What went wrong with COVID-19 vaccine trials

If there’s a common theme in the errors of the U.S. response to COVID19, it’s been the astounding amount of squandering. Our leaders squandered time, as well as public trust and people’s economic and emotional resources. And they squandered the chance to do good science — testing drugs and vaccines in a waythat serves the public interest rather than pharmaceutical companies.

There’s no question that COVID-19 vaccines and therapies will save many lives. But we’re not doing the kinds of scientific studies needed to determine the best vaccines and therapies to maximize lives saved and minimize the weeks we endure unprecedented social and economic constraints. It’s not too late to change course.

It’s not too late, for example to test the possibility some have raised that the return to normal could be advanced by months if the Pfizer vaccine is given as a single shot. Though clinical trials determined safety and efficacy for two shots, supplies are running short and there’s some evidence that one shot provides some protection.

The company could test the idea by picking a group of volunteers in the early rollout to get one shot, and compare them with those getting two, says Peter Bach, a physician and director of the drug pricing lab at Memorial Sloan Kettering Cancer Center. A trial would be the only way to justify giving people a single shot.

He says he also stands by a recommendation he made in September, that vaccines be tested against one another. There’s much valuable data that could be gathered quickly given that there are more than 40 vaccines in the testing stage, with many different technological approaches. Some use inactive virus, others pieces of the virus and still others viral DNA encased in various kinds of harmless viruses. Then there are the two front runners, which use messenger RNA.

As researchers told me last spring, some of these vaccines might be better at preventing high-risk people from getting fatal cases, while others might be better for keeping lower-risk individuals from spreading the virus. Some will be cheaper and easier to manufacture. Somewill induce fewer side effects. Pfizer’s product requires extreme refrigeration; others don’t. One candidate might even work as an oral vaccine rather than an injection.

The first vaccines across the finish line of FDA authorization might not be the best ones for achieving worldwide immunity. As STATnews reported in September, several of the “tortoises” in the race, from Merck and Sanofi, look very strong.

“You don’t lose anything if you do 50,000 people with Pfizer versus (Johnson & Johnson),” says Bach. “It’s not like you’re squandering the Pfizer vaccines.” Such tests would be in the public interest, ensuring weget the maximumamountof data in a minimum of time.

The way clinical trials usually work, companies design their owntrials within some constraints established by regulators like the FDA. But in this unprecedented situation, weshould have a much moreuniform standard for scientific testing. In fact, last June, the FDAdidlay out some standard experimental guidelines for vaccine manufacturers, says Bach. “That was completely ignored.”

A mandatory standard might have given us much-needed information on how well those newly approved Pfizer and Moderna vaccines protect against asymptomatic infection and thereby help us all achieve herd immunity. Testing subjects regularly for COVID-19 would have told us this, but Pfizer and Moderna didn’t collect that data. The AstraZeneca trial did collect data on asymptomatic cases, though the trial was marred by a serious mistake with dosing. And contact tracing subjects might even help us learn if vaccinated people can transmit silent infections to others. Those are not normal procedures, but this is not a normal situation.

The other looming mystery is how long vaccine-induced immunity lasts. The best way to learn about longer-term safety and efficacy is to keep the placebo-controlled trials going. But Pfizer is already talking about ending its trial by giving the people in the control arm the vaccine. Thegesture mayseemaltruistic, but there’s a selfish side to it: It undercuts the ability to keep getting data and uncover less common safety issues.

The same idea applies to drug that could treat COVID-19, which should be tested in a standardized system designed for our benefit. Last spring, the antiviral drug remdesivir wasapproved, for example, with minimal data on efficacy, timing and dosing. It’s proven disappointing.

The public is so worn downthat we’re grateful for any ray of hope, and disinclined to question something that would end the pandemic — even though pharmaceutical companies are getting a great bargain out of this. They deserve some praise, but not as much as the public deserves the best possible public health campaign.