Balancing the Need for Guidance, Communications, and Education to Support Innovation in Personalized Medicine Diagnostics

Recently, I had the opportunity to moderate a thought-provoking panel at the PMC/BIO Solutions Summit. The summit brought together key stakeholders to discuss solutions to barriers in the development of innovative personalized medicine diagnostics. A big question for those developing potentially game-changing technologies in an increasingly cost conscious environment is the need for “Evidentiary Standards and Data Requirements for Payer Coverage.”

Determining the data requirements for coverage is becoming an increasingly frustrating issue for diagnostics manufacturers, which face rising demands for evidence but continued lack of clarity about payer standards for evidence-based decision-making, leading many to ask the question, “Why can’t payers just tell us what their standards are?” Complicating the picture is that diagnostics can come to market via different pathways with different levels of supporting evidence (e.g., companion diagnostics reviewed by FDA for clinical validity with the companion therapeutic and tests developed, validated, and introduced to the market by laboratories).

The panelists – who represented leaders from industry, non-profit advocacy, and government working to create solutions for some of these market access barriers – noted a couple of issues at play. One is that having a payer “pick list” or hard criteria for coverage removes the flexibility that is so often needed in these gray-area coverage decisions. The second is that given the volume of products they are evaluating, most payers don’t have the bandwidth to be experts in the nuances of the trial design for every technology. Third is that across all stakeholders, there is a wide range of knowledge on innovative products and personalized medicine and that basic education for the majority of stakeholders to better understand these products is lacking.

Several lessons and next steps came out of this discussion. First, panelists agreed that there must be more education for all stakeholders so that each stakeholder can actually evaluate novel products appropriately, a key finding echoed throughout the day. Second, the emphasis on outcomes must shift from only clinical outcomes to clinical outcomes and quality of life for patients. Finally, all panelists agreed the ideal situation is open, trusting lines of communication and split of the responsibility according to expertise.

At the end of the day, it may be incumbent on the molecular diagnostic community to shape the paradigm for evidence requirements so that payers can act as enablers, rather than watchdogs.

PMC’s Suggestions to PCORI’s Methodology Committee

The September 14, 2012 (11:59 PM ET) deadline for submitting public comment on the Draft Methodology Report recently published by the Patient-Centered Outcomes Research Institute’s (PCORI) Methodology Committee quickly approaches.

We encourage you all to submit comment as the revised version will be considered for adoption by the PCORI Board of Governors at its November 2012 public meeting in Boston, Mass.

PCORI was designed to do something new and very different – to define how practical, feasible, and useful patient-centered research is to be conducted and the legislation authorizing it directed the methodology committee to address the role of molecular and genetic variation in comparative effectiveness research. With this bold goal outlined, the Personalized Medicine Coalition (PMC) issued its comments to Dr. Joe Selby and Dr. Sherine Gabriel, the Executive Director and Chair of PCORI on September 13, 2012. You can find a copy of that letter here.

Citing our prior work with the Lewin Group, PMC stressed the importance of PCORI moving beyond conventional CER analysis, noting that “comparative effectiveness research (CER) studies to date have rarely accommodated the collection and reporting of genomic, behavioral, environmental, and other individual patient differences.”

To ensure that the tenets of personalized medicine outlined in the authorizing legislation are upheld, PMC reiterated our call for creation of a PCORI Advisory Panel on Personalized Medicine and Innovation and for establishment of standards for updating studies and analyses based on changes in the science or evidence base. We also are making recommendations to address:

1. Heterogeneity of Treatment Effectiveness Standards: Recommend that either a separate section on standards for biomarkers and genetic variables be added to the report or an additional section on heterogeneity of treatment effectiveness be developed to guide the use of biomarker data in patient-centered outcomes research.
2. Diagnostic Test Study Standards: Develop a new paradigm for collecting and analyzing evidence by recommending variations in new clinical trial design, using patient registries to identify respondents, analyzing archived biospecimens, and implementing retrospective analysis of laboratory data.
3. Stakeholder Engagement: Release a table outlining the categories of specific comments received in all future comment submission periods with an explanation of how PCORI addressed the comments as a way to re-emphasize the importance of stakeholder engagement.

PCORI Announces Comment Period; Feedback Critical to Ensure Quality Research

The Patient-Centered Outcomes Research Institute (PCORI) announced this week the public comment period for its landmark draft Methodology Report, which proposes standards for the conduct of patient-centered outcomes research.  While the draft report came out last month, the comment period closes on Friday, September 14, 2012.

The Personalized Medicine Coalition (PMC) has a long history with PCORI starting from when the legislation creating it was being drafted.  We advocated for recognition of personalized medicine in the conduct of comparative effectiveness research, which was incorporated into the legislation.  PMC’s methodology committee is charged with ensuring that the research funded by PCORI examines, among other things, research question responses based on patient molecular subgroup.

As part of the comment period announcement, PCORI stated that feedback received during the comment period would be reviewed for potential incorporation into a revised version of the report. The revised version will be considered for adoption by the PCORI Board of Governors at its November 2012 public meeting in Boston, Mass.  We have previously urged PCORI to be explicit in how the public comments are considered and incorporated. That, and other institutional development, is essential for the proper functioning of the organization.

The current report does not adequately address personalized medicine as an important factor in improving health outcomes through patient-centered outcomes research methodology. PMC will comment on the methodology report, and we urge our member organizations and others to do the same.  Active input from the community is required so that the research will live up to the high expectations that we have for it.

PCORI’s Selby Defines Research Agenda; Tells PMC that Institute Will Solicit Continued Feedback to Ensure CER Supports Personalized Medicine

The Patient-Centered Outcomes Research Institute’s (PCORI) Board of Governors held a conference call meeting Wednesday afternoon.  During the call, they announced the finalization of their research agenda and discussed changes made from the initial draft in response to stakeholder comments.

Given the many criticisms PCORI received for being too broad and vague in its draft, I was surprised by how quickly the research agenda was finalized.  I was gratified that the Institute publicly detailed how stakeholder comments shaped the final agenda, as urged by the Personalized Medicine Coalition (PMC) in our letter to the Institute last month.

Last week, PCORI Executive Director Joe Selby also addressed PMC’s public policy committee, discussed the Institute’s rationale for its agenda – which was short on specifics – and answered questions from PMC members.

During his talk, Selby shared that PCORI’s goal for its research agenda was to be a foundation for future work.  Through funding announcements, the Institute hopes to solicit a broad range of research proposals that will offer many options on approaches to implement and conditions to study.

Selby suggested that PCORI aims to keep the door open to provide funding for comparative effectiveness research (CER) studies that may benefit small subpopulations or rare disease research, and not to fund only research addressing common conditions such as heart disease, depression or diabetes.  However, several PMC members pointed out that ultimately PCORI’s funding decisions will pick winners and losers.

Selby encouraged the submission of proposals to the Institute for studies designed to demonstrate what types of treatments will work for different subgroups of patients (as PMC believes all CER studies should aim to do).  PMC was disappointed that he did not commit the Institute to such an approach as we believe the statute requires, although he noted that research announcements will solicit thematic proposals in addition to disease-specific ones that may address some personalized medicine topics.

PMC Members asked Dr. Selby about the development of PCORI’s infrastructure and questioned whether the Institute has what it needs to align CER with personalized medicine.  As I noted previously, PMC does not believe that the Institute has developed the internal structure necessary to carry out its mission at this time.  Dr. Selby informed the PMC policy committee that PCORI welcomes its feedback about how to assure that funded CER-studies align with personalized medicine through its open meetings, public comments, and advisory committees.

To facilitate personalized medicine, CER must explain not only what works best – but also for whom.  The future of medicine depends on a careful and critical answer to this critical question.  We are not yet sure that PCORI has embraced this idea.  For example, when the Board met to discuss altering the research agenda based on public comment, it tried to more clearly define the need to study personalized medicine. It failed to cite the most common definition of personalized medicine, and instead, discussed mostly demographic characteristics. The PMC will respond to the altered language with the expectation that the definition of personalized medicine will be accepted into the research agenda language. This is the most basic, first step to aligning CER with personalized medicine.

We valued Dr. Selby’s willingness to dialog with the PMC community and look forward to continued engagement with PCORI to ensure that CER can be supportive of quality health information, tailored to patients’ values and individual biology.

Improved PCORI Infrastructure Needed to Deliver on Personalized CER Mandate

As I mentioned previously, the Patient-Centered Outcomes Research Institute (PCORI) issued its draft research priorities earlier this year.  The Personalized Medicine Coalition (PMC) provided comments on the draft that outline how PCORI must address fundamental structural issues to meet Congressional intent.  Specifically, the intent is that the research overseen and conducted by PCORI should support personalized medicine and align comparative effectiveness research with personalized medicine.

In the public comments on the draft research priorities, PMC offered five recommendations, outlining how PCORI can build the infrastructure needed to execute its mission as Congress intended:

 1.  Define a public engagement process: PCORI should outline a transparent process for obtaining input from all stakeholders, including patients, clinical experts and scientists, and detail how stakeholder input will be used. One possibility is to assemble all comments in a document and demonstrate how they informed the final draft.

 2. Establish a personalized medicine expert advisory panel: PCORI has the statutory authority to create expert advisory panels, on any topic, to carry out its mission. To assist PCORI with assuring that its work supports personalized medicine, PMC strongly requests that PCORI develop an expert advisory panel devoted to personalized medicine. As an educational organization dedicated to advancing the field and populated by stakeholders from all sectors of the health care universe, the PMC Clinical Science Committee offers its assistance in identifying potential members for this proposed expert advisory panel.

 3. Improve the science behind comparative effectiveness research (CER): One of PCORI’s Congressionally mandated tasks is to improve the quality of CER by incorporating new information and technological innovations into its studies, reviewing and updating the evidence as necessary and identifying future research that is needed to address information gaps. PMC suggests creating the infrastructure (and the processes) to achieve this goal now as the foundations of the organization are being established.

4. Make the research priorities more specific: The PCORI draft research priorities envisioned by statute were broad, encompassing all aspects of the health care system that relate to high-quality, effective patient care–and specific, calling for a transparent process to identify and prioritize research topics based on explicit criteria and public input. PMC strongly suggests that PCORI’s materials address the second point, assuming that the statute envisions a broad scope of research.

 5. Develop in-house capacity to engage broad scientific and clinical expertise: The mission of PCORI is unique and to carry it out PCORI must call on the capacity of a unique set of individuals to develop calls for research proposals, evaluate them, make awards, follow the progress of the research, and engage the public at all steps in the process. Having this infrastructure “in-house” is a necessary step in the Institute’s development.

We look forward to working with PCORI on these initiatives to strengthen its research agenda and infrastructure.  Personalized CER has great potential to elevate the quality of care in the United States and we are ready to do our part.

PCORI Research Priorities, Will They Support Personalized Medicine?

The Board of Directors of the Patient-Centered Outcomes Research Institute (PCORI) met last week, outlined research priorities, and asked for public feedback. What I found most interesting, and a little disheartening, is that the priorities are drafted in vague language, making it difficult to determine how they may (or may not) support personalized medicine.

I hope that as PCORI moves forward, it will give assurance to the Personalized Medicine Coalition (PMC) and other stakeholders that its research supports personalized medicine, as was the intent of Congress at the time of the Institute’s formation.

Specifically, research conducted in the category, “Comparative Assessment of Options for Prevention, Diagnosis, and Treatment,” will compare treatments, but at what level?  Researchers now know more about individual response to some drugs based on biomarker information. For example, when comparing a red pill to a blue pill, it is imperative that biomarker information be included in those examinations, especially when biomarker information is in the label for the drug. A list of drugs with biomarker information in the label can be found on pages 20-25 of The Case for Personalized Medicine, 3^rd edition. But, without clearly defining the details of PCORI’s research, we really can’t know whether or how the Institute will consider biomarker information in its priorities and research agenda.

The research priority “Improving Healthcare System” can support patient-centered care through innovations, but how? PMC suggests that the research be predictive, preventative, personalized and participatory. By emphasizing the “4Ps,” health system evaluation can support personalized medicine. However, without getting more specific about research priorities, we don’t know whether PCORI will include research that addresses these aspects of care delivery.

To support personalized medicine, the “Communication and Dissemination Research” priority should require researchers to answer one question: “Why does this treatment work and for whom?” (or, more frequently, “How likely is this treatment to work for me, and what are the potential trade-offs?”).  It is not enough, in the PMC’s opinion, to say that one therapy works for most people. PMC suggests that the research should explain why a therapy works (or is more likely to work) and for whom. For example, in research comparing red and blue pills, the communication and dissemination of the research results should stress that although the red pill works for most, the blue pill is particularly effective for people with a specific biomarker.

We are at a pivotal stage in the design of an entity that is tasked with assisting patients, clinicians, purchasers and policymakers in making informed, evidenced-based health decisions. PCORI could foster research that answers the important questions about what interventions work, and for whom. Or, PCORI could be another investigator-driven research institute that allows funded researchers to pursue questions of great scientific import, regardless of their practicality. Such a mission would be redundant with many others, most notably the National Institutes of Health, would be less likely to result in a cohesive national research program, and less likely to ensure personalized medicine is appropriately integrated.

It is my hope that PCORI supports the science that will drive personalized medicine forward, and will engage stakeholders in driving personalized medicine forward, by proposing specific research priorities and research questions to get answers to the questions that science, medicine and, ultimately, patients demand.

PCORI: Together Moving Comparative Effectiveness Research and Personalized Medicine Forward

Today, I had the privilege of addressing the Patient-Centered Outcomes Research Institute (PCORI) Board of Governors on behalf of the Personalized Medicine Coalition (PMC).  As noted in my previous blog on its member selection, the PCORI Board of Governors was established by the Patient Protection and Affordable Care Act and is tasked with assisting patients, clinicians, purchasers, and policymakers in making informed, evidence-based, health decisions. 

As a science-driven organization, PMC supports health decisions made on sound science.  When working with legislative drafters and the community to develop the legislation creating PCORI, we recognized the need to ensure that the research supported by this group must be personalized and continually updated.  The resulting law creating PCORI aligned the principles of personalized medicine with those of comparative effectiveness research.  It underscores the importance of eliminating an “average effects” approach to CER, which obscures subgroup differences and skews treatment decision-making away from individualized care.

To make sure this opportunity is realized, we requested that the Board designate an ad hoc committee on personalized medicine to work with both the Board and the Methodology Committee.  We believe that such an ad hoc committee will help the Board and methodology committee comply with the Congressional intent that the research overseen and conducted by PCORI be personalized when appropriate.  High levels of communication and collaboration have been essential to the advancement of personalized medicine, and the same will hold true for advancing CER that is aligned with personalized medicine.

Achieving alignment between CER and personalized medicine holds substantial opportunities, but we realize it will be challenging. These challenges cut across a range of issues, from study designs, to operating procedures, to research priorities.  An ad hoc committee will provide a venue for bringing a diversity of expertise and perspectives together to focus on this common objective.  Such a group will help in coordinating research across a range of public and private sector activities and ensure that the most relevant evidence gaps and research questions are identified related to personalized medicine, and will help with matching study designs to questions.

The science of personalized medicine is fast moving and sometimes highly specialized. Legislation and regulation takes time to catch up. The personalized medicine community is committed to seeing that PCORI’s research keeps pace with scientific advancement and welcomes the opportunity to achieve this end.

We are at a crossroads of research, regulation and legislation. It is an exciting time!

CER and Personalized Medicine: More Work to Be Done

I just got back from a meeting of the Board of Governors of the Patient-Centered Outcomes Research Institute in New York City. PCORI, as you probably know, is the independent Institute established by the health reform law to conduct comparative clinical effectiveness research. Regarding CER and personalized medicine, I’ll say now what I said late in late 2009: in the midst of the debate over health care reform — it remains to be seen whether CER will align with personalized medicine. CER that aligns with personalized medicine should be  patient-centered, because it will be structured to recognize and respect patient differences. 

We’ve made important progress toward that goal, with CER statute for the first time referencing genetics and individual patient difference.  I am hopeful we’ll  eventually get there, but we’re not there yet. Personalized medicine was, as far as I saw, mentioned only once during the PCORI Board meeting. NIH Director Francis Collins raised it during a discussion of the report from the PCORI Methodology Committee. Commenting on the Committee’s charter and the “perceived tension between CER and personalized medicine,” he said he “would hope that the Methodology Committee would take that on,” and suggested emphasizing alignment with personalized medicine and patient preferences in the document. I applaud Dr. Collins for raising this point, but we will need more voices joining him to make sure the Board and Methodology Committee to integrate CER and PM. It seems to reinforce some concerns expressed earlier by PMC about lack of an expert in genomics or personalized medicine on the Methodology Committee. The idea proposed by PMC of creating an advisory panel on personalized medicine and innovation could be one step to help ensure alignment between CER and personalized medicine.
   
One of the big news items from the PCORI Board meeting was the appointment of Dr. Joe Selby as the PCORI Executive Director. I was heartened by Dr. Selby’s comments at the meeting, in which he stressed the importance of hearing from, and focusing on, patients. It will be equally important for Dr. Selby and the additional staff he hires to understand that part of the Institute’s charge from Congress is to account for genomics and subpopulation differences. Failure to do so will prevent us from realizing the potential for personalized medicine to improve health care quality and value. 

The next meeting of the PCORI Board of Governors is in Washington, D.C. on July 18 and 19th. I hope you’ll join me there in support of comparative clinical effectiveness research that is centered on patient needs and aligned with personalized medicine.

PCORI Methodology Committee Named; No Private Sector PM Experts Included

The  Government Accountability Office (GAO) today announced the members of the Methodology Committee for the Patient Centered Outcomes Research Institute (PCORI). We don’t  dispute the credentials of the 17 appointed members,  and we appreciate NIH Director Francis Collins’ participation on the committee. Yet it is nonetheless disappointing to see that none of these appointed members from the private sector bring expertise in personalized medicine, particularly since including experts in genomics was one of the specific fields identified in statute.  This will make it all the more important for leaders in the personalized medicine field to continue to advocate for alignment of PM and CER in development of research methods and study designs.   For the past year, the Personalized Medicine Coalition (PMC) has been a strong advocate in support of CER that is aligned with personalized medicine.   In October, PMC submitted a letter to GAO nominating ten experts in personalized medicine from across academia and industry.   While many on the methodology committee  bring strong expertise in their research fields, the lack of in-depth expertise in genomics and personalized medicine will make it more challenging to advance research methods that are aligned with personalized medicine and recognize “advances in medical technology” as specified by statute. 

Perhaps  the PCORI Board could create an  ad hoc advisory panel focused on personalized medicine and innovation that would help to ensure that sufficient focus is brought to these important issues as PCORI  moves forward with developing research methods and priorities .   Having such a committee could help PCORI fulfill other mandates such as public engagement, stakeholder representation, and keeping the science up-to-date.

PMC Nominee Dr. Freda Lewis-Hall Selected for PCORI Board of Governors

In June, PMC nominated a slate of individuals representing the diversity of our coalition including representatives from patient advocacy groups, hospitals and health systems, the pharmaceutical and diagnostics industries, and public health agencies for appointment to the Patient-Centered Outcomes Research Institute (PCORI) Board of Governors.  We were pleased that the Government Accountability Office (GAO) included Pfizer’s Chief Medical Officer Dr. Freda Lewis-Hall, a PMC nominee with expertise in and a commitment to personalized medicine, as a member of the PCORI Board of Governors.

But while we thank GAO for selecting a group of individuals for the PCORI Board of Governors who are committed to improving the health of the American people through research that will, we hope, improve outcomes, we also recognize that our work is not finished. We must continue to advocate for personalized medicine both with the PCORI Board of Governors and eventually with its Methodology Committee, to ensure that comparative effectiveness research considers population subtypes, individual variation, and personalized medicine in general.

 The 21-member PCORI Board of Governors, established by the Patient Protection and Affordable Care Act, is tasked with assisting patients, clinicians, purchasers, and policymakers in making informed, evidence-based, health decisions.  It will identify research priorities, carry out a research agenda, and receive support from a Methodology Committee and expert advisory panels.

We were disappointed that the newly selected members of the PCORI Board of Governors did not include more individuals with specific expertise in personalized medicine, in particular, individuals representing small, innovative diagnostics companies.  Small diagnostics companies, which develop new tests for detecting disease, are central to the field of personalized medicine and will play a necessary and important role in the research PCORI will conduct. We hope that the yet-to-be-named Methodology Committee will include more representation from this important sector.  

The members picked today by the GAO include the 19 members below, as well as the Director of the National Institutes of Health and the Director of the Agency for Healthcare Research and Quality, or their designees:

• Freda Lewis-Hall, Pfizer
• Eugene Washington, MD, UCLA
• Steven Lipstein, MHA, BJC Health Care
• Christine Goertz, Palmer College of Chiropractic
• Sharon Levine, MD, Permanente
• Ellen Sigal, PhD, Friends of Cancer Research
• Harlan Weisman, MD, Johnson and Johnson
• Robert Zwolak, MD, Dartmouth-Hitchcock
• Lawrence Becker, Xerox
• Arnold Epstein, MD, Harvard/Brigham and Women’s
• Andrew Imperato, AAPD
• Robert Jesse, MD, Department of Veterans Affairs
• Grayson Norquist, MD, Dept of Psychiatry and Human Behavior,  University of Mississippi Medical Center
• Debra Barksdale, UNC Chapel Hill School of Nursing
• Kerry Barnett, The Regence Group
• Allen Douma, AARP
• Leah Hole-Currty, JD, Washington State HTA program
• Harlan Krumholz, MD, Yale University
• Richard Kuntz, Medtronic