A group you’ve probably never heard of holds powerful sway over which coronavirus vaccines will end up on the market.
It’s known as the DSMB.
Members of a Data and Safety Monitoring Board are the only ones who get to look under the hood while a trial is ongoing. They know who has been given a Covid-19 vaccine, and who has gotten a placebo. The very doctors running the trials, the pharmaceutical companies that developed the vaccines, and even the US Food and Drug Administration don’t know.
Armed with that secret, only the DSMB can monitor how safe and effective a vaccine is shaping up to be.
One word from the DSMB, and a trial can be stopped. That’s what happened to the AstraZeneca trial in early September after a study participant developed neurological symptoms. Shortly after, it came to light that the same trial had been paused briefly in July for similar reasons. While the vaccine trial resumed in the UK, it is still on pause in the US.
“They’re very powerful. They’re key guardians of science and safety and are as important if not more important than the FDA,” said bioethicist Art Caplan.
The need for anonymity
Earlier this year, the National Institutes of Health appointed a common DSMB to monitor Covid-19 vaccine clinical trials that are being funded by the federal government under Operation Warp Speed. This DSMB has 10 to 15 members with specialties including vaccine development, statistics and ethics.
It’s not a glamorous or public-facing job. They’re paid only a modest honorarium by the NIH – just $200 per meeting – and there are no press conferences, no TV interviews, no fame and no glory.
That’s because members’ names aren’t typically revealed while trials are in progress to shield them from external pressures.
Caplan, who has served on about 20 DSMBs, said there’s a good reason members’ names are kept secret.
“You wouldn’t want some investor calling a DSMB member and saying ‘Hey, how’s this clinical trial looking? If you tell me, I’ll give you 10% of whatever I make,’” said Caplan.
Carrie Wolinetz, associate director for science policy at the National Institutes of Health, said various types of people might try to influence DSMB members.
“It doesn’t have to be nefarious. Parents of a very ill child might be anxious about how the trial of a drug that could help their child is going, and they might contact the folks at the DSMB. Keeping their names private is a way to preserve independence of the group,” she said.
There’s a lot at stake. They scrutinize the data carefully. One word from them, and a vaccine’s chances of coming to market could be squashed. Millions of dollars spent on research and development could all be for naught.
While there are good arguments for secrecy, Caplan said he disagrees with the confidentiality that currently shrouds the DSMBs for Covid-19 vaccine candidates.
“We need to know if we can trust the vaccine, so the more transparency the better,” Caplan said.
In order to reach population immunity through a vaccine, a large proportion of the US public needs to get vaccinated. But confidence in a potential vaccine is low – 49% of Americans say they definitely or probably would not get a vaccine if one were available now, according to a recent poll by the Pew Research Center.
“We want to know they’re fully independent, that they have no prior relationships with the company. So they’re not conflicted in any way,” said Dr. Eric Topol, professor of molecular medicine at Scripps Research. “We want to know about their expertise. It’s important to know who they are.”
How DSMBs work
The job of the DSMB, as the name suggests, is to monitor the data that comes out of clinical trials.
In clinical trials, there can be thousands, or tens of thousands, of study participants. Some are randomly assigned to receive an intervention – in this case, the vaccine – and some receive a placebo.
The studies are what’s called “double-blinded.” The participants don’t know which they’re getting, and neither do the doctors running the trials.
If a study volunteer has what appears to be a side effect or “adverse event,” the DSMB can look and see if they received the vaccine or the placebo.
“If it was a placebo, then it’s one of these random things,” Susan Ellenberg, a member of Covid-19-related DSMBs, told CNN’s Chief Medical Correspondent Dr. Sanjay Gupta. “If it was the vaccine, it could still have been a random thing. But then people have to wring their hands and try and consider how likely is it that the vaccine could cause this kind of event?”
If these events are concerning enough, the DSMB can recommend that the trial be stopped for safety reasons. The stakes are especially high in Covid-19 vaccine trials, which may ultimately be administered to millions of healthy people – unlike drug trials intended for those who are already sick and may have few options.
“Even an adverse event that happens as infrequently as one in 10,000 people or one in 20,000 people – that would be a lot of people who would have a serious adverse event,” explained Ellenberg, a professor of biostatistics at the Perelman School of Medicine at the University of Pennsylvania.
At pre-determined intervals, the DSMB also checks on efficacy. If people receiving the vaccine get sick roughly as often as those who get the placebo, that’s not a good sign. The board can recommend that the trial be stopped due to “futility.”
They may also look at the quality of the data, Ellenberg said. If there’s missing data, participants who drop out, or if the trial is being conducted poorly, it’s the DSMB that can weigh in.
“Most of the time, a data monitoring committee will say, ‘Everything looks fine, keep going,’ ” Ellenberg said. “But sometimes – you never know when … a hard decision is going to have to be made. And that’s the value of these committees.”
Conversely, if it looks like the vaccine is working exceptionally well, the DSMB may recommend that the study sponsor submit an application to the FDA before the official end of the trial, in order to get it more quickly to market.
‘Thoroughly vetted’
“The people who serve on these committees are thoroughly vetted for conflicts of interest,” Ellenberg said.
Members are screened to make sure they don’t have a financial interest in the pharmaceutical company that’s sponsoring the vaccine trial.
“DSMB members or their family members should have no professional, proprietary, or financial relationship with the sponsoring companies,” according to a statement from the National Institute of Allergy and Infectious Diseases, which organized the common DSMB for the Covid-19 vaccine candidates under Operation Warp Speed – including Moderna, AstraZeneca and Johnson & Johnson. “Selected DSMB members and their family members were not allowed to work for other companies developing COVID-19 vaccines.”
Topol, of Scripps Research, said it’s “unprecedented to have a DSMB with that much authority.” Typically, each clinical trial has its own DSMB.
Such is the case with Pfizer, whose trial is not neither under the common DSMB nor funded by the government. Pfizer’s DSMB comprises “a chairperson and 4 additional members that meets on a weekly basis,” according to a spokeswoman.
Topol considers that small for a trial that aims to enroll up to 44,000 participants. “The trials that I ran always had six or seven at least, sometimes eight or nine,” he said. “In large trials, you got to have a bioethicist, virologist, an immunologist, epidemiologist… You have all the critical areas covered.”
Big honor, but no bragging rights
It’s a big honor to be named to a DSMB.
But it’s a no-no to brag about it, as one university recently found out.
The university proudly posted that one of its professors was named chair of the DSMB for the government-supported trials of coronavirus vaccines.
When CNN called to ask why the professor was publicly identified, the university quickly removed the press release.
“It looks like a staff member shared that news and was unaware that it was not for public consumption,” a university spokesperson wrote to CNN.
CNN is not revealing the professor’s name or the name of the university.
Despite the lack of public recognition, fame and glory, Ellenberg says there’s plenty of motivation to serve on these boards.
“You feel a great responsibility when you’re on these trials,” she said. “Everybody’s trusting you with these data.”
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She remains faithful in the DSMB process. If it goes as it’s supposed to, “I would take the vaccine myself, and I would recommend that other people take it,” she said.
Still, downstream from the DSMB, Ellenberg acknowledges “we’re in uncharted territory.”
Last week, President Trump claimed the White House can overrule the FDA’s attempt to toughen its Covid-19 vaccine guidelines – guidelines that could push hopes of a vaccine authorization past Election Day.
“It never occurred to anybody that anybody outside the FDA would would try and interfere with that,” Ellenberg said. “And I’m hopeful that they won’t.”
CNN’s Sierra Jenkins contributed to this report.