To support a transition towards a precision medicine approach to treatments, the NHLBI in partnership with the Cardiovascular Medical Research and Education Fund (CMREF) organized a workshop to address the barriers, gaps and opportunities to applying precision medicine to PVD including pulmonary hypertension. The workshop generated recommendations to the NHLBI for future research priorities in this area in line with NHLBI Strategic Vision Goals.
This workshop was timely to leverage the anticipated scientific output from the recently launched “Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics” (PVDOMICS) program with the Precision Medicine Initiative. PVDOMICS is supporting collaborative, protocol driven, comprehensive, deep phenotyping across all groups of PH patient populations in order to define novel pulmonary vascular disease (PVD) phenotypes. As such, new cohorts will emerge for testing: a) currently available drugs in those predicted by molecular phenotype to be the most responsive and b) novel therapies derived from our increasing mechanistic understanding of disease. Stakeholders in PVD need to be brought together (scientists, clinicians, patient advocacy organizations, regulatory agency representatives, and pharmaceutical industries) to discuss the current needs, challenges, and new opportunities in applying precision medicine to PVD clinical research and treatments. Critical protocol elements including diagnostic tests, biomarkers, and meaningful outcomes need discussion to develop PH interventional trials using a more granular, phenotype-based disease classification.
The workshop addressed multiple topics that are central to the development of true personalized medicine in PVD, including inputs from all the stakeholders, from basic science, to drug development to clinical trials to master protocol. Each expert addressed the needs in their area of expertise to advance the field. The overall goal was to identify needs, and make recommendations for future progress.
Future clinical trials to evaluate therapies for PVD with a precision medicines approach will need a common platform that satisfy the needs and concerns of regulatory authorities, industry, patients, and clinicians. This master protocol would target a patient population that will be defined by novel phenotyping based on validated studies over a broad range of biomarkers including clinical features, proteomics, metabolomics, and genomics. It will incorporate advances in trial design science to allow for a precision approach that includes adaptive and enrichment strategies and should address important concerns of academia by selecting appropriate endpoints which reflect meaningful treatment effects, inform the mechanism of drug effect, and reveal any disease modifying effects.