Despite widespread criticism, a stalled clinical trial of a hepatitis B vaccine in Guinea-Bissau moved forward last month for the most obvious reason: The $1.6 million grant money needed by Danish researchers to conduct the study was expiring in the budget of the Centers for Disease Control and Prevention. rolling stone Have you learnt.
The study seeks to investigate whether the birth dose of hepatitis B vaccine, which has been used safely for decades, has potential negative health effects such as skin diseases or neurodevelopmental disorders. To do this, it plans to give birth doses to only half of the 14,000 newborns enrolled, raising the risk that in the country where hepatitis B is endemic, the other 7,000 could face infection and lifelong consequences including cirrhosis and liver cancer if birth doses are not provided.
Although not routinely administered in Guinea-Bissau, a birth dose of hepatitis B vaccine will become standard there in 2028. Vaccinations will be provided to all participants in the study starting at six weeks of age, as is current practice in Guinea-Bissau.
After World Health Organization study condemnedResearchers revised the protocol last August to provide more advance screening for hepatitis B to expectant mothers. new protocol”Children of mothers who are known to have hepatitis B, test positive, or whose status cannot be determined will not be randomized and will receive the birth-dose vaccine immediately,” the study is posted on the website of the Bandim Health Project, the research organization leading the study.
Hepatitis B experts say the amendments do not address the study’s underlying medical and ethical problems, especially given the high rates of the disease in Guinea-Bissau. Dr. Robert Gish, director of the Hepatitis B Foundation, says, “Maternal screening alone cannot prevent transmission, and this study will sensitize infants to exposure to maternal infection, household contacts, or other routes of transmission in early childhood.”
rolling stone It was the first to report last week that the study has been revived and is on its way to final approval.
Given the ethics issues and risks to patients, the effort to evaluate the study should have been slowed, not faster, says Dr. Arthur Caplan, founding head of the Division of Medical Ethics at the NYU Grossman School of Medicine. “When people are in crisis, in a dirt-poor country, where there are allegations of exploitation, and knowing that we have a treatment” that can help people, “that’s the wrong place to rush into a review.”
But the ticking clock on expiring funds also put time pressure on members of an ethics research committee at the University of Southern Denmark (SDU), with only a month to consider whether to ratify the study, a safeguard later added after irregularities in the Guinea-Bissau ethics review surfaced.
That pressure led the SDU committee to cut the deliberations short and schedule a vote before all members were present, raising questions about whether the panel’s independence, as required by international ethics principles, was compromised to enable affiliates to receive grant money, two committee members said. rolling stone.
On September 30, the committee voted five to four to ratify the study, and the SDU Dean of the Faculty of Health Sciences gave final approval on October 7.
A spokesperson for the SDU says, “The committee’s assessment of this case was based on the revised protocol, the ethical issues identified during its deliberations, and input from external experts.” “The fact that the research was conducted by SDU researchers does not change this [the Research Ethics Committee’s] Responsibility for conducting an independent review.
But Søren Birkelund, one of the committee members who was not able to vote, says, “The final decision was taken very hastily by the board – I and the remaining board members were not allowed to be present at the final discussion.” He further stated that he was “strongly against sanctioning”, as he made clear in a previous post In a Danish medical news site.
Another committee member who voted not to approve the study, Stig Bjorn Hansen, explains rolling stone“There was a clear connection between the deadline and our going straight to the polls.” He adds, “Working under the pressure of knowing and reasoning that people could lose their funding bogged down the process. We came to a bad decision in a bad way.” As first reported, four committee members resigned in protest Guardian. Hansen and Birkelund were among them.
Inside CDC, while officials in the Director’s Office awaited the SDU Ethics Panel’s decision, expiring funds prompted officials in the Chief of Staff’s Office to seek alternative funding. On September 17, an official there informed Stuart Burns, a senior adviser in the Office of the Director and an aide to Health Secretary Robert F. Kennedy Jr., who had supported the study, “If we don’t obligate these funds by 9/30, we lose them and will have to request funding in FY27 to support this work if it goes forward.”
Ultimately, according to interviews and documents obtained, officials received funds that had been designated by Congress for global health security. rolling stone. Those funds could have been used to respond to the ongoing Ebola outbreak in the Democratic Republic of the Congo, or to aid in epidemic prevention as a laboratory accident in eastern Siberia has raised fears of a possible plague spread.
Last week, the dean of the Faculty of Health Sciences at the University of Southern Denmark said the study could not proceed without final approval from health authorities in Guinea-Bissau. A news report On Friday, October 9, Guinea-Bissau authorities were said to have signed off on the study. But in Tuesday’s press conference, the country’s Health Minister Quinhin Nantote denied this. Reuters reportedThat said, the study will need further review. The CDC and Guinea-Bissau’s Ministry of Public Health did not respond to requests for comment.
Danish researchers have strongly defended the ethics of the clinical trial, claiming that no child would receive less than the standard of care in Guinea-Bissau, and no participant would be denied treatment that they otherwise would have received. “The trial complies with the current national policy in Guinea-Bissau and has been reviewed and approved by the competent national ethics committee,” lead Danish researcher Christine Stabel Benn previously reported. rolling stone. She and her research colleagues did not respond to requests for comment for this story.
On September 2, one of the Danish researchers, Frederik Schultz-Buchholzer, emailed members of the SDU Ethics Committee, informing them that the research team had revised the protocol following WHO’s criticism of the trial.
He also said the researchers would allow the university’s committee to seek guidance from outside experts to assess the study. But he added, “Given the time-limited policy context of the project, we respectfully ask that external consultation begin immediately.”
On 16 September, committee administrator Jakob Osegger wrote a Danish-language letter to committee members saying that researchers “expressed concern about what the involvement of external experts would mean for the time frame of the committee’s deliberations”. “According to the researchers, the project’s grant expires at the end of September if they do not have the green light to start at that time.”
The next day, an official with CDC’s Chief of Staff noted in an email to colleagues that if the funds were not paid by September 30, they would be lost due to the end of the fiscal year.
The official from the Office of the Chief of Staff then wrote, “My understanding from Stuart is that we are waiting for the Ethics Office of the University of Southern Denmark to approve it. If they approve, we can proceed with the award.”
It is unclear why the CDC, long seen as a global leader in ethical standards, was completely trusting the university whose researchers benefited from the award.
By September 21, as uncertainty remained over the Danish university’s ethics panel’s timetable, CDC officials began considering what other funds they should use. “Can we replace annual measles funds with multi-year funds?”. The official in the Office of the Chief of Staff emailed an employee of the Budget Service Office. “This will allow [the Global Health Center] To redirect measles annual funding to other priorities, and if this is ever approved, we will have multi-year funds to use for grants.
In addition to the problem of running out of funds, researchers faced even tighter deadlines. Starting in 2028, Guinea-Bissau will provide a birth dose of hepatitis B vaccine to all newborns and so one of the researchers’ central justifications for the study – that providing a birth dose is not consistent with the current standard of care in Guinea-Bissau – will end with that change.
However, the Helsinki Declaration, a global set of ethical principles for research on human subjects, discourages matching a clinical trial to the local standard of care if a higher, proven standard is available elsewhere.
On September 30, the SDU ethics panel voted to approve the study and the CDC pledged $1.6 million in global health security funding. The Pershing Square Foundation, founded by billionaire hedge-fund manager Bill Ackman, had previously pledged $1.8 million.
As global public health experts renew their criticism, Dr. Gavin Yami, professor of global health and public policy at Duke University, explains rolling stone“It does not surprise me that federal health leadership would take money where it is desperately needed and funnel it into a study that is unnecessary and highly unethical and puts some of the world’s most vulnerable infants at risk of infection, suffering and early death.”
But he asks the researchers, “If there is outrage among ethicists around the world, why wouldn’t you listen to your critics?”
As medical ethicist Dr. Arthur Caplan says: “If you vaccinate everyone, that would be a whopping $1.6 million for Guinea-Bissau.”