Since the passage of the Orphan Drug Act in 1983, hundreds of new drugs to treat rare diseases and conditions have been approved by the United States (US) Food and Drug Administration (FDA); however, there are still no approved therapies for most rare diseases (FDA 2019). As stated by the Institute of Medicine (2010), in the aggregate, rare diseases are not rare. The roughly 7,000 recognized rare diseases impact millions of individuals in the US and are responsible for a significant burden on patients, families, communities, and the health care system. Hence, a significant unmet public health need remains unfulfilled (FDA 2019). Although there have been tremendous advances in our knowledge of the genetic, molecular, and biochemical bases of many rare diseases, there are persistent challenges in the evaluation of clinical benefit of treatments aimed at these diseases. The uncertainty around appropriate clinical trial endpoints?whether they are based on clinical outcome assessments (COAs) or biomarkers as validated surrogates for clinical benefit?is a huge hurdle for drug development as well as health technology assessment (Nestler-Parr et al. 2018). The bottom line is that fit-for-purpose clinical trial endpoints are not available for most rare diseases (FDA 2019). To work toward filling this unmet need, this initiative's specific aim is to establish the Rare Disease COA Consortium. The first step will be the creation of the Rare Disease Subcommittee within Critical Path Institute's (C-Path's) Patient-Reported Outcome (PRO) Consortium. The PRO Consortium will serve as an incubator for the maturation of the Rare Disease COA Consortium. Starting within an existing organizational infrastructure will provide time to work with the National Organization for Rare Disorders (NORD) and other relevant stakeholders to identify a funding model that will enable the spin out of a financially sustainable consortium. Once established, the primary goal of the consortium will be the creation and curation of a database of publicly available COAs (and supporting evidence) deemed fit-for-purpose for use as endpoint measures in treatment trials for multiple rare diseases. The strategy for accomplishing the specific aim includes a pre-consortium summit to define the scope of the Rare Disease COA Consortium and to assure alignment and avoid duplication of effort among high-level stakeholders. This summit will involve representatives from FDA, NORD, National Center for Advancing Translational Science, Patient-Centered Outcomes Research Institute, and C-Path. Subsequently, a public workshop will be held for representatives from organizations that have expressed interest in participating in the consortium. The workshop goal is to gain consensus on the consortium's vision and mission, membership structure, membership agreement, and deliverables.
Millions of people in the US have one or more of the approximately 7,000 recognized rare diseases or conditions, which result in substantial burden on patients, families, communities, and health care systems. Since there are no approved therapies for most rare diseases and there is considerable uncertainty around appropriate treatment trial endpoints, a significant unmet public health need remains unfulfilled. This proposed pre-competitive, multi-stakeholder consortium is aimed at accelerating the development of new medical products intended to safely and effectively treat people with these diseases by creating and curating a database of publicly available fit-for-purpose tools that can be used to assess the clinical benefit of emerging treatments.
