WASHINGTON – In Seattle, where the coronavirus pandemic first exploded in the United States, Dr. Larry Corey is preparing to oversee clinical trials that will determine the effectiveness of the most promising vaccine candidates for COVID-19.
A friend and colleague to Dr. Anthony Fauci over several decades, Corey has overseen hundreds of similar trials over the years — a practiced scientific process in which the potency of a vaccine is tested in volunteers.
This time, however, as part of the Trump administration's Operation Warp Speed, Corey and his colleagues face an unprecedented timeline in trying to meet the program's goal to deliver 300 million doses of a proven COVID-19 vaccine by January.
Under normal circumstances, Phase III clinical trials — the last step before a drug goes to market — take up to four years, with only a quarter of candidates succeeding. Even when conducted under a typical yearslong process, vaccine trials can identify "long-term or rare side effects," according to the Food and Drug Administration website.
Corey is part of a nationwide group of scientists designing the program who were hand-picked by Fauci, the nation's top infectious disease expert, and other leaders at the National Institutes of Health.
The integrity of their work will help determine public confidence in whatever vaccine emerges from the program by the Trump administration to expedite the discovery, production and delivery of the medicine by year-end.
But scientists working on the effort, as well as those monitoring its progress, are in agreement that everything in the process would have to go perfectly in order to meet the Trump administration's end-of-year goal.
While the government is able to rush the massive spending and investments necessary to produce vaccine candidates that have yet to be proven, the scientists say it cannot rush clinical trials.
For example, a vaccine entering the market after a six-month-long Phase III clinical trial would only have a track record of being safe, and effective, for six months.
"There are so many unknowns," said Dr. John Moore, a professor of microbiology and immunology at Weill Cornell Medical College, questioning the stated goals of Trump's program. "These are easy comments to make, but to prove that something works is far more difficult."
The Trump administration has committed billions of dollars to Operation Warp Speed, hoping to accelerate the development and production of five promising vaccine candidates from AstraZeneca, Moderna, Johnson & Johnson, Sanofi and Merck, all major pharmaceutical firms.
Despite the program's name, scientists say the basic mechanics of the clinical trials process cannot be sped up.
"I think one has to recognize that there's absolutely no cutting of the safety corners, and there's no cutting of the process, really — the clinical trials process," Corey, director of the Fred Hutchinson Cancer Research Center, said in an interview.
"Certainly the trials themselves are really, you know, quite standard in their structure, and the quality of the work that's being done. We feel quite comfortable that the answers will have veracity," he said.
Recruiting volunteers for the trials takes time, and the speed with which those volunteers are naturally exposed in real-world conditions will depend on the prevalence of the virus in the communities where the trials are taking place.
Comparing the vaccine's safety and effectiveness on young and old volunteers, as well as healthy individuals vs. those with preconditions, will be key to understanding the true extent of the effectiveness of a vaccine.
It is possible, for example, that the vaccine that emerges from Operation Warp Speed will only be recommended to a younger age group — leaving older Americans who have been more vulnerable to severe illness and death from the virus still unprotected.
And as complicated a process as it is to collect all of that data, sorting through it will also take patience, said Dr. Michael Diamond, associate director of the Center for Human Immunology and Immunotherapy Programs at the Washington University School of Medicine in St. Louis.
Each company will want to conduct their own internal review of the data before it is examined by a data safety monitoring board, or DSMB.
"There are a lot of mechanics of doing vaccine trials — all of that takes some time, and even of the best of circumstances, it still takes some months," Diamond said. "If everything goes well we might have a vaccine for the general public several months after that, which might mean the spring or summer of 2021."
Vaccine candidates will only enter effectiveness trials — which will involve up to 30,000 volunteers across the United States — after a thorough review of their safety profile and of their ability to provoke an immune response, Corey said.
But Corey, Fauci and their peers are confident that at least one candidate will get there.
"I know people are saying, 'now wait a minute, you're going so fast, no one has ever done a vaccine this quickly.' And that's true," Fauci said in an interview. "But the technologies that we have now of scaling up completely dwarf what we had years ago in the standard development of a vaccine."
Fauci speaks regularly with Corey and other vaccine development experts recruited for the government program, and both men said that the virus' behavior throughout the pandemic has convinced them that a vaccine is theoretically possible to develop.
But the vaccine that emerges might only be strong enough to protect an individual against getting sick once they are infected — not against getting infected in the first place.
A vaccine that only prevents illness, and not the initial infection, might leave individuals contagious and able to spread the virus to others.
"When the body recovers from natural infections, it at least tells you it has the capability," Fauci said. "So that's the reason why I feel, as a person who has developed several vaccines, that there's a pretty good chance that we're going to be able to induce in the body a response that could either protect you from infection or, at worst, could protect you against getting disease from that infection."
Fauci vowed to oppose any effort by the Trump administration to prematurely announce the discovery of a vaccine.
Corey said the very structure of the clinical trials protects their outcome from political influence.
"Look — the trial has a life of its own that's determined by the DSMB, and not by any political process, all right? That's the way that clinical trials are supposed to be done," Corey said. "That's the way it's been done. And we're designing it to continue to be done that way."
At a congressional hearing on Tuesday, Dr. Stephen Hahn, commissioner of the FDA, made a similar promise The FDA is the final reviewing agency. "Let me clear that data and science will dictate when we will have safe and effective treatments and vaccines for COVID-19," Hahn said.