> Dr. Mandrola is right that this trial was not large enough to fully “inform the safety of a vaccine that will be given to many millions”. It was too small to detect rare events, such as myocarditis from the vaccine or serious complications from the virus. However, only the largest trials can detect rare events, and the rarer the event, the larger the trial must be to detect it. The adult vaccine trials, which were about twenty-times larger than the adolescent trials, also did not detect rare events, such as blood clotting with the Johnson & Johnson vaccine. The inability to detect rare events is a fundamental limitation of clinical trials, not a flaw of this particular trial.
Rare events can usually be detected once a vaccine or medication is taken by large numbers of people. This is why post-marketing surveillance, called a phase IV trial, is so crucial. It’s a fact that no serious safety signal emerged during the trial. The authors were not only justified to report this finding, the data from their study required it. They didn’t claim that rare side effects would not emerge once millions of children received the vaccine.
All of this makes me wonder. Other than a trial that enrolled hundreds of thousands of adolescents, which would be required to meaningfully detect a rare event such as myocarditis, is there anything a trial could do so Dr. Mandrola wouldn’t feel he had to put “positive” in quotes? Did he make his objections known when the plans for the adolescent vaccine trial were announced or only after it was completed? Has he been similarly critical of other randomized-controlled trials, or is this the only trial he has singled out this way? As he does not feel someone getting COVID-19 is a “clinical outcome”, what would he call it? Why didn’t he inform his readers that the vaccine prevented COVID-19 in adolescents? Would he have been similarly silent had the vaccine been significantly less effective at preventing COVID-19? We can only guess.
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So basically, yeah these clinical trials aren't big enough to catch these side effects, but the motivations of any doctor pointing that out must be suspect!