Thursday, November 17, 2011

IRBs Must Review and Approve Plans for Data and Safety Monitoring

The regulatory criteria for approval of research includes the requirement that, when appropriate, the research plan makes adequate provisions for monitoring the data collected to ensure the safety of participants. The researchers and the IRB must “satisfy” this criterion before the research can be approved and conducted. The National Institutes of Health (NIH) require all clinical trials to have data and safety monitoring, with the method and degree of monitoring commensurate with the risks.1 Every NIH institute offers guidance on data and safety monitoring plans. The Food and Drug Administration (FDA) provides guidance for the establishment and operation of clinical trial data monitoring committees and in August released draft guidance for oversight of clinical investigations with a risk-based approach to monitoring.2-3  AAHRPP has incorporated this requirement into Element II.3.B.: The IRB or EC has and follows written policies and procedures for reviewing the plan for data and safety monitoring, when applicable, and determines that the data and safety monitoring plan provides adequate protection for participants. In general, data and safety monitoring plans should be required for research that involves greater than minimal risk, but in some instances the IRB may find such plans important for a particular research project that is considered no greater than minimal risk.

The Evaluation Instrument for Accreditation gives some details about what such a plan may include. For investigator-initiated research, the researcher must develop and submit a data and safety monitoring plan as part of the research protocol. If the researcher is conducting a study as part of a multisite or industry-sponsored trial, the researcher must obtain and submit the overall data and safety monitoring plan to the IRB (when the protocol is being reviewed locally). Whether the data and safety monitoring report is self-generated or received from the sponsor or data and safety monitoring board, the researcher has the obligation to submit it to the IRB at least on an annual basis and in an emergent situation when necessary. IRB applications should list questions for researchers and allow space for them to describe their data and safety monitoring plans. All researchers should read data and safety monitoring reports and take any appropriate actions. While research staff should also read the reports, it is imperative for the researcher responsible for the care of the participant to be aware of potential problems that the reports may highlight.

The IRB has the responsibility to review the data and safety monitoring plan and determine that it is adequate for the proposed research. Unless IRB members determine that a plan is not required, they should not approve the research without also reviewing and approving the data and safety monitoring plan. This holds true for both investigator-initiated and sponsor-initiated research. The data and safety monitoring plan should incorporate an analysis of risks and potential benefits and, based on that assessment, steps for monitoring the research for safety. It should stipulate the individual or entity responsible for monitoring, the measures that will be monitored, the method and frequency of analysis, and whether these functions will be carried out by an individual or by a data and safety monitoring board or committee. It is often appropriate for a data and safety monitoring board to be independent of the research team to ensure an unbiased analysis of the data. Data and safety monitoring boards should meet periodically on a predetermined schedule. The data and safety monitoring plan should consider what conditions would trigger the suspension or termination of the study and what precautions need to be taken to ensure the validity and integrity of the data. Finally, the plan should include a mechanism for reporting emergent issues and routine data and safety monitoring results. The data and safety monitoring reports must always be sent to the reviewing IRBs. AAHRPP Element I.8.C. requires the sponsor to submit reports in accordance with the data and safety monitoring plan approved by the IRB.

Monitoring plans do not always require data and safety monitoring boards or committees. The plan may mandate enhanced adverse event reporting and monitoring, data verification, interim analyses and stopping points, or protocol compliance monitoring. These tasks can be performed by the researchers or research staff or by designated monitors. The IRB may require reporting after a set number of participants are enrolled or receive the interventions, or require continuing review more frequent than annually.

When appropriate, IRB members should question a data and safety monitoring plan if they believe it is not adequate, even when the research follows an industry-sponsored protocol. This is especially true when there is no requirement to provide data and safety monitoring reports at least annually. Researchers should be required to submit data and safety monitoring reports at continuing review. IRBs need to review data safety monitoring reports and consider them when granting continuing approval of research.

A common, and somewhat controversial, question is whether there should be a data and safety monitoring plan in social and behavioral research. The answer: Sometimes it is appropriate. Even in research posing low risk a researcher might impose stopping points if one group is faring better than another group, or one group is placed at a detriment because of the research. For example, if an experimental curriculum in education research is not working and students are failing at a higher rate, a stopping rule might be important to minimize risk associated with the study. Researchers and IRBs should consider these issues during the development and review of research proposals. These deliberations are a normal and routine part of research development and not just a requirement of the IRB. This is true of social and behavioral as well as biomedical research.

Data and safety monitoring plans are an important, and required, component for protecting human participants in research. Researchers should integrate these plans into their research design and methods, and IRBs should review and approve them, and when necessary require changes, to protect participants.

1. NIH Guide, June 12, 1998: NIH Policy for Data and Safety Monitoring.
2. Guidance for Clinical Trial Sponsors: Establishment and Operation of Clinical Trial Data Monitoring Committees. Food and Drug Administration, March 2006.
3. Guidance for Industry: Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring. Food and Drug Administration, Draft Guidance, August 2011.

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