The year of the coronavirus pandemic has ushered in a time when the quiet, behind-the-scenes work of data safety monitoring boards (DSMBs) has entered national consciousness.

“The pandemic has brought DSMBs into the limelight. They were always important, but a quiet part of clinical trials; now, CNN and CBS News try to explain their role to the public,” said Jonathan Seltzer, MD, MBA, MA, FACC, chief scientific officer at WCG in Philadelphia. Seltzer spoke at a Dec. 2 WCG webinar on COVID-19 research.

DSMBs have been an essential fabric of clinical trials in recent decades, but until 2020, their work largely was under the public radar. When interim information came out about a few vaccines for SARS-CoV-2, this all changed. Television, newspaper, and online journalists began to talk about DSMBs and their role in pausing studies and watching for safety issues.

“It’s amazing to get people to understand DSMBs and that they’re now mainstream,” says Mitchell Warren, executive director of AVAC, a global HIV prevention organization in New York. Warren is on a DSMB for HIV research as an advocate member. “Now, my mother knows about stopping clinical trials. As her son, who has been working on this for years, I don’t think she knew about DSMBs before COVID,” Warren says. “COVID has opened up opportunities to explain research. It has changed the conversation.”

The DSMB, as defined by the Department of Health and Human Services (HHS), is “a committee of experts responsible for reviewing clinical trial data on an ongoing basis to ensure the safety of study subjects and validity and integrity of the data.”1

In November, DSMBs monitoring the Pfizer/BioNTech coronavirus vaccine and the MODERNA mRNA-1273 vaccine candidate found positive interim results in how the two products prevented SARS-CoV-2 infection.2 The National Institutes of Health (NIH) reported on Nov. 16 that an independent DSMB found the NIH-Moderna vaccine to be safe and effective for adults.3

DSMB members are independent experts who have no vested interest in a specific treatment, according to the HHS Office of Inspector General (OIG), in a 2013 report, titled Data and Safety Monitoring Boards in NIH Clinical Trials: Meeting Guidance, But Facing Some Issues.

DSMBs meet regularly to review interim trial data. If they find issues related to safety or data integrity, they can make a recommendation about whether the clinical trial should continue or be stopped.4

In the 2013 report, the OIG found that four of seven trials the DSMBs recommended stopping were based on findings that the treatment was ineffective. The other three were based on the trials’ problems with enrolling enough research participants in the allotted time necessary for useful results.

Recent DSMB recommendations with the Pfizer and Moderna vaccine candidates were to make the study intervention more widely available because of its efficacy.

“Rapid evaluation of vaccine therapy has allowed manufacturers to move toward an emergency use authorization [EUA],” Seltzer says. “If they show a modicum of success, we’d like to end those trials so people can avail themselves of those therapies.”

DSMBs need several characteristics to succeed at these data reviews. First, they must be independent. Members cannot have any personal or academic interest in the trial they evaluate, he says.

“That’s harder than you might think, especially in a highly politicized environment,” Seltzer explains. “DSMB folks need to understand the impact of their decisions and have a good deal of comfort with the uncertainty of evaluating clinical trial data.”

This is especially true during the pandemic, when DSMBs must avoid public perceptions of political or financial influence over their decisions. They also must be vigilant to view data more often in case of safety or efficacy concerns.

“As we look back at 2020, the public might see the traditional role of data safety monitoring boards, and this has forced DSMBs to be more responsive and faster acting than ever,” Seltzer adds. “I hope these changes to DSMBs will endure and be a silver lining at the end of [the pandemic].”

To a DSMB, safety is the primary focus: “Every conversation begins with, ‘Is it safe?’” Warren says. “Even if a product is effective, the board spends an inordinate amount of time to see if it’s safe.”

Warren says DSMBs review studies at various points in clinical research, assessing study design, and asking these sorts of questions:

  • Are there specific issues?
  • Is there a clear analysis plan?
  • Are there clear stopping rules?

“There can be hundreds of pages of data tables, safety events, and anything that has occurred, including diarrhea, nausea,” Warren says. “The frequency of DSMB meetings depends on the clinical trial.”

Members of DSMBs should reflect all aspects of a clinical trial, he says.

“Clinical trials need statistics, medical professionals, an ethicist, and someone who represents the community that will be impacted by the trial,” Warren explains. “Their independence is fiercely protected.”

For instance, one DSMB member stepped off the board when her employer began to fund a trial that was related to — but not the same as — the one the DSMB was monitoring, he recalls.

“Most DSMB meetings are boring. They look at data and see if the product looks safe,” Warren says. “They want stringent data to show benefit, and if you stop for efficacy, it’s hard to do; stopping for harm is much more focused.”

REFERENCES

  1. Office of Inspector General. Data and Safety Monitoring Boards in NIH Clinical Trials: Meeting Guidance, but Facing Some Issues. OEI-12-11-00070. June 2013. https://bit.ly/3qvEdlf
  2. Martin-Moreno JM, Middleton J, Sheek-Hussein M, Green MS. Covid-19 vaccines: Where are the data? BMJ Opinion. https://bit.ly/2VGOxZD
  3. National Institutes of Health. Promising interim results from clinical trial of NIH-Moderna COVID-19 vaccine. Nov. 16, 2020. https://bit.ly/39T7lND
  4. Department of Health and Human Services. Office of Inspector General. Data and Safety Monitoring Boards in NIH Clinical Trials: Meeting Guidance, but Facing Some Issues. June 28, 2013. https://bit.ly/3qE061F