Essential documents Deep Dive: The clinical protocol and amendments


Hart’s Good Clinical Practice glossary series

Welcome back to the Hart GCP knowledge series. We have been reviewing essential documents, and we looked specifically at the Investigator brochure in our last glossary post. In today’s post, we will dive a bit deeper into what is required for a clinical study protocol.

The guideline defines a protocol as “a document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents. Throughout the ICH GCP Guidance, the term protocol refers to protocol and protocol amendments”.  The definition for a protocol amendment is, “a written description of a change(s) to or formal clarification of a protocol.

Protocol and its amendments are the map to a clinical study.  These documents lay out the plan for the study and for continent plans if things don’t go according to plan.  They form the blueprint for each study’s conduct for the sponsor, sites, IRB/EC, and regulatory agencies to gauge the scientific merit and likelihood of successful execution for each study.

Section 6 of the guideline provides the minimum information that should be included in a clinical protocol and suggests options for its layout.  Site-specific information, pre-clinical background information, or other required information may be contained is separate documents that are referenced within the study protocol.  These may include documents such as the investigator brochure, statistical analysis plan, monitoring plan, financial contract, or insurance, etc.

For details on the preparation of a study protocol and amendments, please see the E6 guideline, here. Generally, a protocol (or its reference documents) should include the following:

  • General information
  • Background information
  • Details about the objectives and purpose of the trial
  • Trial design details
  • Selection and withdrawal of study participants
  • Treatment of study participants
  • Assessment of efficacy
  • Assessment of safety
  • Statistics
  • Assurance of direct access to source data and documents for monitoring, audits, IRB/EC review, etc.
  • Quality control and quality assurance
  • Financing and insurance
  • Publication policy
  • Supplements

The protocol should have an area for the primary investigator’s signature, which asserts that the trial will be conducted in compliance with the protocol, good clinical practices, and all applicable regulatory requirements.  All protocol amendments should include revision numbers, dates, and the primary investigator’s signature.

Thank you for reading HCC’s glossary series! Next time we will continue to examine key essential documents by looking at advertisements used during a trial.