A Phase-Gated Protocol for Managing Mid-study Principal Investigator Transitions in Multi-site Investigational Device Exemption Trials.

Multi-site clinical investigations of high-risk medical devices conducted under the United States Investigational Device Exemption (IDE) framework depend on an unbroken chain of investigator authorization at every active site. When a principal investigator departs mid-study, that chain is tested. A poorly managed transition can interrupt enrollment, leave delegation of authority records out of date, lapse institutional review board (IRB) approvals, and create the documentation gaps that most commonly attract regulatory scrutiny. Despite how routinely these transitions occur in multi-year cardiovascular trials, the literature offers sponsors little practical guidance on how to run one. This technical report describes a phase-gated protocol for managing mid-study principal investigator transitions, developed as the investigator lifecycle component of a broader prospective regulatory governance model for Class III device investigations. The protocol divides each transition into four sequential gates: continuity assessment, successor qualification, authorization transfer, and verification and release. Each gate specifies the documents that must exist, the party responsible for producing them, and the criterion that must be satisfied before the transition may advance. Enrollment at the affected site is governed by an explicit hold-or-continue decision made at the first gate rather than by improvisation. The protocol was applied prospectively during principal investigator transitions in an active, FDA-authorized IDE investigation of a transcatheter structural heart device (ClinicalTrials.gov: NCT05537753), where transitions were completed without enrollment authorization gaps, delegation discontinuity, or IRB approval lapses at the affected sites. As the protocol is constructed entirely from obligations that apply to every IDE sponsor, including 21 CFR Part 812 investigator selection and agreement requirements, financial disclosure under 21 CFR Part 54, and the quality-by-design expectations of ICH E6(R3), it is transferable to any multi-site device investigation. It is offered as a working template that sponsors, particularly those with small regulatory teams, can adopt directly or adapt to local procedures.