“(a) In order to approve research covered by this policy the IRB shall determine that all of the following requirements are satisfied:
(6) When [Where FDA] appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.” 45 CFR 46.111(Pre-2018 Requirements), 45 CFR 46.111(2018 Requirements), 21 CFR 56.111
When appropriate, the IRB will require that the research plan makes adequate provisions for monitoring the data collected to ensure the safety of subjects or ensure negative outcomes do not occur. If required, the data oversight and monitoring plan will depend on the nature, size, risk, and complexity of the study.
Determination of Whether Data and Safety Monitoring Plan is Required
In the process of evaluating whether the IRB will require provisions for monitoring the data, the IRB assesses the following:
Development of a Data and Safety Monitoring Plan
If it is determined that the research requires data and safety monitoring, the investigator must describe the provisions for monitoring the data to ensure the safety of subjects. When required or appropriate, the PI will submit a Data Safety and Monitoring Plan (DSMP) with the IRB application. A sample template for such a plan is available on the Human Research Protection Program (HRPP) website (hrpp.msu.edu).
Data oversight and monitoring plans should vary depending on the nature, size, risk (e.g., low risk, high risk intervention) and complexity of the clinical trial (e.g., single-site, multi-site). The oversight and monitoring plan may be conducted by various individuals or groups and in various ways. For example, the PI of a small Phase I or II study involving a low-risk intervention may be qualified to monitor the progress of such a study.
Alternatively, an independent Data Safety Monitoring Board (DSMB) may be the only entity qualified to monitor the progress of a Phase I or II clinical trial involving multiple sites, blinding, high-risk interventions or vulnerable populations. DSMBs are typically committees of non-conflicted experts, including scientists, physicians, statisticians, bioethicists, and others that perform ongoing monitoring of the data and safety of interventional research trials. These committees are usually external to the research team. A DSMB evaluates the research to assure it is safe and effective, recommends conclusion of the trial when significant risks have developed, determines if the trial is deemed unlikely to be concluded successfully, or may recommend expansion of treatment beyond experimental use if significant benefits have developed. At each meeting, DSMBs typically review summary reports of adverse events, analyze interim data, cumulative toxicity summaries, reports of related studies, major proposed protocol amendments, data and monitoring plans/reports, safety and efficacy outcomes, and other aspects of protocol compliance. Following each meeting of the DSMB, the investigator should be provided with written information concerning findings or concerns related to the study. These reports should be provided to the IRB and the Sponsor.
Several methods of data and safety monitoring can be employed, depending on the level of risk. The plan should state how the safety information will be collected (e.g. with case report forms, at study visits, by telephone calls with subjects) and who would be responsible for monitoring subject safety, protocol compliance, and adverse event (including serious) reporting. Specific monitoring parameters may include the frequency or periodicity of review of cumulative safety data, subjects screened and enrolled, dropouts, primary and secondary efficacy endpoints, and/or the informed consent process. The following entities are examples of entities that can monitor subject safety and protocol compliance:
For studies that do not have or are not required to have a data monitoring committee and are blinded, have multiple sites, enter vulnerable populations, or employ high-risk interventions, the IRB will carefully review the data and safety monitoring plan and determine whether a data monitoring committee is needed. If not using a data monitoring committee, and if applicable, statistical tests for analyzing the safety data may be required to determine whether harm is occurring.
Investigators submitting applications for the National Institutes of Health (NIH) support of grants, cooperative agreements, or contracts should be aware that each specific institute may have its own policies regarding data and safety monitoring. Investigators are encouraged to visit the NIH website for the appropriate agency.
Assessment of Data and Safety Monitoring Plan
If it is determined that the research requires data and safety monitoring, as part of the IRB review process, the IRB will assess the appropriateness and adequacy of a study’s proposed data oversight and safety monitoring plan (or the justification as to why such a plan is not possible) based on the following criteria:
The IRB is guided by the NIH Policy for Data and Safety Monitoring, further NIH Guidance on Data and Safety Monitoring for Phase I and Phase II Trials, and Good Clinical Practice Guidance.
Data and Safety Monitoring Reports
The PI must submit data and safety monitoring reports received from the monitor or reports generated by the PI (when the PI is the monitor) to the IRB at the time of continuing review. If a third party monitor’s report suggests a change in the study design, a temporary or permanent closure to accrual, or any other information of note, those reports should be forwarded to the IRB immediately.
Additional Considerations
For research studies subject to the requirements of the U.S. Department of Defense, see HRPP Manual 2-2-A, “U.S. Department of Defense.”
This policy and procedure supersedes those previously drafted.
Approved By: Vice President of Research and Graduate Studies, 3-3-2005. Revision 1 approved by VP Research & Graduate Studies on 3-9-2008. Revision 2 approved by VP Research & Graduate Studies on 5-6-2008. Revision 3 approved by VP Research & Graduate Studies on 7-21-2011. Revision 4 approved by Assistant VP Regulatory Affairs on 11-24-2015. Revision 5 approved by Senior VP for Research and Innovation on 1-18-2019.