3.6 - Importance of the Research Protocol

A protocol is a document that specifies the research plan for the clinical trial. It is the single-most-important quality control tool for all aspects of a clinical trial. (Piantadosi 2005) This is especially true in a multi-center clinical trial, which requires collaboration in the research activities of many investigators and their staffs at multiple institutions.

Every clinical trial experiences violations of the protocol. Some violations are due to differences in interpretation, some are due to carelessness, and some are due to unforeseen circumstances. Some protocol deviations are inconsequential but others can affect the validity of the trial. For instance, a patient might be unaware of a condition that is present in its early or latent stage or a patient may mislead a researcher intentionally, thinking they will receive special treatment from participating in a study – both result in violations of the patient exclusion criteria established in the research protocol. Protocol amendments are common as a long-term multi-center study progresses. The most serious violations are those which may affect the conclusions of the study.

The SPIRIT 2013 statement by an international collaboration of persons or groups responsible for funding, conducting, and publishing results of clinical trials, along with ethicists, sets forth minimal elements that should be included in a clinical trial protocol and provides a checklist. The US NIH has its own template for a phase 2 or 3 clinical trial protocol.

If the conduct of a particular trial is particularly difficult, and especially if it is a multi-center study, the investigators will construct a manual of operations (MOP). The MOP has more detailed explanations than the protocol for how the measurements should be taken, how the data collection forms should be completed, etc.