Although two ongoing clinical trials with 30,000 volunteers are expected to be completed by the end of the year, an independent committee has the power to terminate the trials weeks early if the interim results are predominantly positive or negative.
The data and security oversight board could say, “The data is so good right now that you can say it is safe and effective,” Fauci said. If so, the researchers would have “a moral obligation” to end the trial early and make the active vaccine available to all study participants, including those given placebos – and expedite the process of giving the vaccine to millions.
Fauci, director of the National Institute for Allergies and Infectious Diseases, said he trusted the independent members of the DSMB – who are not government employees – to keep vaccines high without being politically influenced. The board members are usually experts in vaccination science and biostatistics who teach in major medical schools.
“When making a decision about the vaccine you should be sure that you have very good evidence that it is both safe and effective,” said Fauci. “I’m not worried about political pressure.”
The Safety Board periodically reviews data from a clinical trial to determine whether it is ethical to continue enrolling volunteers who are randomly given either an experimental vaccine or a placebo shot. Neither the volunteers nor the health workers who vaccinate them know what shot they are receiving.
Manufacturers are currently testing three COVID vaccines in large-scale US studies. The first two studies – one from Moderna and the National Institutes of Health and the other from Pfizer and BioNTech – began in late July. Each study was designed for 30,000 participants.
According to company officials, both studies enrolled about half of that total number. AstraZeneca, which has conducted large-scale clinical trials in the UK, Brazil and South Africa, started another large-scale vaccine study this week in the US with 30,000 volunteers. More vaccine trials are expected to begin this month.
In studies of this size, researchers will know if a vaccine is effective after just 150 to 175 infections, said Dr. Robert Redfield, director of the Centers for Disease Control and Prevention, spoke to reporters on Friday.
“It may come as a surprise, but the number of events that must occur is relatively small,” said Redfield.
Currently, only the security agency has access to the trial data, said Paul Mango, deputy chief of staff for policy at the Department of Health and Human Services. When the test results will be available, “we cannot determine whether it will be mid-October or December.”
Safety boards set “stopping rules” at the beginning of a study and made their criteria for ending a trial very clear, said Dr. Eric Topol, executive vice president of research for Scripps Research in San Diego and an expert on the use of data in medical research.
Although the safety agency may recommend stopping a study, the scientists conducting the study make the final decision to stop a study, Topol said.
A vaccine manufacturer could then apply to the Food and Drug Administration for emergency clearance, which can be granted quickly, or continue the regular drug approval process, which requires more time and evidence.
Safety monitors can also cancel an attempt for safety reasons “if it looks like it is actually causing harm to people in the vaccine arm due to a large number of adverse events,” said Fauci.
According to Fauci, people can trust the process because any data that external observers used to make their decisions would be made public.
“All of this has to be transparent,” said Fauci. “The only time you worry is the pressure to stop the study before you have enough data on safety and effectiveness.”
Topol and other scientists have harshly criticized the FDA in the past few weeks, accusing Commissioner Stephen Hahn of bowing to political pressure from the Trump administration, which has pushed the agency to approve COVID treatments faster.
Quitting studies early carries a number of risks, such as making a vaccine look more effective than it actually is, Topol said.
“If you stop something early, you can get exaggerated benefit that isn’t real,” Topol said because less positive evidence comes later.
Stopping studies prematurely could also prevent researchers from recruiting more minority volunteers. So far, only about every fifth study participant is black or Spanish. Given that blacks and Hispanics are harder hit by the pandemic than other groups, it is important that they make up a larger proportion of vaccination attempts, according to Topol.
Ending vaccine trials prematurely also carries safety risks, said Dr. Paul Offit, a vaccine developer who serves on an NIH advisory board on COVID vaccines and treatments.
A smaller, shorter study might fail to detect key vaccine side effects that might only become apparent after millions of people are immunized, said Offit, director of the Vaccine Education Center at Philadelphia’s Children’s Hospital.
The researchers will continue to follow vaccinated volunteers for a full year looking for long-term side effects, Redfield said.
And Fauci acknowledged that cutting a study could undermine public confidence in COVID vaccines. One in three Americans is unwilling to get a COVID vaccine, according to a recent Gallup poll.