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By Rachana Pradhan, KHN correspondent, reports on a broad array of national health policy decisions and their effect on everyday Americans. Originally published at Kaiser Health News.
Most Americans have never heard of Dr. Richard Whitley, an expert in pediatric infectious diseases at the University of Alabama-Birmingham.
Yet as the coronavirus pandemic drags on and the public eagerly awaits a vaccine, he may well be among the most powerful people in the country.
Whitley leads a small, secret panel of experts tasked with reviewing crucial data on the safety and effectiveness of coronavirus vaccines that U.S. taxpayers have helped fund, including products from Moderna, AstraZeneca, Johnson & Johnson and others. The data and safety monitoring board — known as a DSMB — is supposed to make sure the medicine is safe and it works. It has the power to halt a clinical trial or fast-track it.
Shielding the identities of clinicians and statisticians on the board is meant to insulate them from pressure by the company sponsoring the trial, government officials or the public, according to multiple clinical trial experts who have served on such panels. That could be especially important in the pressure-cooker environment of COVID vaccine research, fueled by President Donald Trump’s promises to deliver a vaccine before Election Day.
As pharmaceutical companies work to produce one as quickly as possible, the board’s anonymity has stirred concerns that the cloak of secrecy could, paradoxically, allow undue influence. Whitley, for example, represents the specialized world these experts inhabit — a professor revered in academia who also is paid by the drug industry.
Any political pressure to rush pharmaceutical companies or lean on federal regulators to prematurely greenlight a vaccine would undermine a system put in place to ensure public safety. Calls are growing for companies and the government to be more open about who’s involved in reviewing the vaccine trials and whether board members have any conflicts of interest.
“We want to know they’re truly independent,” said Dr. Eric Topol, director of the Scripps Research Translational Institute and a specialist in clinical trials. “The lack of transparency is exasperating.”
Data and safety monitoring boards have existed for decades to vet new drugs and vaccines, acting as a backstop to help ensure unsafe products don’t make their way to the public. Typically, there’s one board for each product. This time, a joint DSMB with 10 to 15 experts will review unblinded data across trials for multiple coronavirus vaccines whose development the U.S. government has helped fund, according to five people involved in the Trump administration’s Operation Warp Speed or other coronavirus vaccine work. It is run through the National Institute of Allergy and Infectious Diseases at the National Institutes of Health and consists of outside scientists and statistical experts, not federal employees, NIH Director Francis Collins said on a call with reporters.
“Until they are convinced that there’s something there that looks promising, nothing is unblinded and sent to the FDA,” Collins said. “I doubt if there have been very many vaccine trials ever that have been subjected to this size and the rigor with which it’s being evaluated.”
The NIH safety board oversees trials in the U.S. from Moderna, Johnson & Johnson and AstraZeneca, U.S. officials and others involved in Operation Warp Speed said, but not Pfizer, which is fully funding its clinical trial work and established its own five-member safety panel. Pfizer has attested that it can conclusively determine by late October the effectiveness of its vaccine, being jointly developed with German company BioNTech. It secured a $1.95 billion purchase agreement with the Department of Health and Human Services for the first 100 million doses produced. The agreement gives HHS the option to buy an additional 500 million doses.
Moderna, Johnson & Johnson and AstraZeneca, which have either started or are aiming to soon begin large-scale trials in the U.S. involving thousands of patients, collectively have received more than $2 billion in government funds for vaccine development; billions more have been meted out under agreements similar to the HHS contract with Pfizer to buy millions of vaccine doses. Having one safety board oversee multiple trials could allow researchers to better understand the field of products and apply consistency across evaluations, clinical trial experts said in interviews.
One big advantage “could be more standardization,” said Dr. Walter Orenstein, associate director of the Emory Vaccine Center at Emory University and a former senior official at the Centers for Disease Control and Prevention. “They can look at that data and look at all the trials instead of just doing one trial.”
But it also means that one board has an outsize influence to dictate which coronavirus vaccines eventually succeed or come to a halt, all while most of their identities remain secret. The NIH declined to name them, saying they were “confidential” and could be identified only once a study was complete.
One exception to the mystery is Whitley, who was appointed as chair by Dr. Anthony Fauci, the nation’s top infectious disease official. Fauci said that following a “combination of input from us and from him and other colleagues, the people who had the greatest expertise in a variety of areas, including statistics, clinical trials, vaccinology, immunology, clinical work,” were selected for the panel.
Whitley’s role became public when his university announced it, an unusual move. He is a professor as well as a board member of Gilead Sciences, which recently signed a contract with Pfizer to manufacture remdesivir to treat COVID-19 patients. Whitley, who’s been on Gilead’s board since 2008, conducted research that led to remdesivir’s development.
In 2019, he was paid roughly $430,000 as a Gilead board member, according to documents filed with the Securities and Exchange Commission. That same year, he received more than $7,700 in payments from GlaxoSmithKline for consulting, food and travel, according to a federal database that tracks drug and device company payments to physicians.
GlaxoSmithKline and Sanofi are jointly developing a vaccine that’s received $2 billion from the U.S. government under Operation Warp Speed; however, Whitley, through a university spokesperson, said his DSMB has not seen any GlaxoSmithKline COVID protocols. The companies have yet to begin phase 3 trials. Although he chairs a separate GSK data and safety monitoring board for a pediatric vaccine, he was vetted and cleared by the NIH conflict-of-interest committee with its knowledge of his involvement, the spokesperson said.
“When handled responsibly, it is appropriate for physicians to collaborate with external entities,” said UAB spokesperson Beena Thannickal, saying the university works with physicians to ensure that industry engagement is appropriate. “It facilitates a critical exchange of knowledge and accelerates and advances clinical treatments and cures, and it fuels discovery.”
Multiple experts praised his skill — Dr. Walter Straus, an associate vice president at the drug company Merck & Co., said Whitley is an “éminence grise” in pediatrics whom people trust.
“I actually trust that process, and the fact that they asked Rich to do it makes me feel reassured because he’s so good,” said Dr. Jeanne Marrazzo, director of the University of Alabama-Birmingham’s division of infectious diseases.
Multiple scientists who have participated in data and safety monitoring boards maintain it’s important to keep the board anonymous to shield them against pressure or even for their safety. For example, when trials were conducted in San Francisco for HIV/AIDS research, the board was confidential to protect members from patients desperate for treatment, said Susan Ellenberg, a professor of biostatistics, medical ethics and health policy at the University of Pennsylvania who’s written extensively on the history of DSMBs.
If approached by a patient, it “would be very hard to tell you, ‘Oh I can’t help you.’ It’s an unreasonable burden,” said Ellenberg, who said she was involved in coronavirus-related safety boards but would not name them.
As part of a large-scale clinical trial, the DSMB and a statistician or team that prepares data for those individuals are generally the only ones who see unblinded data about the trial, making it clear who is getting what treatment. A firewall is set up between them and executives from the sponsoring company with financial interests in the trial. The companies sponsoring COVID vaccine trials are not part of any closed sessions during which unblinded data is reviewed. Those are limited to members of the DSMB, the NIAID executive secretary and the independent unblinded statistician who is presenting the data, a NIAID spokesperson said.
DSMB members or their family members should have no professional, proprietary or financial relationship with the sponsoring companies, and the NIAID DSMB executive secretary vetted all members for potential conflicts of interest, NIAID said in response to questions from KHN. Members are paid $200 per meeting.
“It’s generally done out of a sense of public service,” said Dr. Larry Corey of the Fred Hutchinson Cancer Research Center, who is working with NIH officials to oversee the U.S. coronavirus vaccine clinical trials. “You’re doing it because of your sense of altruism and obligation to knowing the important role it plays in clinical research and the important role it plays in preserving the scientific integrity of important trials.”
Moderna, AstraZeneca, Johnson & Johnson and Pfizer have each released protocols that include details on when their DSMBs would review unblinded information about trial participants, and at what points they could recommend pausing or stopping trials. The vaccine data and safety board organized by NIAID advises a broader oversight group consisting of the drug companies sponsoring the trial and representatives from NIAID and HHS’ Biomedical Advanced Research and Development Authority that reviews the DSMB recommendations. Ultimately, the drug company has final authority over whether to submit its data to the Food and Drug Administration.
Moderna and Johnson & Johnson are each aiming for their vaccines to have 60% efficacy, which means there would need to be 60% fewer COVID cases among vaccinated individuals in their trials. AstraZeneca’s target is 50%. The FDA has said any coronavirus vaccine must be at least 50% effective to secure approval from regulators. While the parameters of their clinical trials have similarities, there are some differences, including when and how many times the DSMB can conduct interim reviews to assess whether each vaccine works.
Pfizer is similarly aiming for its vaccine to be 60% effective. The company allows for four interim reviews of the data starting at 32 cases — a schedule that has been criticized by some researchers who contend it makes it easier for the company to stop the trial prematurely.
Pfizer declined to name the individuals on its monitoring committee, saying only that the group consisted of four people “with extensive experience in pediatric and adult infectious diseases and vaccine safety” and one statistician with a background in vaccine clinical trials. An unblinded team supporting its data-monitoring committee — which includes a medical monitor and statistician — will review severe cases of COVID-19 as they are received and any adverse events associated with the trial at least weekly.
“There is an irresolvable tension between speed and safety,” said Dr. Gregory Poland, the head of Mayo Clinic’s Vaccine Research Group. “Efficacy is pretty easy to figure out. It’s safety that’s the issue.”
California Healthline editor Arthur Allen contributed to this report.
Pfizer is the company pushing more agressively for speed. If I remember correctly Pfizer’s CEO was in June pushing for voluntary challenging of vaccinated subjects to accelerate vaccine development (na gonna happen). Now they go with this October surprise stupidity (na gonna happen at least regarding mass vaccine deployment). If someone can offer an explanation on why such aggressivity -it doesn’t make any sense, IMO- I would appreciate unless Pfizer’s CEO is engaged in Trump candidacy.
There is no way safety issues have been meaningfully resolved by October in any of the candidates mentioned above.It also must be noted that efficacy is not an instant measure, you have to make reads after Ab titres peak and when these go to basal levels some weeks after the boost injection. I haven’t seen Pfizer protocols but they need a boost about 2-4 weeks after the prime dose, then wait for Ab peak, wait for Ab stabilization, and see how this protects. No way they can have meaningful data by October except for emergency use. The 32 cases claim is just laughable.
Any insight into how these poor souls are chosen to participate in these trials? I can’t comprehend what would motivate someone to want to be a guinea pig for any of these proposed vaccines.
And thank you for your contributions here on this topic, very insightful.
See here for previous comments on NC, including a commenter who is part of a trial.
Ask WobblyTelomeres why they joined the Pfizer trial. I’m sure they will appreciate you talking down to them.
My wife and I are in our 60s, my mom is 85. My father-in-law, who lives with us, is 87. I do almost all of the shopping. My RN kid brother works the Covid ward at UAB (it is not pretty). I have been called a “new age boy scout” as I keep volunteering for the things most don’t want to do.
Because of all this, I volunteered for the Phase 3 trial. I did not do it for the token amount of money, although I am sure many do (it is a hard and cruel world, but I am sure notabanker knows this). I did it because it seemed the right thing to do.
Visited an old friend in New Orleans yesterday, a fellow SSTPer, in his final days of hospice. Looking upon death can bring things into focus.
I guess you signed the informed consent form and confidentiality regarding whatever information relevant for the review of the vaccine. I will not ask you what reactogenicity you had but i guess that if you experienced some systemic symptoms as head-ache or fever, particularly after the booster (apart from the local symptoms in the site of vaccine administration) would be for you an indication if you were in the placebo group or not.
As a citizen, I feel grateful that people like you have engaged in a Phase III trial. Just notice you still have to behave as if you weren’t protected.So, take care. Don’t be worried about safety issues which I think will be uncommon or rare but any case given there is a slight possibility that in some cases the immune response (this is valid also for people that has readily been infected) could in certain circumstances induce disease enhancement (not yet seen in Covid vaccines fortunately), the precautionary principle is there to be followed.
I don’t think is that problematic entering one of those Phase III trials. So far except that vaccine reactogenicity is quite nasty. As a fact, so much that removes blindness from the trial I guess. So if WT has noticed fever, headache (particularly after the booster)… ups, should I shut my mouth?
1st thanks to all who enroll in trials. IMHO, the problems for trial subjects are complex. There is the safety risk of the candidate vaccine. Also, there the dilemma of what to do when EUAs start coming out, and the trial subject has an option to take a competing vaccine under an EUA. Taking a competing vaccine voids the subject’s future trial participation, but no one can stop that. Further, the safety of combined doses of competing vaccines is not likely to ever be settled.
I joined the phase 3 AZ Oxford vaccine trial in London. I just came across a link, put my email on a very simple form, and then got contacted and put through a selection process that included interviews and several blood tests.
Initially I did it to jump the queue for a vaccine. Who does not want to get vaccinated? The risk is smaller than being out there with no immunity. Also for the altruistic reason of helping develop it, of course, and the curiosity of seeing how a trial like this works from the inside.
Latter I found it has its perks. I get tested weekly. If I get sick (of anything!), I will have top teams of research clinicians finding out what I have. It seems someone in the trial got a multiple sclerosis diagnosis already (https://www.statnews.com/2020/09/09/astrazeneca-covid19-vaccine-trial-hold-patient-report/)
To a later comment about reactogenicity as a sign of being in the experimental or control group, the Oxford team uses a similar meningitis vaccine for the control group, created with the same process. So you can count it as another perk.
What? So you get the vaccine and you can still get covid?
Yeah that’s been my question with all this. Admittedly I have been suffering from covid media overload and have not been doing deep reads on the subject much lately. But that being said, in some articles on vaccinations I’ve seen, it’s mentioned that such and such a vaccine looks promising or doesn’t based on the side effects produced, but they neglect to mention whether the vaccine actually prevents you from getting covid-19. That seems a rather glaring omission.
My guess is Pfizer comes up with something they can shoot into you arm that doesn’t cause immediate death and they’ll make a mint from it whether it actually cures anything or not. They’ve already arranged a nearly 2 billion dollar deal and they aren’t going to just jump of that gravy train from Uncle Sugar. Then if the virus dissipates on its own, as pandemics do eventually or we wouldn’t be here to discuss it, they will claim it worked. Kaching!!
Vaccine candidates are judged on safety and effectiveness and compromises are necessarily made on both fronts since I don’t think 100% safe and 100% effective is an achievable target. If a tiny percentage of the population reacts with Guillain-Barre syndrome but the overwhelming majority get a robust immune response preventing or severely mitigating COVID-19, it’s probably defensible to do widespread vaccination. See here for a discussion by actual virologists.
I place no faith in the morality of drug company executives, so I hope Dr. Whitley isn’t similarly compromised.
It is worth noting that viral INFECTIONS are also associated with cases of transverse myelitis.
SO, as long as the vaccine causes FEWER cases of transverse myelitis [or other bad thing of your choice] than the disease causes, the vaccine is preferable to taking my chances with the disease.
There is more. You don’t get just one measure of vaccine efficacy. There will be some. An important one is hospitalization rate of infected which would correlate very much with how efficiently the vaccine prevents pneumonia/severe pneumonia. Another important question: How many deaths could be prevented? Addressing these efficacy measures of course require for longer time than just looking at preventing infection. Too long for the October surprise IMO.
The goal is to get the disease from spreading. If the virus doesn’t spread, people don’t get the disease. 50% effectiveness would make a huge difference there already, though not good enough to be the sole measure against the virus.
Note that it is -at least- 50% , at statistically significant levels. The vaccines are expected to be better than that level. But the higher you set the target, the longer it takes to have enough cases in the trials to prove that level.
Well if it’s all simply part of some partial mitigation strategy I don’t think you are going to get people to take the shot. As Lyman Alpha says above by the time they even get a final vaccine the pandemic may be largely over anyway so the only reason to then get vaccinated would be some kind of insurance. Insurance companies don’t sign up customers by saying you have a fifty percent chance that we will pay your claim.
I’m no youngster but I’ve never gotten a flu shot and I’ve also never get the flu. You don’t have to be a vaxxer to distrust what is going on.
Please get a flu shot.
There are more goals. A vaccine that is not that efficient but prevents hospitalizations and deaths could be appropriate to deploy in populations at high risk. May be not so proper for the population at large but this would be a goal as long as it prevents many deaths and helps HC management. Wouldn’t be?
So we have to expect there is not an imminent solution that will get us back to normal that fast. It will take some time, years, and on the meantime we have to figure out how to try to return to some normalcy.
Regarding secrecy, the article makes a good point on whether the panels should be shielded during the process of review. Secrecy ends when the reviews are finished and evaluations delivered. Besides, some of the candidates will be evaluated by other panels in different countries. Importantly, the mechanisms keeping trials blind must be strong enough and the people in charge are also shielded against pressures. The case of Astra Zeneca’s report on an adverse effect days ago could give an indication that so far the mechanisms work in their UK trial. No secret kept in that case.
Given the number of armed screwballs in USA!USA! [speaking as a Canadian physician] I would be reluctant to sit on a monitoring panel unless I was anonymous, at least until the trial is over.
It’s a lot like grand juries. They are usually anonymous until they release their findings. The temporary secrecy in monitoring COVID vaccine testing is similar and exists for similar reasons.
I have no intention of taking any vaccine which is developed in secret and judged by unknown people. Blind trials are one thing, they are fine, but all data should be completely open and subject to peer review before a vaccine is offered to, or inflicted upon, the public.
Real science is done with open access, free access to data, and in collaboration with the science/medical community and public. There is no way I would trust either the government or big pharma corporations. Better to get the Russian vaccine, or one of the Chinese ones. Never trust a US corporate-state fascist or politician: they constantly lie, cheat, and steal, and people’s lives and health mean nothing to them. Just look at recent history.
Exactly. A blog post of interest:
What the author writes about “intellectual property” is important. Richard Stallman, a free software advocate recently cancelled by the snowflake culture, is strongly against the use of the term. Previously there were just patents and copyrights. “Intellectual property” is a grandiose term designed to invest the over-long periods of patents and copyrights with gravity.
Please note that Data Safety Monitoring Boards exist exactly to provide oversight for clinical trials, and ultimately, it would be the FDA in the US that decides if the vaccine is approved or not, not the DSMB. The FDA publishes its full reviews and all relevant clinical and pre-clinical data, along with reviewer names, on its website. For example, see this and the associated supporting documents available for download for a recently approved vaccine: https://www.fda.gov/vaccines-blood-biologics/vaccines/shingrix
Ultimately it’s not the “government” as a faceless entity reviewing these vaccines but a group of physicians at the FDA who have chosen to leave lucrative private practices and prestigious academic posts to serve the public, and their work is subject to full public scrutiny.
The material I saw about shingrix from the link you gave looks adequate. My question, especially regarding a vaccine for sars-cov-2, with all the money involved, is if the information would be true or would lie. I consider war propaganda, employment figures, ‘Russiagate’, and a host of other things said, and I conclude that lying is rampant and driven by politics and money. That’s the problem.
$430k with no real liability, who pays the malpractice insurance?
Billions prepaid to big pharma, etc. Etc. No liabilty to pharma, no price controll, but an election due before the problems will surface.
Maybe if the Trump private family and his official family all got a test shot out of the same bottle I may volunteer for a test vaccination from the same bottle. Then go to church and pray over a candle.
Boeing should come up with a vaccine. They have no product liability exposure or moral accountability. More importantly both Team Red and Team Blue have their backs.
Hear hear! I don’t know about secrecy as such, but there’s no reason that conflicts of interest shouldn’t be public. I also wonder exactly what we the public are going to get for our $1billion plus subsidy.
There are going to be a lot of problems measuring efficacy. After all, masks and social distancing are going to affect outcomes. But then there’s the issue of mildly symptomatic and asymptomatic cases. Those cases may be counted as a Covid case in the non-vaccinated groups (especially if more contact tracing is done).
In the past, vaccine manufacturers touted milder cases as a vaccine win. But it just may mean that the vaccine was totally ineffective.
And, of course, if the demographics of the vaccinated subjects doesn’t match the comparison group, it’s not going to be easy to make conclusions.
There is no doubt that this data is going to be cherry picked and spiked with investor bias.