Who Decides When Vaccine Studies Are Done? Internal Documents Show Fauci Plays a Key Role.

Dr. Anthony Fauci, the nation’s top infectious disease official, will oversee most of the ongoing COVID-19 vaccine trials in the U.S., but not that of the current front-runner made by Pfizer, documents obtained by ProPublica show.

According to a draft charter spelling out how most of the advanced COVID-19 vaccine trials will be monitored, Fauci is the “designated senior representative” of the U.S. government who will be part of the first look at the results. That puts Fauci in the room with the companies — including Moderna, Johnson & Johnson and AstraZeneca — in deciding whether the vaccines are ready to seek approval from the Food and Drug Administration.

Fauci’s role, which has not been previously reported and was confirmed for ProPublica by the National Institutes of Health, could offer some reassurance in the face of widespread concerns that President Donald Trump wants to rush through an unproven vaccine. As Sen. Kamala Harris, the Democratic nominee for vice president, put it at last week’s debate, “If the public health professionals, if Dr. Fauci, if the doctors tell us that we should take it, I’ll be the first in line to take it.”

But there’s a big caveat. Fauci doesn’t have the same hands-on role for the vaccine that seems poised to show results soonest: Pfizer’s. That’s because Pfizer opted not to accept government funding and participate in the federal program to develop a coronavirus vaccine, known as Operation Warp Speed. (The government did make an almost $2 billion deal with Pfizer to preorder up to 600 million doses of the company’s vaccine, but it isn’t contributing money to the vaccine’s development like it is for other companies.)

“(We) offered opportunities for collaboration with Pfizer,” said a spokesperson for the National Institutes of Allergy and Infectious Diseases, a branch of the NIH. “Pfizer chose to conduct their Phase 3 study without Operation Warp Speed or NIH support.”

Pfizer’s CEO, Albert Bourla, said Friday that the earliest his company would be ready to apply for authorization would be the third week of November. While Pfizer might know by the end of October if its vaccine is effective, it would need additional time to gather sufficient safety data to present to the FDA, Bourla said in an open letter on the company’s website.

Fauci’s role in overseeing the companies that are participating in Operation Warp Speed arises from a unique arrangement that the government set up to monitor the trials. Typically, clinical trials set up their own independent panels of scientists, known as a data safety monitoring board or DSMB, to watch out for safety concerns or early signs of success. But all of the vaccine trials in Operation Warp Speed are sharing a common DSMB whose members were selected by Fauci’s agency, the NIAID. They’re also sharing a network of clinical trial sites where some volunteers are recruited for the studies.

A DSMB is responsible for making recommendations such as halting the trial if there is a safety concern or letting the manufacturer know that there’s enough evidence to submit an application to the FDA. Ordinarily, a DSMB’s recommendation goes to the company running the trial. In this case, the U.S. government — which gets two representatives, one from the NIAID and one from the Biomedical Advanced Research and Development Authority — will also have a seat at the table in deciding what to do next.

“Once the DSMB makes a decision, the DSMB provides the recommendation to not only the study sponsor but also to the” U.S. government, whose “designated senior representative” is Fauci, the NIAID confirmed in an email. Fauci declined to be interviewed.

That’s not the same as saying Fauci has the last word. The company and the government are supposed to reach a consensus, the agency said. But if they can’t all agree, the ultimate decision belongs with the company.

Still, it would be an improbably brazen move for a company to move ahead over Fauci’s objection, given his public stature, experts said. “These are the most important trials in medical history, this is the ultimate fishbowl,” said Dr. Eric Topol, director of the Scripps Research Translational Institute. “I don’t think any sponsor would dare defy the DSMB’s recommendation.”

While the mechanics of a DSMB may be unfamiliar to most members of the public, people probably know and trust Fauci, according to Amy Pisani, executive director of the national nonprofit organization Vaccinate Your Family. “(He’s) the sweetheart of the nation right now,” Pisani said. “I do think people have faith in Anthony Fauci.”

“Having Fauci with oversight is terrific,” Topol added. “The more people who are experts looking at it, the better. You can’t be careful enough.”

Other members of the DSMB for the COVID-19 vaccines, though not as well known as Fauci, are also widely respected in their fields. DSMB members are typically kept confidential to shield them from outside influence, but ProPublica has been able to identify a few members. The charter obtained by ProPublica described the group, which has about a dozen members, as having expertise in “biostatistics, clinical trials, infectious diseases, vaccine development and ethics.”

The panel’s chair is Dr. Richard Whitley, a professor of pediatrics, microbiology, medicine and neurosurgery at the University of Alabama at Birmingham. His role became public when the university announced it, though the webpage was later taken down.

His leadership provides another level of comfort in the trustworthiness of the trials to those who know him. “He is not only famously bright but he is famously independent and outspoken,” said Dr. William Schaffner, professor of preventive medicine and infectious diseases at Vanderbilt Medicine. “He’ll look at the data and tell you exactly what he thinks.”

Whitley didn’t respond to requests for an interview.

Susan Ellenberg, professor of biostatistics at the University of Pennsylvania and a former director at the FDA, told ProPublica in an interview that many people, including herself, were worried the NIH might be “pushed by the political leadership at HHS to release data” from trials prematurely, which could undermine the integrity of a trial. HHS, the U.S. Department of Health and Human Services, is the NIH’s parent agency. Her concern was that political leaders might not understand scientific arguments to not disrupt the trials when wanting to have data “to be able to move quickly in an urgent situation,” she said.

At the time of the interview, Ellenberg had not identified herself as a member of the NIH’s DSMB, but later acknowledged that she was a member.

Dr. Malegapuru William Makgoba, an immunologist based in South Africa, is one of a few international members of the DSMB. Makgoba is well known for his work on public health initiatives around HIV/AIDS, including the South African AIDS Vaccine Initiative. Makgoba confirmed his role on the DSMB but declined to comment further.

The common DSMB appears to be unprecedented, if only because there have not previously been multiple vaccines in development for the same disease at the same time. Experts said the arrangement offers benefits such as bolstering the evidence available to show that any one shot is safe and effective.

Standardizing trial measurements should make the vaccines easier to compare head to head, which may be useful for knowing whether one is better or worse than another in certain subgroups, such as the elderly or people with compromised immune systems, according to Vanderbilt’s Schaffner.

“To me, it’s better for public health to have a fairly common assessment,” said Dr. Gregory Glenn, president of research and development at Novavax, which has received $1.6 billion from Operation Warp Speed and hopes to begin its Phase 3 trial in the U.S. this month as part of the NIH’s clinical trial network.

There may also be some benefits from a safety perspective.

If a potential safety issue appears in one trial, having a common data safety monitoring board for multiple trials means that the board knows to look out for that same issue across all the trials, said Dr. Tal Zaks, chief medical officer of Moderna. “When AstraZeneca had an adverse side effect, we have a DSMB looking at our trial — the fact that it’s the same DSMB means that there’s not one DSMB that has to go educate another DSMB,” Zaks said. (ProPublica’s board chairman, Paul Sagan, is a member of Moderna’s board and a company stockholder.)

AstraZeneca’s trial has been put on hold in the U.S. while the company and the FDA investigates what happened with a participant who had a bad reaction. It’s not yet clear whether the reaction was due to the vaccine or unrelated.

“AstraZeneca is committed to working with governments and key partners to ensure we develop and gain regulatory approval for an effective vaccine as quickly as possible,” the company said in a statement.

AstraZeneca added that another benefit of joining the government’s consortium was that its large network of trial sites can help reach minority communities that are historically less represented in clinical trials and also more vulnerable to COVID-19.

Pfizer’s decision not to participate means that it and the other companies may miss out on some of these benefits of pooling resources. “It’s at least unfortunate, and not very sporting, as the British would say,” Schaffner said.

At the same time, there could be advantages to Pfizer’s going solo. “One of the greatest risks to this process is the perception of political influence, and in that regard, having parallel efforts, especially efforts seen as independent of one another and/or independent of perceived sources of political influence, is a good thing,” said Mari Foroohar, an analyst at the investment bank SVB Leerink.

Pfizer declined to comment on its decision not to join the government’s shared DSMB and trial network.

Whether it’s Pfizer or one of the companies participating in Operation Warp Speed, the final say on whether a vaccine is ready for public use belongs to the FDA.

The FDA has promised to present the data to an advisory committee of external experts in a public meeting. A preliminary meeting will be held on Oct. 22 to discuss, generally, the standards the FDA will seek to see before authorizing any vaccine. The agency has also committed to holding advisory committee meetings to review data from individual vaccine candidates.

Between the independent trial safety monitoring boards and the public advisory committee meetings, “any kind of hanky-panky there that people are worried about is going to (go through) multiple checkpoints,” Fauci said in an interview with Dr. Howard Bachner on the JAMA Network podcast on Sept. 25. “The big elephant in the room is, is somebody going to try to make a political end run to interfere with the process? … If you look at the standard process of how these things work, I think you can feel comfortable that it is really unlikely that that is going to happen.”