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As PCORI Looks to Finalize Priorities, Commitment to Personalized Rx Remains Unclear

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Originally published May 14.

As the Patient-Centered Outcomes Research Institute looks to finalize its national research priorities later this month, personalized medicine proponents are concerned that the institute's focus on "patient-centeredness" does not sufficiently account for molecularly guided individualized therapy.

Amy Miller, VP for public policy for the non-profit advocacy organization Personalized Medicine Coalition, noted that PCORI seems to be conflating personalized medicine with patient-centeredness, a term that has taken center stage in all of the institute's research aims.

"Personalized medicine is part of patient-centeredness, but it's not patient-centeredness exactly," Miller told PGx Reporter. "We [at PMC] see personalized medicine as scientific methodology. It's about figuring out what therapies are going to work for whom and why."

During an April 25 meeting of its board of governors, PCORI voted to make certain changes to its draft research agenda based on public input, but did not make any changes to its national priorities for research, noting that "public comments did not identify significant gaps in the five proposed priorities."

However, during the public comment period, the PMC urged the institute to ensure that its research will be methodologically sound from a personalized medicine perspective —a request that has gone unanswered in the amended version of the document.

PCORI, an organization formed by the 2010 Patient Protection and Affordable Care Act, issued its draft research priorities and agenda in January. When finalized at its next board of governors meeting on May 21, the document will serve as a roadmap for the institute's efforts to conduct and fund comparative effectiveness research of medical products.

The national priorities section of the draft document highlights five primary research focus areas: assessing prevention, diagnosis, and treatment options that work best in specific patient populations; improving healthcare services, particularly for patients with chronic conditions; improving research communication and dissemination so people can make more informed healthcare choices; ensuring that research addresses healthcare disparities; and promoting efficient and safe patient-centered outcomes research.

The research agenda section of the document discusses specific research areas within each national priority.

In a presentation at the April meeting, PCORI said it had received more than 450 public comment submissions, most of which came from physicians, researchers, patient advocates and professional associations. The comments were reviewed and analyzed by PCORI staff and aggregated into key themes.

One of the key themes that emerged from public comments was that stakeholders wanted PCORI's research to have a "greater focus on the patient, with particular attention to methods of engagement." To this, PCORI responded that patient engagement is central to its mission, and noted that its national priorities and research agenda "reflect the patient-centered focus of PCORI." In the amended version, "language has been added to the agenda to specifically reflect the need for study of self care and to more clearly define personalized medicine."

However, since the draft research priorities and agenda were first released, proponents of molecularly guided individualized therapy have expressed concern about the way PCORI is defining "personalized medicine." In particular, stakeholders have worried that the bulk of PCORI's work will be focused on conducting CER on drugs and tests for the general population, and will fail to incorporate molecular data on patient subpopulations in study designs.

The language approved at the April 25 meeting characterizes "personalized medicine" as healthcare that is guided by patient decisions, preferences, and choice:

"Clinical effectiveness compares the effectiveness and safety of preventive, diagnostic, and treatment options to create a foundation of information for personalized decision-making. Personalized decisions acknowledge the centrality of patient preference and the need to provide information that is appropriate for each individual. For example, personalized information about what a patient might expect might take advantage of information about the patient’s profile as defined by a wide range of characteristics that might affect their outcomes, including but not limited to biology, demography, culture, socioeconomic status, co-morbidity, and geography. This research places emphasis on the practical utility of the comparisons, the examination of all outcomes that may be important to patients and the possible differences in outcomes across patient subgroups."

This description, however, bears little resemblance to the definition of the discipline put forth by the President’s Council of Advisors for Science and Technology. Personalized medicine, according to PCAST, refers "to the tailoring of medical treatment to the individual characteristics of each patient."

In its definition, PCAST clarifies that personalized medicine "does not literally mean the creation of drugs or medical devices that are unique to a patient, but rather the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment."

PCORI's working definition of "patient-centered outcomes research" describes it as "research [that] helps people make informed healthcare decisions and allows their voice to be heard in assessing the value of healthcare options."

Counter to PCORI's claims that there weren't significant objections to its draft national priorities, PMC's Miller asserted that "many, many stakeholders told them that [the priorities] were so vaguely drafted that they couldn't respond.

"That is very different from saying, 'It's fine. Move forward,'" Miller noted. "I think the community was asking for a redraft."

During the public comment period, the PMC issued a statement urging the institute to make the language describing its research priorities more specific. In particular, PMC would like PCORI to state more explicitly that it will ensure that the design of its CER investigations will be methodologically sound from a personalized medicine perspective.

"If they're going to do CER, we want them to do it right," Miller said. "If they're going to fund a head-to-head drug comparison, for example, it must take into account … what we know about the role of genetics, drug metabolism, and sensitivity. It must take into account any pharmacogenomic information in the drug labels of the drugs that are going to be compared.

PMC feels that PCORI should detail where CER should factor in pharmacogenomics information so that applicants for research grants will know to present study designs that consider these issues.

PCORI plans to spend $122 million for research activities in 2012, and personalized medicine supporters are still hopeful that some of this money will fund CER on molecularly targeted personalized medicine products. The institute's statutory purpose states that the research the institute supports must consider how disease can be prevented, diagnosed, and treated in patient subpopulations, which could include groups defined by molecular subtypes.

Other observers of PCORI's process have suggested that the institute is keeping its research agenda broad on purpose in order to cast a wide net when soliciting CER projects. They remain hopeful that the limited discussion of personalized medicine's role in CER in PCORI's priorities documents is not necessarily a sign that the institute doesn't think it's important.

"I think we will know a lot more about what they are thinking about personalized medicine when PCORI's methodology committee report comes out later this month," said Sean Tunis, director of the Center for Medical Technology Policy, a non-profit that forms public-private collaborations to design and implement CER for guiding informed healthcare decisions and policy.

"Right now it is not readily apparent how they are thinking about these issues," Tunis, a CER expert, told PGx Reporter. "They have certainly taken the notion of patient-centered outcomes as a central focus."

In Tunis's view, however, "there is no direct indication that they are confused about [the term patient centered] versus personalized medicine."

PCORI Executive Director Joe Selby addressed PMC's public policy committee on April 25 and indicated that the institute hopes to conduct CER that will benefit small subpopulations or rare disease research, and does not intend to fund only research addressing common conditions such as heart disease, depression, or diabetes.

At the same meeting, he said that PCORI would work with PMC to ensure the alliance between personalized medicine and CER.

In public comments to the draft research agenda, PMC has also requested that PCORI form an expert advisory panel to align its CER efforts with personalized medicine objectives; and hire experts with the scientific knowledge to evaluate a variety of research proposals.