In the late 1990s, a U.S.-funded study randomized HIV-positive pregnant women in Bangkok, Thailand, to either a placebo group or a group treated with a short course of AZT. At the time, AZT was the standard of care in the U.S., and researchers knew the medication protocol worked at reducing mother-to-child HIV transmission by nearly 70 percent. The study looked at whether a shortened protocol could meaningfully reduce HIV transmission compared with no treatment.
The short-course AZT study in Thailand sparked controversy over the ethics of using placebo controls when a proven standard of care (full AZT regimen) already existed. Physicians and bioethicists criticized the trial design, arguing that it exploited disadvantaged populations in low-resource countries. The U.S. defended the study, noting that in these settings, the standard of care was no AZT, so participants who did not get the intervention were not receiving less than they would have otherwise.
Repeating history in Guinea-Bissau
Until recently, RFK Jr. was set to repeat this unethical study design, but with the hepatitis B vaccine and in Guinea-Bissau. He approved $1.6 million to fund a 14,000-person study in which one group will receive the hepatitis B vaccine at birth and the other at six weeks of age. The standard of care, as recognized by the World Health Organization, is a birth dose to prevent mother-to-child transmission of hepatitis B. While in Guinea-Bissau, where disease prevalence is high, with over 11 percent of infants having hepatitis B, the standard of care is to delay the vaccine until six weeks.
Those supporting this study design argue that, in these settings, the standard of care is no birth dose of hepatitis B vaccine, so participants who do not get the intervention are not receiving less than they would have otherwise.
Sound familiar? This is the exact argument used in the 1990s to support withholding medications to reduce mother-to-child HIV transmission in Thailand. It is also a study design recognized by the WHO as unethical, and perhaps the reason officials in Guinea-Bissau recently halted the controversial U.S.-funded clinical trial.
Ignoring local public health goals
In Guinea-Bissau, where nearly one in five people is infected with hepatitis B, health authorities acknowledge the risks of delaying vaccination until six weeks and have committed to implementing a routine hepatitis B birth dose by 2027. Instead of helping the country move closer to its goal, RFK Jr. tried to take advantage of the people of Guinea-Bissau, where 60 percent live in poverty, and use them to test his anti-vaccine theories. The study planned to follow participants for five years to assess not whether they contract hepatitis B, but other non-specific effects of vaccines (NSE).
Some observational studies have suggested beneficial NSEs (e.g., lower overall mortality after certain live vaccines), while other studies have found no effect or negative effects. WHO has reviewed the evidence multiple times and concluded that the findings are inconclusive and insufficient to change policy. Although further investigation of NSEs is a reasonable approach, NSE research should not be prioritized over efforts to prevent infection in a high-risk, low-income infant population.
In addition to putting thousands of infants at risk of contracting hepatitis B, the study has additional ethical flaws. It is single-blinded, meaning researchers know which participants receive the intervention and which do not. This creates opportunities for conscious or unconscious bias to influence data collection and interpretation. Compounding these concerns, RFK Jr. bypassed the standard competitive bidding process and selected the researchers himself. Unsurprisingly, the individuals he chose have ties to the U.S. anti-vaccination movement, raising serious questions about objectivity and scientific integrity.
Why delaying the vaccine is dangerous
Infants who contract hepatitis B are at much greater risk of serious complications than those who contract it later in life. While 10 percent of adults who acquire hepatitis B go on to experience chronic liver complications, over 90 percent of infected infants will experience lifelong, and sometimes deadly, infections. In other words, babies are incredibly vulnerable to chronic hepatitis B, making protection starting in infancy crucial.
[Image comparing the progression rates of acute to chronic hepatitis B infection in infants versus adults]
In the U.S., between 1990, one year before routine hepatitis B vaccination, and 2006, incidences of the virus declined by 98 percent in children under 15. In 1990, 1.2 per 100,000 children under 15 were diagnosed with hepatitis B, and by 2006, that rate dropped to 0.02. This decline illustrates the success of the hepatitis B vaccination program in the U.S. and has significantly narrowed racial disparities among hepatitis B diagnoses.
Poverty is not a control group
RFK Jr. testing his anti-vaccination theories in a country with a high prevalence of hepatitis B, a poverty rate of around 60 percent, and a lack of access to health care is wildly unethical. If scientific inquiry were prioritized over exploitation, such a study could be conducted in high-income countries that do not administer a hepatitis B birth dose, like Denmark, without placing disproportionate risk on a vulnerable population.
A subpar standard of care in a poverty-stricken country should not be an acceptable control group. The HIV trials of the 1990s are a historical lesson to avoid, not a blueprint to repeat. Guinea-Bissau does not need to relive that history so outsiders can test theories on the bodies of its infants. Knowingly exposing individuals to preventable harm in the name of science demonstrates a fundamental misunderstanding of research standards. Ethical research advances health by narrowing inequities, not exploiting them.
Meghan Johnston is a laboratory scientist.
