Comment from Cureledger, Inc.

Cureledger, Inc. submits this comment on Docket FDA-2026-N-4390 in support of the AI-Enabled Optimization of Early-Phase Clinical Trials Pilot Program. Cureledger is a life data trust dedicated to advancing the development of safe and effective therapies for people living with rare diseases. Cureledger previously submitted a comment on the Plausible Mechanism Framework draft guidance (Docket FDA-2026-D-1256). The undersigned is a lawyer, verified systems developer, project founder, and the parent of a child with phenylketonuria. This comment offers three recommendations to FDA regarding the design and evaluation of the proposed pilot: a decision-quality framework appropriate to small populations; an architectural approach to privacy protections for rare-disease cohorts; and a fiduciary custody model for the longitudinal data on which the pilot's results will compound. Each is grounded in prior Agency guidance and federal precedent cited in the attached comment. The substantive comment, including responses to the questions enumerated in Section II.A and Section II.B of the RFI, is filed as the attached document. I respectfully request that FDA consider these recommendations in shaping the pilot's evaluation framework, particularly under Section II.A.3 (Collaboration Models), Section II.B.2 (Decision Quality), Section II.B.5 (Trustworthiness aligned with NIST AI RMF), and Section II.B.6 (Comparative Evaluation). Nina Kilbride, JD Founder and Chief Executive Officer Cureledger, Inc.