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A large scale malaria vaccine study led by the World Health Organization (WHO) has been criticized in a special report published in the BMJ for committing a “serious breach” of international ethical standards. Bioethicists claim that the pilot study does not adequately inform parents and caretakers that their children are participating in the study and fails to address potential side effects associated with the disease.
The WHO says that its rollout of the Mosquirix (RTS,S) vaccine currently underway in Malawi, Ghana, and Kenya is a “pilot introduction” and not a “research activity”. The report argues otherwise.
“If an activity is classified as research, then all sorts of rules and oversight mechanisms are activated. For example, the activity must receive the prospective ethical review. Unless certain conditions are met, human subjects must provide informed consent,” said bioethicist Jonathan Kimmelman in the report.
“The fact that the activity has been registered in clinicaltrials.gov [NCT03806465] amounts to an open declaration that this is research,” he adds.
First developed in 1987, Mosquirix is the world’s first licensed malaria vaccine. The European Medicines Agency reviewed its use in children between 6 weeks and 17 months, followed shortly by a WHO recommendation for large-scale pilot implementations in children 5 to 9 months of age despite outstanding safety concerns brought up in previous clinical trials during which children who received the vaccine were 10 times more likely to contract meningitis or had an increased risk for cerebral malaria. The risk of death was doubled in girls who had received the vaccination.
An estimated 720,000 children are expected to receive the RTS,S vaccine over the next two years in randomly assigned areas as a part of their other routine vaccinations. However, it is not clear whether health care professionals will disclose whether or not the child is receiving Mosquirix. The WHO argues that consent is implied; if a parent or guardian wants to be informed about the potential vaccine then they may turn to local community initiatives meant to provide outreach about the vaccination. Furthermore, parents still have the option to vaccinate their child or not.
The report argues the failure to obtain informed consent from parents who are told that they are part of a study violates the Ottawa Statement, a consensus statement regarding the ethical design standards for cluster randomized trials. Charles Weijer, a bioethicist at Western University in Canada, tells The BMJ that implied consent is "no substitute for informed consent. Indeed, implied consent is no consent at all. We have no assurance that parents, in fact, received information about the study let alone that they understood it."
The report also states that WHO sent training information to country partners about the potential risk of Mosquirix but failed to mention the increased risk of death in girls. When asked why it did not include female mortality findings, the organization cited “insufficient evidence to classify gender-specific mortality as a known or potential risk.”
“I think parents should be made aware of this doubled female mortality. Imagine that this mortality was a true finding. If true, then how will this be perceived by the participants—that their children were unknowingly involved in a huge experiment by the authorities? This could be a disaster for public trust in vaccines and health authorities,” said vaccine expert Christine Stabell Benn of the University of Southern Denmark.
Weijer doubts that the ethics committee would have granted permission for any potential waiving of informed consent requirements. He also adds that the human rights provision of the Malawi constitution reads: No person shall be subjected to medical or scientific experimentation without his or her consent.
