- Dr. Anthony Fauci explained in an interview that Phase 3 trials for novel coronavirus vaccines can end early in two different scenarios, but politics wouldn’t play a role.
- If the independent Data and Safety Monitoring Board finds that the drug is effective, it could stop the trial so the group of volunteers who gets placebos will also receive the real vaccine.
- The other reason a trial might end early would be if a drug has side effects so severe that the safety board decides to terminate the research early.
- Fauci’s comments came in response to recent COVID-19 vaccine controversies, from the early use of Russian and Chinese vaccines to the rumors that say Trump wants to have a vaccine approved before the November election.
All the toxic coronavirus vaccine chatter from the past few weeks isn’t really going to help the initiative to speed up COVID-19 immunization campaigns. On one hand, we have Russia and China that are already using vaccines before Phase 3 trials are completed. Of those, the Russian vaccine is the most disturbing, considering there’s no scientific evidence at all to back up the emergency use authorization. China, on the other hand, has published several papers that prove the efficacy and safety of some of the vaccines it’s testing.
On the other hand, some people believe that President Trump will attempt to pressure officials into speeding up the emergency use authorization (EUA) for at least one vaccine candidate that’s currently in the works to help his reelection bid. Dr. Anthony Fauci explained why such a decision would be dangerous for the entire vaccine research effort, saying that clear scientific evidence is needed before emergency approvals are given. He did concede that we might have an answer in November. FDA Commissioner Stephen Hahn, who faced plenty of criticism for the way he promoted plasma therapy during a White House briefing last week, said that some companies might seek EUAs before Phase 3 trials are ready. The FDA will have to analyze the request and issue a decision, the official added, explaining that politics will not play any role in such determinations.
It turns out there are two scenarios where a Phase 3 trial may end earlier than expected, and they have nothing to do with politics or election schedules. Both can apply to any of the coronavirus vaccines that are currently in the final stage of testing, or to any other drugs that are being developed.
As you might already suspect, there’s good and bad news. A Phase 3 trial can be terminated early if researchers discover significant side effects that can harm volunteers. This wouldn’t be the first time a COVID-19 study was stopped because of safety concerns. It happened with hydroxychloroquine, with a study in Brazil being a prime example of that. Others, including officials in Australia, the UK, and the World Health Organization, also halted or paused hydroxychloroquine studies after papers said the drug could be harmful.
None of the vaccines that are in Phase 3 trials right now have caused significant side effects, according to published literature on the matter. But there are no guarantee things will stay that way. “If it looks like it’s actually harming people in the vaccine arm, due to a lot of adverse events,” Fauci said in an interview with KHN that CNN cited.
That’s the worst-case scenario, and certainly not one we want to envision. Other drugs did fail to show efficacy in Phase 3 trials, and the same might happen to some of the more than 170 vaccine candidates that are in the works, including the three frontrunners. These are the Moderna, Pfizer/BioNtech, and AstraZeneca/Oxford drugs that are in Phase 3 tests right now. The US government has invested considerable amounts of money in all three of them, ensuring the US will be among the first to get access to the drugs once if they’re approved.
The other scenario where a Phase 3 trial would be stopped early is the ideal one. The Data and Safety Monitoring Board could say, “The data is so good right now that you can say it’s safe and effective,” Fauci explained. In such a case, the researchers would have a “moral obligation” to end the trial early and make the vaccine available to everyone in the study, including the volunteers who initially received placebo drugs. Phase 3 trials will need 30,000 volunteers per experimental drug, and half of that will represent control cohorts.
Fauci said he trusts the members of the DSMB to hold vaccines to high standards without being influenced politically. “If you are making a decision about the vaccine, you’d better be sure you have very good evidence that it is both safe and effective,” Fauci said. “I’m not concerned about political pressure.” He added that whatever happens during research, the data will be made public so that the entire process will be transparent.
There’s already precedent for this, and it comes from a different COVID-19 trial. When the same Fauci announced that remdesivir had been approved for use, he did it without waiting for the scientific data to be published in a peer-reviewed paper. At the time, he said that remdesivir was also given to the placebo patients in that study once it was clear that the drug can help.
When it comes to vaccines, the safety board will periodically analyze data to see if it’s ethical to continue enrolling volunteers in the trial. Neither the people who are willing to test the drugs nor the scientists know who is getting the drug and who is getting the placebo, which makes it impossible for anybody else to tell whether the medicine is working as intended.
Director of the Centers for Disease Control and Prevention Dr. Robert Redfield explained to reporters that trials of such magnitude could show some results relatively fast. “It may be surprising, but the number of events that need to occur is relatively small,” Redfield said. By events, he meant the number of infections in a study that enrolls 30,000 people. He said that as few as 150 to 175 infections could tell researchers whether a vaccine is effective or note. But only the safety board has access to the data.
That said, the enrollment process is not compete for the Moderna or Pfizer Phase 3 trials in the US. Each of them has enrolled just half of that 30,000-volunteer goal. AstraZeneca started trials in Great Britain, Brazil, and South Africa, and plans to begin its own US Phase 3 test that must include 30,000 volunteers as well.
Stopping a trial early could have additional implications. One of the goals of the tests is to research more minority volunteers, but only about one in five participants are Black or Hispanic so far. These communities have been hit the hardest by the virus. Moreover, ending trials faster could further erode the trust of Americans in vaccines in general. The most recent polls show that one in three people could refuse a COVID-19 vaccine.
Even if the safety board recommends that a trial should be stopped, it’s up to the scientists running the research to actually stop the trial. If the drug is indeed effective, they could then seek an EUA for it.