By Gregory Twachtman & Mary Houghton, The goals of comparative effectiveness research and personalized medicine might appear at odds or at least as leading to divergent paths,
with one focusing on the best treatment for a population and the other on the best treatment for an individual.
But FDA’s Janet Woodcock believes the two are not only complementary, they may actually best succeed if developed together.
“Personalized medicine and comparative effectiveness research are actually synergistic facets of improving health care quality,” Woodcock, director of the agency’s Center for Drug Evaluation and Research, said Oct. 28 at a conference examining the two research areas, hosted by the National Pharmaceutical Council and the Personalized Medicine Coalition.
“They’re two sides of the same coin,” she continued. “They are not antagonistic. They are synergistic. One will actually, in my mind, not succeed without the other.”
Woodcock noted that comparative effectiveness is already starting to play a role in drug development, but when combined with personalized medicine, it can truly provide the useful information to help improve the quality of care delivered.
Woodcock again highlighted the example of the platelet inhibitor prasugrel (Lilly and Daiichi Sankyo’s Effient ), and Sanofi-Aventis/Bristol-Myers Squibb’s Plavix (clopidogrel).
Many industry observers are following those drugs as a potential case-study of how marketing of major products might tap into personalized medicine approaches. And Woodcock herself drew attention early on to these drugs, and how data on prasugrel’s efficacy in individuals who have a genetic marker indicating non-response to Plavix might suggest the potential to use genetic screening to select patients for prasugrel treatment (1 ‘The Pink Sheet’ DAILY, May 6, 2009).
Woodcock suggested that Effient’s head-to-head trial versus Plavix could have been even better designed to elicit more targeted information for different patient populations.
She noted that some individuals lack the enzyme needed to metabolize clopidogrel into its active ingredient, meaning the drug has no effect in them. Effient addresses this population, but it has other safety risks associated with its usage, the primary one being bleeding.
“What we don’t know is if we took out the clopidogrel people who actually didn’t have the active drug, how would these two drugs have performed against one another?” Woodcock asked. “A better way to do this, obviously, would be not to expose people to clopidogrel if they don’t have a chance of benefit. A better comparative effectiveness trial would be to compare people genotyped, who have a benefit of clopidogrel versus prasugrel.”
“One of the reasons prasugrel was developed is we don’t have the capacity to rapidly do genotyping in the setting of acute coronary problems,” Woodcock noted.
Improved Infrastructure Needed
In order to get the most out of comparative effectiveness and personalized medicine, Woodcock said major improvements are needed in the research infrastructure, including more involvement from community organizations that can tap into larger population groups.
“I am worried that both of these areas of research need a research infrastructure that doesn’t exist in the United States right now,” she said. “We need to translate and investigate personalized medicine interventions and we need to perform comparative effectiveness evaluations on a pretty large scale.”
Woodcock pointed to the recent list of comparative effectiveness research priorities identified by the Institute of Medicine (2 ‘The Pink Sheet.’ July 6, 2009), saying the number of questions to be studied exceeds available research resources. “We don’t have a good machine to put all these questions in and rapidly evaluate the response.”
“One of the principles of comparative effectiveness is that it is generalizable to health care,” she said. “To me, that means it needs to be done, at least in part, in the community where health care is delivered, not in academic medical centers strictly. We don’t have the kind of infrastructure that includes the community.”
Woodcock observed that patients would prefer to be treated by their own doctors rather than going off somewhere to be part of a study. Additionally, for many diseases, “such as psychiatric diseases, there aren’t many patients in academic medical centers. They are treated in the community, maybe not even by physicians and they want to stay within the community.”
She continued: “I believe the United States needs to build research infrastructure to support both academic and community docs and other health care professionals in performing this kind of research. We are not going to get from point A to where we want to be without this kind of investment.”
[Editor’s note: to further explore Woodcock’s views on CER and personalized medicine, see 3 “The Rush to Comparative Effectiveness: FDA’s Woodcock Hopes It Won’t Overshadow Personalized Medicine,” The RPM Report, February 2009.]
At an Oct. 26 event hosted by American Association for the Advancement of Science and the Food and Drug Law Institute, FDA Commissioner Margaret Hamburg noted that the regulatory environment has not caught up with the advances in genomics to enable the advancement of personalized medicine, but she pledged the agency would “establish a clear and illuminated pathway for product approval.” (4 ‘The Pink Sheet’ DAILY, Oct. 26, 2009).
Other Leaders See Synergies
Also speaking at the conference was Agency for Healthcare Research and Quality Director Carolyn Clancy, who said that employing CER and personalized medicine together is “pivotal to individualized care and innovation.”
But in order to make sure the two areas of research are conducted in a complementary way, “we are going to need a whole lot of new kinds of collaborations,” she said. She could have a direct opportunity to implement that vision, as some of the health reform proposals to expand CER call for it to be run out of a new center within her agency (5 ‘The Pink Sheet’ DAILY, Oct. 29, 2009).
National Institutes of Health Director Francis Collins, speaking at the American Association for the Advancement of Science and the Food and Drug Law Institute event, echoed the views of his federal officials.
“If you’re going to be conducting comparative effectiveness, you need to be sure you are doing appropriate genotyping to look for subsets of individuals [whose] response to a therapy within the overall average seems slightly inferior, but for that subset might have been considerably superior.”
Collins added that he thinks “we need to keep our eyes on the goal here in comparative effectiveness research and not lose all that we have gained in terms of progress and understanding of how individuals differ and how that can be factored into better diagnostics and preventive strategies.
