First, do no harm. Second, withhold no benefit.

The when and why of placebos in vaccine trials.

The new anti-vaccine, anti-public health talking point is the idea that skeptics just want to “see the evidence” in the form of placebo-controlled randomized trials. They say that if only these trials were done, they would be happy to accept the results.

But placebo-controlled randomized trials have been done. For everything we vaccinate against. And that’s how we know our vaccines work. And how we know they are safe.

Because the first principle of medical research is to do no harm. And when we are trying to develop a completely new medical treatment or a completely new vaccine or similar, we need to first be certain that this treatment will not cause harm.

We do this by testing against a completely inert placebo. For vaccines, this tends to be a simple injection of saline. If we are testing a pill, we might give people an identical looking pill made out of sugar.

We make the placebo look similar to the treatment we are testing so that people don’t know which one they got, because when they do know which they got it can change their behavior. Sometimes they will even try to go get the experimental treatment somewhere else, which could ruin the trial.

But there’s also a second principle of medical research. This one can be summed up as “to withhold no benefit”. That is, when people are putting their health in our hands and trusting us enough to participate in our research, it is vital that we, as medical researchers and the public that funds the research, earn that trust by not withholding medical care unnecessarily.

This means that if there exists a treatment, vaccine, or other preventive intervention which we know works, even just a little bit better than doing nothing, then we are obligated to allow participants in our research study to access that treatment.

When we don’t have a vaccine at all against a disease, and we haven’t yet done our placebo-controlled randomized trial, then we can’t know that our experimental vaccine is better than nothing (even though we certainly hope it is!). This is why we can use placebo as a control for testing brand-new vaccines. We call this state of not knowing ‘equipoise’.

Randomized trials are monitored by an independent third-party group of statisticians and experts who are carefully watching to see if the evidence for or against the experimental treatment becomes strong enough to conclude that we no longer have equipoise.

Because eventually (and this decision point is pre-specified in the statistical protocol), there comes a point during a randomized trial where it’s clear that the new treatment either does or does not work, or that it is or is not safe. At that point, it’s not true anymore that we don’t know if our new treatment works better than nothing or not. We do.

Since it’s important that we withhold no benefit, at this point we can no longer withhold the new treatment from study participants. Generally, once the trial is stopped all participants are informed whether they got placebo or the new treatment, and if they got placebo they are offered the new treatment (assuming the trial showed the new treatment works).

And once we have a working treatment, that becomes our standard against which we test new treatments for the same medical condition. New medications shouldn’t just be better than nothing. They need to be better than the standard of care.

This is the principle of withholding no benefit. And it’s why we do not do large-scale placebo-controlled trials with long-term follow-up for medications or vaccines that we know work.

And we do know that the vaccines we use work. Because we have done the randomized controlled trials. First, to test if they worked better than nothing at preventing infection. And later to test if new versions worked better than older versions at preventing those same infections.

RFK Jr and other anti-vaccine, anti-public health voices want to ignore all that prior work. They reject the time and effort and trust that hundreds of thousands of vaccine-trial participants have offered to the scientific community and to the public at large.

They reject the sacrifices made by those who, when no working vaccine yet existed, were assigned to placebo, became infected, and sickened or died.

They say ‘not good enough’. They demand more suffering and death.

We cannot give it to them.

---