The Importance of Real-time Data and Safety Monitoring

Researchers at Baylor College of Medicine Houston announced this week that they were stopping a clinical trial investigating the efficacy of convalescent plasma therapy in the treatment of patients with COVID-19. The reason, according to the principal investigator, was that statisticians had deemed the NIH-funded study to be futile. In other words, even with more patients enrolled in the study, the experts monitoring the data did not believe there was a realistic chance that convalescent plasma therapy would demonstrate efficacy.

Behind the headline is another important consideration: the importance for Institutional Review Boards (IRBs) to ensure that studies they approve have strong data and safety monitoring plans (DSMP). Data and safety monitoring functions are distinct from the requirement for study review and approval by an Institutional Review Board (IRB).

“Since IRB review occurs only at certain intervals, real-time data monitoring is typically done by a formal Data Safety Monitoring Board (DSMB) or another similar independent committee, as designated by the DSMP,” according to Linda Reuter, BRANY’s IRB Director. “As such, it is crucial for IRBs to consider the IRB approval criteria that risks to subjects are minimized and the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects by confirming that there is a plan to analyze the data at the appropriate intervals.”

“The IRB must determine that the provisions for data and safety monitoring are appropriate in order to approve a protocol,” adds Raffaella Hart, BRANY’s Sr Vice President for IRB and IBC Services. “Clinical trials should have a provision for data and safety monitoring that corresponds to the risks of the study.” The NIH has guidance on determining which studies require a Data and Safety Monitoring Board (DSMB). Multi-site clinical trials involving interventions that entail potential risk to the participants require DSMBs.

Review by an independent monitoring committee is especially important for multicenter clinical trials, as data from one site may not be enough to notice a safety signal at an early stage, but when data from multiple sites are aggregated and analyzed by the safety committee certain safety signals may become evident.

The method and degree of monitoring varies from one clinical trial to another and is based on the degree of risk involved, as well as the size and complexity of the trial. While not all clinical trials require a data and safety monitoring board, the NIH does set minimum standards for monitoring, including ensuring that monitoring is timely and effective and that those responsible for monitoring have the appropriate expertise to accomplish its mission. Monitoring plans typically include the following:

  • Safety reporting requirements and procedures
  • Rules for when to conduct interim analyses to assess safety and/or efficacy
  • How the study will comply with any applicable regulatory requirements
  • How the study will monitor site performance, including patient recruitment
  • How to protect data integrity and participant confidentiality
  • Statistical analysis procedures

Data and Safety Monitoring Board determines the safe and effective conduct of the trial, and establishes rules for deciding when it may be time to conclude the trial. The committee makes this important decision based on evaluating if significant benefits or risks have developed or the trial is unlikely to be concluded successfully. This was the case in the above-mentioned plasma therapy trial.  DSMBs should include clinical trial experts, biostatisticians, bioethicists, and clinicians knowledgeable about the disease and treatment under study. Ideally, members should not have a vested interest in the outcome of the study, in order to avoid conflicts of interest.

“Early and ongoing data analysis is critical to the safety and protection of study participants,” says Ms. Reuter.