An interesting story about a planned Hepatitis B vaccine trial in Guinea-Bissau made its rounds on various internet social media sites.1 It is a variation of an argument readers interested in research ethics will be familiar with. The United States Centers for Disease Control, currently under the control of vaccine skeptics allied with the government's Health Secretary2 has chipped away at vaccination gold standards of prevention that have been in place for decades. The gold standard of hep B prevention in newborns since the 1990s is to vaccinate the newborns. The American Academy of Pediatrics published in 2022 its up-dated evidence-based consensus statement recommending that all newborns ‘with a birth weight of greater than or equal to 2000 g receive hepatitis B vaccine by 24 h of age.’3 This has been the gold standard of prevention in much of the world. However, in many countries of the global south this is not so, not because of considered scientific doubts but because of a lack of resources. A case in point is Guinea-Bissau. At the time of writing children will be vaccinated against hep B at weeks 6, 10, and 14, report the investigators of the planned study that caused an international outcry.4 However, hep B prevalence is high in Guinea-Bissau, and to reduce the incidence of hep B Guinea-Bissau has decided to implement the gold standard of prevention (vaccination at birth) going forward from 2027 or 2028. Here then is a quick summary of the reported salient details of the trial. A researcher from Denmark designed a randomised placebo controlled study that aims to investigate a question of interest to him, namely whether there are other positive or negative non-specific health effects caused by these vaccines that go beyond what is known already, namely the successful prevention of hep B infection. The researcher considers the absence of the gold standard of care until 2027 or 2028 as an excellent opportunity to undertake a randomised controlled trial in Guinea-Bissau. Reportedly the nation's ethical review committee approved the study in November 2025, with the project originally scheduled to begin in early 2026. A member of the review committee is employed by the Danish health research group working in the country. Reportedly, after the international outcry, the new government of Guinea-Bissau put the study on hold, because the country's health minister thought that the country's ethical review committee didn't review the science of the trial adequately. The trial design provides 50% of the enrolled newborns with the vaccine, and 50% receive the local standard of care, in this case a placebo. The researcher then plans to monitor what the non-specific effects of the vaccine are, versus the placebo control group. Critics of the trial charge, with good reason, that there is no true clinical equipoise. They argue that there is no good justification for this trial, because it is clear that there will be a higher percentage of infections in the placebo control group, and the effects of the hep B vaccine are well-known, given that it is the global standard of prevention in newborns since the 1990s. The investigators do not deny this; their interest is in non-specific effects of the vaccine. Whether it is justifiable to investigate those while knowing that the placebo control group is more likely to see hep B infections with all their known harmful health consequences is the ethical question. The Danish principal investigators thinks the knowledge generated vis a vis their research interest, namely ‘non-specific health effects,’ justifies this trial. They also note that no newborn is any worse off as a result of trial participation, because the gold standard of prevention would not have been available to these newborns in any case, at least until 2027 or 2028, when Guinea-Bissau is aligning its vaccine roll-out with the global gold standard. And this is the ethical argument that readers interested in research ethics will be all too familiar with. Even if the hep B vaccine is uncontroversially better for newborns to have than not to have, none of the newborns will be any worse off as a result of their trial participation, because those in the placebo control arm would not have received the vaccine in any case. For that reason comparisons, that were made in media outlets by several clinicians, to the infamous Tuskegee syphilis study, are mistaken. Abdulhammad Babatunde, a medical doctor and global health researcher in Nigeria, argued ‘To prevent things like the Tuskegee study and others, the control group has to get the standard of care, and the intervention group should get potentially better care.’ Ironically, this is exactly what the study design proposed to do. Unlike in the Tuskegee syphilis study the placebo control would have actually constituted the local standard of care. Because of that the investigator's consequentialist argument seems right. The vaccine skeptic US government agency would not have funded a trial where every newborn would have received the beneficial vaccine, even if such a trial design had been methodologically possible, and in the absence of that funding no newborn would have received the vaccine either, resulting in an even greater number of infections than will occur courtesy of the trial arm providing the protective vaccine. Critics will point out that these kinds of trial designs are exploitative in that they benefit unfairly from the local lack of resources. That the global gold standard of prevention is locally considered uncontroversially a good thing is demonstrated by Guinea-Bissau implementing this standard from 2027 or 2028. The ethical question is whether the trial investigators owe the provision of that gold standard of care to the trial participants. If they had provided the gold standard of care, as part of their trial design, the vaccine skeptics in charge at the United Stated Center for Disease Control would not have funded the trial, no matter the investigator's interest in ‘non-specific effects’. Then no newborn would have received the gold standard of care. Despite the investigator's protestations to the contrary, it is difficult to see how this trial would be relevant to the local communities in which it takes place, given that from 2027 or 2028 the gold standard of care will rightly, if belatedly, be implemented there. My view would be that ultimately the investigator's consequentialist ethical rationale in defense of the trial is sound because the newborns in the vaccine arm will uncontroversially benefit, and those in the placebo control arm will not be worse off for their trial participation. I do not think the ‘non-specific effects’ rationale exercising the principal investigator amounts to a good scientific justification for the placebo control, given that these vaccines have been used globally in newborns for decades. It is unlikely that anything changing the global gold standard of care will result from this trial. If beneficial effects are found, the vaccine will continue to be provided as the gold standard of care. If harmful effects are found they will not be such as to change existing vaccination regimes, because severe effects would have been noticed already. All things considered, this trial design would have been ethically impermissible in a society where the global gold standard of prevention is already the local standard of prevention. However, nobody will get harmed because of their trial participation in Guinea-Bissau, and about half of those newborns, namely those randomised into the vaccine arm, will benefit. And still, that this trial's ethical justification depends on the existence of unjust background conditions of poverty as a necessary condition for justifying its below global gold standards of prevention trial design remains deeply unsettling. The author declares no conflicts of interest.
Udo Schuklenk (Sun,) studied this question.