Members of the clinical trial research team (IRB institutional review board, Co–PI coprincipal investigator)
1.2 Key Members of the Clinical Trial Research Team
1.2.1 Principal Investigator
The principal investigator (PI) oversees, and is ultimately responsible for, all aspects of the clinical trial. As specifically outlined in the Code of Federal Regulations (21 CFR 312.60), “an investigator is responsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulation; for protecting the rights, safety and welfare of subjects under the investigator’s care; and for the control of drugs under investigation” . As outlined in Table 1.1, the PI is integrally involved in all aspects of the clinical trial, from reviewing the scientific merit of the study, deciding if the trial is appropriate for the study site and the patient population, developing the budget, obtaining approval from the appropriate governing bodies (Scientific Review Committee (SRC), Investigational Review Board (IRB)), screening and enrolling patients, conducting study visits, entering data, coordinating care with the patients’ clinical care team, and monitoring safety. Ideally, the PI should have a focused clinical and research interest in the clinical question being asked. He or she should have a sufficiently robust clinical practice from which to screen patients. Indeed, some have suggested that one of the most important considerations when selecting a PI is the availability of the appropriate study participants. Experience in clinical trials is obviously extremely helpful, but perhaps not essential. Well-known scientists who do not have sufficient time to devote to the trial may not be successful. As such, it is crucial that the PI assemble a clinical trial research team. While oversight is required, PIs that have to handle all of the tasks and procedures in the clinical trial may not have the appropriate time and perspective for true oversight and may not be able to enroll a sufficient number of patients to support the trial. Teamwork and delegation are essential. This is especially important for clinical trials that have complex protocols and are data intensive. Interestingly, in a study published by Shea and colleagues, factors associated with enrollment of eligible participants with documented myocardial infarction were reported. Possible correlations were found in institutions in which study participants were cared for by staff other than attending physicians and with the presence of a committed nurse coordinator .
Responsibilities of the principal investigator
Reading and understanding the investigator brochure
Obtaining IRB approval and complying with all decisions
Conducting the study in accordance with the protocol
Maintaining adequate records and making them available for review
Personally conducting the study or supervising other trained personnel
Ensure that research team members are qualified and appropriately trained and retrained
Informing study participants about the investigational nature of clinical trials
Ensuring that informed consent is properly obtained
Reporting adverse events in accordance with federal and institutional code
Reporting any change in the research
Reporting protocol violations
Making no change in the protocol without the prior approval of the IRB
1.2.2 Co-principal Investigators
It may be important to have additional co-PIs involved in the oversight of the clinical trial. They may be clinical partners that can help to identify potential study subjects or be a part of a larger multidisciplinary group. They may have expertise in slightly different clinical or research areas. Often, expertise in other specialities may be needed for consultation regarding risk. For example, if a study drug is known to have cardiac side effects, IRBs may require that a cardiologist review the protocol and be a formal member of the research team. Another collaborative co-PI to consider in the study team may be a radiologist or pathologist, brought on to read x-rays or review cytopathology for a clinical trial. This approach leads to less variability in the interpretation of the data but a greater potential for bias.
1.2.3 Clinical Research Coordinator/Data Manager
The clinical research coordinator is in many ways the engine of the clinical trial. The importance of their role cannot be overemphasized. The research coordinator helps prepare the informed consent and the clinical trial submission to local IRBs and interacts with patients during the screening, enrollment, and study visits. They enter data and organize study documents. They interface with industry, contracts and grants, and study monitors. They submit invoices for billing and facilitate communication with primary care physicians (www.clinicaltrialguru.com). An excellent clinical research coordinator is a true prize. Some of the more critical traits in a research coordinator include the following: organizational skills, attention to detail, interpersonal skills, and computer and database experience. A medical or scientific background may be helpful, but it is not essential and may be easier taught than the other more innate personal characteristics. It is desirable that the job be held by someone who can commit to a reasonable length of time (e.g., 1–2 years, such that multiple RCs are not needed throughout the life of the trial). Suffice to say, it is worthwhile spending considerable time and effort in hiring a research coordinator. They can make or break the clinical trial.
1.2.4 Nurse Coordinator/Research Nurse
There is some overlap between a clinical research coordinator and a nurse coordinator. In a complex clinical trial, both roles may be essential to complete the procedures, regulatory requirements, and data entry outlined in the protocol. As the clinical research coordinator focuses on the regulatory aspects of the trial, the nurse coordinator can focus on the clinical “arm” of the study. He or she can assist in screening and enrollment of study participants, both of which are data intensive. Nurse coordinators are extremely important in clinical trials involving multiple study procedures, such as electrocardiograms, venipunctures, and hemodynamic testing. Depending on their level of training, research coordinators may not be able to perform these tests.
At some institutions with well-developed infrastructure for clinical research, either or both the clinical research coordinator and the nurse coordinator may be centralized positions, in which they are involved in multiple studies that do not require 100 % time.
A biostatistician should be an integral and early member of the clinical trial research team . He or she must review the design and methodology of the clinical trial and ensure that the study is adequately powered to answer the proposed question . They perform statistical analysis when the data have been collected and may be involved in interim analysis of the data. Clearly, this is crucial to the eventual success of the trial. Many academic institutions have skilled biostatisticians that can be consulted.
A budget is essential to ensure that a clinical trial can be conducted effectively and safely and in the black. Therefore, a financial expert needs to be identified to carefully prepare and review the budget. In-depth discussion of preparing the budget is outside the scope of this chapter. However, in general, the investigators and the sponsor must take into account (1) what the cost for study procedures are, (2) what procedures will be covered by a third-party payer, and (3) what constitutes direct and indirect costs in the study . The financial expert also has the responsibility of documenting and justifying expenditures for external or extramural funding sources. In an investigator-initiated clinical trial, the financial expert may be the PI of the study. However, if the PI does not have sufficient experience in preparing budgets, it may be a senior partner or another colleague with this particular skill set. In industry-sponsored trials, the budget may be proposed by the sponsor and then reviewed and adjusted by the PI. It is important for the budget to be as comprehensive as possible, with frequent and careful review of the protocol. Depending on the complexity of the trial and ongoing requirements of time and energy, it may be appropriate to budget in a percentage of the PI salary or support for a nurse or data coordinator.