Definition

An amendment to a clinical trial that significantly affects subject safety, scientific value, or conduct. Requires regulatory and ethics approval before implementation.

Example

Change of inclusion criteria, new dose, additional safety monitoring, or change of principal investigator may be substantial.

Regulatory source

EU Regulation 536/2014, national transposition

Common mistakes

Implementing the change at sites before receiving approval from all required bodies.

Inspector question

What is your process for determining substantial vs non-substantial and for obtaining approvals?

Related terms