Pfizer and its partner BioNTech plan to offer their Covid-19 vaccine to any volunteer clinical trials who received placebo by March 1, a few 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 with Moderna, who developed its own Covid-19 vaccine. The FDA and its advisers have strongly urged volunteers to stay on the placebo for as long as possible to gather more safety and efficacy data on the vaccines, while the companies argued that volunteers should receive the vaccines for both ethical and practical reasons. .
Among some participants in the trial, the issue has become hampered, with numerous protests over the delays in heated messages on social media and in letters to media organizations, including STAT.
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Michael Tovar, a volunteer who publicly campaigned for Pfizer to offer the vaccine faster to participants in the 44,000-person clinical trial, thanked the company and its CEO on Twitter.
“Thank you for listening and for changing your study protocol to inoculate your placebo arm quickly,” Tovar wrote. “You made this new year so much brighter for the 22,000 placebo volunteers who worked for this vaccine.”
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Pfizer and BioNTech announced the decision on a website for participants in clinical trials and in a letter, obtained by STAT, sent to researchers who conducted the clinical trial.
The letter to researchers indicates that participants are also asked to take additional Covid tests, conducted at home by clinical trial volunteers, to help understand whether the vaccine, which reduces symptomatic infections by 95%, is also asymptomatic. infection occurs. The answer to the question is important; currently there is no way to know if people who have received the vaccine can still pass it on to others.
In medicine, the most reliable answers about treatments and contraceptives come from double-blind placebo-controlled trials. This means that patients are randomly assigned to receive the treatment, in this case a vaccine, or placebo. Neither they nor their doctor know what they received. In many trials, such as those for cancer, it is simply assumed that patients who received placebo will receive the treatment once the study is completed. This step is known as crossover.
The issue of how to handle the placebo crossover during a pandemic was left open by the FDA and the US government’s Operation Warp Speed effort, which accelerated vaccine development, when studies began in July. Forms of consent given by STAT to volunteers made no mention of when and whether those who received placebo would receive the two-dose vaccine.
At a Dec. 10 meeting of an advisory committee on the authorization for emergency use of the Pfizer / BioNTech vaccine, the FDA discussed how to handle the placebo crossover. Steven Goodman, co-dean of clinical and translational research at Stanford University School of Medicine, argued during the session that there was no ethical reason volunteers in the placebo group deserved to receive vaccine in front of the general public.
Goodman outlined a complex scheme known as a double-blind crossover study, in which all volunteers who wanted to be sure they were receiving the vaccine were offered two more shots. Those who received the vaccine would be offered placebo, and those who received placebo would be offered the vaccine.
William Gruber, one of Pfizer’s top vaccine managers, argued that this plan was unworkable. In essence, it is necessary to run a large portion of the study a second time.
Instead, Pfizer has outlined a plan in which volunteers who want the vaccine can receive it when they are able to receive the vaccine in their local area. Healthcare personnel or residents in long-term care facilities, who could already be vaccinated, would receive the vaccination immediately.
‘If you are not a healthcare professional or a resident of a long-term care facility (or in any other future group), we will discuss an option during your fourth study visit to switch from the placebo group to the vaccine group. six months after you originally received your second injection, ”reads a letter sent to participants at the end of December. “We respectfully ask you to wait until your study visit # 4 is discussed to discuss the option for vaccine transition.”
This complicated process progressed rapidly, as many of the participants in the study were healthcare providers. According to the letter obtained by STAT, 2,000 volunteers who received placebo had already received their first dose of Pfizer vaccine. But it was clear that others would have to wait.
But then, on December 17, the FDA held another advisory meeting, this time for the Moderna vaccine, which was more closely developed with Operation Warp Speed. Again, Goodman made his submission. A Moderna researcher, like Pfizer, made a case that his idea was impractical, and outlined a plan to give volunteers the placebo-receiving volunteers the vaccine much faster than Pfizer would do. They do not have to wait until they are eligible to be vaccinated outside the trial.
The FDA’s advisers spent a lot of time comparing Goodman’s plan to Moderna, and eventually agreed that Goodman’s was unworkable. But they spent little time comparing Pfizer’s plan, which delayed the vaccine longer, with Moderna.
This brought Pfizer to the forefront as more and more volunteers publicly argued that they should be offered the vaccine if they were given placebo.
Alan S. Goldsmith, a retired Florida doctor who presented for the Pfizer trial, told STAT that he and his wife, who also volunteered for the study, did not even expect to receive the vaccine if they were not in the placebo group. They just wanted to know if they had already received the vaccine.
“What will enable us to know is our vaccination status, which can offer a little more freedom to do things like visit our grandchildren,” he wrote.
On December 23, Moncef Slaoui, the head of Operation Warp Speed, told reporters that he thought volunteers who received placebo should receive the vaccine immediately, which contradicts the FDA. He also called the Pfizer plan intellectually elegant but impractical, saying it was difficult to apply with all 50 countries’ vaccination requirements.
Pfizer was apparently already making its crossover plan more like that of Moderna. New language posted on his website for trial participants on New Year’s Eve said that the vaccine doses were guaranteed, and that it and BioNTech aimed to give all participants who received the placebo the opportunity to receive their first dose by 1 March if they wished.
A letter from Nicholas Kitchin, a senior director of Pfizer’s clinical research and development group for vaccines, set a cheerful tone for a clinical document.
“We realize that our participants in clinical trials are selfless volunteers who have made the important choice to make a difference and fight this pandemic,” Kitchin wrote.
‘While the study continues to blind us to answer key public health questions, such as continued protection, long-term safety and protection against asymptomatic infections, we are committed to ensuring that our trial participants are recognized for their contributions and that placebo recipients who wish can receive BNT162b2 within the study. ”