ICMR looking at introducing Controlled Human Infection Studies in India

There’s rising concern among research ethics activists in India over Controlled Human Infection Studies (CHIS). This system, practised in many countries for decades to facilitate the prevention and treatment of infectious diseases, may soon be practised in India as well.

The Indian Council of Medical Research (ICMR), the apex body in India for the formulation, coordination and promotion of biomedical research, released a consensus policy statement on July 17 for the ethical conduct of CHIS in India. It also invited comments from the public within a month.

Those working on research ethics have pointed out some crucial loopholes — ethical, legal, scientific, and regulatory — in the draft policy statement. They fear it may potentially “exploit vulnerable people and violate human rights”.

What exactly does CHIS entail? Should we be worried?

What is CHIS?

The World Health Organization (WHO) explains CHIS as a method in which “healthy volunteers are intentionally exposed to pathogens in a controlled environment, in order to promote understanding of the pathogenesis, transmission, prevention and treatment of infectious diseases in humans”.

The WHO explains: “Such studies may be conducted to gain insights into how pathogens infect human hosts and cause disease, to better understand immune responses to infection, or to evaluate the efficacy of vaccines and drugs designed to prevent and treat infectious diseases.”

To put it simply, CHIS is a faster and cheaper method for developing new drugs and vaccines. In its introduction to the draft policy statement, the ICMR has stated: “In contrast to natural infection studies, which can take longer to observe, researchers obtain data more quickly and efficiently from controlled studies…”

What are the concerns?

One of the major concerns about CHIS revolves around its ethics. The ICMR does point it out in the introduction, saying: “…these studies are ethically sensitive and raise concerns about contentious research ethics — such as issues like deliberate harm, possible disproportionate payment and hence inducements, third-party risk, withdrawal from the study and research with vulnerable participants.”

And it is in this regard that a group of citizens working in the area of research ethics have submitted their comments. They have highlighted the issues of potential concern, the changes needed in the statement, and how it appears to have been finalised with little engagement with civil society organisations.

One of the six signatories of the document is health researcher and consulting editor of the Indian Journal of Medical Ethics, Sandhya Srinivasan. She pointed out while speaking with The Federal that the fact that CHIS has been practised for years in other countries offers little comfort, for the circumstances are vastly different in India.

“These studies have so far been largely confined to high-income countries,” she explained. “Now, they will be started in India where we don’t have the technical capacity and regulatory apparatus, but there will be many poor people willing to get infected for payment. There are many issues — of ethics, science, regulation, public health — that need thorough discussion and must be addressed before CHIS are even considered for India.”

What’s problematic about ICMR’s statement?

The experts point out that the statement “lacks clarity, and proposes low standards for the conduct of CHIS”. They add that it needs to be redrafted after incorporating high scientific and ethical standards, and that it should offer protection for participants and society.

For instance, the vaguely drafted statement may allow “loopholes, and leeway for legal and ethical violations”, they have pointed out. Also, it “does not prescribe any accountability for violations…by researchers, institutions and sponsors/funders conducting CHIS”.

In the 8,000-word document, the group has mentioned that the ICMR statement leaves a lot to imagination with many “contradictory points”, and no “information on the capacity, effectiveness and efficiency of current regulatory mechanisms for clinical trials”. Importantly, there’s nothing to suggest that CHIS is “cost-effective”, as claimed by ICMR, since there is no Indian data to support such a claim. So, if even the cost-effectiveness is not proved, what’s the point at all in taking up such a risky endeavour? That appears to be the key issue.

Also, the ICMR has harped on CHIS’ benefits while underplaying its limitations, the group has pointed out. The apex research body has not explained how the studies are carried out and has failed to mention that “participants in a CHIS are exposed to both the risks of deliberate infection and the classical risks of drug trials, doubling their risks”, says the group.

Other concerns? Children, consent, care and more…

The WHO, in its Core Values in addressing the ethical issues of CHIS, mentions the need to have “respect for persons, including the obligation to respect and protect the dignity, interests, agency, and human rights of research participants”. The ICMR statement seems to be lacking on several counts in this regard, the experts have pointed out.

For instance, the statement mentions that studies should not be conducted on children “at present” but may be included at a later point “when deemed appropriate”. The group of experts has argued that this option must be removed altogether.

Most importantly, the risks of CHIS have not been defined in certain terms. Also, the statement assures participants that they will get “healthy meals” and “basic hygiene such as clean water”, which is vague to say the least. The experts have pointed out that it should also include “the provision of the highest standards of hygiene, water and sanitation”.

Also, the draft states that participants “will receive a standard of care as appropriate for the disease under study”, without specifying what is meant by “appropriate”.

The group has also objected to how the compensation-related provisions seem like a “potential inducement to participate”. For instance, the draft states that the exact amount of payment to be made to a participant must be revealed only after she or he consents to participate. Hence, once they have consented, the participants will be compelled not to withdraw from a CHIS, which vitiates the consent process, the experts have argued.

“The statement should spell out how the quantum of compensation will be calculated for patients, families, hospital staff and the community who may be exposed to the pathogens being tried in CHIS, and who will be responsible for payment of this compensation,” the experts’ document says.