The FDA’s Green Light for a Vaccine Might Tank Ongoing Trials

According to the documents released this week, Pfizer researchers plan to tell any study participants who ask whether they received placebo or the vaccine. If that volunteer falls into a group eligible to receive the vaccine based on their state’s prioritization schedule, the company will provide the shot as part of the study. In other words, the volunteer won’t have to drop out to get the active shot. That means the company will be able to follow vaccinated participants for up to 18 months to monitor them for any side effects. As a further incentive, Pfizer is also proposing to provide vaccines to anyone in the placebo arm who completes 6 months of follow-up, regardless of where they fall in their state’s queue for priority in getting inoculated.

That’s not going to be good enough, according to Steven Goodman, an epidemiologist and Associate Dean of Clinical and Translational Research at the Stanford University School of Medicine. At Thursday’s meeting, Goodman addressed the ethical questions swirling around a potential EUA for the Pfizer vaccine. Echoing the case made last week by bioethicists from the National Institutes of Health in Science, he outlined how the continuation of placebo-controlled vaccine trials could be ethically justified, because there are still so many important things to learn from them about who the shot works best best and what its limitations are. He also pointed out that, even without the vaccine, participants have ways to lower their risks of catching Covid—masks, social distancing, the full Swiss Cheese suite. The issue with continuing the studies as planned, with a placebo group, isn’t the ethics, said Goodman, but rather feasibility.

To that end, he offered a potential compromise. In the immediate future, manufacturers like Pfizer could pivot to a trial design called a “double crossover.” Instead of telling participants which study arm they’re enrolled in, investigators could offer everyone another round of shots when they become eligible for the vaccine—based on both national and local priority schedules. This time, anyone in the placebo group would get the vaccine, and those in the vaccine group would get placebo. Everyone would get vaccinated, but none of the subjects would know who had originally been in the placebo group. This would protect some of the study’s blinding, while eliminating the incentive for participants to drop out. While that design might mean it would take longer to get answers to questions about durability and long-term safety, it would at least preserve the ability to answer them at all.

Down the road, as more vaccines become available via EUA, Goodman proposed that trials will have to evolve toward a head-to-head model, comparing vaccines to one another without a true placebo arm, similar to the types of trials that yielded the first-ever Ebola treatment last year.

Executives from Pfizer didn’t commit to make any changes to its proposed plan during Thursday’s meeting. William Gruber, the company’s senior vice president of vaccine clinical research and development, said it would be one of the things Pfizer would be hashing out with both the FDA and CDC in coming days and weeks. The company estimates that healthcare workers, who will be first in line for a vaccine made available through an EUA, make up 20 percent of its Phase 3 study cohort. Gruber said that losing that group wouldn’t derail the study entirely. Where it could get dicey is if CDC officials quickly expand the number of groups they are recommending to be immunized, he said. “We want to be conscientious of providing vaccine to people who qualify.” Gruber suggested that would be easiest under Pfizer’s current plan. He voiced skepticism that it would be possible to pull off a double crossover. “The logistics are not trivial,” he said.

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