Top FDA vaccine official says vaccine guidance may never be released

The battle over the FDA guidance comes amid concerns that political pressure will prompt the agency to greenlight a vaccine based on thin evidence.

White House objections may prevent FDA from releasing stricter guidelines it has drawn up for the emergency authorization of coronavirus vaccines, the agency’s No. 2 vaccine official said Monday.

Nevertheless, the FDA wants vaccine developers to know that it will insist on seeing through clinical trials for any shot that receives emergency authorization,said Phillip Krause, deputy director for the FDA’s Center for Biologics Evaluation and Research.

“It’s a point of significant importance to make sure that the companies understand what’s needed for an emergency authorization,” he said at the World Vaccine Congress. “The key point is an EUA vaccine is still investigational — clinical trials will continue and more safety data will be collected.”

Background: FDA Commissioner Stephen Hahnand the agency’s vaccine chief, Peter Marks, said earlier this month that the agency would soon release the new, tougher guidance, bringing the bar for emergency use of a coronavirus vaccine closer to the standard for a full approval.

But the guidance stalled last week when it reached the White House, with President Donald Trump saying he “may or may not approve it.” HHS Secretary Alex Azar, who signed off on the policy before it hit Trump’s desk, has sinceraised concerns about the policy. And White House chief of staff Mark Meadows on Sunday questioned the need for the guidance on CBS News’ “Face the Nation.”

Executives from at least two major pharmaceutical companies — Johnson & Johnson chief scientific officer Paul Stoffels and Julie Gerberding, executive vice president of Merck — said Monday that the guidance should be released as a matter of public transparency.

“Transparency really matters right now,” Gerberding said. “Even if the guidance isn’t shocking, we need to err on the side of transparency.”

Numbers game: The battle over the FDA guidance comes amid concerns that political pressure will prompt the agency to greenlight a vaccine based on thin evidence. Trump has repeatedly predicted that a vaccine will be ready by Election Day— something that top federal health officials, including infectious disease expert Anthony Fauci, have said is unlikely.

For that to happen, one of the late-stage, or phase three, trials of coronavirus vaccines now underway would need to demonstrate that a shot was effective based on a review of early data. The vaccine’s developer would normally then halt the trial, based on the logic that the vaccine had been shown to be effective enough that it would be unethical to continue giving some participants a placebo.

Guidance the FDA released in June says that vaccine developers should discuss whether to unblind a study at that point and offer a vaccine to participants who had been given a placebo.

But Krause questioned whether a vaccine developer would have enough safety data if the trials are halted too early.

“The earlier a [vaccine] developer chooses to look at their data, and there are statistical rules for when and how to they can do this, the less likely it is they’ll have accumulated the full complement of data that we would like to see in order to make a decision to deploy a vaccine in a more widespread way,” he said.

Each phase three trial has predetermined points at which scientists will analyze early data. These are set based on the number of coronavirus infections reported by trial participants — with the first analysis in Pfizer’s trial coming at32 infectionsand at 53 infections for Moderna’s trial.

Eric Topol, director of the Scripps Research Translational Institute, agrees with the idea of continuing trials after an EUA is granted. “What is the rush? Why not finish the trial?” Topol said.

What’s next: Several phase three trials of coronavirus vaccines are now underway in the United States, and two vaccine developers are close to full enrollment.

Pfizer has administered the second of two doses to more than 24,000 participants in its 44,000-person clinical trial. Moderna has administered both doses of its vaccine to more than 15,000 of its 30,000 trial participants.

Read original article here