Moderna Inc. is planning to offer its vaccine to all trial participants who received the placebo, without having them wait until they might be eligible outside of the study. The company is hoping that the move will keep individuals enrolled in the trial, so that it can continue to collect longer-term data.
Some health authorities, however, have pushed back against the proposal, saying that telling participants that they had received the placebo and then vaccinating them will make studying the vaccine’s efficacy and safety more challenging.
The Food and Drug Administration “needs to ensure the blinded, randomized, controlled trial is continued,” said Dr. Diana Zuckerman, president of the National Center for Health Research.
Whether or not placebo patients in the Moderna and Pfizer studies will automatically receive those vaccines is one of the issues an FDA advisory panel faces as it reviews the new Covid-19 vaccine from Moderna on Thursday.
That vaccine was found to be 94.1% effective at preventing Covid-19 with certain symptoms, including severe disease. The FDA is expected to authorize Moderna’s vaccine on Friday, following a favorable recommendation. Some 30,000 people were enrolled in the trial.
Including placebo recipients in clinical trials helps researchers track safety and effectiveness because they provide a control group to measure against those that receive the potential treatment.
With emergency-use authorizations, however, there is an ethical argument to be made that those who received the placebo should then get the vaccine, especially if they are in a high-priority group.
In a briefing document released earlier this week, Moderna proposed allowing participants who got the placebo to re-consent and then receive the vaccine, to keep them enrolled in the trial for the full two years. Approximately 25% of the participants are health-care workers and in the high-priority group currently eligible for Pfizer’s vaccine, which was shown to be 95% effective.
Dr. Lindsey Baden of Brigham and Women’s Hospital, one of the lead investigators for Moderna’s large vaccine study, said: “We are currently having substantial dropout from the study participation given the availability of the Pfizer vaccine.”
Under Moderna’s proposal, participants who received the placebo wouldn’t have to wait until they might be eligible to receive the vaccine outside of the trial. The design differs from the one proposed by Pfizer, which said it would make the vaccine available to placebo-group subjects only at the point when the individuals might become eligible otherwise, and that people can choose to not know what they had received through the end of the study.
Moderna Chief Medical Officer Tal Zaks said there are clinical-trial supplies of the vaccine that would go to waste if certain placebo recipients in the study had to wait to receive the vaccine because they are in a lower-priority group outside of the trial.
Steven Goodman, associate dean of clinical and translational research at the Stanford School of Medicine, told the FDA panel that fully unblinding participants and vaccinating them would make tracking long-term hazards and protection more difficult. People who know that they have been vaccinated might also behave differently, affecting the trial results.
Having different ethical trade-offs or designs for each trial could also erode trust in the process and cause issues with retention, he said. If these authorizations set precedent for how trials are done in the future, people might opt to join certain trials that provide more personal benefit.
“If we’re consistent across all trials, I think they will both be more comparable. We will enhance trust in the system,” said Dr. Goodman.
Last week, Dr. Goodman proposed a “blinded crossover” trial, where people who received the placebo would get vaccinated, and those who were already vaccinated would receive a placebo. The study design would still keep people in the dark about when they got vaccinated, but all participants would have some level of protection.
Thomas M. Burton and Peter Loftus contributed to this article.