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Q&A: CDC's Khoury Discusses GAPPNet's Strategy to Drive Adoption of Personalized Medicine

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By Turna Ray

Khoury.jpgGAPPNet, or the Genomic Applications in Practice and Prevention Network, is a collaborative effort recently launched by the Centers for Disease Control and Prevention and the National Cancer Institute to drive the adoption of validated and clinically useful genomic technologies.

The effort, led by CDC's Office of Public Health Genomics and NCI's Division of Cancer Control and Population Sciences, aims to convene partners from multiple sectors to translate advances in genomic research into healthcare practice.

The four key activities of GAPPNet, as outlined in a Genetics in Medicine article earlier this year, include: convening individuals and groups conducting genomics translation research, programs, and policy activities; sponsoring new translational research; synthesizing and evaluating available research findings, and developing and disseminating "validated, useful genomic knowledge and applications for use in medicine and public health."

According to Muin Khoury, director of the Office of Public Health Genomics at CDC and one of the leaders of the GAPPNet project, millions of private and public healthcare dollars are spent on genomic research in the US, but there is little money dedicated to actually sifting through the accumulating data to figure out what can and cannot be used in clinical practice. GAPPNet is an attempt to close to this translational gap by attempting to bring consensus among key players in healthcare — payors, researchers, industry representatives, health regulators, and policy experts — on what is known, unknown, acceptable and unacceptable, in the practice of genomic medicine. .

One of the main features of GAPPNet is to build an online information portal, where consumers and healthcare providers can find "useful" information about various genomic technologies and interventions. This online portal could eventually be integrated into a mandatory registry for genetic tests, an idea that is being considered by various groups in and outside of government [see PGx Reporter 07-08-2009].

In an interview with Pharmacogenomics Reporter earlier this month, Khoury detailed GAPPNet's plans to close the hole in translational research and discussed how "the stars are aligning" in healthcare reform to further drive the integration of genomics and personalized medicine into clinical practice.

Below is an edited transcript of the interview.

Why did you decide to form this collaboration at this time? Is this effort distinct from EGAPP [Evaluation of Genomic Applications in Practice and Prevention, an independent initiative that was established by the CDC]?

EGAPP is really a process we developed a few years ago to evaluate the evidence and come out with evidence-based recommendations. What has happened over the last few years is that we've realized it's relatively easy to do this process. It's much more important, however, to come up with processes that plug in the gaps in our knowledge, as well as implementing what is ready. So, we need a quicker process not just to do gene discoveries, which is what the whole world is doing now, but to translate these discoveries into actions.

So, EGAPP has been really helpful in identifying what needs to be done. Another thing that has happened is that there are institutes at the NIH and CDC that have begun funding what we call translational research efforts. So, we thought we could put our heads together and try to coordinate these activities. There aren't enough people out in the field who are doing genomics translation. There are far more who are doing discovery work in genomics.

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GAPPNet represents the initial convening of this energy. We're going to do lots of planning and strategic discussion leading up to the initial meeting in Michigan, at the end of October, where hopefully some of the plans of action [for GAPPNet] will materialize.

In the paper, you use a hypothetical genetic test that uses "a panel of genetic markers to aid selection of drug choice and dosing for the management of type 2 diabetes," to illustrate how a collaborative effort such as GAPPNet would disseminate useful information about and drive adoption of genomic medicine. Can you use a real-world example, such as a genetic test to dose the anticoagulant warfarin, to discuss how GAPPNet would operate?

Warfarin is a good example, but there are many, many other examples like warfarin. So, what GAPPNet will do is scan the horizon and shine the spotlight on topics like warfarin. We want to find the low-hanging fruit at first, [and identify] 50 to 100 applications. Then, we will figure out what the sum total of the knowledge is on a particular topic. Groups like EGAPP can do their evidence recommendations and if there are gaps in the knowledge then maybe you can empower and fund some of the research that is needed.

For warfarin, the National Heart, Lung, and Blood Institute is already doing a clinical trial to plug the ultimate gap in clinical utility. It's a good example, and it predates GAPPNet. [With groups like] NHLBI, who are part of this collaboration also, we're going to try to find projects like warfarin to spotlight.

While this work is being done, consumers really want and demand information. In the absence of information, what can you tell them? There are lots of things going on out there, including test developers selling tests directly to the consumers, even without the research being done to figure out the impact of this information on health.

The combination of GAPPNet's four aims — knowledge synthesis and dissemination; evidence recommendations; translational research; and translational programs — is the total sum of what this effort is about. At the center of this effort is a network of stakeholders, and we have begun convening these stakeholder groups ... Because we don't want to be reinventing the wheel. There are just too many stakeholder groups, such as the Genetic Alliance and the Personalized Medicine Coalition.

GAPPNet is trying to focus the energy of these groups to come up with a list of candidate applications, summarize what we know and what we don't know, put what we know into decision-support tools, [and] empower research. We plan to disseminate all this through the web as part of a GAPPNet knowledgebase that we are currently developing. My thinking is that this would move the process of genomic applications and practice much more quickly than where we are right now.

In building the online network for GAPPNet, will you be coordinating with GeneTests, the voluntary web-based resource currently run by the National Center for Biotechnology Information? Could GAPPNet's web-based network be a preliminary form of the online registry for genetic tests that the HHS Secretary's Advisory Committee for Genetics, Health, and Society recommended?

I happen to represent CDC on SACGHS. When they made this recommendation last year, what they had in mind was a mandatory registry for genetic tests that the US Food and Drug Administration would be hosting. I don't know what shape or form this registry would evolve into, given that we have a new administration and the principals haven't really gotten their act together yet.

What we are likely to move towards, however, is a distributed model where test developers may submit some data to the FDA. If there is a registry that is in the public domain, then it could be a mixture of FDA information, GeneTests information, and the stuff that GAPPNet would be producing.

It's not clear yet how this [registry] will evolve, but I think the GAPPNet knowledgebase that we're developing could become an integral component of the information that would be part of that eventual registry. It's a bit early in the process to see exactly how it will unfold. Of course, there is no funding or resources for any of this. But the idea is to empower consumers and providers with the information they need so the right health decisions can be made.

How will you ensure GAPPNet's recommendations are incorporated by payors and impact coverage decisions?

This is where the rubber meets the road at the end of the day, because you can develop tests, but if no one pays for them, then there is no way for these tests to be integrated into the healthcare delivery system. We already have GAPPNet members from Blue Cross Blue Shield's health-tech assessment group. There are members from Kaiser Permanente and other [payors], as well …

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There is a push and pull going on right now. There are the drivers of [research] that are being [pulled] by technology that is faster and cheaper. But there is also a push from the payor side, who want to see more evidence that these products can do more good than harm in a clinical setting. We have a clash of cultures so to speak … By bringing everyone together [through GAPPNet] it ensures that everyone is on the same page of information.

Frankly, one of my motives behind this is when there is not enough evidence to integrate [genomic medicine] into practice right away, then at least we will be accelerating the research on clinical utility that will allow us to gather this data more quickly. So, if there is something potentially useful then it won't get lost in translation, and [we] won't have to wait another five to ten years before it is implemented. On the other hand, if there are truly atrocious products that are not worthy of being implemented, then the GAPPNet process I think will also uncover them.

So, this is both a process to accelerate translation [of genomic medicine] that is worthwhile, and also a process to highlight the stuff that is not worth moving forward at this point. It's not going to happen overnight, because we have different components of the healthcare system that interact independently from one another. In the long run, though, I'm hoping GAPPNet could become part of the health reform discussion that is going on in the country. Certainly, genomics and personalized medicine are those disruptive technologies that need to be paid attention to from a health reform perspective.

Recently, two reports were released on comparative effectiveness research. We're trying to spend some of those resources in comparing genome-based approaches to care and prevention to non-genome-based approaches. They basically fall under the rubric of comparative effectiveness research. I think three or four of the top CER applications put forth by the [Institute of Medicine's] report were genomics and personalized medicine applications. So, I think all the stars are aligning in a certain direction so that hopefully, we'll get more resources to drive the research and translation [of genomic medicine], and empower consumers and providers at the same time.

Regarding those two reports on CER, one by the Federal Coordinating Council for Comparative Effectiveness Research and the other by IoM, what are your thoughts on how personalized medicine and the issue of subpopulations were addressed?

Depends on how you look at this, whether the glass is half full or half empty. Comparative effectiveness research grew out of years, if not decades, of frustration in the healthcare system with the inability to evaluate outcomes and processes in the real world. That predates genomics and personalized medicine. There are lots of things we do in practice that we don't know whether it is better to do A versus B, B versus C, or C versus D. Things become more expensive without evidence. There are plenty of topics that are worthy of comparative effectiveness research, even before you get to genomics and personalized medicine research.

Obviously, because I work in this area, I'd like to see more of these topics integrated [into healthcare policy]. The IoM, in its report, I thought did a good job integrating those concepts. The Federal Coordinating Council did the best they could. In any such committee there [are] always competing demands for attention. I think there is enough there from both reports for us to hang our hats on from a genomics and personalized medicine perspective.

It is still early days for GAPPNet. How much funding do you have currently for this project and how much money do you think you'll need going forward?

There is currently no dedicated funding for GAPPNet, but there are dedicated pots of money for components of GAPPNet. EGAPP, for example, has been ongoing for four or five years. It's a well-funded effort. We also are funding the translational research programs [at CDC], and we funded five such projects last year. The National Cancer Institute has around 20 projects funded. The Agency for Health Research & Quality is funding a few projects. The National Institute of Diabetes and Digestive and Kidney Diseases will be funding more.

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So, I think components of GAPPNet have begun to be funded. As an enterprise, putting it together, there is no funding per se. But to me, more important than the funding is the convening and coordinating effort. When we are able to do this, then the funding will probably go to the components of GAPPNet that require the funding.

For example, if an application like warfarin [genetic testing] comes up and GAPPNet shines the light on it, then depending on where that application resides, then the funding could go to some NIH institute or some CDC program. In the case of warfarin, it is an NHLBI-funded effort. So, GAPPNet will not dictate or interfere with the funding priorities of different agencies. But, by highlighting what needs to be done, having enough information out there by getting stakeholders together, my hope is that they will take that back to their constituency and the funding will flow.

If you take a 30,000-foot look at genomics in this country, we're spending millions, if not billions, of dollars on genomic discoveries, but we're hardly spending any on those next steps that will put genomics into clinical care and disease prevention. I'd say 90 percent of the [spending] in genomics — both by industry and by the federal government — is going to discovery. As a nation, if we want to make a health impact out of these discoveries, we had better invest more in these next steps.

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