The FDA Is Ready. The Infrastructure Is Not.
The regulatory architecture for N-of-1 therapeutics exists. What's missing is the patient-side data to feed it.
The FDA's Plausible Mechanism Framework says it plainly: if you can demonstrate a well-characterized mechanism and sufficient natural history data, you do not need a traditional randomized controlled trial with thousands of patients.
The 21st Century Cures Act formalized Real-World Evidence as a valid basis for regulatory submissions. The ISTAND pilot established pathways for novel biomarkers. Draft guidance on individualized therapeutics explicitly requires daily natural history data at a granularity that clinical encounters cannot produce.
The regulatory architecture for N-of-1 is being built right now. What is missing is the patient-side data infrastructure to feed it. Disorders and their mechanisms constellate: an array of genetic variations that only reveal their patterns in data, not in any single doctor's office.
Regulatory foundations already in place
- Plausible Mechanism Framework: N-of-1 pathway for individualized therapies
- 21st Century Cures Act: Real-World Evidence for regulatory submissions
- ISTAND Pilot: Novel biomarker qualification pathways
- Draft guidance on individualized therapeutics: Requires daily natural history data
What patient data enables
- Natural history studies at population scale
- Biomarker discovery across disorder clusters
- Genotype-phenotype correlations for undercharacterized variants
- Quality-of-life baselines the FDA can reference