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.
  
• Treatment Plan—a detailed description of the treatment that enrolled patients will receive. CTEP uses the treatment plan to derive the Treatment Assignment Codes and Descriptors (TACs/TADs). CTEP has posted to the Web site a guide for the development of TACs and TADs (http://ctep.cancer.gov/protocolDevelopment/docs/TreatmentAssignment.pdf).5
  
• Procedures for Patient Entry on Study—describes how eligible patients, as indicated by the protocol, are registered in the study according to the procedure set by the sponsor or the institution or both.
  
• Dose Modifications for Adverse Events—describes how the principal investigator will modify the administration of the agent under study in the event that an adverse event (AE) is experienced. This modification is specified by nature and grade of the AE (see “Adverse Event Reporting” section later in the chapter).
  
• Criteria for Response Assessment—the CTEP Web site contains information about the use of the Response Evaluation Criteria in Solid Tumors (http://ctep.cancer.gov/protocolDevelopment/docs/recist_guideline.pdf).6
  
• Monitoring of Patients—specifically describes how patients will be monitored and at what frequency.
  
• Off-Study Criteria—describes the conditions under which a subject will need to be taken off the study due to certain adverse events or conditions that may not be beneficial to the subject if he/she continues to participate. Also addresses how patients will be followed once off-study.
  
• Adverse Event Reporting—see “Adverse Event Reporting” section later in the chapter.
  
• Tissue Handling, Laboratory, and Correlative Science Studies—describes what materials if any are needed to be processed for analysis and how these materials are to be handled and stored.
  
• Statistical Considerations—this is an essential component that is used in the formulation of the most basic hypothesis and objectives for the trial, the analyses, and eventual publication of the study.
  
• Informed Consent—see the separate section on “Informed Consent” later in the chapter.

The IRB can be a local hospital or university-based, independent, or central IRB. Independent IRBs are generally for-profit organizations and are most often used by industry-sponsored clinical trials. The central IRB is sponsored by the National Cancer Institute and used for cooperative group studies. An IRB is an administrative body established to protect the rights and welfare of human subjects recruited to participate in research activities conducted under the auspices of the institution with which it is affiliated. The IRB has the authority to approve, require modifications in, or disapprove all research activities that fall within its jurisdiction as specified by both federal regulations and institutional policy. The involvement of human subjects in research will not be permitted until the IRB has reviewed and approved the research protocol and informed consent document. IRB members may include physicians, scientists, pharmacists, a chaplain, a social worker, a retired nurse, an attorney, and a patient. The IRB reviews new protocols, ongoing protocols, protocol amendments, and any adverse reactions experienced by protocol patients. The IRB Guidebook on the Web site of the Office for Human Research Protections (OHRP) is an excellent resource that provides OHRP’s interpretation of the federal regulations regarding the function of IRBs. The guidebook discusses many aspects of how IRBs function (http://www.hhs.gov/ohrp/irb/irb_guidebook.htm).7

The safe and effective delivery of a clinical research trial is dependent on key research personnel who conduct the day-to-day “hands-on” functions of the clinical trial. One such key research personnel in the majority of academic and private clinics is the research nurse (RN), who is responsible for conducting the daily activities of the clinical trial, ensuring patient safety, and maintaining a large body of specialized knowledge. Historically, for example, at The University of Texas MD Anderson Cancer Center, before the late 1970s the role of the RN in clinical research trials was mainly that of a data manager (collect the data, enter the data), with occasional administration of treatment. However, over the last 2 decades, the role of the RN has undergone a significant evolution to that of a broader role due to the increasing volume. The clinical RN frequently performs multiple roles all throughout the conduction of the clinical research trial that incorporate the nursing process: educator, patient advocate, direct care provider, coordinator of care, data manager, and protocol manager. The RN’s role in clinical research today is critical, requiring the daily performance of a set of multiple and complex tasks while having a large body of specialized knowledge in order to promote patient safety and effectiveness of the clinical trial.