By Turna Ray
In a recent report, the Federal Coordinating Council for Comparative Effectiveness Research broadly acknowledged the importance of studying patient subgroups to help doctors and patients make informed healthcare decisions — a recognition that could help integrate personalized medicine into US healthcare reform, several healthcare officials and industry observers believe.
In the report, released June 30, the council cites comparative effectiveness research into treatments for certain populations and subgroups as a funding priority for HHS Secretary Kathleen Sebelius. The council identified "priority" populations and subgroups as demographic groups that are under-represented in medical research, including ethnic minorities, children, the elderly, and the disabled, but did not specifically cite any genetic subpopulations for study.
"Comparative effectiveness should complement the trend in medicine to develop personalized medicine — the ability to customize a drug and dose based on individual patient and disease characteristics," the council states in the report. "One of the advantages of large comparative effectiveness studies is the power to investigate effects at the subgroup level that often cannot be determined in a randomized trial. This power needs to be harnessed so personalized medicine and comparative effectiveness complement each other."
Although the commission's recommendations still seek to advance traditional population-based studies, the report highlights the utility of targeted strategies in determining the safest and most efficacious treatment in a particular group of patients. The report emphasizes that comparative effectiveness research is a "patient-centered" approach to filling evidence gaps on which treatments work best for the majority and for individual patients.
"At the same time that CER is being used to identify which interventions and strategies work best on average, it can also help to identify different responses by different groups of patients," the council points out in the report. "In some cases, different existing therapies may be identified as most effective for specific subgroups. In other cases, CER may help to identify significant subgroups for whom effective therapies do not yet exist. CER may also help steer research efforts toward the development of products and strategies for areas of significant need."
Carolyn Clancy, director of the Agency for Healthcare Research and Quality and a member of the Federal Coordinating Council for Comparative Effectiveness Research, told Pharmacogenomics Reporter this week that the broad scope of the report will be helpful when AHRQ, the National Institutes of Health, and Sebelius sit down in the coming weeks to finalize CER priorities to be funded by HHS.
"The report from the council was intended to be fairly broad," Clancy said. "If the report had been too detailed and granular, it wouldn't have been as helpful in creating the broad framework."
By July 30, the HHS is slated to release a integrated plan for the $1.1 billion received for comparative effectiveness research under the America Recovery and Reinvestment Act of 2009.
At the same time the Federal Coordinating Council released its report on CER, the Institute of Medicine released its 100 top CER priorities, which include some proposals for comparing the effectiveness of using pharmacogenetic strategies and standard methods to guide treatment, promote behavior change, and improve clinical outcomes.
Ahead of the July 30 deadline, the Personalized Medicine Coalition plans to request a meeting with Sebelius to discuss the role of personalized medicine in the Federal Coordination Council and IOM report.
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According to PMC Public Policy Director Amy Miller, while the council's report offers a starting point for discussions, the bulk of the funding priorities identified by the council would still primarily support traditional research methods and its discussion of personalized medicine in the report is confusing at times.
The Report
As part of the ARRA, the US Congress granted $400 million to the NIH, $300 million to AHRQ, and $400 million to the Office of the HHS Secretary to create the Federal Coordinating Council for Comparative Effectiveness Research.
The council in its report proposed CER priorities for the HHS Secretary to consider when allocating the $400 million from ARRA. According to the council, the Secretary's primary investment should be in creating the data infrastructure for CER. The council identified as a secondary funding priority, investments to disseminate and translate CER and research into priority populations.
"The council struggled a lot with getting a very clear definition of what are the boundaries of comparative effectiveness research and also creating a strategic framework. How is it that these investments from the secretary could actually complement the ongoing work now done and to be done by AHRQ, NIH, and so forth?" Clancy said.
"The council gave quite a bit of weight to investments in infrastructure, particularly data. After all, the right kind of data would [not only] help us do the research more rapidly but could conceivably provide the best platform for getting the findings to clinicians and patients in a very rapid fashion," she added.
"With respect to personalized medicine, it would actually help us identify which patients benefited from breakthrough treatments and which patients didn't. That's very important scientific information, which in today's environment is generally signal that's lost."
According to Clancy, nothing has yet been decided about which agency or group will be responsible for conducting comparative effectiveness reviews.
The Patient-Centered Outcomes Research Act of 2009, sponsored by Sens. Max Baucus (D – Mont.) and Kent Conrad (D – ND), would create an independent institute for comparative effectiveness research and emphasizes on the role of personalized medicine more than the previous version of the bill.
While the AHRQ has been conducting comparative effectiveness reviews for several years under its Effective Health Care program, and the stimulus bill has provided funds to expand this program, the agency has not been using pharmacogenomic strategies specifically.
According to Clancy, no matter which agency is given charge of conducting CER, AHRQ is sure to play an integral role and will use pharmacogenomics strategies to compare the effectiveness and safety of treatments in specific populations.
Pharmacogenomics strategies "will definitely be a part of our work in the future," Clancy said. She noted that the reviews of genomic technologies by the Centers for Disease Control and Prevention's Evaluation of Genomic Applications in Practice and Prevention program has informed AHRQ's work in conducting CER.
Problem Areas
While the Federal Coordinating Council's report formally introduces personalized treatments into healthcare policy reform discussions, there are areas in the report that are unclear or contradictory about the role of personalized medicine in CER.
"The quality of patient care was highlighted throughout the report, and personalized medicine was recognized as important to the future of comparative effectiveness research," PMC's Miller told Pharmacogenomics Reporter this week. "However, both quality and personalized medicine wasn't fully integrated in the report.
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"They are still talking about research as usual, in terms of population-based research, and it does seem contradictory at times," she said, recognizing that the council had a short timeline to write the report.
For instance, although the council's report mentions the need to look beyond randomized-controlled studies to advance personalized medicine, most of the priority areas identified for funding correspond to traditional clinical trials to determine the "interventions and strategies [that] work best on average" populations.
Another area of concern for the PMC is that the report seems to define priority and subpopulations in terms of traditional demographic categories, rather than as genetic subpopulations.
"I'm a little confused as to why they are confounding personalized medicine [based on genes] with traditional demographic variables," Miller pointed out. "Let's not forget, [AstraZeneca's non-small cell lung cancer drug] Iressa works in Asian women, not because they are Asian but because they have a particular biomarker."
Using pharmacogenomics to guide treatment for subpopulations based on genetic differences is "where we see better value in healthcare, no matter what demographic subgroup they find themselves in," Miller added.
In its 2007 report on pharmacogenomics, the HHS Secretary's Advisory Committee on Genetics, Health, and Society cautioned against using ethnic, racial, other demographic information as a "proxy for more precise selection criteria" using genetics [see PGx Reporter 04-04-2007].
Nevertheless, some consider Federal Coordinating Council's report a step in the right direction for pharmacogenomics, despite this lack of clarity.
"The Federal Coordinating Council did the best that it could. In any such group, there are competing demands for attention," Muin Khoury, director of the Office of Public Health Genomics at the Centers for Disease Control and Prevention, told Pharmacogenomics Reporter this week. "There is enough there from both [the council and IOM] reports to hang our hats on from a genomic and personalized medicine perspective.
"Obviously, because I work in this area, I'd like to see more of these kinds of topics," Khoury added.
In meeting with Sebelius, PMC hopes to discuss how the ongoing focus on personalized medicine at HHS can be harnessed for CER.
"The PMC wants to work with this administration to get CER right," Miller said. "Done right, CER can do more to promote personalized medicine than any other policy recommendation under consideration right now."