National Institutes of Health - Introduction to the Principles and Practice of Clinical Research (Developing Protocols & Manuals of Operating Procedures: An Introduction - Part 1, February 6, 2022): 15-min webinar.

• Summary: Dr. Wendy Weber defines the components of a clinical trial protocol, the importance of this document, and delineates between several related documents (e.g., a trial protocol vs. a regulatory or funding application vs. a manual of operations and procedures). The purpose of the protocol (the “roadmap” for the trial) is overviewed, e.g., the protocol serves to operationalize (potential) further applications to regulators, funders, research ethics boards; to anticipate potential problems; to safeguard participants’ health and safety; to facilitate communication among collaborators, staff, and partners; and to assist in manuscript preparation. The specific components of a trial protocol, and the value of protocol templates, are briefly introduced.

Nova Scotia Health Innovation Hub (Research Methods Unit) - A Guide for Creating a Comprehensive Research Protocol for a Clinical Trial, Observational Study or Qualitative Study (July 2023): 21-page guide.

• Summary: This guide aims to help researchers write a research protocol for a clinical trial (as well as an observational or a qualitative/mixed methods study). This guide walks through each section of a protocol giving guidance on what should be included in that section. It is emphasized that many of the methodological aspects of designing a research study and writing the protocol can benefit from the advice of a statistician and an epidemiologist trained in clinical trial methods. 

Collection of clinical trial protocol templates from various Canadian institutions: 10-page template (Bruyere Health - University of Ottawa) (2024), 42-page template (Women’s College Hospital) (November 2022), 14-page template (University of Calgary) (April 2022), 34-page template (CIHR Pan-Canadian Network for HIV and STBBI Clinical Trials Research) (2020), 52-page template (The Hospital for Sick Children) (January 2019), 13-page template (University of Alberta) (August 2009)

• Summary: The specific requirements for a clinical trial protocol may vary depending on its intended use (e.g., for submission to a regulator, to a funder, to a research ethics board, and/or to a peer-reviewed journal). Therefore, a non-exhaustive collection of protocol templates from Canadian institutions (ordered by newest to oldest) have been provided. Some elements included in these templates may not apply to clinical trials that are more pragmatic in nature, and some features relevant to pragmatic trials may not be listed in these templates. Therefore, it is recommended to use these templates while also reviewing the published pragmatic trial protocols from each of the exemplar trials covered to date (which are available under “Optional resources” on each trial-specific page: EnAKT LKD, AToM, ISLAND, MyTEMP).

NIH Pragmatic Trials Collaboratory - Reporting Pragmatic Clinical Trials (February 22, 2024): 15-page document.

• Summary: This recent pragmatic trial reporting guideline document, which includes elements from the Consolidated Standards of Reporting Trials (CONSORT) statement and its extensions, effectively highlights what should be included in a pragmatic trial protocol. Specifically, alongside the generic trial protocol templates and published pragmatic trial protocols (see above), it is useful to “reverse engineer” reporting guidelines to determine what elements should be discussed at the protocol development stage of a pragmatic trial.

Glasgow RE, et al. Protocol refinement for a diabetes pragmatic trial using the PRECIS-2 framework. BMC Health Serv Res. 2021 Oct 2;21(1):1039. (11-page paper)

• Summary: This report describes how a research team refined a protocol for a pragmatic trial and used the PRECIS-2 tool to evaluate these adaptations. The report expands on prior research by describing actions to achieve higher levels of pragmatism and provides guidance for how to revise a trial protocol to reflect these choices.

Rushforth A. Meeting pragmatism halfway: making a pragmatic clinical trial protocol. Sociol Health Illn. 2015 Nov;37(8):1285-98. (14-page paper)

• Summary: This unique paper documents the experience of clinical trial researchers working with the United Kingdom’s National Health Service (NHS); it is an overview of the co-construction of a pragmatic trial protocol with key partners, including clinicians and health care system leaders. The primary material was taken from a meeting that took place prior to the launch of a multi-centre pragmatic trial on a maternal health intervention already partly used in the NHS. The trial sought to obtain evidence as to whether the intervention could be adopted as standard care. The meeting included the “trial management group” who were the protocol authors (i.e., the researchers), along with the “trial steering committee” and “data monitoring committee” members who were independent monitors of the trial. This experience illustrated the co-production of a pragmatic clinical trial protocol, illustrating how a cross-disciplinary group navigated dual demands for being “systematic” (for instance in attending to the randomized trial and its conventions) and “pragmatic” (in accommodating the complex and heterogenous world of clinical practice).