PFizer and his partner BioNTech plan to offer their Covid-19 vaccine to any clinical trial volunteer who received a placebo by March 1, several months earlier than originally planned.
The decision represents the conclusion of a complex and public kabuki dance between the Food and Drug Administration, Pfizer and vaccine volunteers, as well as Moderna, which developed its own Covid-19 vaccine. The FDA and its advisers pressured strongly for volunteers to stay with the placebo as long as possible to gather more safety and efficacy data about vaccines, while companies argued that volunteers should receive vaccines earlier for ethical and practical reasons.
Among some trial participants, the issue became a concern, with many protesting further delays in heated social media messages and letters to media organizations, including STAT.
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Michael Tovar, a volunteer who publicly campaigned for Pfizer to offer the vaccine more quickly to participants in the 44,000-person clinical trial, thanked the company and its chief executive on Twitter.
“Thank you for listening and for changing your study protocol to allow for rapid vaccination of your arm with placebo,” wrote Tovar. “You made this New Year a lot brighter for the 22,000 placebo volunteers who prepared for this vaccine.”
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Pfizer and BioNTech released the decision on a website for clinical trial participants and in a letter, obtained by STAT, sent to the researchers who were conducting the clinical trial.
The letter to the researchers indicates that they are also asking participants to do additional Covid tests, to be conducted by clinical trial volunteers at home, to help understand whether the vaccine, which reduces symptomatic infections by 95%, also prevents asymptomatic infection. The answer to that question is important; there is currently no way of knowing whether people who received the vaccine can still pass it on to others.
In medicine, the most reliable responses to treatments and preventives come from double-blind, placebo-controlled studies. This means that patients are randomly assigned to receive treatment, in this case a vaccine, or a placebo. Neither they nor their doctor know what they have received. In many trials, such as cancer, it is simply assumed that patients who received a placebo will receive treatment as soon as the study is completed. This step is known as a crossover.
But the question of how the placebo crossover should be handled during a pandemic was left open by both the FDA and the US government’s Operation Warp Speed effort, which accelerated vaccine development, when studies began in July. The consent forms given to volunteers, obtained by STAT, made no mention of when or if those who received the placebo would receive the two-dose vaccine.
At a December 10 meeting of an advisory committee on the emergency use authorization of the Pfizer / BioNTech vaccine, the FDA discussed how the placebo crossover should be treated. In that session, Steven Goodman, associate dean of clinical and translational research at Stanford University School of Medicine, argued that there was no ethical reason why volunteers in the placebo group deserved to receive the vaccine before the general public.
Goodman outlined a complicated scheme, known as a double-blind crossover study, in which all volunteers who wanted to be sure they received the vaccine would receive two more injections. Those who received the vaccine would receive a placebo, and those who received a placebo would receive the vaccine.
William Gruber, one of Pfizer’s top vaccine executives, argued that this plan was impractical. Essentially, it would be necessary to run a large part of the study a second time.
Instead, Pfizer has established a plan in which volunteers who want the vaccine can receive it when they are eligible to receive it in their local area. Health professionals or residents of long-term care facilities, who were already eligible to be vaccinated, would receive the vaccine immediately.
“If you are not a healthcare professional or a resident of a long-term healthcare institution (or any other group added in the future), we will discuss an option to transition from the placebo group to the vaccine group on your fourth study visit, approximately six months after you originally received your second injection, ”said a letter sent to participants in late December. “We respectfully ask that you wait until Study Visit # 4 to discuss the Vaccine Transition Option.”
This complicated process was advancing rapidly, because many of the study participants were health professionals. According to the letter obtained by STAT, 2,000 volunteers who received a placebo have already received their first dose of the Pfizer vaccine. But it was clear that others would have to wait.
But then, on December 17, the FDA held another consultative meeting, this time for Moderna’s vaccine, which had been developed more closely with Operation Warp Speed. Once again, Goodman made his presentation. A researcher representing Moderna argued, like Pfizer, that his idea was impractical and drew up a plan to give the vaccine to volunteers who received placebo much faster than Pfizer would. They would not have to wait until they were eligible to be vaccinated outside the study.
FDA advisers spent considerable time comparing Goodman’s plan to that of Moderna, eventually agreeing that Goodman’s plan was impractical. But they spent little time comparing Pfizer’s plan, which delayed the vaccine the most, to that of Moderna.
This left Pfizer in trouble, as more and more volunteers publicly protested that they should get the vaccine if they were given a placebo.
Alan S. Goldsmith, a retired Florida doctor who volunteered for the Pfizer study, told STAT that he and his wife, who also volunteered for the study, did not even expect they would receive the vaccine if they were in the placebo group. They just wanted to know if they had already received the vaccine.
“What this would allow us to do is to know our vaccination status, which can allow a little more freedom to do things like visit our grandchildren,” he wrote.
On December 23, Moncef Slaoui, chief of Operation Warp Speed, told reporters that he thought the volunteers who received the placebo should receive the vaccine immediately, contradicting the FDA. He also found Pfizer’s plan intellectually elegant, but impractical, saying that with different vaccination requirements in all 50 states, it would be difficult to manage.
Pfizer was apparently already working to make its crossover plan more like that of Moderna. New language posted on your Internet network location for trial participants on New Year’s Eve stated that vaccine doses were guaranteed and that she and BioNTech aimed to ensure that all participants who received the placebo had the opportunity to receive their first dose of the vaccine by March 1, if they so wished. .
A letter from Nicholas Kitchin, senior director of the Pfizer vaccine research and clinical development group, gave a cheerful tone to a clinical document.
“We recognize that our clinical trial participants are selfless volunteers who made the important choice to make a difference and fight this pandemic,” wrote Kitchin.
“While the study remains blind to addressing important public health issues, such as persistent protection, long-term safety and protection against asymptomatic infections, we are committed to ensuring that our study participants are recognized for their contributions and that recipients placebo users can receive BNT162b2 within the study. “