As pressure for vaccine builds, regulators may face difficult decision

With multiple pharmaceutical firms wading deeper into human testing of a vaccine, federal regulators may soon face their toughest decisions yet in the global battle to subdue the novel coronavirus.

In a matter of months, the Food and Drug Administration will likely have to determine when to approve mass production and distribution of a vaccine that will likely be injected into the arms of tens of millions of Americans.

At that time, regulators will grapple with the fragile balancing act of speed and safety: Approving an inoculation regimen too early carries a risk of endangering the public with unforeseen side effects. But waiting too long bears the likelihood of losing countless more lives to a virus already known to have killed over 400,000 people worldwide.

"Hopefully, by the time we get to mid and late fall, if the process goes well, we will have enough information to be able to make a decision whether the vaccine is safe and effective," said Dr. Anthony Fauci, the administration's chief infectious disease expert, on "Good Morning America" on Wednesday.

"If we are in good shape and that happens," Fauci continued, "we could have a vaccine either by the end of this calendar year or in the first few months of 2021."

With such an ambitious timeline for a product that normally takes years to develop, some researchers fear that federal regulators will buckle under immense public and political pressure to greenlight a vaccine with promising early results -- without being thoroughly examined for possible side effects.

In an effort to save time, the methodical steps of vaccine development that usually occur one after another -- from preclinical trials to manufacturing and development -- have been condensed and carried out simultaneously. Moderna Inc., which is developing what is considered to be the lead candidate, for example, was given permission to begin testing in humans before waiting until testing in animals was complete. Animal testing is ongoing.

The National Institutes of Health confirmed this week that the Moderna vaccine candidate would enter a government-funded phase 3 human trial in July, followed by candidates from Oxford University and Johnson & Johnson later in the summer. Public health officials have suggested the phase 3 trial will involve 30,000 human participants -- 20,000 of whom would receive a vaccine and 10,000 a placebo.

But Dr. Paul Offit, a vaccine expert at the Children's Hospital of Philadelphia, envisioned a scenario in which one or more vaccine candidates drop out of the trial after demonstrating some level of viability.

"I really worry that we're not going to complete those trials," Offit said, "that maybe some companies will break away from [the phase 3 trial] and do a few thousand people -- maybe 6[,000] or 7,000 people – but that's not enough."

Offit and his colleague at the University of Pennsylvania, Dr. Ezekiel Emmanuel, also suggested political forces could impose additional pressure to roll out a vaccine expeditiously, warning in a recent New York Times op-ed of a possible "October surprise" ahead of the November presidential election.

"Three months after the N.I.H. trials begin in July -- so, mid-October -- studies reveal many patients are developing high levels of antibodies to the coronavirus without severe side effects," Emanuel and Offit wrote of this possible scenario. "As the White House did with its relentless promotion of hydroxychloroquine as a cure, it would badger the F.D.A. to permit use of the vaccine."

Dr. Peter Hotez, a Baylor University virologist, said he shares Offit's concerns in the abstract, but remained confident that institutional buffers would prevail in ensuring a safe vaccine emerges from the trials.

"I think our system of checks and balances is robust and could halt any potential meddling or tampering," Hotez said. "Also, these last few months have given the scientists a more powerful voice. ... I'm confident we can prevent an 'October surprise.'"

Dr. Jennifer Miller, a bioethics professor at Yale University School of Medicine, added the risks associated with finding a coronavirus vaccine are found in any vaccine development, but so far the safety precautions have been followed.

"There's always some level of uncertainty around a new drug or vaccine, which is why we continue to do surveillance, so the risk is never zero," Miller told ABC News. "But the studies are robust and being well done, so I don't think there's a significantly heightened risk."

To help craft efficacy trial standards, the federal government has enlisted experts from academia -- including both Offit and Hotez -- to consult with public health officials and pharmaceutical executives. That panel -- called Accelerating COVID-19 Therapeutic Interventions and Vaccines, or ACTIV -- has been instrumental in determining the guidelines adopted by NIH for the phase 3 trials.

The head of ACTIV's clinical trials subgroup, Dr. Larry Corey, a vaccine specialist at the Fred Hutchinson Cancer Research Center in Seattle, dismissed concerns that the government would allow an untested vaccine to be cleared for use.

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"We have the best doctors and infectious disease experts in our country who have all been leaders in their local communities and COVID-19," Corey said. "We've been at this business for a long time, and I have no doubt that we will design -- and have designed and will design -- as careful safety and as high standards as possible that exist in the world."

Even so, other infectious disease experts posit that possible side effects and other unknowns often arise over time -- particularly in certain at-risk populations, like the elderly.

"Sometimes it takes a year for the safety profile to pop up," said Dr. William Haseltine, a former Harvard Medical School professor and researcher. "And we already know that vaccines don't work very well in old people. ... To get a vaccine to work in old people you've got to give them repeated doses -- most people are talking about single dose."

Haseltine lamented the apparent secrecy of the government's vaccine rollout plan, ominously named Operation Warp Speed. He suggested the title could be interpreted differently in the context of the looming decision regulators face about authorizing a prospective vaccine for large-scale use.

"'Warp' may mean warping the regulatory process, not just speed," Haseltine said. "Remember, 'warp' means to distort. And I really worry about damaging our regulatory process in the interest of speed."