A protocol amendment represents the formal mechanism for modifying an approved clinical trial protocol. Unlike protocol deviations, which are unplanned departures from protocol requirements, amendments are prospective changes that undergo proper review and approval before being implemented. The amendment process ensures that proposed modifications are scientifically justified, do not compromise participant safety, and maintain the integrity of the trial.

Protocol amendments may be necessary for various reasons throughout a trial's duration. New scientific information may require changes to inclusion criteria, dosing regimens, or safety monitoring procedures. Emerging safety signals may necessitate additional assessments or modified eligibility requirements. Operational challenges may require adjustments to visit schedules or sample collection procedures. Regulatory authority feedback may require protocol clarifications or modifications. Regardless of the reason, all amendments must be properly justified and documented.

The amendment approval process typically involves sequential review by the sponsor, IRB/IEC, and regulatory authorities where required. The sponsor initiates amendments and must ensure that they are scientifically appropriate and adequately documented. The IRB/IEC reviews amendments to confirm that the changes do not adversely affect the rights and welfare of participants. Regulatory authorities review amendments to ensure continued compliance with applicable requirements. Implementation cannot occur until all required approvals are obtained, and sites must be formally notified and trained on new requirements.