By Arthur Allen, KHN
As I prepared to get vaccinated in mid-December as part of a COVID-19 vaccine trial led by Janssen Pharmaceuticals, I considered the exit routes. The bailout of the trial was a very real consideration since two other vaccines, manufactured by Moderna and Pfizer-BioNTech, had been found to be safe and effective for emergency approval.
Leaving the trial would make a perfect sense for me or anyone who had volunteered for an ongoing COVID experience. Why risk getting COVID if I was given a placebo, an injection without a vaccine? The way the tests are designed, I may not be told if I received the vaccine before the clinical trial is over, in months.
Dropping the placebo arm could also be ethically valid from a business perspective. Researchers frequently stop trials when they have a product that works – or clearly doesn’t. And the two approved vaccines are 95% effective.
This very real choice for the thousands of people who are offering to participate or stay in the ongoing vaccine trials creates an enigma for science and for society. If the trials cannot proceed, it could very well have an impact on the global supply of COVID vaccines and possibly on vaccine prices, especially if booster shots are required in the years to come. In markets where there are only two competing drugs, prices can soar. If there are four or five in the market, competition usually comes in to control costs.
In short, the welcome arrival of two COVID vaccines deemed safe has revealed a series of ethical and logistical challenges. And it has governments, businesses and scientists looking for solutions.
“Global vaccine experts say the longer we can run a placebo-controlled trial the better,” Matthew Hepburn, who heads the vaccine development arm of Operation Warp Speed, told me. multi-billion dollar federal government fight against COVID-19. . “But as a volunteer in the Janssen trial, you can always give up.”
As to how best to solve larger problems, “it’s a real-time debate,” he said.
In general, the debate has two aspects. First off, what should be done with the placebo recipients in the Moderna and Pfizer trials now that it is clear that both injections prevent disease and appear safe? Second, how can the dozens of companies in the United States and abroad that are still testing COVID vaccines adapt when there are already seemingly reliable products on the market?
The FDA advisory committee debated the first issue at two meetings in December. They heard statistician Steven Goodman of Stanford University advocate for a “double-blind crossover” modification of the Pfizer and Moderna trials. Anyone who received placebo injections in the trials would now receive two doses of the real vaccine, and vice versa. This way everyone would be protected, but still “blind” to when they were properly vaccinated.
Such a review of the current trial would provide more data on vaccine safety and durability of protection, although the longer-term comparison of the vaccine versus placebo would be lost. It’s a wonderful idea in principle, the panelists agreed, but quite difficult to achieve. Neither Moderna nor Pfizer accepted it.
Pfizer wants to “unblock” the placebo recipients of its vaccine – to reveal that they got the saline solution and give them the real solution – once their risk group has their turn in line for the vaccine. He has already started vaccinating healthcare workers who received the placebo.
Moderna, who has thousands of remaining doses from her trial about to expire, said she plans to cancel her trial and vaccinate all placebo recipients. In doing so, it would be acknowledging the selfless service that the test subjects have rendered to science and society by joining the trial.
Another proposal would divide the placebo beneficiaries of the trial into two groups. In a group, everyone would receive a single dose of the vaccine. In the other, each would receive two doses. This would be one way to test the evidence that emerged during the Pfizer and Moderna trials that a single dose could provide sufficient protection. If this were true, the country’s vaccination could happen almost twice as fast, as there would be twice as many doses of vaccine to distribute.
No one knows how far the Food and Drug Administration could force the hands of the two companies, which still hope to obtain a full license for their vaccines in 2021. Moderna is considered more receptive to the suggestion because, unlike Pfizer, it has obtained nearly $ 1 billion in federal funding to develop its vaccine.
Other vaccine developers, including Operation Warp Speed participants, Janssen (owned by Johnson & Johnson), AstraZeneca, Novavax, Sanofi and Merck & Co., are closely watching the way forward.
They are in a race against time – a race that may not end well for those who are late to get their shots. And stopping these efforts could harm billions of people around the world whose lives and livelihoods will depend on the availability of abundant and inexpensive vaccines.
One problem is finding voluntary test subjects. As more Americans are vaccinated and the virus moves away from our shores, “fewer people are eligible to participate in trials,” said Susan Ellenberg, professor of biostatistics at the University of Pennsylvania.
For now, AstraZeneca and Janssen seem to be well situated. Both have closed registration for their trials in the United States and are likely to file emergency use authorizations within months, like those that allowed Moderna and Pfizer to begin vaccinating the public.
Novavax officials hope to begin their advanced stage trial in the United States soon and predict that they can be fully enrolled in a trial before the majority of the U.S. population is vaccinated.
Sanofi and Merck, with longer hours, are more likely to conduct most of their trials overseas.
In theory, pharmaceutical companies could overcome these barriers by testing multiple vaccines against each other and against approved vaccines. Dr. Steven Joffe, a bioethicist at the University of Pennsylvania, proposed in a recent JAMA article that Operation Warp Speed is paying for such a trial.
Scientists and policymakers wrestled with the idea of a single US trial, with multiple vaccine candidates competing against each other and a single placebo arm, during the first spring discussions about creating the operation. Warp Speed.
The idea went nowhere in the United States. It has been picked up by officials from the World Health Organization and major biomedical research groups, who have attempted to create such a vaccine trial in the rest of the world – with little success so far.
So, for now, future vaccine trials are somewhat on hold.
“There’s this tension created by bringing the first vaccines to market so quickly,” said David Wendler, senior bioethics researcher at the National Institutes of Health Clinical Center. “For public health it’s good, but it has the potential to undermine our ability to continue with research and really eliminate the virus.”
Businesses, governments and external funders must quickly develop consensus on appropriate trial designs and regulatory processes for additional COVID vaccines, added Mark Feinberg, president and CEO of the International AIDS Vaccine Initiative.
As for me, I decided to stay in the Janssen trial. However, the day before I was due to receive my injection – real or fake – the immunization research agency called to say I had failed to make the cut: J&J had stopped enrolling in the trial. .
So I’m going to buy new masks and line up for my vaccine with everyone.
Arthur Allen is an editor at KHN and author of “Vaccine: The Controversial Story of Medicine’s Greatest Lifesaver” (WW Norton, 2007).
KHN (Kaiser Health News) is a non-profit news service covering health issues. This is an independent editorial program of KFF (Kaiser Family Foundation) which is not affiliated with Kaiser Permanente.
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