The saga of the US-funded hepatitis B vaccine trial in Guinea-Bissau took another turn today, with health officials in the western African nation saying the study has been suspended pending further technical review.
The comments were made during a press briefing today from the Africa Centres for Disease Control and Prevention (Africa CDC). Guinea-Bissau’s director general for public health, Armando Sifna, and public health minister Quinhin Nantote said that the trial is suspended until a committee reviewing the study has the technical resources required to make a final decision.
Last week, Africa CDC officials indicated the trial, which has set to begin this month, had been canceled. But their statements were challenged by officials with the US Department of Health and Human Services (HHS), who said the trial was going ahead as planned.
Decision up to Guinea-Bissau
Africa CDC Director-General Jean Kaseya, MD, MPH, said the decision about whether to move forward with the trial belongs to Guinea-Bissau.
“Africa CDC is respecting and supporting the sovereignty of the country,” Kaseya said. “It’s not Africa CDC that will say this clinical trial will take place or not. It’s not any other international body that will say this clinical trial is taking place or not.”
Kaseya added that he was told by a health official in Guinea-Bissau earlier this week that they were still awaiting a briefing and recommendations from the country’s National Medicine Regulatory Authority (NMRA) and National Ethical Committee (NEC) before making a final decision.
“As leader of Africa CDC, I fully support that,” Kaseya said, adding that the agency will provide technical support to help officials in Guinea-Bissau evaluate the study.
It’s not Africa CDC that will say this clinical trial will take place or not. It’s not any other international body that will say this clinical trial is taking place or not.
Kaseya also reviewed a checklist that sponsors must meet to conduct a clinical trial in an African country. The list includes written authorization from the country’s NMRA, approval from the NEC, and explicit clearance from the government.
HHS did not respond to a request for comment.
A host of ethical concerns
The trial, which was awarded a $1.6 million grant from the US Centers for Disease Control and Prevention (CDC), has caused controversy since it was first announced in a notice in the Federal Register last month. Led by researchers from the Bandim Health Project at the University of Southern Denmark, the study is designed to enroll 14,000 infants in Guinea-Bissau and randomize half of them to receive a birth dose of the hepatitis B vaccine, along with vaccines against tuberculosis (TB) and polio. The other half will only receive the TB and polio vaccines at birth.
The primary objective of the trial, according to the updated study protocol, is whether administration of the hepatitis B vaccine within one week of birth is associated with a composite outcome of all-cause morbidity and mortality within 42 days after birth. The secondary objective is to see whether the vaccine is associated with “non-specific effects,” including atopic dermatitis by age 2 and neurodevelopmental issues by age 5.
The trial has been widely criticized as unethical, given the known efficacy of a birth dose of the hepatitis B vaccine and the high prevalence of chronic hepatitis B infection in Guinea-Bissau. Roughly 90% of infants exposed to the disease at birth develop a chronic infection, which can lead to cirrhosis and liver cancer, and 15% to 25% of those infected go on to die from the disease. Withholding the birth dose from infants in a country where the disease is endemic could leave them highly vulnerable to infection.
Critics have also noted that measuring mortality after 6 months doesn’t make sense, because the effects of hepatitis B infection take years to develop.
The World Health Organization recommends that all babies receive a dose of the vaccine within 24 hours of birth, followed by two or three doses four weeks apart. The United States followed that recommendation for more than 30 years, but in December the CDC’s Advisory Committee on Immunization Practices overturned the universal birth dose policy, instead recommending a birth dose only for infants born to mothers who test positive for hepatitis B, or whose status is unknown.
Currently, infants in Guinea-Bissau receive their first hepatitis B shot at 6 weeks. The Bandim Health Project says there is a “unique window of opportunity” to conduct the trial now because the Guinean Ministry of Health will implement a universal hepatitis B vaccine policy starting in 2027-28. If the trial does go ahead as planned, investigators say they will enroll participants until that policy begins.
