Last week the Institute of Medicine (IOM) held a workshop in Washington DC entitled “Refining Processes for the Co-Development of Genome-Based Therapeutics and Companion Diagnostic Tests.” The program represented another in a series of work products of the IOM “Roundtable on Translating Genomic-Based Research for Health,” an ambitious multi-disciplinary group formed by IOM with the mission of advancing the field of genomics. Consistent with the diverse membership of the Roundtable itself, this workshop brought together representatives from academia, industry, government, foundations and associations and representatives of patient and consumer groups.
The purpose of the workshop was to examine and discuss challenges and potential solutions for the co-development of precision therapeutics and companion diagnostic tests. As a starting point IOM queried key stakeholders and identified what were considered problems with current paradigms for addressing drug diagnostic co-development. Potential solutions were also sought.
There was general agreement that the co-development arena was plagued by regulatory uncertainty, reimbursement uncertainty, the unpredictable nature of outcomes in phase III drug trials, and sampling issues, particularly problematic if multiple platforms are needed to complete a disease profile from a single tissue biopsy. The response to some of these common concerns was, however, a bit different depending on the perspective of the participant.
Companies (both diagnostic and drug manufacturers) tended to agree that uniform, risk based regulation by FDA , regardless of the business model used to develop a new test, was the right solution to ensure regulatory parity. However, laboratory advocates continued to call for the flexibility and lighter touch of CLIA oversight of laboratory developed tests (LDTs). In particular Next Generation Sequencing (NGS) was cited as a game changer that would challenge conventional regulatory paradigms through a rapid flood of complex and iterative laboratory data that might not lend itself to traditional regulatory models. FDA signaled that although it had no easy answers it believed it was up to the challenge. All agreed there was a clear need to develop a regulatory path to guide this new disruptive but revolutionary technology into clinical practice.
While most participants concluded that all was not well in the realm of test reimbursement and that value based test reimbursement would be desirable, no easy fixes were identified. It was noted that continued growth in our 2.7 trillion dollar yearly health care bill was likely to be unsustainable and constraints on laboratory reimbursement likely to become the norm. Laboratories are very good at showing the quality of their work processes. But quality induced improvements in outcomes used to fuel differential payment for clinical services are unfamiliar measurements in the world of laboratory medicine.
Finally the role of science in the evolution of co-development was discussed. It was noted that co-development is to some extent an interim step in the process of understanding disease. As information about the biology and testing of disease accumulates, the way tests are deployed and regulated may evolve. A plea was made, however, for better science. It was suggested that while more than 30,000 articles on biomarkers were published in the past year alone, many were of poor quality. This lack of scientific rigor makes it hard to move the field of personalized medicine forward.
The need for advocacy for better science was perhaps best captured by a patient advocate with a quote from the book How We Do Harm by Otis Brawley (Chief Medical Officer of the American Cancer Society): “Proponents of science as a foundation for health care have not come together to form a grassroots movement, and until this happens, all of us will have to live with a system built on pseudoscience, greed, myths, lies, fraud and looking the other way.”
The good news is that no-one at the work shop was looking the other way and the discussion was spirited, lively and insightful. The bad news is that, perhaps as inevitable, there will be no easy answers. A written report is likely to follow with an effort to use the material from this workshop to suggest paths forward.