Proposed CDC-funded hep B trial in Africa unethical, WHO chief says

The director-general of the World Health Organization said Wednesday that a U.S.-funded study of the hepatitis B vaccine in Guinea-Bissau would be “unethical” if it proceeds as planned.

“Of course, a sovereign country can decide whatever they want, but as far as WHO’s position is concerned, it’s unethical to proceed with this study,” Tedros Adhanom Ghebreyesus said during a WHO news conference.

“I think it’s better to give it its name.”

A spokesperson for the Department of Health and Human Services did not directly address Tedros’ criticism, but defended the proposed trial.

“This research aims to fill existing evidence gaps to help inform global hepatitis B vaccine policy and is based on the highest scientific and ethical standards,” Emily Hilliard said in an email. 

And the researchers involved said they “respectfully disagree” with Tedros’ assessment of their proposed work, arguing that as structured, none of the children in the study would be deprived of an intervention — a birth dose of hepatitis B vaccine — that they would get if they were not in the study.

“No child in the study receives fewer vaccines than under current national policy,” Christine Stabell Benn wrote in a response to questions. “All children receive routine vaccines; half receive an additional hepatitis B birth dose that they would not otherwise receive.”

Stabell Benn, a professor of global health at South Denmark University, noted the protocol had been reviewed and approved by the Guinea-Bissau’s ethics committee.

The study, which is being partially funded by the Centers for Disease Control and Prevention, is meant to test whether giving a birth dose of hepatitis B vaccine has previously undetected impacts on the health of infants who receive it.

The vaccine has been given to babies at birth for over 40 years, and there are multiple studies supporting its safety and efficacy.

But in December, a panel that advises the CDC on vaccine policy advised the CDC to drop the country’s long-standing policy of recommending a birth dose of hepatitis B vaccine for all children, moving instead to a policy whereby only babies born to mothers who tested positive during pregnancy or whose mothers’ hepatitis B status is unknown would be offered a dose of the vaccine at birth. 

For other infants, the CDC — which accepted the advice — now advises that the first dose of hepatitis B not be administered before a baby is at least 2 months old.

The WHO recommends that babies be given hepatitis B vaccine at birth to prevent infections that could result in liver cancer and other chronic health issues. Kate O’Brien, ​​director of the agency’s immunization, vaccination, and biologics program, said at least 150 countries around the world follow that advice. “We have a very strong experience with hepatitis B [vaccine],” O’Brien said. “It’s a safe and it’s an extremely effective vaccine.”

Guinea-Bissau does not currently give infants a birth dose, but had previously announced plans to adopt the policy in 2027. It has been reported the country has pushed back the start date to 2028.

Stabell Benn and her colleagues planned to use the period before the birth dose policy goes into effect to run a randomized controlled trial involving about 14,500 infants, half of whom would receive the birth dose and a similar number who would get their first dose of hepatitis B vaccine at 2 months, the current standard of care in the country. 

The study, according to protocols that have become public, would not be structured to capture the impact on hepatitis B rates among the two groups, nor the benefits of giving the vaccine. The motivation to vaccinate babies at birth is to prevent them from becoming chronically infected with hepatitis B. Newborns infected with the virus run about a 90% chance of being chronically infected, and about a quarter of those who do will die prematurely from liver disease.

Rather, the study appears focused on looking for possible harms in the children who receive the vaccine at birth. A statement from the CDC announcing its $1.6 million grant for the project said the goal is to assess the hepatitis B birth dose’s impact on “early-life mortality, morbidity, and long-term developmental outcomes.”

Tedros noted that Guinea-Bissau has a high prevalence of hepatitis B infection, meaning there is a significant risk that newborns who go unvaccinated in the trial could contract the disease. A study conducted by the research team planning the hepatitis B trial reported that nearly 19% of adults in the country were hepatitis B positive.

Tedros suggested that denying half the children in the trial an intervention that has been proven to be safe and effective would be unethical. 

“From WHO’s side, the position is very clear. But the country can proceed, knowing full well that it’s unethical,” he said. “And the scientists can proceed, knowing full well that it’s unethical. That’s what I would like to say. Maybe it’s better to say it bluntly and straight.”

Though HHS spokespeople have characterized the study as a way to capture important information about the hepatitis B birth dose, critics have questioned what relevance any findings generated in Guinea-Bissau will have in an American context. Stabbell Benn’s defense of the work appears to bolster their arguments.

“The study does not question the vaccine’s effectiveness against hepatitis B infection, which is well established,” she wrote. “Its purpose is to evaluate the broader health effects of introducing the birth dose into national policy in a randomized setting, including when given together with BCG” — a tuberculosis vaccine — “and oral polio vaccines, in order to strengthen the evidence base for public health decision-making.”

Neither of those vaccines are routinely given to American children. In the United States, inactivated polio vaccine has been used exclusively since the late 1990s.

The status of the study is currently unclear. 

In the period from when the study was first approved, the government of Guinea-Bissau changed. In January, the new administration raised objections to the protocol for the trial. While an HHS spokesperson — and the researchers themselves — insist the trial will proceed, the study does not appear to have begun. There is no listing for the trial in clinicaltrials.gov, the U.S. government website where clinical trial protocols are supposed to be listed.

Stabell Benn declined to answer questions about the status of the proposed study, but did say that it would be registered in clinicaltrials.gov “prior to initiation as per standard procedure.”

This article was updated to add comments from the co-principal investigator of the clinical trial.