DATA AND SAFETY-MONITORING BOARDS
An additional question that arises in the conduct of behavioral intervention research is whether there is a need for a DSMB. Usually, this question is relevant at the later stages of the pipeline when the efficacy or the effectiveness of an intervention is being evaluated. As is the case with other aspects of research ethics, there is also some lack of consistency regarding the requirements for a DSMB across government-funding agencies. Other funding agencies such as foundations may also have requirements for the establishment of a monitoring entity for a trial. The NIH guidelines state that DSMBs are required for multisite clinical trials with interventions that entail risk(s) to participants and generally required for Phase III clinical trials (see Chapter 2). In addition, the guidelines state that a DSMB may be required for Phase I or Phase II clinical trials if it is blinded, involves a high-risk intervention, or includes vulnerable populations (National Institutes of Health, 2010). For example, a DSMB was required for the REACH II trial as it was a multisite test of an intervention and involved a vulnerable population—family caregivers and persons with dementia. However, the guidelines for when a DSMB is required are somewhat general. Thus, it is always important to review this issue with the funding official for an intervention study such as a program officer at the NIH since most institutes at the NIH have specific policies regarding the need for, and the actual structure and set of processes to follow for, a DSMB. For example, the NIA requires that all applications proposing interventions that involve humans such as behavioral interventions describe a DSMP, which includes information regarding how the study will be monitored and a plan for determination, monitoring, and a reporting system for AEs and SAEs as well as protocols for resolution of these events. In addition, the NIA may require the establishment of a DSMB depending on the characteristics of the study, and if so, will review the plan and approve its membership.
A DSMB is an independent group of experts who advise the funding agency and the investigators. That is, DSMB members must not be part of the investigative team of the study in question. Some funding agencies also insist that members are selected who are not affiliated with the institution in which the study is conducted. In general, the primary responsibilities of a DSMB are to: (a) review and approve the research protocol (including the selected outcome measures) and manual of procedures (MOPs) (see Chapter 6); (b) review and approve the safety data for the study participants and study conduct and progress (e.g., recruitment); and (c) make recommendations to the funding agency regarding continuation, modification, or termination of the trial. Generally, investigators do not nominate specific individuals for the DSMB in an application, but rather provide a list of prospective members to the funding officer (e.g., program officer) if a study is funded. The DSMB typically includes individuals with expertise in the research area and the target population, biostatistics, and research ethics. Once members are selected, the DSMB will work with the PI to determine the meeting schedule (typically twice per year) and the protocols (e.g., data table templates, what will be reported, frequency of reporting, and in-person vs. telephone vs. e-mail updates) for data reporting.
The initial meeting of the DSMB must take place at the beginning of a trial prior to entering the field or collecting data, as the DSMB is expected to review the entire IRB-approved study protocol and the MOP with regard to: subject safety, recruitment, randomization, intervention, data management, and quality control and analysis; the informed consent document with regard to applicability and readability; and protocols for identification, monitoring, reporting, and resolving AEs and SAEs (National Institute on Aging, 2015). At an initial meeting, the processes and data-reporting protocols are also determined and recommendations and/or requirements for any modifications to the protocol are provided to the PI. At subsequent meetings, the DSMB monitors the progress of the trial and the data related to the safety of the research participants. If the trial involves randomization, the committee will also review randomization outcomes. At midpoint assessment periods, they may also request to review the primary outcomes, blinded to condition. Although not typical in behavioral intervention research, they may recommend that the trial be stopped if there are significant numbers of AEs or the intervention is clearly causing harm; or the opposite, the intervention benefits are so dramatic that it is determined there is not a need to continue the study and that all participants should receive the intervention. The latter is, of course, rare.
For some intervention studies, a full DSMB may not be required and instead an independent safety monitor or Safety Monitoring Committee (SMC) is acceptable. An independent safety monitor is an “appropriate expert” who is available to review and recommend actions regarding safety events and other safety issues. An SMC is a small group of experts with at least two members who are independent of the protocol and can review the protocol and data for a study Members of an SMC can usually be selected by the PI and research team and, of course, should have expertise relevant to the trial. A member with a strong background in biostatistics is highly recommended. As with the DSMB, a plan must be in place for the responsibilities, structure, and processes of a SMC.