The dilemma of trying out new cures for malaria

The alarming rise of drug-resistant malaria in South-East Asia necessitates the development of new treatment regimes in India. Controlled human infection model (CHIM) studies could expedite this process but raise significant ethical concerns. A robust ethical and regulatory framework is essential to proceed with such studies.

This article was first published in The Mint. You can read the original at this link.

In 2015, the World Health Report stated that there had been 214 million cases of malaria worldwide with 438,000 deaths from it. This represents an 18% decrease in cases and a 48% decrease in mortality compared to 2000. However, what these figures hide is that over the past decade, there has been an alarming rise in reported cases of drug-resistant malaria all over South-East Asia—from Vietnam to Myanmar — and in Pakistan. Given this geographical spread, it is inevitable that drug-resistant malaria will come to India sooner rather than later. There is, therefore, an urgent need for us to develop new treatment regimes for this disease.

The trouble with using therapies developed in the West on Indian populations, particularly in the case of vector-borne diseases such as malaria, is that the host-pathogen relationships in those countries could vary significantly when compared with India. Given our genetics, history of infections, co-infections, immune status and even environmental factors, it is more than likely that treatments that work well on European populations will be somewhat less effective in Asia. What we need to do is to find ways to effectively test new therapies on the Indian population to identify remedies that best address the risk drug-resistant malaria poses to us.

Controlled human infection model (CHIM) studies offer a means by which this can be done. A CHIM study calls for the infection of perfectly healthy adult volunteers with a carefully selected strain of a disease. This allows researchers to observe the progress of the infection, its response to treatment and the efficacy of both naturally acquired as well as vaccine-induced immune responses. Everything, from the strain of the pathogen to the timing, route and dose of infection, is carefully controlled to avoid causing harm to the volunteers and to allow researchers to make accurate observations of the disease that they would otherwise have been unable to do.

The benefit of this method is that it makes results available in far shorter time frames than would have been possible with traditional clinical trials, resulting in considerable reductions in the cost of drug discovery. As far fewer participants are exposed to experimental therapies, it puts a much smaller proportion of the population at risk.

That said, CHIM studies throw up several ethical issues that need to be addressed before we proceed. In the first place, the basic premise of a CHIM study requires doctors to intentionally infect previously healthy human beings with a disease. This approach bears an uncomfortable resemblance to the experiments that Nazis conducted on prisoners in concentration camps, making it impossible to even consider without dealing with the revulsion that such images invoke. In addition, the doctors and medical researchers who conduct these studies will have to consider for themselves how the act of intentionally making a healthy person ill sits with their Hippocratic obligation to do no harm.

Though all CHIM studies obtain, as a pre-condition, the informed consent of volunteers before proceeding, there is understandable scepticism as to whether, in the Indian context, those who participate in these studies will actually understand the many known, unknown, and potential risks of these experiments. This is further exacerbated by the poor reputation of the Indian research community with clinical trials in general—particularly following the death of seven girls who participated in Human Papillomavirus Vaccine trials in 2009.

If we are to take advantage of the many benefits that CHIM studies offer, we must first establish an appropriately robust ethical framework within which these studies will be conducted. Crucial to this is ensuring that the consent that we obtain from participants is truly informed. I would argue that, given that the participants in these studies will actually be infected with a disease, the bar to evaluate their appreciation of the consequences should be set exceptionally high. As even well-educated laypersons will most likely be unable to appreciate all the potential complications that could arise from participation, I would argue that only persons with an appropriately high level of scientific training should be allowed to take part in these studies.

Most trials offer volunteers a stipend to participate. Among poorer sections of society, financial incentives have the effect of being coercive, impairing the consent they provide. One way to address this could be to stipulate that CHIM studies in India should not offer any financial incentives whatsoever, other than covering the cost of treatment during the study and beyond in case of complications. This will ensure that anyone who takes part only does so altruistically with no interest other than to further the scientific understanding of the disease.

Above all, the government needs to quickly establish a robust regulatory framework within which any such study should proceed, with strict punishments prescribed for anyone attempting to conduct rogue trials. Only research institutions with impeccable credentials should be granted a licence to conduct CHIM studies and should, throughout the process, be subject to the supervision of an independent ethics board.

CHIM studies offer many benefits. However, before we take advantage of them, we need to address the many ethical challenges they pose.