The Ethics of Engagement in Patient-Focused Drug Development for Rare Diseases - Project Summary: Patient and family groups (PFGs) have long supported rare disease research as fundraisers and advisers. But today, they increasingly drive the research agenda, working in partnership with academic institutions, drug developers, and regulators to shepherd new therapies from basic research to commercialization. While patient engagement has become common in many areas of biomedical research, this model of PFG-led, therapy-focused, collaborative research—known as “patient-focused drug development” (PFDD)—is especially prominent in the rare disease space, where small patient populations, dispersed expertise, and limited financial incentives for drug discovery necessitate active engagement of PFGs across the drug development pipeline. When collaborations are successful, PFDD can fuel scientific advancement and accelerate cures for rare diseases with limited therapeutic options. However, this emerging model has also created new ethical challenges, as PFGs and their partners navigate competing values, interests, and expectations throughout the PFDD process. These ethical challenges have the potential to disrupt PFDD, erode trust, consume scarce resources, and exacerbate inequities, but they remain poorly understood. The objective of this proposal is to gain a multi-perspective account of ethical challenges raised by PFDD in rare diseases and to use collaborative methods to develop tools to manage these challenges. Our proposal includes three specific aims. Aim 1: To explore stakeholder perspectives on the ethical challenges arising in PFDD, as well as ways in which they currently manage these challenges, though semi-structured interviews with representatives of key stakeholder groups including PFGs representing a variety of rare diseases, academic institutions, industry partners, government agencies and rare disease umbrella organizations. Aim 2: To characterize the values, interests, resources, roles, and relationships of stakeholder groups, and to identify nodes of conflict and alignment of values and interests within and across groups, suggesting additional ethical challenges and management strategies, using the framework of stakeholder analysis. Aim 3: To evaluate the tradeoffs and downstream implications of potential strategies for managing ethical challenges identified in Aims 1 and 2, to seek multi-stakeholder consensus regarding recommended strategies, and to develop an implementation strategy. We will engage representatives of key stakeholder groups in a conventional Delphi panel consisting of three rounds of iterative surveys and an in-person consensus meeting. Our study will culminate in an “ethics roadmap” outlining the ethical challenges stakeholders may encounter in PFDD and recommended approaches to managing or resolving these challenges. The roadmap will have a positive impact by helping stakeholders anticipate, understand, and respond to the ethical challenges they may encounter at each stage of PFDD. Future work will evaluate the impact of the roadmap on the process and outcomes of PFDD for rare diseases and will seek to adapt it for other types of research.
