A scathing opinion piece in the BMJ is accusing the World Health Organization of conducting a pilot program in Africa for an experimental malaria vaccine without acquiring the informed consent of participants. Experts are calling it a “serious breach” of international bioethical standards and potentially “a disaster for public trust in vaccines.”
The trial in question is currently underway in Malawi, Ghana, and Kenya and is slated to involve over 720,000 children, who will be administered the experimental malaria vaccine, called Mosquirix, over the next two years, according to the BMJ opinion piece, authored by Peter Doshi, the journal’s associate editor. Doshi claims the World Health Organization, which is leading the trial, is not acquiring the informed consent of participants.
“Recipients of the malaria vaccine are not being informed that they are in a study,” declared Doshi in the BMJ article. “And the extent to which parents are being given information about the known safety concerns before vaccination is unclear.”
Bioethicist Charles Weijer from Western University in London, Ontario, Canada, was quoted in the opinion piece as saying the failure to receive informed consent is a “serious breach of international ethical standards.”
Mosquirix, also known as the RTS,S vaccine, is the first licensed vaccine for malaria in the world. The drug has already gone through early clinical trials, and preliminary results have mostly been positive—but some serious safety concerns have emerged. In particular, rates of meningitis appears to be 10 times higher in participants receiving Mosquirix compared to individuals who did not receive it. In addition, Mosquirix has been linked to higher rates of cerebral malaria (when parasite-infected blood cells block small blood vessels to the brain), and, very troublingly, a two-fold risk of all-cause mortality in girls.
For the pilot, WHO is randomly assigning areas, or clusters, in which the vaccine will be rolled out. After two years, the health agency will evaluate the data and make a decision about whether or not to roll out Mosquirix on a much larger scale.
Mosquirix “was positively reviewed by the European Medicines Agency, but its use is being limited to pilot implementation, in part to evaluate outstanding safety concerns that emerged from previous clinical trials,” wrote Doshi. That said, WHO describes the study as a “pilot introduction” and not a “research activity,” according to the BMJ article, and says participants who receive this experimental vaccination are doing so according to their country’s routine vaccination schedule. Because of this, consent is implied, according to the WHO.
Weijer, one of several bioethicists cited in the BMJ piece, said the WHO pilot violates the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials. Forged in 2012, the Ottawa Statement provides the most comprehensive international ethical guidelines for these types of trials.
“As with all other international research ethics guidelines, the Ottawa Statement articulates a strong presumption for informed consent from research participants,” Weijer, who helped to develop the guidelines, told Gizmodo. “Research participants have a right to be informed of the purpose of the research, the benefits and risks of study interventions, alternative to participation, and their rights as participants. In special circumstances, the requirement for informed consent may be set aside with a waiver of consent. But the use of a waiver of consent is never appropriate for a cluster trial involving a drug or vaccine intervention.”
Writing in his BMJ piece, Doshi said it’s not clear if an ethical review board signed off on the “implied consent” process. When asked by Doshi about this, WHO said the “vaccine deployment is led by the countries and it is done in the context of routine vaccinations, where there is no requirement for written individual consent,” according to the BMJ article.
As previously noted, WHO claims the study is a “pilot introduction,” and not a “research activity,” which is why the organization is using the implied consent rationale. Here’s how a WHO spokesperson explained it to Doshi, as quoted from the BMJ article:
An implied consent process is one in which parents are informed of imminent vaccination through social mobilisation and communication, sometimes including letters directly addressed to parents. Subsequently, the physical presence of the child or adolescent, with or without an accompanying parent at the vaccination session, is considered to imply consent.
Weijer doesn’t buy it.
“An implied consent process is no substitute for informed consent. Indeed, implied consent is no consent at all,” he told Gizmodo. “We have no assurance that parents in fact received information about the study let alone that they understood it. Parents attending a clinic for routine vaccination of their child may therefore be unaware of the study and the fact that they can decline.”
The WHO’s claim that this isn’t a “research activity” certainly seems strange, even disingenuous. Its own Q&A document on the trial claims the purpose is to provide “further evaluation [of the new malaria vaccine] before considering wide-scale deployment.” Research, according to Weijer, is a “systematic investigation designed to produce generalizable knowledge.” WHO’s malaria vaccine pilot “plainly meets this definition and is—rather obviously—research,” he told Gizmodo.
What’s more, the pilot was registered in clinicaltrials.gov, which “amounts to an open declaration that this is research,” according to McGill bioethicist Jonathan Kimmelman, who was quoted in the BMJ article. By describing the project as a pilot implementation, the WHO, it can cynically be said, was able to avoid a slew of ethical red tape.
That WHO chose to ignore or disregard potential health risks is yet another alarming aspect of this story. Previous clinical trials of Mosquirix showed that 2.3 percent (67 of 2,967) girls died in the vaccine group, compared to 1.1 percent (17 of 1,503 girls) not administered the vaccine. When BMJ asked why this “female mortality signal” was not considered, WHO said there was “insufficient evidence to classify gender specific mortality as a known or potential risk.”
In the BMJ article, Christine Stabell Benn from the University of Southern Denmark said parents should be made aware of the two-fold mortality risk for girls. If this turn out to be a real health risk, “how will this be perceived by the participants—that their children were unknowingly involved in a huge experiment by the authorities?” said Benn, adding that this “could be a disaster for public trust in vaccines and health authorities.”
No doubt, this controversy comes at a terrible time, as it will likely provide fuel for the anti-vaccine movement. What’s more, the seemingly cavalier and irresponsible nature of this field experiment smacks of colonialism, racism, and even misogyny. Sadly, it’s yet another example of medical experimentation done at the expense of African individuals.
That WHO would like to roll out a vaccine as quickly as possible is understandable, as malaria kills approximately 435,000 people around the globe each year. But that’s no excuse for violating established ethics guidelines and potentially endangering human lives in the process.
Gizmodo reached out to WHO for comment, but did not receive a response by the time of publication.