Progress in Cancer Highlighted by NEJM Retrospective; Turning the Tide Conference to Catalyze Comprehensive Dialogue on How to Sustain Cancer Innovation

In honor of the New England Journal of Medicine’s (NEJM’s) 200^th Anniversary, the journal examined how medicine has evolved over the last two centuries, looking in particular at oncology diagnosis, prevention, and treatment. But while there has been tremendous progress in cancer, questions remain:  Where do we go from here?  And how do we get there in an era of immense fiscal discipline?  These are questions that we plan to address on Tuesday at our conference, Turning the Tide Against Cancer Through Sustained Medical Innovation.

In a similar vein to what Siddhartha Mukherjee, M.D., a special guest speaker at the conference, lays out in his book The Emperor of All Maladies: A Biography of Cancer, the authors of the NEJM article “Two Hundred Years of Cancer Research” provide a timeline of major discoveries and advances in cancer research and care.

They show how each milestone is built on the ones that came before it and trace the evolution of cancer progress from the early efforts to control the disease through surgery, advances in radiation, chemotherapy, and the targeted therapies that are redefining cancer treatment today.

The underlying science that made these treatment advances possible takes years to translate into clinical benefits for patients, but the original investments pay off. Our understanding of the genetic basis of cancer became possible only after decades of work on the basic biology of DNA beginning in the 1940s and 50s, but it was not until after the sequencing of the human genome that researchers were able to begin to translate genetics knowledge into new medicines.

Genetic understandings of cancer have led to breakthrough new medicines such as Xalkori® (for non-small cell lung cancer) and Zelboraf® (for melanoma) and more targeted therapies are on the way.  A new report issued by the Pharmaceutical Research and Manufacturers of America (PhRMA) found that there are 981 new medicines and vaccines for cancer in development today, many of which are likely to be personalized medicines.

Tomorrow’s progress in cancer therapies and treatment approaches depend on today’s policy makers recognizing the need for policies that holistically support cancer research and innovation.  In advance of next week’s conference, a Discussion Paper “Sustaining Progress Against Cancer in an Era of Cost Containment” coalesces the views of the conference advisory committee and other leading cancer experts about new models for cancer innovation, how to define value in cancer care, and how policy can support continued progress against cancer.

National Bioeconomy Blueprint Showcases Personalized Medicine as Model for Strengthening U.S. Bioeconomy

Last week, the White House released its National Bioeconomy Blueprint.  It lays out some strategic objectives designed to help realize the full potential of the U.S. biotechnology sector to generate economic growth by creating jobs and addressing societal needs.

As an example of how the government’s efforts can facilitate the development of a more robust bioeconomy, the report discusses the impact of the Human Genome Project and the development of personalized medicine. The Blueprint cites the Case for Personalized Medicine, 3^rd Edition, noting “advances in recent technologies have increased the momentum of personalized medicine – customized healthcare based on specific genetic or other information of an individual patient.”

While we agree that policies are needed to help support research and development (R&D), improve translational and regulatory science, improve regulation in other areas, enhance workforce training, and develop new public-private partnerships and precompetitive collaborations, we are concerned they are not sufficient to allow us to realize Adriana Jenkins’ dying wish, that all patients have access to personalized treatments.

The White House is correct to shine a light on FDA and direct the agency to focus attention on application review times, coordinated parallel reviews of products, and continued improvement of regulatory science. In reality, we are already seeing the benefits of this increased coordination – with FDA’s accelerated review and approval of Kalydeco™ for cystic fibrosis and Xalkori^® for non-small cell lung cancer, each with a companion diagnostic approved together and in advance of FDA time lines.

Still, engaging on regulatory science and streamlining FDA processes will only go so far to improve the bioeconomy and bring personalized medicine to patients. For instance, current comparative effectiveness research (CER) and health technology assessment (HTA) models, which are not addressed in the Blueprint, are not well aligned with the science of personalized medicine and such misalignment causes additional barriers to market entry and patient access after FDA approval. The Blueprint highlights coverage with evidence development (CED) as a potential HTA model, but it should be noted that although CED can be a good tool, if done wrong, it can also chill innovation.

Likewise, unclear and unrealistic expectations for obtaining Medicare coverage and adequate payment for personalized medicine products and services are a substantial hurdle, preventing companies from seizing the full scientific potential and translating that into new treatments and the resulting high-paying jobs and economic contributions that follow.

We look forward to working with the Administration and with Congress to shape policies that will help support the ability of companies to continue to develop personalized medicines and bring them to patients, including research and development tax credits, delivery system reforms, and regulatory and reimbursement policies. Given the tremendous potential of personalized medicines, it’s key that we get the policies right to foster companies working on personalized medicine and thereby improve patients’ lives and our economy.

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.

The Genomics and Personalized Medicine Act Needs a “Fresh Look”

“Now is the time for a national effort to move personalized medicine forward,” said Representative Anna Eshoo at the Center for the Study of the Presidency and Congress and Health Affairs’ Capitol Hill briefing held last week, on the same day that the Food and Drug Administration (FDA) released its plan Driving Biomedical Innovation:  Initiatives for Improving Products for Patients.

At the briefing, Congresswoman Eshoo affirmed the Personalized Medicine Coalition’s long-held contention that the 2010 version of the Genomics and Personalized Medicine Act needed an infusion of new ideas.  (See my blog post from August 23, 2011.)

Also speaking to the audience of congressional staff, reporters, patient advocates industry representatives, and others, were several government officials tasked with enforcing policies that affect personalized medicine innovation.  They presented their thoughts on the state of personalized medicine and their respective agencies’ roles, highlighting their progress. Both Janet Woodcock, M.D. and Elizabeth Mansfield, Ph.D. of FDA highlighted FDA’s efforts in bringing regulators and industry to the table to discuss the challenges of regulating personalized medicine products and services.  These discussions informed the agency’s new report—dubbed a blueprint for innovation—which includes major focus areas in building the infrastructure to drive and support personalized medicine and in creating a rapid drug development pathway for important targeted therapies.  They also acknowledged that changes are still needed at FDA to accommodate personalized medicine and that the agency will continue its leadership role by building a system to support the development of personalized medicines, including investments in regulatory science and by clarifying agency policies.

At the same time, Jeffrey Roche, M.D., M.P.H. from the Centers for Medicare and Medicaid services (CMS), underscored his agency’s time-consuming coverage decision-making process, which is based on published research used to determine what is “reasonable and necessary.”

Indeed more coordination is needed at the federal level.  Speakers representing academe, industry, and patients reinforced this sentiment, in addition to emphasizing the need for industry incentives to develop new products and services and a CMS reimbursement policy that can speed the adoption of personalized medicine by paying enough for personalized medicine diagnostic tests so that research and development costs are recouped.

Patient advocate and PMC-member Donna Cryer summed it up best, when sharing her thoughts on what can foster innovation and the adoption of personalized medicine: We need HHS level coordination, and a streamlined FDA process for personalized medicines and their diagnostic partners.  CMS needs to support the science of personalized medicine through a system of care that repays innovators for the research that goes into the development of these products.  And tax credits are necessary to help companies through what is still very difficult science. 

PMC is pleased by Rep. Eshoo’s leadership in advancing personalized medicine as evidenced by her participation in this event and her willingness to consider all of the policy proposals PMC and others have put forth.  We look forward to working with her to vet policy recommendations suggested by others and to see the Genomics and Personalized Medicine Act introduced in this Congress.

Our Health Policies Can’t Ignore Where Science Is Leading Us

Do we want continued progress in personalized medicine, or don’t we? Based on events last week, the answer might be ‘both.’ I attended a press conference here in Washington that celebrated the achievements made by the health sector in our efforts to turn cancer from a sure death sentence into a chronic disease. Simultaneous to this, the Medicare Payment Advisory Commission (MedPAC) proposed policies to offset the cost of a physician payment fix under Medicare. The disconnect between the two was striking. Unfortunately, the MedPAC proposals have the unintended effect of heavily impacting those on the leading edge of personalized medicine. Of the $233 billion in 10-year savings, $114 billion would come out of the biopharmaceutical and clinical laboratory sectors, thus possibly robbing seniors of access to the latest targeted therapies and the diagnostics used to guide them. The proposal includes savings from giving the Centers for Medicare and Medicaid Services (CMS) new authority to impose “least costly alternative” payment, which would result in locking us into our current one-size-fits-all medical paradigm and weakening physicians’ power to tailor care using diagnostics and targeted therapies.  Another troubling aspect of these suggestions is that they propose cuts by sector, ignoring the reality that personalized medicine brings efficiencies to the system of health care.

The proposal appears to reflect a lack of awareness of the impact that personalized medicine is making in health care and underscores the importance of the Personalized Medicine Coalition’s legislative work.  One of our policy suggestions, released over the summer, calls for inclusion of a personalized medicine representative on MedPAC and the creation of a new personalized medicine advisory committee to foster alignment of the policies across the entire Department of Health and Human Services with the science of personalized medicine. Personalized medicine challenges the status quo in medicine – the blockbuster business model, diagnostic coding and payment, or health care delivery systems. Maybe it’s time it challenged MedPAC, too.

Legislative Specifications Would Create a Path Forward for Personalized Medicine

The Personalized Medicine Coalition has a long history of working with Congress on the Genomics and Personalized Medicine Act (GPMA); a bipartisan bill first introduced by Senators Obama and Burr in 2007.  The original bill was designed to take full advantage of our federal investment in the Human Genome Project by putting policies in place to enable personalized medicine.  Subsequent versions of the bill have not gone far enough to realign the health care system with personalized medicine.  In an effort to see a more effective version of GPMA introduced in this Congress – one that would move personalized medicine forward and would enjoy community support — PMC members developed a set of legislative specifications for Congressional consideration that are complementary to previous versions of GPMA.  We’ve asked Congresswoman Anna Eshoo to consider including them in her new version of the bill.

These recommendations include a range of important regulatory and policy concepts that can have a meaningful impact on advancing the discovery of and access to personalized medicine products.  They also echo important themes that emerged at the PMC’s Capitol Hill briefing in May.

Specifically, we propose codifying the Department of Health and Human Services’ Personalized Healthcare Initiative and providing the Secretary with an advisory committee populated by experts inside and outside of the government. We also reiterate the importance of ensuring adequate personalized medicine expertise and input on various federal advisory committees and within policy proposals.

Sponsors of personalized medicine products have had challenges taking drug-diagnostic combination products through the Food and Drug Administration (FDA). These experiences suggest that innovators need a predictable regulatory path at FDA so we propose an office for personalized medicine to coordinate therapeutic and diagnostic review, and enforce review timelines for both.

While the path from regulatory approval at FDA to adequate coverage and payment is clear (and usually predictable) for therapeutics, adequate coverage and payment for diagnostics can be long, complicated and frustrating.  To ensure that patients have access to the latest personalized medicines and diagnostics, we suggest policies at the Centers for Medicare and Medicaid Services that will ensure timely coverage and reimbursement for them.

Finally, to ease business model barriers, and incentivize the types of relationships that are the hallmark of personalized medicine, we suggest extending the qualifying therapeutic discovery tax credit from health care reform and expanding it to include personalized medicine companies.  We also suggest a new research and development tax credit to entities developing personalized medicine products.

We look forward to working with members of Congress in both chambers and in both parties to see that the Genomic and Personalized Medicine Act is introduced and signed into law.

The details of the legislative specifications can be found here.

FDA Issues Draft Guidance for Rx/Dx Co-Development – What’s Next?

FDA released long-awaited draft guidance on its regulation of co-developed drug diagnostic combination products.  PMC asked FDA to issue a draft guidance on this topic since innovators had many questions about how regulation of these two products together would work.  I can describe it in one word: short.

It outlines a collaborative process through FDA where the device and drug centers will coordinate review.  It reiterates the FDA practice of using ‘generic’ descriptors of diagnostic tests in drug labels and offers some flexibility and examples around products where a drug might be ready to go to market but the diagnostic is not yet.

While the community welcomes FDA’s current thinking on the topic, given the brevity of the document, I wonder if it left much unsaid.

For example: The focus (which will probably be welcomed by sponsors) is on collaboration between the drug and device centers but no details are given.  Also, while the personalized medicine community generally agrees that FDA regulation of companion diagnostics should be risk-based, there is a lot of debate in the community about what FDA means by risk in the case of a diagnostic.

In recent months, PMC has been working with over 100 members to develop legislative specifications for the next iteration of the Genomics and Personalized Medicine Act.  I will provide more detail on this in an upcoming blog entry, but one of the key concepts of these specifications is to “incentivize personalized medicine by creating a transparent and predictable regulatory environment for personalized medicine products.”  While the FDA’s draft guidance issued last week certainly leaves me wanting more, I do believe this represents an important step in that direction.

Nevertheless, our efforts toward this goal must continue. The FDA is seeking comment on the document for the next 60 days, and I encourage you to submit feedback.  We also welcome your participation in a discussion here at The Age of Personalized Medicine Blog by submitting a comment below.  We expect that FDA will continue to expand its guidance in the coming months, and receiving input from all stakeholders in the development, regulation, and use of co-developed drug diagnostic combination products is essential to their success.

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!