375. Monitoring Data for Participant Safety

Updated July 1, 2019

Among the 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 subjects (§ 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, 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 subjects, or should be closed to enrollment or terminated.

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

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?

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

How will the individual participant be notified of findings that may affect her/his 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

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 gives additional consideration to 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.