Talk about a shot in the dark. Two weeks ago, a nurse injected me with what may — or may not — be the experimental Novavax COVID-19 vaccine as part of a phase III clinical trial. I don’t know which one it is, but I do know that the publicly available Pfizer and Moderna vaccines appear to work. So I may – or may not — drop out of the trial when one of those becomes available to me.
This kind of uncertainty isn’t uncommon for those who sponsor clinical trials and the subjects who take part in them. But this time around, the stakes are huge: the authorized vaccines have limitations, such as the requirements for multiple doses and extreme refrigeration. We need better ones, especially as new variants crop up. The outcome of the world’s war against the pandemic could depend on whether drugmakers can convince subjects like me to not only sign up but also stick around.
“We have a pandemic, with a need for more vaccines, and safe and extremely effective vaccines available in some countries. This combination is unprecedented,” National Institutes of Health bioethicist David Wendler, PhD, told me.”No one really knows how to [launch a trial now] or whether it will be feasible to do it.”
Exposure and Uncertainty
For me, taking part in the Novavax trial was a no-brainer once I learned that it was underway here in San Diego. We’re in the middle of a pandemic surge and a worrisome local jump in cases of the U.K. variant. But at the age of 52, I’m months away – at least — from being eligible for an authorized vaccine, and the local rollout has been a mess. No one knows when my age group, classified as 1C in California, will get shots.
So I signed up for the Novavax trial last month.
The worst thing about getting my first shot wasn’t the needle stick. Instead, it was the preliminaries, which exposed me to the scariest of sights during the pandemic – people everywhere! At various times, I shared rooms with nurses, screeners, participants, and a doctor. This was by far the most human contact I’ve had in almost a year, and enough to put my nerves on edge. Leave it to me to get COVID in a COVID vaccine trial.
Then came a blood test and a self-administered nasal swab to test me for COVID-19, followed by the actual shot. While a recent shingles vaccine made me mildly fluish for almost 3 days, I had no side effects this time around. As a result, I suspect I got the placebo, like 33% of those in the Novavax trial.
I’m one of more than 21,000 people who are taking part in the trial in the U.S. and Mexico so far, according to Novavax, which has a goal of 30,000 participants. A spokeswoman for the company, which launched its trial late after reportedly encountering manufacturing problems, told me the response is “robust.” But as of Feb. 3, Novavax reported that only 3,186, or 15%, of participants are over the age of 65. The target for that age group is 25%. Meanwhile, Novavax earlier reported that 1% of participants had dropped out, including 2% of those 65 and up.
Existing Vaccines ‘A Huge Barrier’
The existence of available vaccines is a “huge barrier” to successful vaccine trials, said internist Jeffrey Carson, MD, who managed the Johnson & Johnson COVID-19 vaccine trial’s site at Rutgers University in New Jersey.
Anyone who joins a trial when they’re already eligible for an authorized vaccine is “putting themselves at risk unnecessarily,” he told me. “A very significant portion of potentially eligible participants will decline to be in the study and rather will try to get one of the vaccines that are approved.”
What can be done so the vaccine trials can run smoothly and effectively? Transparency is key, bioethicist Wendler said. “The companies really have to make sure they’re honest partners with the people who are enrolling in these trials. They need to tell you that you may be on a placebo, these are the risks, here’s why we’re doing this trial, and here’s why it’s valuable. And then it’s up to you.”
If anything, Novavax may provide too much transparency. I received a 23-page document explaining the trial, which is a lot to take in and more than many people will bother to read and understand. But the alternative – providing less information – may not be ethical.
Drugmakers can also make their trials more attractive to potential participants. Unlike previous COVID-19 vaccine trials that randomized participants evenly to the vaccine or placebo, the Novavax trial is giving the vaccine to 66% of participants. This will reduce the trial’s statistical power, making it harder to detect small differences between groups, said Carson. “But the upside is that it’s more likely that people will be willing to participate because they have a two-out-of-three chance of getting a vaccine instead of a one-out-of-two.”
Another strategy is to boost payments to trial subjects. For taking part in the Novavax trial, I will receive $150 or $125 for each of nine scheduled visits plus $75 each for any unscheduled visits. Drugmakers could dramatically boost these kinds of stipends, “but then you get on a slippery slope,” Carson said. “If the financial rewards of participating are too high, then you’re potentially creating coercion – and it’s no longer viewed as an ethical trial.”
Big Choice Looms
For now, I’m in the Novavax trial; I’m to receive my second shot this week. But later this year — when California will presumably make me eligible for one of the authorized vaccines — I’ll face a choice between whether to stick with the trial, and the uncertainty over whether I was genuinely immunized, or withdraw in order to get a definitely active vaccine.
“You have no obligation to stay in the trial. You’re free to drop out at any point in time,” bioethicist Alison Bateman-House, PhD, MPH, of NYU Langone Health, told me. “It comes down to the question of, are you more interested in seeing the trial successfully conducted? Or are you more interested in getting a shot in your arm as quickly as possible?”
If I decide to pull out, the trial researchers will unblind me as to whether I received the real test vaccine or a placebo. If it turns out I got the real thing, I’ll face another dilemma. According to Carson, it’s unclear whether receiving two vaccines is dangerous. “It may turn out there’s not a safety issue, but we don’t know that yet.”
Another option would be to stay in the study and, at some point, get the real Novavax vaccine. The company has amended the study protocol to incorporate a blinded crossover system. While details aren’t immediately available, that means I’ll be given the opposite of what I’m getting now at some point: If I’m currently getting the placebo, I’ll be switched to the experimental vaccine.
Whatever happens, I’m especially motivated to protect myself since COVID-19 took the life of my 85-year-old father and severely sickened my mother. (I wrote about my dad’s wrenching final days in an essay for MedPage Today.) I can’t expose my mom to any more loss or worry. Or, for that matter, myself.
What will I do? I’m leaning toward taking a bit of advice from Carson: “If you can get [an authorized] vaccine,” he said, “go get it.”
Source: MedicalNewsToday.com
