let me ask a question. I clearly sense that people want to be engaged in all of this bid is the model we identified to the committee members to work with Rod's advisory committee work Group, a task force, whatever is finally constructed based on this, the model we would like to go forward with?

Just one minor clarification. So if that happens and then, you know, some of us work with other committees. You know, what comes next? Going back to the results of the discussion. I mean, this group, do we have to weigh in, do we have to accept what the other groups as. Will this be a joint effort? I know the other group will be the lead in this but we kind of have to work this a couple steps down the road in terms of what would be the outcomes and will come to the whole group for a vote on what the final report will look like?

I think it depends on what finally emerges. Obviously Rob's committee can make recommendations and if they ask for a joint recommendations then we would need to get those and vote on those.

Certainly the persons on this committee should be active participants, they should not be observers. Obviously if it were a joint recommendation it would have to be approved by both committees.

In the meanwhile of Representatives would be working closely, actively, and as issues arise that need to be brought back, you know, on an interim basis or finally those are things that could be done. And I think what we're seeing with these residual blood spots that we will get to next, they have been soliciting comments directly from us which we very much participate but we are in an advisory capacity and not in an approval capacity and I think all of that needs to be worked out as we go for depending on what the nature of the recommendations to.

This SMA conference was extremely interesting and which as far as text.

We had one group, one foundation that was established exclusively to support carrier screening through SMA and we had another large foundation that did the support that at all. So in the final analysis this document that she and Jonathan had been working on at great length was reviewed and did you agreed with a view signed on and if you did not, you didn't.

Stuff that they did not teach you in grad school [ laughter ]

All right. What we have outlined here is a reasonable way to go forward and if so, let's identify individuals who would like to perform that function on that task force or that or group.

I am assuming it would not mean going to the meetings in person.

I do not know how much you know about how our task force's work but they to meet offline by phone and I guess occasionally and person. So that is how we work but you might want to explain how you all go about your business.

At the mic, please.

They need an electronic mic, electronic Communication did I do not visualize repeated meetings and so forth our group always meets in the D.C. area and I would visualize and again, Sarah would be convening in getting things to work.

Of the task force members do not necessarily come to your overall committee meetings?

They do not but they are always welcome.

They are open meetings at our so people are welcome.

Yes.

Do you have a rough time when and how you see this proceeding?

Hmm [ laughter ]

It sounds like you have already begun.

I would visualize that we would try to get the group convened relatively soon could this is a rough time of the year and I think it would have to be a practical issue that we get started as soon as possible.

Are we talking about a year, two years? That is the question that I always get asked, is it going to be a letter cover report, a recommendation, major research endeavor. I guess all of that will be worked out.

Yes.

[ laughter ]

That is usually what I say, too, yes.

So understanding those parameters and some of that to be solidifying, who is interested in working on bad as what we call a liaison but presumably be part of the task group as it going.

I see Adam, Charmaine, Jim. Janice if we need more.

That is a great group because he had people who brings a great perspective.

Phyllis just raised her hand.

You are in so much trouble [ laughter ]

Be careful what you ask for, you may get it.

[ laughter ]

There are clearly a lot of issues here that need to be flushed out and we look forward to keeping some interim reports. And hope that these folks report back to West on progress -- to us on progress.

I think we have been little time, do you want to get started on the residual dried blood spots? I do not know where we are. Are they ready? And Do they have the lunch out there?

Would it be destructive if we started before lunch and then had a break?

I would say -- the people who follow online or who show up for specific sessions and I know that committee business is committee business.

We can start but we certainly are not going to wait until 1245 because I know we will lose people at the other end.

It is not set up yet?

Why don't we go ahead at least with Adam, are you prepared? Do you want to introduce the session and then we will continue after lunch with the remainder.

We are pleased to have this committees and put on the dried blood spot issue and Adam is going to address the IOM meeting on the subject.

To you want to say a few words because I know you have been busy preparing responses so I want to introduce this.

Okay actually I was just going to introduce the overall session appeared at the February meeting our committee decided to form a steering Group to comment on the Secretary's Advisory Committee on inheritable disorders and newborn children on retention and use of residual dry blood spot specimens and you have the full paper under tab 9. The report is out for public comment and before I go over the recommendations, we wanted to introduce our first two speakers who were going to provide us with the background on issues facing the state in the nation regarding residual dried blood spot specimens. So Dr. Adam Berger is from the Institute of Medicine and he will tell us about a recent IOM workshop that explore the challenges and opportunities in using newborn screening samples were transitional research and then we will hear after that from Dr. Rodney Howell and as already has been alluded to in February he provided us with an overview of the draft briefing paper and will today gives us an update on the current revised version.

Okay, Dr. Berger?

Thank you very much for inviting me here today. I'm Adam Berger and I am the -- [ Indiscernible ] Institute of Medicine and what I am here to talk to you about today is a recent workshop that was put on regarding challenges and opportunities using newborn screening samples for transitional research.

I will give you a little bit of background. So newborn screening programs are actually state mandated as well as public health services that identify children that are born with serious or life-threatening disorders. The goal of the program is to provide treatment for children who typically appear normal at fourth but have a in Herod's disorder that will lead to a disability or death and -- at birth but who have a disorder that will lead to disability or death.

The specific testing -- the specific testing is determined on a state-by-state basis. The screen is performed on blood samples and collection samples for dried blood spots is being collected. In order to be sure that the specimens can be reevaluated based on the screening results excess blood sample is collected and since it is state mandated, or mandated by legislation and is not -- informed consent is that obtained and legal challenges, highly publicized lawsuits which have come up in Minnesota and Texas and I believe that Rod will allude to these later on this afternoon to.

Although in this case the Minnesota case was dismissed in taxes by million dried blood spots where -- 5 million dried blood spots were destroyed.

So we have autonomy, consent, and as newborn screening expands it will only become more significant. With this in mind you can imagine putting together this workshop on the challenges and opportunities for research. And what we did is in sure the workshop was done and we decided to coincide with a public comment period for that report that Rod will talk about this afternoon and stakeholders were identified and in this case we want to promote an open and honest discussion where everyone can basically come together and potentially find a common ground. Just a quick disclaimer, I will be presenting information and it comes from statements and opinions of those participating in the workshop is of it should not be construed as reflecting any group consensus from the members of the Roundtable for the IOM.

So whether the benefits and how do we protect the rights of individuals if we allow them to be used as such and how do we make them the norms of that research can progress without actually compromising the program itself. We look at the status of the state in terms of the policies they have on the book as well as the rationale as well as the challenge and value versus the cost to the program.

So we looked at the state practice policy and I know that Rod will go into a battle bit more detail. As of May 2010 what we found is that there are 18 states with legislation that could easily be identified if you go through the state laws. And the policies vary based on storage and retention and what educational materials are provided. The individual states are storing these samples not only on newborn screenings but secondary uses as well and there are at 162 -- 162 analytes and can be used for retrospective studies, even unexpected uses in -- and Discovery.

Wire the been stored? That are -- they are irreplacable and also looking at the public health benefits and the feedback of the newborn screening process.

In addition we looked at the proper research implications as well as the implications of data set linkage.

There are a number of usages but this will give you an idea of what came up with there is an epidemiological public health benefit because these problems with susceptibility and in this case HIV was product, Global Health, Research in developing countries, a case control studies and longitudinal studies could be helped in these samples is, another major instance is expanding the screening process itself. We saw things such as private screenings and we see similar testing going on for Disease right now. I will pull up a little bit and I want to thank David Hunt yesterday for setting this up and I want to create a virtual halt profile which integrates much of the databases out there and will provide protection for privacy and taking into account legal and regulatory and technology issues.

If you take a look at this this is a bit like any of the work and -- a look at this, a different aspect you have these sites in here you have immunization and child health, and national levels, local levels, feeding into the state health departments and managed care clinics, physicians' offices as well as hospitals, nursing homes all feeding into what will eventually become or what we hope will become a patient Cedric database. The purpose is to move from the current application for that is having each of these that individual databases that only readable to one station to something that is much more workable and accessible and all of this feeds into a view for you would have restricted access Team to insure that the data is accessed properly the benefits of this that were highlighted is a lot better information of care and treatment as well as a meaningful health information exchange and one of the other benefits is that you could create a standardization for the data.

One of the other benefits of this is basically movable with in the state and from other locales or even a national level so with all of these potential benefits it is still by official to weigh the value and the samples end all of the resources are secondary to that.

So we look at the challenges and values of this would have and the core mission and how do you retain that? We look at informed consent and the stewardship of this data examples, legal issues that were involved and the value.

The cost.

So what can Auden this is -- that can of this is what can a lot of research to proceed while still maintaining and protecting the value -- the cable service that is newborn screening. And as we heard Bin Cheng briefly discuss this yesterday education, funding, consent, transparency and trust, stewardship and accountability as well as policies involving regulation. So if we explore this a little bit more in terms of what was action developed, a lot of it is the lack of public knowledge about the newborn screening itself alone the alternative uses for samples.

In this case, it was the idea of seeing that trend needs to be some kind of public out reach and more of a constant out reach in keep informed that newborn screening as well as another use and in addition we heard a call for informing about the public health and for structure including databases and give permission that is explored in the system. They seem to be fairly related to.

In addition to a patient education is also necessary to educate providers, the providers themselves. And then something else that was somewhat novel in the workshop. Letting parents know the risk of destroying samples. That if you opt to destroy samples today they will not be available for your family or your child 18 years from now. This comes down to the question and this was brought up quite well, we are the financial resources to provide education and the answer is they are currently not available. One of the second point that I think came out well in the workshop which was funding. And this is actually from a different context.

In this case of funding from the state program perspective and how there is actually a lack of the needed resources to for the the program. Currently they have a minimal amount of funding and there is actual concern that there would not be enough staff the.

In terms of the many states that looking at destroying samples due to financial constraints. This is leading to basically and an ability to store samples long-term. This is also something that was discussed. So as we heard from Charmaine this morning, about patients not fully understanding the process, the information that was -- this was brought up and the IOM workshop in number of viewpoints, one of them is that there is concern from the public health perspective is that if there was mandated language being adopted and we talked this morning different ways of obtaining consent. And how do you make it more attractive and manageable by the consent team and we heard from a number of people that there are ways developed of the key dynamic handshakes in which the consent fees would be able to change concents depending on their information that the developed over time. So making it more attractive to the process.

And lastly there was concern in trying to apply a single standard across projects. They may not be applicable to all there for there should be somewhat of a project specific approval consent.

Transparency and trust is also a major issue product by the partisans and is centered around allow access to their own data and allowing patients to go in and see what is being produced from this and integrating participants into the process itself into the decision-making process and helping to build a trust in this case that would be needed to insure the participants that their resources are being used properly.

And lastly one of the ideas that was found was building relationships proactively rather than in response to an adverse event. This leads some went into stewardship and the part of that trust is involving the community and business making process. And having oversight of their own samples be looking at the oversight committee themselves and the IRB committees and review the recent proposals that come through and make them more reflective of the community from which these samples are obtained.

There is also a question about ownership. The question about ownership is brought up and what constitutes fair use and I think the analogy that was brought up, I on my car but I do not have the right to throw my keys as somebody or when somebody over in my car. Just because I own something does that mean I can use it in any way I feel so that is the point that is made and needs to be defined.

There is also the project specific approval pertaining to stewardship and going through the IRB approval process.

Accountability was also one of the things that has come up that was found at the workshop did this is really crafting data and hold the signor accountable to uphold the agreement in the contract in it they are in.

Also with ongoing follow up, health samples, reviews, who has access and why as well as the outcome of the project is still pretty relating some of this information back to either participants or its proper authority so that they can continue to follow up on the project itself once it has been approved.

And then lastly, something that was really focused on was how do you prioritize the different uses of samples? This is by night research so how do you prioritize research when one, you do not know what the research is going to come up with and you do not know what the future will hold and also leaving some of this planet research intact and allowing the patient to go back later in life if needed.

And then lately as they mentioned the policies and laws and the question about the adequacy of HIPAA and developing policies around law-enforcement as well as return of results. We heard some of that today already so with that I would like to thank you very much. I am happy to take any questions if anybody has any.

Okay. If there are some direct questions for Adam we will have a chance for more discussion later.

In your slide under consent score first bullet point was the mandated language of consent may hamper programs function. Can you explain a little bit more what that means?

Essentially concerning the Public Health and they had basically question whether or not there was going to be mandates being sent down from legislation, if they would actually mandate is specific type of language that would hamper their ability to function and it was really a question of -- it really would be a question of what the language actually said and there was some concern on the Public Health said that if there was a mandate for a specific language that it would be mandatory.

Are you talking about consent to do the newborn screening or consent for secondary research uses?

In this case it would be consent for secondary cases.

Paul?

Thank you, this is a very articulate, diplomatic style.

[ laughter ]

Right, but we could take some lessons. My question is, what are the real controversies in this process and which of these bullets makes you least happy about the way that you are in a sense bourse to convey a -- forced to convey what Kmart of the group.

Since I am representing the IOM and we are -- The Roundtable actually [ Indiscernible ] and so I will hang my hat and my own personal need you. Just to make sure this is my own personal mandate and what I think are some of the most important size of this. I think this is really what it came down to, we heard from quite a number of people that actually came up and spoke at this workshop. Coming from Minnesota in relating to the cases versus Minnesota which was dismissed. There is a question of how the public health department had knocked down the trust from her point of view so far down that they really do not trust going back to the public health side and I think trust is probably the most important issue with the dressing newborn screening and the samples and trust is, we to have to go into making sure people understand what is there going into.

And in the state of Washington in this case, Washington is having the consent and going back and re-consenting if they research them down the line and how do you make people trust and say okay we cannot make sure that there is adequate security for your information, that is an impossibility but if you trust this enough's we have done a very good job so far we will continue doing that job. I think some of the viewpoints put out during workshop was surprised that people are willing to put up so much information freely on their own on things like Facebook and the Internet and with things like this they are apt to say no and I think trust is probably the biggest stumbling block to get past.

And while this is related to the whole public service announcement I think if you follow some of the news stories that are still going on in Texas as well as over in England now out of various still I think a lot of negative press. And I think made it to press -- it is not a freak -- it is free to get a negative press and it is hard to get positive press so how do you make some kind of public service announcement that is going to continuing informed the public that is going on and if you allowed us to use the samples will be able to have a better impact of public health and drawn.

Dave?

I was going to extend Paul's question about the Round Table, who was around the table and what sort of consensus does this represent?

I will say again putting on my hat again as represented on the IOM the Round table brings together people and academic, industry, public to discuss issue around in this case translating genomic issues to help it because of the way that we are formed way cannot actually make a consensus recommendation out of the Round table. But what we can do is highlight issues and bring in people to discuss these important topics and those people when they participate are able to make their own recommendations and that is what I have reflected in today's' call is what people in the workshop action went ahead and sometimes recommended or not. As I said, talking from the IOM's perspective of 4IMI do not even like to use the word recommendations for that purpose -- I do not even like to use the word recommendations for that purpose and I tried to refund that in the latter half of the talk, and with the issues of concern to funding, policy, trust, and transparency. That is really where the consensus comes out is by the participants in the workshop.

Any other comments?

All right. Why don't we break here. Why don't we take three-quarters of an hour for lunch. That will take us to about 1245 and for those of you who do not know if there is a buffet set aside for $15 otherwise you are free to eat where you wish be we will meet in 45 minutes -- and we will meet in 45 minutes to finish this discussion.

Adam, thank you very much.

NIH SACGHS Committee Meeting is on a 45-minute lunch break and will reconvene at 12:45 p.m. Eastern time. .

We're going to continue with the discussion that we began this morning on the draft report on the retension and use of residual drug spots. Janice has been facilitating our comments back to -- in response to those recommendations. I will turn it over to her to give everyone an update.

Actually, thank you, Steve. First we wanted to hear from Dr. Howl on the update on his committee's work on the briefing paper.

I'll try to be brief. Our committee has been working on this for sometime. I would like to go through a few comments that set the stage for this whole thing. The committee, which I chair, is a legislatively mandated committee. It originally mandated under "healthy children" in 2000. I will spend a little bit of time on that. Some of the things under the law that establish the committee, the new law that was signed into law in 2008 brought up some of the issues that we will discuss.There are a variety of issues. The bill require it's the secretary to develop a national plan for newborn screening. It gives the NIH oversight and names the research program at the NIH after one of the major advocates of the newborn screening. It basically reauthorized the committee that I mentioned and established an interagency coordinating committee, et cetera, et cetera.

Now this bill, interestingly enough, that reauthorized the committee and signed as newborn screening in 2008, was originally drafted by senator Hillary Clinton. As she left the Senate the bill in a was introduced and passed into law was under the leadership of senator Dodd. The bill had extremely wide bipartisan support. It was passed by unanimous consent by the house and Senate. It was just at the end of that bill -- went to the White House just in last few months of president bush. Interestingly enough, within this bill there's a good bit of discussion about newborn screening spots, et cetera, et cetera. One of the comments issued at that time is quoted here. President Bush last week signed in law that will give the federal government screen the DNA of all newborn babies in the U.S., a move which critics described as a first step towards the establishment of a national DNA database.

There have been a handful of folks, particularly in Minnesota, they spent a good bit of time in Texas, that have been focused on the potential harm that might come from the dried blood spots. A widely pub liesed case was settled in Texas. A lawsuit was brought by a couple of families in tech text who contended that DNA was stored on their babies without their information indefinitely for undisclosed future uses. They charged that it was a violation of their 4th amendment rights. And under the agreement that the state developed in settling this lawsuit -- [ Speaker/Audio Faint or Unclear ] that were stored within Texas. Now, that was a controversial lawsuit, et cetera. And when the lawsuit was settled Dr. Nancy Dicky issued the following statement for you to review.

Now, I simply give that background to point out this has been a fairly visible question in recent months. And in the past year. And there are polar opposites in some of the comments that have come about the dried blood spots. Now, the status of the residual dried blood spots are showed on this slide. Some states save the sample for just a few months. Then you get over to the right and you see there are a group of states that keep the samples for a long time. And some keep them indefinitely. Now, I might point out that the folks on the right is where most of the babies are. At the current time 54% of the newborn population is stored for more than 18 years. You will notice that the big states are over on the right by and large. And 46% have them stored for less than 3 years. There have been a variety of articles and guidelines published. One was published in 1996 has guidelines for the retension, storage and use of dried blood spots. In another paper published that has policies and controversies about storing dried blood spots. One of the best known repositories in the world is in Denmark. It was established in '93, although it has samples that go back to the '80s. It's been under the leadership of Dr. Peterson, who is shown here. They have millions of samples that go back for a very long time. That bank operates with very strict criteria that are part of the law in Denmark.

The American academy of pediatrics issued a statement in 2000. They recommended that you develop policies for length of sample, standards for storage, and consider a specimen resource. The APHL also issued policies about residual dried blood spots. The ACMG statement has one interesting statement, if a parent lives in a state that gets rid of the sample the families should be able to retain them for the future.

Now the advisory committee has recognized that developing some guidelines about storage of dried blood spots is very important. And we have gone through the following process: The staff of the committee prepared a draft outline. Our committee approved the outline and recommended working groups, that you can see, to validate current storage lines, literature review, draft recommendations. We then had a draft that was approved. We had informal comments, it was really circulated among some of the federal agencies and various public health organizations, et cetera, for comments. And we had three webinars on this particular area. It was designed to provide newborn screening stakeholder communities with information about the subject and also have input into the white paper draft, of which you have before you. We have three major participants. The genetic alliance, the regional collaborative under HRSA, and we had the association of public health laboratories. There were substantial participants.

The comments that we requested were in three types. We had technical, education and policy questions. The technical questions that we wanted input on: What is the temperature of the bank? What sorts of things should you aim for? What should be done with unsatisfactory specimens? Prenatal providers education material, et cetera.

We had comments that said will you discuss the possibility that more parents will opt-out for fear of research on their children's DNA? In examining informed consent for storage one of the things that you don't want to have happen is for families to opt-out of newborn screening. Really no informed family would opt-out of newborn screening for things such as [ Indiscernible ], PKU, et cetera.

Do you have support for improving educational materials? Educational materials is a consistent issue that comes up. The states need to be more proactive in prenatal -- it would be helpful if we would make similar recommendations to professional organizations.

The policy is that any of the states that don't keep blood spots, are they thinking of changing their policies? There are many reasons that states don't keep samples. Adam talked about economic. The other thing is that it also gets you out of legal arguements about the spots. Some states would rather not deal with it. Would you comment about the added costs that come from requiring the expanded collection, staff, in the retension of dried blood spots.

Now the other questions that came in. What type of policy and recommendations can you speculate are needed?Is there potential for a recommendation regarding what researchers can do regarding anonymous findings that might be of interest to the newborn? The committee has a series of recommendations that I will go through. And the first recommendation is that all newborn screening programs should have a policy in place that has been reviewed by the state AG addressing the disposition of dried specimens. Policymakers should consider the value of them as a promising resource for research. And the necessity of ensuring the public's trust.

In discussing the whole issue with the public one recurring issue is the fact that so many people don't know that the spots have been stored. I might point out very few things have been done on dried blood spots that we would consider research without permission. We can go there if you would like. Some folks would consider if you are trying to develop a new test in the laboratory that would be research, we would consider that laboratory QA.

Recommendation 2. All state newborn screening programs should have a policy in place that specifies who may use the specimens once they arrive at the center. Third, all state programs should have a well defined strategy to educate healthcare professionals and the potential use of the spots for research. All states should work proactively to ensure that all families of newborns are educated about newborn screening as a part of pre and postnatal care. It's amazing how many families don't know that their baby has had newborn screening done. They go home with a bandage on their heel and they're unaware of why it's there. There's so many things in the hospital that it goes over the head of most. If the specimens are available for any purpose other than legally required newborn screening an indication of the parents' awareness and willingness should be in place.

The secretary should provide administrative support and funding to the committee to facilitate a national dialogue about policy on retension and use of the blood samples, including model, consent and dissent processes. And collect and analyze national data on the utility. The final recommendation is to provide administrative support and funding to HRSA to award grants to states to develop model educational programs for the general public on the importance of newborn screening. And to create educational materials to get consumers the facts related to these issues. The final recommendation was that the federal government is encucialged to provide support on the utility. And educational material with facts about uses for consumers and healthcare providers.

The next steps, the document that is before you has been posted in the Federal Register. And is requesting public comment. There's a goodly number of comments that have come in. That process will be complete June 30. The briefing paper will be revised accordingingly. We're anticipating the document that this group is preparing. Then we are planning to revise our report and review it at our September meeting of this year, and we will plan to send in final recommendations to the secretary of HHS soon there after. Thank you very much.

Are there specific comments, or questions, directed to Rod before we have Janice go over what we propose to respond? Rod, thank you.

Thank you.

All right, Janice, go ahead, please.

Okay. Kathy is going to get the slides on.Okay. So we appreciated the opportunity to review and comment on ACHDNC briefing paper. And I would like to acknowledge and thank our steering group, which had several of our members, and ex officios. I would also like to thank the staff who worked very hard with me.

Our goals right now are to review our steering group comments on the briefing paper, discuss the recommendations regarding the paper, and come to a consensus on comments that we would like to submit to our sister committee.

And the, um, summary of the comments that we're proposing to submit were distributed this morning and should be on your table. Everybody -- it's just a one-page.

Dark with -- comments on the draft briefing paper, looks like this. It was placed at your spots this morning. If you need a copy let me know.

Okay. In general our steering group felt that the paper does address the issues and concerns that are related to retension and use of dried blood spots. It recognizes that newborn screening programs are administered by states and yet still calls for development of national guidance. The paper at this point does not put forward any models or policy options to facilitate adoption of state policies.

We also felt that the paper may in some ways not give enough attention to state costs of supporting the ongoing oversight involved in potential secondary uses of dried blood spots. Dry dry -- it does not necessarily address the recent concerns about deinstruction by some states.

Another point was that while the paper does appear to call for establishment of a voluntary national repository, it really did not rise to the level of one of their seven final recommendations. And we thought there was insufficient discussion of the need for and value of such a repository as well how it would be developed and the oversight for that. These are some of the elements we would like want to know in more completely discussing it. Are we talking about data or specimens or both? Who would provide the stewardship? Who would have access to the repository? How would decisions be made about uses of those?

The recommendations of our steering group were that our committee endorsed the draft paper with the following comments: In developing national guidance and model policies of dried blood spots for research purposes that such organizations organizations be included in the dialogue as stakeholders as they maybe helpful in helping states for late their policies. And also to consider providing some examples of actual model legislation that states could use.

Also to facilitate state adoption of the retension and use of dried blood spots, to add a recommendation to funding be provided to support states as they implement. And also to consider elaborating on the call for that national repository and clarify if it's intended to be a formal recommendation coming out of the committee. And also, um, we wondered about in light of the movement towards development of the national guidance, should there be a recommendation calling on the secretary to at this point discourage states from making premature changes that might shorten their retension policies, or lead to disposal before the issues are fully discussed.

Okay. So these are some of the questions that we would like to discuss this afternoon. Some of you may have others that we would want to consider. But one of the things is: Does the briefing paper address the issues and concerns? Should the paper give specific guidance on how research allocation decisions should be made? Should the paper address the availability of costs incurred by states? We had mentioned what some of the costs potentially could be. Should SACGHS encourage ACHDNC to express stronger support for the value of research uses of dried blood spots? Should we encourage SACGHS to go further in this paper by actually providing models or policy options for retension and research uses that states could adopt? The paper calls for states to -- states should have policies, it doesn't say what the policies should actually be. And also in the interest of promoting greater harmony across states, should we consider recommending that states defer developing their policies until national guidance has been issued? We felt that in some ways the recommendations might be out of sequence because they're calling for states to develop policies, -- and then talking about a national policy. You could have all of the state policies already in the works and everyone inventing their wheels before the national guidance policy is actually available.

I think that was it for the potential questions that our steering group came up with. We're interested in hearing from other committee members.

Open for discussion.

No comments? What a rare occurrence.

That's right.

I appreciate Janice's work. My general sense is, too, to the extent we can provide stronger guidance like model laws that states could use would be pretty helpful in strengthening this report, to facilitate greater adopings. Any other thoughts on these issues?

Jim --

[ Overlapping Speakers ]

My answers would be yes to the second two. I don't really know -- I don't have a good enough feeling to address this.

[ Speaker/Audio Faint or Unclear ]

Yeah , she was on the last slide, there.

Does anybody want to speak to the issue of if more needs to be said to the area of research?

I want to speak to the first one. I read the report. I was really very impressed with the briefing paper. I didn't identify any issues that would interfere with my wanting to endorse that.

The recommendations --

The draft paper --

Right.

Yeah.

As is? Or with the comments that we have -- that Janice has presented?

Um, I -- I guess I don't feel strongly that any of the comments would necessarily need to be -- it gets to the issue that we talked about previously. Does the process -- we could certainly I suppose make recommendations back. Ultimately this is their paper. They could choose to --

Sure. These are just part of the public comment period that they were kind enough to solicit from us. They would like input from us to the extent that we have constructive suggestions.

[ Speaker/Audio Faint or Unclear ]

-- and the committee, I think, has a variety of other comments that have come on the paper. I think this is certainly not the final thing. I would think it's basically final. I don't think there would be cataclysmic changes. A lot of the things that you have thought about have come up at great length. Is you look at California, they have an great system. It requires a lot of space and material and the ability to access it. For example, when an investigator would like -- most states will make anonymous samples available for tests. If you do that, if you say you want 100,000 samples that's expensive for the state to do. Texas got into serious problems with this. Someone wanted the samples. They said yes, but we cannot take money from you. The person wanting the samplesnded up providing support to the laboratory in forms of the equipment. It hit the papers that the state was selling spots. They were not selling spots, but it does have a real cost tied to it. For those of you that don't know this, Texas when we were required under their court settlement to destroy the samples it cost them $600,000 to do that. You have to have all sorts of carefully mandated things. All aspects of this has costs built into it.

I have had an opportunity to look at how these samples are used. If you go through a 20-year experience of states that keep detailed records the vast majority have come from a couple areas. One, to develop a new test. If you are bringing a new [ Indiscernible ] enzyme you need to standardize. The other things are from families. The families have requested them over many, many years because they have a child that died. They realized that child might have had an [ Indiscernible ] metabolism. Families go back and request these samples am that's the kinds of requests you get.

I think I would recommend that we keep these stronger recommendations, to keep them for future research. I think these are invaluable tools. I think we can foresee other uses in the future. Keep in mind the cost of keeping those dried blood spots that are useable 20 years after, there has to be information associated with the dried blood spots that has to be provided to the investigators. Sometimes just having the dried blood spots doesn't help you much. There might be more costs associated to make it really useable for other research uses.

Do we need to be more specific with that additional information or content?

That's where the phenotyping dollars come in that we talked about earlier today.

Marc?

I would still come back and recommend that we endorse the draft as is. The sense I have from listening to the discussion is there's been a lot of debate about where to fall on this retension issue. It's clearly a major issue. It's clear that we, you know, could be more prescriptive about it. But I think there's also a balance of where we can reasonably be right now. The group has considered that and is comfortable with the current draft. From my perspective I am comfortable with the language as is.

Just send a simple statement, great report, we're supportive.

That's my feeling.

Most of these are gilding the lily.

I'm a little bit more sensitive to the process issues. Are we adding to the discussion that is taking place? If we feel comfortable that the process has struggled with these issues and come down this is where we need to be for right now, recognizing there's more work to do, I am comfortable with that. I trust the people involved in the process. Again, I'm just speaking for me.

I think what I heard from Rod is other public commenters have had similar kinds of comments as assembled. It would be useful if we would be reinforcing some of those, that would be useful to you. Is that fair, Rod?

I do not know the nature of all of the comments. It would not strike me of being an issue to say this group thinks this is a fine document and endorses it. I think you ought to consider these things that we've discussioned. I think that would be well received.

I think back on the reports that we've done. The comments are helpful, right. If there are issues that we think are worth saying this is a great report, we amplefully this or that, they can take it or leave it.

I agree with Jim. They can take or leave the comments that they get from anybody. To the extent that we want to offer them, they're available.

So if we're going to parse this document, the last [ Indiscernible ] on the first page.It would be more efficient to -- I don't, I think if there are policy issues that are deficient at the state level I don't see why we should ask them to wait for whatever this process is going to develop. Assuming that the process will develop some guidance. I guess I don't -- I'm not supportive of that last paragraph on the first page.

A couple of things. One is there's enough information, go forth. The other does deal with the harmonization issue.Had there been real common guidance we could have some model legislation that they could tweak. Do we think there's an advantage to having that kind of a model out there so that we would begin to move towards a more consist yept system?

I don't disagree with the statement that it would be good to have a model. The issue relates to the recommendation, states should hold off on doing anything relating to policy development until we come up with this. Earlier on we say that we recognize that the state's right to do whatever they want. But there might be states that are already moving in that direction. In some ways I'm trying to not put them in an uncomfortable decision of waiting for something that might be a while in coming.

Indicate the model legislation --

The intent is to develop guidance, again, they're going to do what they're going to do.

Maybe they want -- I can see states saying I don't want to do anything. This would give them cover.

I could just add, I agree with you, Marc, on the one hand. You could have states that would go ahead and engage in the policy development process, get it all completed and then in a year or two -- if national guidelines came down they might be reluctant to revisit the process they just completed to change their policies or legislation to be more harmonious. That was the -- the concern there.

Again, I think the notification piece in the prior paragraph, I don't need to wrestle to the death on this. The prior paragraph states the issue -- the convening function, which would happen quite rapidly. You would have national and state stakeholders. The states would have the opportunity to be fully cognisant and use that information. It seems to me a little bit intrue sieve.

I have to agree with Marc. States just go crazy when you told them to hold off. It's just viewed as a real affront to state's rights. Letting states do things sometimes has its advantages. I would agree that removing that paragraph.

David?

I will suggest an intermediate position. If you look at the phrasing of that, I propose we recommend that the other committee, I can't pronounce that word --

[ Speaker/Audio Faint or Unclear ]

Recommend development of national guidance on retension. And ask states to develop the policies with reference to national guidelines. Take out this first "in light of" business.It doesn't speak to telling them not to do it, it just says what somebody should do.

I see Marc is sort of neutral.

Other thoughts on what we need to do with this document? Anyone want to move that we approve it with the change as David suggested?

I just -- I think we could be a little more declarative at the begin. We appreciate the effort and endorse the report with the following suggestions for revisions. We appreciate the opportunity to comment. We could be stronger in terms of an endorsement.

Put it up in the first sentence.

In the first sentence, yeah.

Looking at the last paragraph, I guess what we're -- the recommendation that we would be sending back to the other committee is to perhaps further consider whether a voluntary national repository should be a recommendation that would go to the secretary. It seems to me that may be -- that even that recommendation for consideration goes maybe a bit far. Again, I'm just thinking about the rights issues and how that would work. It seems just, you know, I liked it in the context of the overall discussion in the body, but not as a recommendation. Clearly the other things are much more timely and important to deal with than trying to sort out how a voluntary national repository would work. That seems like work down the road.

Rod? Do you want to talk a little bit about why -- why the committee did not make any recommendation like that?

I think that the committee is extremely sensitive to the states' individual rights. We worked with [ Indiscernible ] and so forth. Those groups are members of our working group. We will tend to not be terribly prescriptive. We're not likely to say "California, we think you should do that."

I just wanted to clarify. What we were trying to do is we felt there wasn't enough description in the body for us to know what was envisioned by that national repository. We weren't trying to say one way or the other if we endorsed it. Just if they wanted to clarify the thoughts behind it.

So then, if that's really the intent, I would suggest we remove the sentence that says to consider the idea of a national repository, our recommendation is to provide more clarity on this issue. Is that a fair statement? Paul?

Responding to my comment earlier about being bland, neutral and diplomatic. I'm concerned that we're being too bland and diplomatic here and not really taking advantage of our ability to be a little more proactive than their committee can be. And trying to emphasize the importance of the briefing paper in the real world right now. Try to elevate the issue that -- not in these words -- that states can create great mischief by not recognizing that work is being done across the country on these issues. And this paper should be viewed as a very important resource for guiding. Deliberation of these issues within each state. To really try to elevate the importance of this briefing paper, given what has been going on, and the lack of informed dialogue in some of the state conversations. Then go into the specifics that we've talked about. The preface here should call attention to the fact that this is a very active conversation and that this briefing paper begins a much more informed conversation than what has been going on at the national or state level previously.

Let me see if I can put that together. Seems to me that some of the other things that we're recommending. Clearer policy recommendations and model laws would help to strengthen the report and give them even more guidance and make it more actionable. We can tie these pieces together in a way that gives this paper more clout.

That would be my suggestion. I think we have an opportunity here as the committee looking at a broader range of issues to elevate this report and not merely endorse it, but endorse it with the strong emphasis that this needs to be taken very seriously, and that this is -- should be viewed as a caution for some of the states. States are not only -- this is from my perspective, what I hear -- are looking for cover. And anything that would elevate the briefing paper, I think we should do that. I think we ought to be strong about how we endorse this and envat its importance if everybody agrees.

I see some nods. Is that --

I agree with Paul. I don't think we should bend over backwards -- I think it's being helpful to say what we think.

I'm sorry, I'm dealing with a bit of a nonsecond witter moment here.-- that we should include that along with some other things?

No, I was completely ignoring your point --

Thank you.

You and my wife.

I guess I would still like to make sure that we have the sense of the whole committee about the very specific comments.

I haven't been taking great notes here. The introduction needs to be strengthened, in terms of an endorsement. I'm hearing that it be strengthened, if you will, as Paul said. That's all in this introduction paragraph. The other suggestion is in the last paragraph on the first page to remove this thing about states should hold off, because -- we sort of delete that. Last, these are a bunch of considerations we think you flush out, but we're not really making a recommendation one way or the other.

Could you say -- I'm just throwing this out. Could you say something to the effect that the ultimate document will be a great resource to states and could help them craft their policies, right. We do want to point out, it seems wasteful to have all of these states going at this will there will be guidance with a well-thought-out plan, you know.

I think what you just said, Jim -- well. Sarah is asking me how we will send this. To the secretary, or directly to Rod. I'm not sure about in a.

[ Speaker/Audio Faint or Unclear ]

I thought that the point of this was to participate in the public comment process.

You know, um, I think that we've done this before, I think we're an advisory committee to our secretary. Our sister advisory committee has asked for input, I would rather do it as a letter from Steve to Dr. Howl, or with regard to what Paul was saying, is that -- writing from us to the secretary with a cc to the chair of that committee. Might that elevate, strengthen, and help them --

Yes. Before we conclude this discussion I wanted to go back and make sure that we are all okay with the statement that we have in the paragraph at the top of page 2, about due to the unique value of these specimens for future research -- are people still in agreement with that? Or do we need to rephrase that?

[ Speaker/Audio Faint or Unclear ]

Be cognisant of forth coming recommendations --

I think it's another chance to be something stronger. I think being too bland here is not the right way to go, it's irretrievable, I would push for being strong.

All right. Let me try again. I think we've had a number of comments and we'll send this forward to Rod. The process from here -- ask for approval from this group. We will incorporate what we think we've heard and send it out to you for fast turn around to make sure we're capturing the nuances before we transmit it out.

Anything else before I ask for a vote? No? All right. All in favor of the recommendations as amended? Signify by raising your hand. Any opposed? Abstentions? Did you count fast enough? Okay.

In honor of this Dr. Evan's has a comment.

Marc wants me to play the vuvuzela. Here, we'll try it. Steve is, like, "what the hell is going on"?

I'm going to have to work on it.

All right.

There.

Here, it wasn't turned up.

One more time. [ buzzing ]

Are you happy now?

It's a suitable finale. Let me recap a little bit. I think we've had a productive meeting. Kathy, can you move this forward? All right. Let's talk about what has happened. Over the course of the last two days we've heard that some of the things that we've been dealing with over the last two years are beginning to make a difference. To me, that's what we're here for. We heard about the registry for genetic tests. That came out of our oversight report. We heard from FDA that they've taken action on a number of things, regarding direct to consumer testing and oversight of laboratory-developed tests.That's terrific. We also heard from clee ac that they've considered some of our recommendations. Maybe what we do around here goes further than the basement of the hotel, that's good. So, um, we did hear a number of updates from NIH, from CLI arcAC. We heard a lot about Whole Genome Sequence, out of that came a task force. The names are up there. If you are omitted or committed in error, let us know. We will look to move that forward in October. The committee will identify some areas we can begin to focus on. We had a good discussion this morning on genomic data sharing, including forcing a -- forming a task force. Thank you for leading us through that. That includes Mike, Dave, Rochelle, Barbara. The focus will be on the group-related issues and will explore other gaps in the policy.

The steering group, in addition to the people listed up there, we will co-opt the people from the steering group.That will be a large group. We look forward to hearing back from them in October.

Is there another thought? The comparative effective research working group was formed under Marc.

That's just a letter --

This is the letter. Yes.

I'm trying to read as I go along. Completing the letter regarding the use of ARRA funds and other things that we think need to move forward. We heard about carrier screening and the committee agreed to work with the advisory committee on diseases of heritable disease of newborns and children. They will work closely together as that gets more detailed and focused and we'll stay abreast of what goes on there.

A couple of other things that happened over the course of the meeting, some of you were not aware of, I have been learning as we go along. We submitted a perspective article to the "new England journal." We received notice that they are asking for revision and submission, we're looking forward to getting that back.Will will be increased visible for our work and the importance. Rod, you provided us information that we needed on this. We were trying to get clarity here around lunch. The AMA house of delegates passed resolution this week on gene patents. Those bullet points are from that, the resolution, that they opposed patent on human genes and their naturally occurring mutations.

Actually, no, they specifically echo our recommendations. Support legislation -- those that use --

You have the written -- as this emerging clearly it's in sync with our report from earlier this year. A lot has been done, a lot has been accomplished. We're making progress. We will be reconvening here in October in Washington somewhere. We will be hearing from the genetics education and training group. We should have the results of our public comments, and an updated set of recommendations for us to consider.

As we talked about, things in GINA are just now unfolding, hopefully we will be able to get our agency colleagues together to give us more detail on that. And Sarah is suggesting we will have some information on the rules and regs and what difference it makes in terms of the implementation on various individuals and groups.

Productive meeting. Thanks to everyone. It's always an enormous amount of work on many people's parts to pull this together and get us to a point of having the discussions around the table. Many thanks to our staff and all of you that have worked so hard on all of this. Safe travels and stay out of blizzards. [ Laughter ]

[ Event Concluded ]