Definition

A change to the clinical trial protocol. Substantial amendments require approval from the competent authority and favourable opinion from the ethics committee before implementation.

Example

Adding a new study arm or changing primary endpoint is usually substantial; typo corrections may be non-substantial.

Regulatory source

EU Regulation 536/2014, 21 CFR 312.30

Common mistakes

Implementing substantial amendments before approval. Not documenting and filing non-substantial amendments.

Inspector question

How do you classify and submit protocol amendments? Show the log of amendments and approvals.

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