Clinical Trials

❘❙❚■ Chapter 3 | Protocol DevelopmentReferencesReferences should be used where required. The design of a study protocolrequires an evidence-based approach. This should justify the study rationale andbackground, and will also be relevant for preclinical and clinical information givenin the ‘investigators’ brochure’. A reference list must be included at the end of theprotocol, before any appendices, relating to rationale and statistical methods.Case record form and trial documentationThe CRF is a printed or electronic document designed to capture a required recordof data and other information for each patient during a clinical trial, as defined bythe clinical protocol. In a protocol, the type of CRF (paper or electronic) and themethod for transmitting data from the CRF to the coordination center (eg, mail,fax, electronic) for data management and analyses should be specified.The investigators’ brochure is a compilation of clinical and nonclinical data on theIMP(s) relevant to the study of the product in human participants. This documentcan be an integrated part of the protocol or prepared as a separate document toprovide researchers with information to help them understand the rationale andcomply with the protocol. Its main aim is to support clinical management of theparticipants in a clinical trial.If any protocol amendments exist, these should be integrated into the protocolor provided in separate appendices. Any other appendices (eg, flow charts,assessments, measurements) should accompany the protocol as appropriate.Documents such as the participant information sheet, consent form, andinformation letter to participants’ physicians are normally provided to the studyinvestigators separately from the protocol.Trial committeesThe study organization will depend on the complexity and size of the trial. Thefollowing committees are usually set up for most Phase III trials and described inthe protocol if relevant.34