Questions raised for vaccine trials in San Diego
Researchers, ethicists are searching for best way to keep the San Diego studies going.
Some researchers and bioethicists struggle to balance the need to collect data versus gaining the public’s trust.
SAN DIEGO — The historic rollout of COVID- 19 vaccines has sparked hopes for eventually ending the pandemic and raised fresh questions for this city’s vaccine trials.
Do study participants deserve to know whether they got the actual vaccine? If so, how soon should those in the placebo group get vaccinated?
Researchers and bioethicists are struggling to balance the need to collect more data on vaccine safety and efficacy with the sense that we owe something to those who signed up for these studies.
Different vaccine makers are devising their own solutions. Their answers will affect the thousands of San Diegans who have enrolled in COVID- 19 vaccine trials — and, potentially, public trust in research.
“I think it’s incredibly challenging,” said Dr. Susan Little, who runs two COVID- 19 vaccine trials at UC San Diego. “In the face of the surge that we are in now, I personally would have a very hard time continuing people on placebo knowing that you’re going to see more cases of COVID and potentially deaths.”
Nearly all large vaccine trials work the same way: Half of the participants get the vaccine and the other half get a placebo ( usually a saltwater injection). Volunteers don’t know which shot they received, which makes these studies “blinded,” and placebo and vaccine are randomly assigned. Researchers then monitor participants to check if the vaccine is safe and see whether it reduced their chances of getting sick.
In theory, participants understand and agree to this setup. But that’s not entirely realistic, said Joseph Stramondo, a bioethicist at San Diego State University.
“It might be too idealized to just sort of say, ‘ Well, they knew what they were getting into,’ ” he said. “A lot of times when people sign up for any clinical trial, they at least hope that they’re getting some kind of benefit.”
That’s what the UnionTribune learned during dozens of conversations with San Diegans who volunteered for these trials. People said they wanted to do their part to help end the pandemic, but they also hoped their participation would protect them against COVID- 19 — both for their own benefit and the sake of family and friends.
Without these volunteers, there would be no vaccine. “What we absolutely owe them is information,” Stramondo said. “That’s sort of the minimum.”
Moderna and Pfizer are doing that in different ways.
Pfizer is offering to gradually let participants know whether they received vaccine or placebo, based on when they’re eligible to be inoculated in their region. Those who learn they got the placebo can then get vaccinated and continue to be monitored as part of the trial.
Moderna study participants, by comparison, will probably get that option much sooner.
“It is our intention to immunize all of those who received placebo in January. We will try to accomplish this as early in the month as possible,” reads an email sent to San Diegans participating in a study site run by UCSD. ( Moderna is still awaiting approval from the Food and Drug Administration for this plan.)
Technically, trial participants can opt not to learn whether they got the vaccine. But that’s unlikely to happen.
“I definitely want to know,” said Elise North, 24, an Ocean Beach resident and study volunteer.
Losing the placebo group would make it harder to detect vaccine- related side effects that arise after several months, though most side effects show up within two months. On the other hand, vaccinating more participants could make it easier to spot rare side effects, said Dr. Stephen Spector, director of UCSD’s Moderna trial. And researchers could still gauge how long the vaccine lasts by comparing when people in the f irst vaccinated group begin to test positive for the coronavirus compared to those who got their shots later.
“You always lose something by not having a group that doesn’t get the study vaccine,” Spector said. “On the other hand, we have to ask whether or not it’s acceptable and ethical given the pandemic to not immunize the participants.”
During a Dec. 10 FDA panel meeting, some experts worried that offering the vaccine to trial participants who aren’t in high- risk groups could give the impression that they’re jumping ahead in line.
Stramondo thinks that concern is probably a bit overblown. Case in point: About 1,200 San Diegans signed up for Moderna’s vaccine study ( including 335 through UCSD), so around 600 would have received the placebo. By comparison, San Diego County received 20,000 initial doses of the vaccine and expects nearly 44,000 total doses by the end of December.
“We’re not talking about huge numbers here,” Stramondo said. “It’s not like, if we offer the vaccine to the study participants, that’s really going to make that big of a dent in our ability to vaccinate older people or people in institutional situations,” such as nursing homes.
The vaccines Pfizer and Moderna have developed are about 95% effective at keeping people from getting sick with COVID- 19. But there’s still good reason to continue testing other vaccines, said Little, who is directing trials for AstraZeneca and Johnson & Johnson at UCSD.
“With two vaccines, yes, we can probably vaccinate the entire American population, and it’s going to take awhile,” she said. “More effective vaccines mean we can vaccinate more people faster.”
The directors of Operation Warp Speed, the U. S. government’s bid to quickly roll out a vaccine, have said 25 million to 30 million Americans could get vaccinated each month next year, but newly authorized vaccines would boost that f igure. The goal, ultimately, is to get enough people vaccinated so the spread of the virus slows dramatically.
Other vaccines come with their own advantages. Johnson & Johnson has a one- shot vaccine, for instance, while Pfizer and Moderna require two shots three or four weeks apart, respectively. Some researchers worry that people won’t get full immunity if they don’t come back for the second shot.
AstraZeneca’s vaccine can be kept in a refrigerator for up to six months, with each dose priced around $ 3 or $ 4 — both factors that could make the vaccine invaluable in rural communities and less aff luent countries where specialized freezers are scarce.
Little has been letting participants eligible for the Moderna and Pfizer vaccines know whether they got the vaccine or placebo. Those who received the placebo can get one of the authorized vaccines and continue to be monitored as part of the AstraZeneca or Johnson & Johnson study. That may be part of why she hasn’t seen people drop out of these trials — if anything, she said, there has been more interest.
That should work for the current trials, which are on track to apply for emergency authorization in early 2020. But by the spring, COVID- 19 vaccines should be widely available, making it impractical for future trials to ever have a placebo group. Researchers are still debating possible workarounds, including vaccinating all participants eventually ( but some sooner than others) or running trials in regions where a vaccine is not yet widely available.
“I think there needs to be a new approach, a new study design,” Little said. “It’s just not ethical to randomize people to placebo when we know we have effective vaccines.”