(Guest Blogger: DeAunne Denmark, MD, Ph.D., Research Associate, Oregon Health and Science University)
A stellar group of speakers and participants from all over the world assembled in Baltimore on October 5-6, 2015 for the
7th Annual Personalized and Precision Medicine Conference. While broad in scope, and covering diverse topics from public policy and data privacy to regulation and reimbursement, from healthcare VC interests to cutting-edge platform innovations, several common themes emerged that reflect some of the most central challenges and opportunities in PM today. Thoughtfully moderated by
Mollie Roth, JD, of
PGx Consulting, the message that current systems are dangerously unsustainable, and effective change will require major paradigm shifts, large infrastructure investments, and open, bilateral, transparent collaborations inclusive of the myriad of stakeholder interests – most importantly, patients – seemed to resonate strongly with all.
DAY ONE kicked off with Elaine Lyon, Ph.D., Co-Medical Director at ARUP and Associate Professor at the University of Utah, sharply covering a core theme across areas and stakeholders – value. Pharmacogenomics requires balancing high complexity with high risk, and clearly demonstrating decision support utility for clinicians – “reasonable + necessary = useful” – to produce better responses faster, and more cost-effectively. She acknowledged important industry challenges, e.g., the absence of supportive evidence is often interpreted as evidence against, large cultural biases, and the reality that PM’s formidable task is to change the standard of care.
Jen Madsen, MPH, Health Policy Advisor at Arnold & Porter, skillfully covered intricacies of policy related to regulation and reimbursement for PM, providing a valuable primer on the 21st Century Cures Bill, PAMA rules, CMS reporting, ADLT payment for innovative tests, and FDA changes, including LDT guidance and authority on software. She reminded us that the upcoming election year would amplify the already daunting complexity, and to expect debates around major underlying issues: scope of practice, tests are NOT devices, and intended use, e.g., allowing computers to make clinical decisions.
Erick Lin, MD, Ph.D., Director of Medical Affairs at Ambry Genetics, reviewed his company’s experience in adopting NGS panels, emphasizing the need for technologically agnostic and flexible applications, as well as the acknowledgment of limitations and profound uncertainty inherent at the leading edge – “we don’t know what we don’t know.”
Kristine Ashcraft, COO at Genelex, tackled how efforts to advance PM are being affected by the move to pay-for-performance, citing a distinct incongruence regarding the PMI announcement in the midst of an apparent “war on reimbursement,” e.g., FDA endorsement of drug-gene guidance equal to drug-drug, yet extremely poor coverage for even the most well-validated. For any given intervention, answering key questions – who to target, how to further stratify, does it actually improve care AND lower costs in the relevant population – through predictive modeling can provide real evidence that such genetic risk assessment improves patient care with positive financial impact. As asserted by others, “learning healthcare systems” will be key to PM in practice.
Paul Sheives, JD, VP of Reimbursement & Regulatory Policy at the ACLA, reminded us that, as LDTs are created to fill a medical need and are critical to decision-making, innovation precedes approval. He highlighted new fast-tracking strategies, including the Cures Initiative, and proposals from the Diagnostic Testing Working Group and Association of Molecular Pathologists to distinguish high and low-risk, and re-framed PAMA as, ideally, a way to positively reflect value.
Morning presenters then convened in a panel for deeper discussion on some pressing hurdles facing PM advancement - better tests are often more complex and thus harder to get approved, current reimbursement is not based on value but on costs, gaps in unequivocal evidence that a test does what it says, and lack of standardization. Shifting paradigms to incorporate algorithms as stand-alone evidence as payment support and increasing collaboration were offered as powerful strategies to forge the way ahead.
The afternoon began with straight-talk by Michael F. Christman, Ph.D., President and CEO at the Coriell Institute, into the ideals of PM in practice. As the gold standard for high-quality biomaterials, the Coriell Personalized Medicine Collaborative (CPMC) collected sequence information on millions of genomes to harvest some of the industry’s lowest hanging fruit – drug response. GeneDose generates a complex risk report and regimen using alternative evaluation methods to model real-time drug-gene and gene-environment interactions. He concluded with another call for payor progressiveness– “the private sector provides information for physicians to make better decisions.”
Gitte Pedersen, CEO at Genomic Expression, enlightened the audience to the promise of RNA sequencing as another powerful tool highly amenable to PM applications, as exemplified by her work in single-payer Denmark whose national biobank is the world’s largest.
Anya Schiess, MBA, General Partner and Co-Founder at Healthy Ventures, offered a compelling perspective on PM investment. Driven by digital health, i.e., the application of technology to healthcare, a surge has been initiated by several current trends - big delivery changes that affect all players, risk-shifting as payment moves from defined benefit to defined contribution, design of panels that are both accurately representative and adequately personalized, and the “retailization” of healthcare. She wisely emphasized the industry’s nascency, and that as it matures, “customer interface is king.” Fragmentation of the stack and who will win the value remain open questions – “everyone is waiting for the wave, and players must stay flexible if they want to catch it when it crests.”
Birgit Reitmaier, Ph.D., Head of Technologies & Biomarkers at Merck Serono division, and Elaine Cheung, Director of Strategic Partnerships at Illumina, team-presented their new collaboration to better address complex decision-making through a universal NGS-based cancer test. Each company can draw on the strengths and expertise of the other to support their individual challenges, while retaining autonomy and proprietization where appropriate. As in other areas, standards of quality, concordance, reliability, and transparency remain an unmet need that, when addressed, can coherently synthesize the currently fragmented market.
In a fantastic keynote, Robert Green, MD, MPH, Director of Genomes2People and Associate Professor of Medicine at Brigham and Women's Hospital/Harvard Medical School, shared some early results of the MedSeq Project which addresses core questions related to effective and efficient use of germline sequencing in practice. Undiagnosed disease is a clear need, but only 20-40% of cases are successfully solved, while generating large incidental findings. Does having this information actually provide benefit? Could it even cause harm? How do we make sense of and use it constructively? As he wisely summarized – “Screening for screening’s sake does not necessarily give a net positive health outcome.” The generation of a complete single-page WGS summary is an early project success and proof-of-concept that a person “doesn’t have to be a geneticist to read a report from whole genome analysis.” He outlined the need to differentiate clinical utility as broad or narrow and apart from personal and societal utility, as well as measure value in terms of gains in prevention, i.e., the costs of NOT knowing, concluding with the assertion that “discovering a variant thru screening is NOT the same as discovering in a person with known family history.”
Ken Ramos, MD, Ph.D., PharmB, Associate VP for Precision Health Sciences and Professor of Medicine at Arizona Health Sciences Center, reviewed some of his institution’s experience with PM platforms, emphasizing the need to include multiple ‘omics for optimal care contextualization. Reiterating previously-raised disparity issues, he stressed the importance of identifying subpopulations most relevant to a geographical area, then individually tailoring programs accordingly.
William Knaus, MD, FACP, Director of Applied Genomics Research and the Center for Biomedical Research Informatics at NorthShore University Research Institute, introduced an exciting new project designed to engage and empower patients. Health Heritage is a personalized, consumer-controlled tool that automatically and agnostically integrates family history data into an EHR, then securely sharing and distilling it to derive composite assessments of disease risk. Importantly, information gets into the right hands AT the point-of-care to communicate what the risk is, why it exists, and what can be done. Providers don’t need to be involved, thereby minimizing workflow impacts and optimizing returns through alignment of payer, provider, and patient interests.
DAY TWO kicked off with back-to-back presentations on highly innovative PM applications. Elaine Mardis, Ph.D., Professor and Co-Director of The Genome Institute at Washington University School of Medicine, introduced exciting work in the design of patient-unique cancer vaccines. Such immunotherapies can even be combined with existing cancer drugs, e.g., checkpoint inhibitors, in priming strategies that “wake-up” the immune system prior to vaccination. She cited pediatric glioma, especially the recurrent setting, as an area of notable success to date.
Angela Davies, MD, FRCP (C), CMO at Champions Oncology, enlightened participants to Patient-Derived Xenografts (PDx), which show distinct promise for functional validation in drug development, allowing faster go/no-go decisions and improved mechanistic understanding to help ameliorate the massive Phase 3 failure problem. PDx models can also better pair translational clinical trial with likely responders, particularly when more diverse biobanks and increased cohort sizes are achieved.
Doctoral candidate Tea Pemovska from the Wennerberg Lab at the University of Helsinki’s Institute for Molecular Medicine Finland (FIMM) spoke about individualized systems medicine, incorporating phenotype-to-genotype approaches such as unsupervised hierarchical clustering to create functional profiles and for relationship discovery.
In a refreshing interactive format, Richard Watts, VP of Business Development in Personalized Healthcare at Qiagen, exposed an array of complex issues surrounding the commercialization of targeted therapies and companion diagnostics. Audience members were challenged to dial in rapid responses to tricky real-world scenarios ranging from panel-based drug recommendations, to balancing test sophistication with increasing development costs and time-to-market, to using in vitro data in clinical decision-making.
David Resnick, JD, Partner at Nixon Peabody, made accessible the convoluted realm of intellectual property (IP) by summarizing a few recent high-profile cases (Myriad, Mayo, and Ariosa v. Sequenom) to illustrate some critical issues raised by PM technologies. He offered the valuable take-homes that, due to IP’s rapid evolution, patents will be much narrower, i.e., specific to methodology or sequences, and even the experts still don’t know exactly what IS patent-eligible, especially regarding computer-based inventions like software or algorithms.
Mark Gerstein, Ph.D., Professor of Biomedical Informatics at Yale University, delved into the murky waters of privacy’s central dilemma – how to balance risk with the imperative to share. He described major difficulties with the current framework, including lack of interoperability, large data files, encrypting, and vulnerability to hacking, and suggested some hybrid solutions to promote better balance: privacy licenses for scientists, reduced glory incentives for hackers, management by larger entities, e.g., UK government, and quantification, including both private and public sector leakage.
Bartha Knoppers, Ph.D., Director of the Centre of Genomics and Policy at McGill University, offered policy lessons from the Canadian experience, focusing on stratification in particular. Advocates for sharing, the Global Alliance for Genomics & Health lays out a framework for a “coalition of the willing” that agrees to act responsibly in the protection of human rights as a move away from patient protectionism.
Laura Lyman Rodriquez, Ph.D., Director of the Office of Policy, Communications and Education at the National Human Genome Research Institute, spoke to how major policy and privacy issues can be progressed by increasing participant involvement. The question of balance among multiple interests arose yet again, as scientific aims, responsible but not over-protection, and advancement must be reconciled with the autonomy and transparency required for participants to trust in the process.
Christopher Ianelli, MD, Ph.D., CEO of iSpecimen, took us full circle from participation back to protection again with an overview of a highly innovative new venture dedicated entirely to the reuse of remnant clinical specimens. Prompted by the recognition that a veritable goldmine of research was being actively wasted, iSpecimen was created as the steward to get discarded tissue and other samples into the R&D pipeline by matching with those who need them in a diversified data-flow network, while simultaneously promoting a more progressive consent process.
Participation remained the theme of the second panel discussion among the afternoon presenters who agreed that defining property and ownership rights of data or samples may not even be necessary as long as patients retain control. The consensus that participant representation be not token, but instead provide truly meaningful input in the entire research system was an inspiring and fitting conclusion to this highly successful, engaging, and information-rich event.
