Protocol development

Protocol development

A protocol is the core document that describes the objectives, design, methodology, statistical considerations, and organisation of a clinical trial. The protocol starts by providing information on the background and rationale of the study, then proceeds to outline the plan of the trial. This plan must be carefully designed to safeguard the health and safety of the participants, as well as answer specific research question(s). The protocol also serves an external purpose by providing a clear and full description of your study’s processes such that the study results can be thoroughly understood by others.

Clinical trial protocols should adhere to the ‘SPIRIT statement‘, which ensures that all important material is clearly documented. In brief, the topics that require coverage in the protocol are:

  1. Background and Rationale to the clinical trial
  2. Study objectives (primary and secondary objectives)
  3. Selection and enrolment of participants (including inclusion/exclusion criteria)
  4. Trial design: full description including (but not limited to) type of trial (e.g. parallel, crossover, factorial, single group), allocation ratio, a description of the intervention in sufficient detail including schedule of tests, procedures, medications and dosages, and duration of trial.
  5. Statistical considerations including outcome assessment (primary and secondary outcomes)
  6. Data collection and management
  7. Ethics and dissemination
  1. Protocols should be controlled documents; with versions numbered and dated. This is essential such that all collaborators are using the same version. A record of changes should be kept.
  2. Patients and public involvement (PPI) help to shape fundamental aspects of the protocol to ensure it takes into account the needs of participants. Examples of PPI are provided by NIHR INVOLVE
  3. Protocol registration: Most journals require many studies to have been listed on an independent, free to access, validated public register (as The trial must be registered before the first patient is recruited. See Trial Registration

Many institutions have developed their own template for clinical trial protocols (see links below). Others set a checklist including recommendations for a minimum set of scientific, ethical, and administrative elements that should be addressed in a clinical trial protocol (e.g. The SPIRIT statement, direct download here). The SPIRIT Statement provides recommendations for a minimum set of scientific, ethical, and administrative elements that should be addressed in a clinical trial protocol. The Statement also details the scope and systematic development methods of the SPIRIT guidance.

The final protocol should be signed off by the Chief Investigator as a minimum, but usually other signatures may be required such as those from the sponsor and trial statistician. The sponsor should specify (usually in their policies/procedures) which signatures are required and the Chief Investigator should be aware of their local requirements. In multi-site trials, it is good practice to ensure the Principal Investigator signs a protocol signature page to confirm receipt and signal their agreement to work to the current version of the protocol.