What COVID-19 vaccine trials still need to do
COVID-19 vaccines are being developed at record speed, but some experts fear the accelerated regulatory process could interfere with ongoing research about the vaccines.
Why it matters: Even after the first COVID-19 vaccines are deployed, scientific questions will remain about how they are working and how to improve them.
The big questions: The first is whether people can have rare or delayed side effects, which could be detected in long-term trials with millions of participants.
- "Most vaccine side effects do occur in the short term," Kathleen Neuzil, director of the Center for Vaccine Development and Global Health, said at an Infectious Diseases Society of America briefing Thursday. "But we don't know a lot about COVID, and we don't know a lot about the long-term consequences of COVID."
- The tens of thousands of people currently enrolled in clinical trials in the U.S. will be tracked for at least two years to determine whether the vaccines pose any rare or delayed side effects.
How long immunity through vaccination lasts, and whether vaccines will stop transmission of the virus or just prevent people from becoming sick, are also open questions.
- "It still has to be proven if the vaccine can flatten the curve and eradicate the virus in its own right," says Mark Poznansky, director of the Vaccine & Immunotherapy Center at Massachusetts General Hospital, adding that the immunology of the virus isn't completely understood.
- On the other hand, Neuzil said early efficacy reports suggest "if we can get enough vaccine out there, we can have an impact on this pandemic very, very quickly."
What's next: The Food and Drug Administration is considering authorizing vaccines for emergency use — a faster process than full approval. Moderna and Pfizer have already submitted their requests for an emergency use authorization.
- But some experts are afraid that once the FDA begins granting those EUAs, it'll be harder to maintain strict, placebo-controlled clinical trials to answer these l0nger-term questions.
- Some argue that continuing to administer a placebo when a vaccine is available would be unethical, and there's also a concern that patients will leave trials where they might be getting a placebo.
The big picture: The accelerated development timeline means that "this question of whether it is appropriate to continue someone on placebo kicks in earlier than usual," says bioethicist David Wendler of the NIH's Clinical Center.
- Trials that are already underway could likely justify continuing to use placebos if participants know they have a choice and consent to still potentially receiving a placebo, Wendler and his colleagues argue today in the journal Science.
- Developers could help keep their trials going by guaranteeing that people who receive placebos will get a vaccine once their participation in the study is complete, they write.
- Future trials would likely test two vaccines against each other, rather than testing one against a placebo, though there are limits to that approach.
What to watch: The FDA is set to meet on Dec. 10 to discuss Pfizer-BioNTech's EUA.
- The breadth or narrowness of those EUAs will determine their impact on future research, says Alison Bateman-House, a professor of medical ethics at NYU's Grossman School of Medicine.
- "If anyone who wants it can get it, you’ve killed the trials."
The bottom line: The EUA "is definitely not the end but hopefully maybe the beginning of the end" of the pandemic, Wendler says. "The question is what more do we need to figure out to get to the end?"