Writing a research protocol is probably one of the most challenging and difficult task in medical writing. Every clinical investigation begins with the development of a clinical protocol. Clinical research is conducted according to a plan (a protocol).

The protocol provides the guidelines for conducting the trial- unmet need (background and rationale), why trial is carried out (objectives, questions that need to be answered), how and when it is carried out (eligibility of the participants, the length of the study, the medications, procedures, visits and the related tests), what are the endpoints (answers and data that need to be collected), statistical considerations, and organisation of a clinical trial. Like any other document that is part of a trial, even a protocol should be version and date controlled, using a standard convention. Once a protocol is finalized, it can be considered a source for development of informed consent form and case report form.

Writing a protocol is a team effort, of key opinion leader, medical writer, statistician, pharmacovigilance leader, research scientist, data manager, project manager, central lab etc who provide their expert inputs in each applicable section. In case of conflicting comments, an adjudication meeting should be held to resolve the same. An ideal protocol should be clear, free of typographical errors, accurate and easy to read. It should safeguard the safety of subjects and should be in perfect alignment with regulatory, scientific, ethical, legal, and operational/logistic standards. In some cases, changes to the research protocol may be necessary. In preparation for this contingency, the team should consider foreseeable deviations from the protocol and have a plan to address and report them.

The trial protocol serves as the basis for trial registration, and facilitates study appraisal by regulators, ethics committees/institutional review boards, and journal editors. Many protocols do not fully address important study elements; thereby leading to burdensome and costly protocol amendments. Many times, there is inter- and intra- protocol variability. It has led to the development of -Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT), statement and checklist which defines standard protocol items for clinical trials and provides recommendations; in line with Declaration of Helsinki, and International Conference on Harmonisation Good Clinical Practice E6 guidance. Recent advances also include FDA NIH common protocol template, risk based monitoring considerations, use of adaptive trial designs.