Despite widespread criticism, a halted hepatitis B vaccine clinical trial in Guinea-Bissau moved forward last month for the most mundane reasons: $1.6 million in grant funding needed by Danish researchers leading the study was expiring in the Centers for Disease Control and Prevention budget, rolling stone learned.
The study aims to examine whether the birth dose of the hepatitis B vaccine, which has been used safely for decades, has potential negative health effects, such as skin conditions or neurodevelopmental disorders. To do this, it plans to give the birth dose to only half of the 14,000 registered newborns, increasing the risk that, in a country where hepatitis B is endemic, the remaining 7,000 who did not receive the birth dose will face infection and lifelong consequences, including cirrhosis and liver cancer.
Although not routinely administered in Guinea-Bissau, the birth dose of hepatitis B vaccine will become the norm there in 2028. The study would vaccinate all participants from the age of six weeks, as is currently the case in Guinea-Bissau.
After the World Health Organization denounced the study, researchers revised the protocol last August to offer pregnant women more advanced screening for hepatitis B. The new protocol, published on the website of the Bandim Health Project, the research organization leading the study, states: “Babies whose mothers are known to have hepatitis B, who test positive or whose status cannot be determined will not be randomized and will be offered the vaccine promptly at birth.” »
Hepatitis B experts say the revisions do not address the medical and ethical issues underlying the study, especially given Guinea-Bissau’s high rates of the disease. “Maternal screening alone cannot prevent transmission, and this study will leave infants vulnerable to exposure through undetected maternal infections, household contacts, or other transmission routes during infancy,” says Dr. Robert Gish, director of the Hepatitis B Foundation.
rolling stone was first to report last week that the study had been resurrected and was on track to finally be approved.
Given the ethical concerns and risks to patients, efforts to evaluate the study should have been slowed down, not sped up, says Dr. Arthur Caplan, founding chief of the division of medical ethics at the NYU Grossman School of Medicine. “When subjects are in danger, in an extremely poor country, where accusations of exploitation are rife, and knowing that we have a treatment” that can help the subjects, “this is not the right place to rush the examination.”
But the countdown to the expiration of funds also put members of an ethics research committee at the University of Southern Denmark (SDU) under pressure, with only about a month to determine whether to confirm the study, a safeguard later added after irregularities in an ethics review in Guinea-Bissau emerged.
That pressure led the SDU committee to shorten deliberations and schedule a vote before all members could be present, raising questions about whether the committee’s independence, as required by international ethical principles, was compromised to allow colleagues to obtain grants, two of the committee members said. rolling stone.
On September 30, the committee voted five to four to confirm the study, and the SDU dean of the Faculty of Health Sciences gave final approval on October 7.
“The committee’s assessment in this matter was based on the revised protocol, ethical issues identified during its deliberations and input from external experts,” an SDU spokesperson said. “The fact that the research was conducted by SDU researchers did not alter (the research ethics committee’s) responsibility to conduct an independent review.”
But Søren Birkeland, one of the committee members who was unable to vote, says: “The final decision of the board was far too hasty – not allowing us and other board members to be present at the final discussions. He added that he was “strongly against approval”, as he had made clear in a previous article on a Danish medical news site.
Another committee member, who voted against approving the study, Stig Børsen Hansen, said rolling stone“There was a clear connection between the deadline and going straight to the vote.” He adds: “Working and reasoning under the pressure of knowing people could lose their funding short-circuited the process. We made a bad decision in the wrong way.” Four committee members resigned in protest, as first reported The Guardian. Hansen and Birkeland were among them.
At CDC, while officials in the director’s office awaited a decision from the SDU Ethics Committee, expiring funds led officials in the chief of staff’s office to seek alternative funding. On September 17, an official informed Stuart Burns, a senior adviser in the director’s office and an ally of Health Secretary Robert F. Kennedy Jr., who had championed the study: “If we do not obligate these funds by September 30, we will lose them and will have to request funding in FY27 to support this work if it moves forward.” »
Ultimately, officials found funds that had been designated by Congress for global health security, according to interviews and documents obtained by rolling stone. These funds could have been used to respond to the ongoing Ebola outbreak in the Democratic Republic of Congo, or to help prevent a pandemic, as a laboratory accident in eastern Siberia has raised fears of a possible plague outbreak.
Last week, the dean of the University of Southern Denmark’s faculty of health sciences said the study could not move forward without final approval from Guinea-Bissau health authorities. A report on Friday October 9 indicated that Guinea-Bissau authorities had approved the study. But at a press conference on Tuesday, the country’s Health Minister, Quinhin Nantote, denied this, Reuters reported, saying the study would require further review. The CDC and Guinea-Bissau’s Ministry of Public Health did not respond to requests for comment.
The Danish researchers vehemently defended the ethics of the clinical trial, saying no child would receive less than standard care in Guinea-Bissau and no participant would be denied treatment they would otherwise receive. “The trial complies with current national policy in Guinea-Bissau and has been reviewed and approved by the relevant national ethics committee,” said Christine Stabell Benn, the Danish lead researcher. rolling stone. She and her research partners did not respond to a request for comment for this story.
On September 2, one of the Danish researchers, Frederik Schaltz-Buchholzer, sent an email to members of the SDU ethics committee, explaining that the research team had revised the protocol following criticism of the trial by the WHO.
He also noted that the researchers would allow the university committee to seek advice from external experts to evaluate the study. But he added: “Given the time-limited political context of the project, we respectfully request that the external consultation be launched immediately. »
On September 16, committee administrator Jakob Ousager wrote in Danish to committee members, saying the researchers “expressed concern about what the involvement of external experts would mean for the duration” of the committee’s deliberations. “According to the researchers, the project 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 for the CDC chief of staff indicated in an email to colleagues that if the funds were not obligated by September 30, they would be lost due to the end of the fiscal year.
In the ensuing exchanges, the head of the chief of staff’s office wrote: “From what I understood from Stuart, we are waiting for the ethics office at the University of Southern Denmark to approve this. If they approve it, we can move forward with the award.”
It is not entirely clear why the CDC, long considered a world leader in ethical standards, relied entirely on the university whose researchers could benefit from this award.
On September 21, as uncertainty persisted over the Danish university’s ethics committee’s timeline, CDC officials began to consider what other funds they should use. “Could we swap the annual measles fund for multi-year funds? the head of the chief of staff’s office sent an email to a staff member in the Office of Budget Services. “This would allow (the Global Health Center) to redirect annual measles funding to other priorities, and we would have multi-year funds to use for the grant, if it is ever approved.”
In addition to the problem of funds expiring, researchers faced an even more inexorable deadline. Starting in 2028, Guinea-Bissau will provide the birth dose of hepatitis B vaccine to all newborns. One of the researchers’ main justifications for the study, namely failure to provide the birth dose consistent with current standards of care in Guinea-Bissau, will expire with this change.
However, the Declaration of Helsinki, a global set of ethical principles for research on human subjects, discourages a clinical trial from simply matching a local standard of care, if a higher, proven standard is available elsewhere.
On September 30, the SDU Ethics Committee voted in favor of the study and the CDC committed $1.6 million in global health security funds. The Pershing Square Foundation – created by billionaire hedge fund manager Bill Ackman – had already pledged $1.8 million.
As global public health experts renew their criticism, Dr. Gavin…
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