While we are all "rooting for the success" of coronavirus vaccine candidates in Phase 3 trials, the odds of success are "not as high as some might think"—and Americans need to reset their expectations accordingly, Peter Lurie, former associate commissioner for public health strategy and analysis at FDA, writes for the Washington Post.
How the 3 phases of vaccine trials work
As Lurie explains, vaccine trials typically occur in three phases. First, a Phase 1 study—which usually involves 20 to 80 healthy people—attempts to determine how the vaccine is metabolized by the body and to ensure it isn't extremely toxic.
Then, the trial will move to Phase 2, which is usually a non-randomized study or series of studies that examines effective dosages and any short-term side effects, Lurie writes.
After that, a Phase 3 trial will start. These trials are usually randomized controlled trials and, for the coronavirus vaccine candidates, involve about 30,000 participants to definitively determine whether the vaccine is both safe and effective.
How often do trials fail?
As of now, there are nine coronavirus vaccines in Phase 3 trials and dozens more in other phases of human testing, Lurie writes—but that doesn't necessarily mean that successful results are imminent.
While at FDA, Lurie writes, he led a team that released a report looking at 22 case studies of medical products that had encouraging Phase 2 results but failed during Phase 3 trials.
Of the case studies, 14 included Phase 3 trials that did not confirm the effectiveness of the product that was indicated in Phase 2 trials, while one identified a safety problem with the product, and seven couldn't verify the effectiveness or safety of the product.
In fact, two of the Phase 3 trials found the products caused a higher rate of the condition they were supposed to prevent, Lurie writes.
One of the case studies, for example, examined a candidate vaccine to prevent herpes. Two Phase 2 trials found that patients developed an antibody response similar to that of patients who naturally acquired herpes—echoing early findings from Phase 1 and Phase 2 trials of coronavirus vaccine candidates.
But in the case of the herpes vaccine, two Phase 3 trials found no benefit of vaccination compared to a placebo.
Some clinical trials for coronavirus vaccine candidates have also run into challenges, such as the pausing of a late-stage trial by drugmaker AstraZeneca after a trial participant reportedly developed an unexplained, serious illness.
In an effort to estimate how likely a medical product is to ultimately get approved, researchers have looked at industry data tracking compounds that started human testing in the past few decades, Lurie writes. These studies estimate that just 10% to 14% of compounds end up getting approved, and even those that make it to a Phase 3 trial have only around a 50% chance of being approved.
"In the midst of a pandemic, it remains appropriate to prepare for the possibility that a vaccine will succeed by preparing plans to administer the product and ramping up production, as the administration has done," Lurie writes. "But what we shouldn't be doing is ramping up public expectation that an effective vaccine is imminent."
Instead, Lurie writes, we should prepare the public "for the possibility that they may have to continue the social distancing and mask-wearing that, when rigorously practiced, have been so effective in this pandemic" (Lurie, Washington Post, 9/15).