Considerations for the use of the Plausible Mechanism Framework to Develop Individualized Therapies that Target Specific Genetic Conditions with Known Biological Cause; Draft Guidance for Industry

Public Responsibility in Medicine and Research (PRIM&R), a nonprofit organization, supports the draft guidance while requesting specific improvements. They advocate for clearer eligibility thresholds to prevent the framework from replacing feasible randomized controlled trials, the inclusion of pediatric assent requirements, and more detailed guidance on using natural history studies as comparators.

A patient and mother of children supports the FDA's efforts to create a pathway for individualized therapies but argues that the draft guidance needs stronger requirements. She specifically calls for enforceable diversity plans in clinical trials, mandatory long-term follow-up requirements (PMRs) at the time of approval, and validated health literacy assessments to ensure meaningful informed consent.

Undergraduate students from the University of California, Berkeley's College of Engineering support the draft guidance but urge the FDA to strengthen it with more robust ethical, safety, and equity protections. They specifically recommend mandatory long-term monitoring, specialized informed consent protocols, and clear selection frameworks to ensure equitable access to individualized therapies.