Two extremely promising Covid-19 vaccines open the door to inoculating those who received placebos during the trials even as scientists will still need volunteers to test the long-term effects of the shots.
The extraordinary effectiveness rates in these interim findings prompted discussions between the National Institutes of Health and pharmaceutical companies about the best approach for the thousands of clinical trial volunteers who received a saline shot instead of the experimental vaccine.
If the data hold up, either or both of the shots could be authorized for use during the public health emergency , which means research will still need to continue. Trial participants who received placebos could still aid scientists by continuing to participate in studies needed to compare the effectiveness of a vaccine given in a single dose or over two shots. Researchers could also ask those volunteers to join what’s known as a “non-inferiority trial,” which pits competing vaccines against each other to see how they compare, with one of the effective vaccines replacing a saline solution as the placebo arm of the study.
Even with promising vaccines in development, some participants may be asked to remain in trials using placebos to answer questions about how long the shots will last, whether they will prevent severe diseases, or how different populations will react to the injection, University of Pennsylvania bioethicist Holly Fernandez Lynch said. The key is ensuring participants are given the information they need to provide consent.
“So you could take participants in an ongoing study and say: ‘We’d like to keep you blinded and here’s why. But this is critical information that might influence their willingness to stay enrolled—the sort of information that the regulations require be shared with participants,” she said.
But New York University bioethicist Arthur L. Caplan said volunteers in the placebo arm should be made aware they didn’t get the vaccine, a process known as unblinding the randomized controlled trial. He acknowledged it would slow down future data and potentially weaken the placebo arm.
“When you have compelling new information, a subject has the right to know it and then to say I don’t want to be in the study anymore,” Caplan said. “And I think they have the right to be unblinded when we have something that might really help them.”
A spokesperson for Pfizer said if its vaccine candidate receives an emergency use authorization, “we believe that we would have the ethical responsibility to inform study participants about the availability of an Emergency Authorized Vaccine and the eligibility requirements for such a vaccine.”
The New York-based pharmaceutical company would propose to allow anyone who received a placebo in the ongoing late-stage clinical trial to cross over into the vaccine arm of the study. But such a change would be subject to the input of the FDA and other regulatory authorities.
ACTIV, the partnership between the NIH, Food and Drug Administration, Centers for Disease Control and Prevention, and 20 pharmaceutical companies developing Covid-19 vaccines and treatments, has already started those discussions, NIH Director Francis S. Collins said.
While the FDA is reviewing the Pfizer and Moderna data, study participants won’t know whether they received a placebo, John Mascola, director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, said during a media briefing on the Moderna findings. After that review, the FDA will make a recommendation on whether to allow an emergency use authorization. At that point, the FDA, NIH, and Moderna will discuss whether those in the placebo group should get vaccinated.
“I think when you have a vaccine of this high degree of efficacy, it weighs more towards making sure that you do something with the placebo group that’s fair and would not put them at a disadvantage,” National Institute of Allergy and Infectious Diseases Director Anthony S. Fauci said.
A participant in the Moderna trial expressed hope the Cambridge, Mass., biotechnology company would make the vaccine available to volunteers who got a placebo.
“This is the morally right thing to do,” the participant, who asked not to be identified, said. “These are the people who quite literally rolled up their sleeves and risked their health to help others. It is a just reward for participants in this trial, and it is a strong signal to participants in future trials that their efforts will be rewarded.”