My Kingdom for a Booster Shot: Hiccups Are Yet Another Vaccine Trial Hassle

From coast to coast and beyond, participants in ongoing clinical trials of COVID-19 vaccines are discovering just how frustrating it can be to take part in medical research.

Belated and unavailable booster shots in the middle of the Omicron surge are the sticking point now, following on the heels of previous hassles over blinded data and delayed vaccine cards.

Participants in the AstraZeneca trial were left in the dark last fall when the federal government declined to approve booster shots. And many Americans in the Novavax vaccine trial — including me — are only now getting booster shots due to unexplained delays. Our jabs are coming 4 weeks after some of our Novavax trial counterparts got them, months after authorized boosters became available to the public at large, and a full year after some of us were first vaccinated. To make things even more dicey, we’re also well into a new era of booster mandates.

“It’s a pretty bad situation for the people who do want their boosters, particularly in the face of the Omicron surge,” said virologist John P. Moore, PhD, of Weill Cornell Medicine in New York City, in an interview with MedPage Today. He took part in the Novavax trial but dropped out last fall because he needed to travel internationally, and the experimental vaccine was not then on a WHO-authorized list.

Another Novavax trial participant, retired Cincinnati chemist Patricia Berger, PhD, is still in the study and got a booster earlier this month. She described herself to MedPage Today as “starting to be very uncomfortable and annoyed when I first read that some folks were getting their shots before Christmas, and my site was still clueless.”

Other participants have stronger words about the booster mess at Novavax, whose vaccine awaits FDA authorization, but is now authorized by the WHO and certain other countries. Social media teems with anger from trial participants in the U.S. and the U.K. who feel let down by the company, the trial research sites, or both. Some have dropped out of the trial in order to get booster shots of authorized vaccines, while others have been waiting anxiously to get calls about setting up appointments to get Novavax boosters.

“Novavax left us hanging on the edge for too much time,” Isaac Ramos, a master electrician in Puerto Rico, told MedPage Today. He’s a participant in the trial along with his mother and sister. They were only able to make booster appointments this week. The trio has been masking up more than they would have otherwise, Ramos said, and he’s not going to Winter League baseball games because attendees are required to be boosted.

Of course, the consequences for the unboosted are worse than missing the seventh-inning stretch: potentially more severe cases of COVID-19 and a greater risk of getting the disease and passing it on.

Novavax Is Mum on Reasons for Booster Hiccups

It’s clear that COVID-19 vaccine booster shots provide extra protection to vaccinated people. The Novavax booster shot, which is identical to the primary vaccine series, seems likely to be strongly protective against COVID-19, or at least serious illness and death.

So why did it take until late December for Novavax boosters to finally start getting into arms, and well into late January for some research sites to get their act together? Novavax announced on December 21 that the first boosters had been given. My research site was well behind, and finally scheduled a booster for January 21.

In response to questions from MedPage Today, Novavax sent answers attributed to spokeswoman Silvia Taylor. “Novavax worked as quickly as possible to initiate the booster program,” she said, declining to offer any explanation.

Other delays have also plagued Novavax, whose vaccine appears to work well. The company expected to get FDA authorization months ago, and it inspired great confidence in the U.S. federal government early on. As Politico reported in October, the feds made an initial $1.6 billion investment in the company’s product in the early days of COVID-19, “but the company has consistently run into production problems” linked to its failures to reach standards set by regulators.

“The vaccine is great. I understand the science and why it would work as intended,” said Berger. “But I think the company signed up to do more than they were ready to, or they didn’t understand what it would take.”

She doesn’t blame Novavax for the booster mess, however. “I do not believe this is their doing. It’s sensible to believe that Novavax sends one communication to all sites at the same time, but different sites react at their own pace.”

Institutional Review Boards Get Some of the Blame

Indeed, accounts from trial participants suggest that slow-moving institutional review boards, better known in medical lingo as IRBs, are getting at least some of the blame for booster delays.

It’s common for every research site in a clinical trial to run protocols through an IRB, said Shane Crotty, PhD, of La Jolla Institute for Immunology, in an interview with MedPage Today. That adds to the bureaucracy and can contribute to delays, especially over holidays. And a review of safety is critical, he noted.

While some IRBs are working at unusually fast speeds during the COVID-19 pandemic, he pointed out, others have been hit by delays. “Our family took part in the Moderna pediatric vaccine trial, and we couldn’t get a vaccine card for our son to prove he’d been vaccinated. They said the IRB had to do something, and months and months went by.”

As for the Novavax vaccine, he said it is strong. “There’s no reason not to have good communication, especially when you have thousands of people, and you expect them to be anxious,” he added. But, he noted, Novavax doesn’t have extensive clinical trial experience.

AstraZeneca to Participants: No Boosters for You

On the bright side, at least Novavax boosters are in the works. There’s no such luck for the 26,100 participants in the U.S. trial of the AstraZeneca vaccine, which is not yet authorized by the FDA but is a leading vaccine in much of the rest of the world.

“The U.S. government has decided not to move forward with an amendment to the trial adding a third dose boost,” an AstraZeneca spokesman told MedPage Today. The company encourages participants to get boosters elsewhere, he added.

This message didn’t get to trial participants in a timely manner, according to Bloomberg News. They reported on December 1 that Montefiore Medical Center in New York City told participants that boosters wouldn’t be available: “We learned this not long ago, and were hoping that there would be a formal announcement from AstraZeneca,” noted a letter sent to trial participants. “In the absence of a formal announcement, we are sending this information in the interest of your health.”

Madelyn Beck, an Idaho public radio reporter and AstraZeneca trial participant, was anxious to get a booster late last year since she got her original vaccine back at the end of 2020. But, as she told MedPage Today, she got a classic runaround: The research site directed her to contact the company, which directed her to contact — you guessed it! — the research site.

A nurse there told her that the company was hoping to soon launch a booster program, so Beck waited. But when she called again to follow up, she learned that no booster would be available. She finally got a Pfizer booster and suffered through some minor side effects on a flight home for the holidays.

For Trial Participants, One Hassle After Another

I joined the Novavax trial in early 2021 just weeks after COVID-19 had killed my 85-year-old father following a wrenchingly extended and isolated hospital stay. Like the other 30,000 Novavax trial participants in the U.S. and Mexico, I got two shots in early 2021 and two shots a few months later. One round was a placebo, the other was the vaccine, and we were blinded as to which one was which.

The staff at my research site in San Diego have been friendly throughout multiple visits for routine blood tests and for a couple colds to see if they were COVID-19. (They don’t seem to have been.) But my interactions as a trial participant with the Maryland-based company have only consisted of a few email messages.

We got no helpful guidance about how to make decisions when authorized vaccines became widely available early last year and it wasn’t clear if we’d gotten the real thing from Novavax due to blinding. Some participants even got tests to “unblind” themselves so they could figure out what to do. A third of us, including me, as it turned out, only received the actual vaccine shots in the spring, with our earlier round of shots being placebos.

Last summer, what virologist Moore called “a ridiculous mess” arose when computer systems, universities, and foreign nations refused to accept that Novavax and AstraZeneca trial participants were vaccinated since our shots weren’t yet authorized by the FDA. After prodding, the companies finally gave us modified vaccine cards.

“They’ve left the trial participants hanging, although we stuck our arms out to hopefully help the human race,” said Cris Sahner, an auto dealership manager and trial participant in Omaha, who puts the responsibility squarely at Novavax’s door.

A Perennial Vaccine Trial Question: Stay or Go?

Of course, I could drop out of the Novavax study with no consequences, per the consent forms I signed. Judging by social media posts, many people have done so over the last several months in the U.S. and in the U.K., where participants have been especially miffed about travel hassles due to the lack of vaccine authorization and, more recently, the lack of boosters.

As for boosters here in the U.S., I could run out and get one easily. That would allow me to visit my elderly mother, who has entered a San Diego nursing facility after her health declined following her own bout with COVID-19 and the death of my father from the disease. Earlier this month, the state of California required indoor visitors to nursing homes to be both vaccinated and boosted.

But I tolerated the Novavax vaccine shots well and might not be so lucky with Pfizer or Moderna. I took an antibody test a few weeks ago, and it said I still had COVID-19 antibodies, although no one seems to be quite sure how to interpret the numbers that antibody tests spit out. And it’s not entirely clear how well a non-Novavax booster would work after a Novavax vaccine, although there are signs that vaccine mixing-and-matching isn’t dangerous.

There are benefits to taking part in research too. I’m compensated for visits required by the Novavax trial, and it did offer me a chance to get vaccinated early. And I still want to be helpful and see this thing through. While the hassles keep adding up, I remain wedded to Novavax.

Berger, the Cincinnati chemist, is also staying in the trial. But this may be the last time she signs up for something like this. When I asked her if she’d take part in clinical research again, her response was distinctly non-committal: “Mmhhh, that’s something I will have to think about a bit more.”

As for me, I’m already signing up for another study. With assistance from Novavax, the La Jolla Institute for Immunology has launched a study of people who got the Novavax vaccine. I’ll be paid to give blood for researchers to analyze and answer personal health questions.

No hassles, communication gaps, or major medical decisions to worry about? It already sounds too easy.

https://www.medpagetoday.com/special-reports/exclusives/96788?xid=fb_o&trw=no&fbclid=IwAR0VdiP0daKBkA7j-31qYgUAsSzjO6VngIGeyIHwXFYu0AFcayBH1JJKzNI

Créditos: Comité científico Covid