How to prevent clinical trial protocol deviations
Protocols serve to protect the people who participate in clinical trials and provide standards so the data collected supports the study objectives. When protocols are not followed, it can create serious issues that slow the study down or significantly increase costs. These best practices can help sponsors and CROs work together seamlessly to prevent and alleviate protocol deviations in their clinical studies keeping development on time and within budget.
The guideline for Good Clinical Practice of the International Council on Harmonization (ICH GCP) defines the protocol as “A document that describes the objective (s), design, methodology, statistical considerations, and organization of a trial.” Protocols should be written in a clear and concise manner to provide all study personnel with a comprehensive understanding of the disease, the study population, and the investigational agent. Consideration must also be given to the burden that will be placed on subjects to participate and investigators to administer with integrity and rigor.
Writing a protocol that is both clear and comprehensive is a challenge for sponsors. The methodology must be as detailed as possible to ensure maximum benefit and minimum risk. However, unique procedures and expanded eligibility criteria increase the complexity of protocols; with this comes an increase in deviations.
What is a protocol deviation?
Protocol deviations, also known as violations or ‘protocol non-compliance,’ are any variances from study procedures that may reduce the quality of the data or impact a subject’s safety, rights, or welfare. GCP regulations require that investigators conduct trials in compliance with a protocol approved by a institutional review board (IRB) and should not implement any changes except when necessary to eliminate immediate risk to subjects.
While not officially defined by the FDA, the guidance also states that a protocol deviation is generally an unplanned excursion from the protocol that is not implemented or intended as a systematic change. One of the most common issues noted by the FDA during audits is that procedures are not being followed or not written down frequently noting “You [investigator] failed to ensure that the investigation was conducted according to the investigational plan [21 CFR 312.60].” This may include deviations to procedures regarding enrollment, randomization, study intervention or data collection…