Should patients who volunteer to be in Covid-19 vaccine studies, but who are assigned to get placebo, be offered the vaccine? As companies and regulators raced to start clinical trials in the summer, that question was left open.
But for Pfizer and partner BioNTech, the answer now is not if but when.
In a memo to researchers conducting the clinical trial, a copy of which was obtained by STAT, Pfizer said that it is working to find a way to eventually give the vaccine to volunteers who were assigned to receive placebo. But that would not occur until the Food and Drug Administration has granted an emergency use authorization or another kind of regulatory approval.
“If our potential vaccine receives an EUA, we would propose amending the study protocol to create a process so that interested, eligible participants who received the placebo could ‘cross-over’ to the vaccine arm of the study,” the memo reads. “Such a change would require input and approval from regulatory bodies, and we are actively exploring this now.”
Before making that offer to participants, Pfizer would have to “unblind” the study — that is, tell volunteers whether they were in the vaccine arm of the trial or the placebo one. In many clinical trials, if a drug or vaccine is proven effective, the process of unblinding and then offering the drug or vaccine before approval to the placebo participants is common.
But the timing of the decision is complicated in the case of Covid-19, with potential consequences for clinical trials. The FDA has indicated it wants vaccine manufacturers to keep their trials blinded for as long as possible; early unblinding could mean that safety and efficacy results would be less reliable after that point. That’s because volunteers who received the vaccine could no longer be compared to an untreated placebo group.
Consent documents given to participants in the Pfizer/BioNTech study, as well as to those in the study of the vaccine developed by Moderna, do not make any reference to whether shots are made available to placebo patients if the vaccines work. Participants are told that if a vaccine becomes available, they are allowed to take it. Copies of the documents were obtained by STAT.
In a consent form for the ongoing study of J&J’s Covid-19 vaccine, the question is addressed directly.
“If you received the placebo, you may be offered the study vaccine at no cost if and when the study vaccine has been shown to be safe and that it works, but it is possible that this may not occur until 2 years after vaccination,” the J&J document reads. “This will be determined after consultation with the national health authorities in your country.”
In an interview earlier this week, William Gruber, a senior vice president of vaccine clinical research and development at Pfizer, said that the company planned to switch people from placebo to a vaccine if there was a regulatory approval and, perhaps, clearance from an expert panel organized by the Centers for Disease Control and Prevention.
In other words, Pfizer would offer the vaccine to volunteers who might be able to obtain it outside the trial. That could mean only a subset of participants at a time — for instance, only health care workers, one of the first populations expected to have access to a vaccine that is authorized, or people over 50. It depends what regulators decide.
But Gruber said that his hope is that the FDA, at that point, would issue a regulatory authorization that would include everyone in the trial. In that case, all the patients on placebo would receive the vaccine.
“Apart from the ethical obligation to make sure they can get the vaccine to which they would otherwise be entitled, I don’t want to lose that data,” Gruber said. “So we’re going to encourage them to stay on the trial and get the vaccine as part of the trial proceedings, but only those that would qualify.”