Protocol development is a meticulous process that requires a team of professionals who are proficient in the performance of the tasks involved. Proper implementation and coordination of the protocol is managed by the research team, which is headed by the principal investigator, who develops the protocol and oversees the overall management of the study. The research nurse or research coordinator is responsible for implementation and coordination of the study according to the protocol requirements. Another important member of the team is a program coordinator, who is knowledgeable about regulatory requirements and ensures that proper documents and updates are submitted to the institutional review board (IRB) in a timely fashion. All members must have a good understanding of the Code of Federal Regulations and International Conference on Harmonisation Guideline for Good Clinical Practice.1
The National Cancer Institute and their Cancer Therapy Evaluation Program (CTEP) have developed aids for assistance with protocol development, as well as a listing of specific protocol elements that should be included in clinical protocols, which are also generally summarized below. This exceptional resource is available on the CTEP Web site (http://ctep.cancer.gov/protocolDevelopment/default.htm#protocol_development).2
Protocols containing complex scientific information can be organized and simplified by utilizing protocol templates, which can also expedite the review process. Using the CTEP protocol template as an example,2 the major components of a protocol are listed below:
- Title Page—lists the title of the study, version date, contact information of the principal investigator, coinvestigators, and other study personnel.
- Treatment Schema—provides a summary of the proposed treatment plan.
- Table of Contents—includes page numbers.
- Objective(s)—description of the primary protocol objectives and secondary objectives.
- Background and Rationale—background information on the various currently accepted treatments available and investigational study agent(s), including the mechanism of action, summaries of clinical and nonclinical studies and pharmacokinetics, safety profile, the rationale for the proposed starting doses and dose-escalation scheme, and the results of other clinical studies using a brief overview. Also included is background information on the study disease and the background and rationale for evaluating the study agent in the study disease.
- Patient Eligibility Criteria—specifically states the conditions under which a patient is eligible to join the study. Includes references to diagnosis, prior therapies, age, performance status, and organ and marrow function. This section will also include criteria that make a patient ineligible for the study, such as treatment with other agents, allergies to the class of agent under study, pregnancy, brain metastasis, and HIV infection. CTEP has also developed guidelines that can be used during the protocol writing process that outline the inclusion of various populations. These guidelines are posted on the CTEP Web site (http://ctep.cancer.gov/guidelines/templates.html).3
- Pharmaceutical Information—The Pharmaceutical Management Branch (PMB) has posted a primer recommending how this section should be completed on the CTEP Web site (http://ctep.cancer.gov/protocolDevelopment/policies_pharm.htm).4 The PMB pharmaceutical data sheet for the CTEP-held investigational new drug agent(s) will be provided with the concept approval letter....