If a protocol amendment is made to increase risk, what is required before implementation?

• A. Prior documented approval by the IRB/IEC, except in emergencies.
• B. Sponsor approval alone suffices.
• C. No approval is required if the trial is already running.
• D. Only an ethics committee at the site is sufficient.

Answer: (A)

Any change to a protocol that increases risk to participants must be reviewed and approved by the IRB/IEC before it is put into place. The IRB/IEC exists to protect participants by evaluating whether the proposed change is acceptable in terms of safety, risk-benefit balance, and how informed consent will be affected. Relying on sponsor approval alone does not provide this independent protection, and a change that increases risk cannot be implemented simply because a trial is already underway. The only exception is an emergency situation where an immediate change is needed to eliminate a hazard; in that case the change can be implemented promptly, but it must be reported to and reviewed by the IRB/IEC as soon as possible.