375. Monitoring Data for Participant Safety

Updated June 2, 2026

Among the Department of Health and Human Services (DHHS) criteria for IRB approval of research at 45 CFR 46.111 is the requirement that when appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of participants (§ CFR 46.111(1)(6)). The University interprets “when appropriate” to apply to all research posing greater than minimal risk. By routinely and periodically examining accruing data for indications of harms (including physical, psychological, economic and social harms, or changes to benefits), Principal Investigators (PIs), sponsors, independent monitors, or monitoring boards or committees may:

• identify new risks or anticipated risks that appear in greater severity or frequency than originally expected; and
• make data-based decisions about whether a study may progress as planned, requires amendments to better protect participants, or should be closed to enrollment or terminated.

Assessment of Data and Safety Monitoring Plans

The IRB will review the data and safety-monitoring plan for protocols involving more than minimal risk during initial review and at continuing review. The initial plan submitted to the IRB should describe the procedures for safety monitoring, reporting of unanticipated problems involving risks to subjects or others, descriptions of interim safety reviews and the procedures planned for transmitting the results to the IRB. This description should include information regarding an independent Data and Safety Monitoring Board (DSMB), if one exists, or an explanation why an independent data safety monitor is not necessary.

The IRB determines that the data and safety-monitoring plan makes adequate provision for monitoring the reactions of subjects and the collection of data to ensure the safety of subjects. The overall elements of the monitoring plan may vary depending on the potential risks, complexity, and nature of the research study. The method and degree of monitoring needed is related to the degree of risk involved. Monitoring may be conducted in various ways or by various individuals or groups, depending on the size and scope of the research effort. These exist on a continuum from monitoring by the principal investigator in a small, low risk study to the establishment of an independent data and safety monitoring board for a large phase III clinical trial.

The factors the IRB will consider in determining whether the data and safety-monitoring plan is adequate for the research are as follows:

• Monitoring is commensurate with the nature, complexity, size and risk involved.
• Monitoring is timely. Frequency should be commensurate with risk. Conclusions are reported to the IRB.
• For low risk studies, continuous, close monitoring by the study investigator or an independent individual may be an adequate and appropriate format for monitoring, with prompt reporting of problems to the IRB, sponsor and regulatory bodies as appropriate.
• For an individual Safety- Monitor the plan must include:
  • Parameters to be assessed.
  • Mechanism to assess the critical efficacy endpoints at intervals in order to determine when to continue, modify, or stop a study.
  • Frequency of monitoring.
  • Procedures for reporting to the IRB.
• For a Data Safety Monitoring Board, the plan must include:
  • The name of the Data Safety Monitoring Board.
  • Where appropriate, is independent from the sponsor.
  • Availability of written reports.
  • Composition of the monitoring group (if a group is to be used): experts in all scientific disciplines needed to interpret the data and ensure patient safety. Clinical trial experts, biostatisticians, bioethicists, and clinicians knowledgeable about the disease and treatment under study should be part of the monitoring group or be available if warranted.
  • Frequency and content of meeting reports.
  • The frequency and character of monitoring meetings (e.g., open or closed, public or private).

In general, it is desirable for a Data and Safety-Monitoring Board (DSMB) to be established by the study sponsor for research that is blinded, involves multiple sites, involves vulnerable subjects, or employs high-risk interventions. For some studies, the National Institutes of Health (NIH) require a DSMB. The IRB has the authority to require a DSMB or research monitor as a condition for approval of research where it determines that such monitoring is needed. When DSMBs are utilized, IRBs conducting continuing review of research may rely on a current statement from the DSMB indicating that it has and will continue to review study-wide AEs, interim findings, and any recent literature that may be relevant to the research, in lieu of requiring that this information be submitted directly to the IRB.

Minimum Requirements for Plans to Monitor Data for Participant Safety

When designing the Data Safety Monitoring Plan (DSMP) (see Policy Manual Definitions), University and affiliate investigators are advised to consider the following questions and examples:

Who will monitor the data for safety concerns?

• Principal investigator or designated co-investigator
• Named designee unassociated with the project (i.e., independent monitor)
• Independent Data Safety Monitoring Board or Committee (DSMB/C) (see Policy Manual Definitions), convened by the principal investigator or sponsor

When the study sponsor is responsible for data and safety monitoring, how will the Principal Investigator's local monitoring activities be integrated into the sponsor's plan?

• Requirements for reporting local adverse events/effects
• Requirements for routine reporting of predetermined outcomes or specified safety information
• Requirements that the contract or funding agreement should include arrangements so that data and safety monitoring plans are provided to the organization or provided to the researcher who provides them to the IRB.

What data or safety information will be reviewed?

• Type, seriousness, number, or frequency of adverse events/effects that occur locally or are pooled across all sites for multisite research
• Unanticipated problems involving participants or others that occur locally or are pooled across all sites for multisite research
• Participant outcomes, including morbidity and mortality, and drop-out rates and profiles
• Interim findings, including vital signs, and anthropometric and laboratory values
• Incidental or secondary findings that affect research risk or the reasonableness of risks with consideration for research benefits
• Reports from independent monitor or DSMB/C
• Findings other studies involving the same or similar investigational drug or device, or experimental intervention

How will the data/safety information be collected?

• Case report forms
• During study visits
• Via telephone calls with participants

How often will routine safety monitoring occur and how often will cumulative data be reviewed to identify patterns?

• Specified number of weeks or months from the onset of the research, and specified intervals thereafter
• Other parameters such as after enrollment of a specified number of participants or following a predetermined number of adverse reactions

How will adverse reactions be assessed to determine intensity, severity, frequency, and relatedness to the research?

• Use of existing standards or definitions to code/categorize adverse reactions
• Use of existing standards to code/grade adverse events
• Use of standardized incidence ranges to codify frequency
• Use of standardized or predetermined scales or categories for relatedness
• Application of knowledge related to the drug pharmacology; known or typical events associated with use of a drug/device, class of drugs/devices, or procedure or intervention; or typical progression of the disease or condition under study

What specific findings would trigger an immediate suspension of the research?

When and how often will data monitoring findings or reports be submitted to the IRB?

• As specified in the University policy for reporting problems to the IRB

How will participants be referred to medical or psychological services that may be required because of participation in the research?

How will the individual participant be notified of findings that may affect their health or welfare?

• Informed consent using a revised and updated informed consent document
• Informed consent using an addendum to the existing consent document
• Investigator or sponsor letter or other correspondence
• Orally, at participant's next research or clinical appointment

Plan for Monitoring Safety/Confidentiality

The DSMP should at a minimum address the following issues:

• A description of the plan to ensure the integrity of the data, including: (a) A description of the systems for storing and backing up the data; (b) A listing of who will monitor and review the data, and a description of the monitor’s qualifications (Note: it may be appropriate for the PI to serve as the monitor); (c) The frequency of review (e.g., specific points in time, or after a specific number of participants have enrolled); (d) A description of the data to be monitored; (e) Procedures for analysis and interpretation of the data; (f) Actions to be taken upon specific events or endpoints.
• Procedures for communication from the data monitor to the IRB and other sites;
• Protection of the rights and welfare of participants during the recruitment, consenting process and study participation;
• Protection of participant privacy and confidentiality;
• A description of the mechanisms for detecting, reviewing and reporting unanticipated problems involving risks to participants or others by the investigative team at a frequency and intensity sufficient to ensure the safety of participants.
• Assurance that research responsibilities delegated by the principal investigator to investigative team members are carried out in accordance with the protocol, federal regulations, federal, state and local laws and institutional policies and procedures.

Plan for Data Management

Investigators are required to:

• Indicate who is responsible for collection and storage of data.
• Describe how data will be organized, managed, and stored. Security measures used to protect study data from loss or inappropriate use (password protection, restricted access to database, database backup etc.).
• Include a description of how often interim data will be reviewed and by whom.
• Indicate who will perform aggregate analysis of data and adverse events, if applicable.

Other Considerations for Data Safety Monitoring

For multicenter trials when the University is the coordinating site, the local PI is responsible for reviewing and assessing safety reports forwarded by sponsors, research monitors, DSMB/C or cooperative groups.

The University IRB considers the data and safety monitoring needs of studies that do not have or are not required to have a DSMB/C; and studies that are blinded, have multiple sites, enroll vulnerable populations, or employ high-risk interventions.

When a DSMB/C is not required, the IRB may determine that statistical tests are warranted for the PI to analyze interim or safety data to determine whether harm is occurring.