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What are the ethical considerations around volunteer infection? Researchers, Maureen Njue and Dorcas Kamuya, discuss their research presenting one of the first studies of a controlled human malaria infection study in an LMIC, looking at the ethical issues of infecting healthy volunteers.

Deliberate infection

Controlled Human Malaria Infection (CHMI) studies involve the deliberate infection of healthy adult volunteers with malaria parasites to assess the efficacy of potential vaccine and drug candidates, and to understand the innate and acquired protection against malaria parasites.

Once infected with the parasites, the volunteers are closely monitored by a medical team to check for evidence of carriage or infection to anticipate and manage any symptoms of the disease.

Immunity

Naturally acquired immunity to malaria is acquired by residents of endemic areas.  Enrolling adult life-long residents of endemic areas into challenge studies allows us to measure the ability of their immune systems to control the malaria parasites that are injected.

We also measure the diversity of antibodies and other immune responses made by the volunteers, and relate these to the observed ability to control malaria parasites, so as to pick out the most effective immune responses.  These can then be targeted for vaccine development.

Participation

In the social science study that we conducted in Kilifi, Kenya, involving 36 participants (22 men and 14 women), participants’ main concern was the seemingly large volumes of blood being taken twice every day, and the discomfort caused by the needle pricks.

Participants were apparently not so worried about being injected with malaria parasites, as many were familiar with it, having had experienced malaria in the past and had recovered after medication. The continuous monitoring and presence of the medical team in case of any eventuality was reassuring to most participants.

Making a contribution

Compensation: Across the group, there were varied motivations for participating in the research. The cash compensation offered in the CHMI Study (and approved by ethics committees) was much higher than that offered in other studies conducted in the same setting, because of the high levels of inconvenience and costs associated with being away from home (maximum of 24 days).

Even when participants showed considerable understanding of the research, it was clear that the monetary compensation was a great motivator with many making a calculated decision based on what they would gain at the end of the study.

Health care benefits: For enrolment into the study, the participants were taken through a wide range of screening tests to ensure they were healthy. Most screening tests are not routinely available in public health facilities and accessing them privately is expensive. Participants highly appreciated the tests and a number felt they were an advantage even if they were not recruited into the study.

Altruistic reasons: Although not mentioned by many, a number of the participants cited wanting to make a contribution to finding a malaria vaccine for future generations as a motivating factor.

A few felt that participating in the research was reciprocal of the support that the research organization had given the community by conducting important and beneficial studies.

Ethics

Risks of participation: CHMI participants did not bring up concerns about potential risks to their health of being deliberately infected with malaria early on in conversations about the challenges they had experienced.

As mentioned earlier, participants generally saw malaria as a relatively common and non-serious condition in adults, and were reassured that they had access to medical care if symptoms developed. Instead other directly experienced burdens of participation, such as frequent painful needle pricks during blood taking, were seen as the main challenge to wellbeing.

Risks of undue inducement: While the financial compensation had been fully justified and set with prior ethics approval, payments were a strong motivating factor for participation. At the same time, participants demonstrated high levels of understanding of the purpose and nature of the study.

From an ethics perspective, it’s important that participants are not financially disadvantaged through participation in research, while also ensuring that the levels of payment/compensation do not unreasonably influence decisions about participation.

Understanding what would constitute an unreasonable influence is complex and requires careful understanding of context.  It is also important to continually assess the implications that levels of compensation might have for household and community relations.

Consent processes: Even though there were varied education levels, all participants passed a test of understanding prior to enrolment, and showed considerable understanding of study information provided during engagement and consent processes.

Use of visuals and multiple opportunities for participants to get information and interact with the clinical teams prior to, and throughout the study period strengthened their understanding of the research.

Community engagement: Deliberately infecting healthy volunteers with disease-causing pathogens (as happens in CHMI) goes against the public’s expectations of medicine, which can be a moral dilemma for physician-researchers, and contribute to reputational risk of the clinical discipline.

We strongly recommend using a carefully developed community engagement strategy. This is to explain the value of the study to various stakeholders, and to provide forums for researchers and communities to interact and learn from each other, as well as to discuss the burdens and risks involved in this form of research.

Future research

Our study shows the potential value of conducting social science elements within CHMI studies, to add insight into perceptions of participants and their communities regarding the research to increase our understanding about any concerns and worries that need to be addressed.