Plausible Mechanism Pathway

Plausible mechanism pathway is Marty Makary’s source-scoped label for a more flexible regulatory route for bespoke therapies. In Supercharging a New FDA: Marty Makary on Science, Power & Patients, he says some cell and gene therapies may not fit ordinary randomized trials because patient populations are too small or individualized.

The concept does not mean mechanism alone should replace evidence. It means that for highly individualized treatments, the regulator may need a different package: credible biological mechanism, manufacturing controls sized to the product and population, patient-specific risk judgment, and post-use monitoring.

Key Claims

• Randomized trials may be impractical for some bespoke therapies, especially rare or individualized cases.
• A plausible mechanism can support access only if manufacturing, dosing, safety, and monitoring remain credible.
• The pathway is meant to reduce cost and delay for therapies such as CAR-T cell therapy without treating all biologics as identical.
• The approach relies on Post-Market Drug Surveillance because small-N premarket evidence leaves more uncertainty after use begins.

Connections

• FDA and Marty Makary - agency and source speaker.
• FDA Review Modernization - umbrella reform frame.
• CAR-T cell therapy, In Vivo CAR-T, and Ex Vivo CAR-T Manufacturing - adjacent cell-therapy routes.
• Clinical Development Capability and Post-Market Drug Surveillance - evidence and monitoring requirements.