Everyone agrees that those who receive the placebo in a randomized double-blind controlled trial (RCT) are losers in the clinical lottery. The question is whether the epistemic gain from RCTs justifies the pain for the losers? I am not a fan of Fauci, but his proposed solution to the dilemma in the case discussed below seems plausible, if we assume (as I do not) that RCTs are a necessary condition for all actionable medical knowledge and yet we still attempt to treat clinical trial volunteers ethically. My even better solution is to allow all willing volunteers to take the experimental drug, with no-one receiving a placebo. Then use some Bayesian updating technique to gather information from the comparison of results for study participants who volunteered to take the drug, with results for study participants who did not volunteer to take the drug. The study would not be blind, but useful information could be obtained, for instance if no one who takes the drug suffers from the disease, but many who do not take the drug, do suffer from the disease. In that case we have evidence that the drug is effective.
(p. A7) In October [2020], Judith Munz and her husband, Scott Petersen, volunteered for a coronavirus vaccine trial. At a clinic near their home in Phoenix, each got a jab in the arm.
Dr. Petersen, a retired physician, became a little fatigued after his shot, and developed redness and swelling on his arm. But Ms. Munz, a social worker, didn’t notice any change. “As much as I wanted it, I couldn’t find a darned thing,” she said. “It was a nothing burger.”
She knew there was a 50-50 chance that she would get the vaccine, developed by Johnson & Johnson. Judging from her lack of symptoms, she guessed she had received the placebo.
At the time, Ms. Munz thought that anyone who had received the placebo would get the real vaccine as soon as the trial showed it was safe and effective. She looked forward to the peace of mind it would bring. But last month, she was asked to sign a modified consent form indicating that people who got the placebo might have to wait up to two years to get the vaccine, if they got one at all.
Ms. Munz found the form vague, confusing and, most of all, unfair. “You put yourself out there with that risk,” she said. “I am owed that vaccine.”
. . .
But on Wednesday [Dec. 2, 2020], 18 leading vaccine experts — including a top regulator at the Food and Drug Administration — argued that vaccinating placebo groups early would be disastrous for the integrity of the trials. If all of the volunteers who received placebo shots were to suddenly get vaccinated, scientists would no longer be able to compare the health of those who were vaccinated with those who were not.
“If you’re going to prioritize people to get vaccinated, the last people you should vaccinate are those who were in a placebo group in a trial,” said Richard Peto, a medical statistician at the University of Oxford. Mr. Peto and his colleagues laid out their concerns in a new commentary in The New England Journal of Medicine.
. . .
Yet the prospect of giving people something useless in the face of a life-threatening disease has always been fraught. Even Jonas Salk balked at the idea of giving people placebos when researchers designed a trial to test his new polio vaccine in 1953.
“I would feel that every child who is injected with a placebo and becomes paralyzed will do so at my hands,” he complained. The study, Dr. Salk declared, “would make Hippocrates turn over in his grave.”
. . .
Dr. Fauci sketched out one possible way to balance the obligation owed to people who took the placebo against the need for more data from the trials. Vaccine makers could give everyone who got the placebo the vaccine — while also giving everyone who got the vaccine the placebo. None of the trial participants would know which order they got the doses. The trial could therefore continue to be blinded.
. . .
After learning that it may take two years before Johnson & Johnson will provide her with the real vaccine, Ms. Munz, who is 68, is considering trying to get Pfizer or Moderna’s version as soon as she’s eligible thanks to her age.
“I’ll drop out, which I can do, and I’ll get the vaccine,” she said.
Holly Janes, a biostatistician at the Fred Hutchinson Cancer Research Center in Seattle, and her colleagues are preparing for this kind of erosion. She and her colleagues are now working on statistical methods to squeeze the most insight out of the trials no matter what their fate.
“It won’t be ideal from a purely scientific vantage point, because we lose the direct comparison between vaccine and placebo,” she said. “But we’re trying to strike a balance between doing what some would argue is right for the participants, and maximizing the public health value that comes out of these trials.”
For the full story see:
(Note: ellipses, and bracketed year and date, added.)
(Note: the online version of the story was updated Dec. 18, 2020 [sic], and has the title “Many Trial Volunteers Got Placebo Vaccines. Do They Now Deserve the Real Ones?”)