‘Human Model’ code for infection studies

 Controlled Human Infection Studies (CHIS) is a highly complex research methodology that involves infecting healthy human volunteers with pathogens in a controlled environment to better understand the immune response and efficacy of vaccines and drugs developed for the treatment of infectious diseases. Ethical issues around CHIS flagged by the World Health Organisation (WHO) have been limiting its application in biomedical research in most countries. The Indian Council of Medical Research (ICMR) releasing the draught policy statement on the ethical conduct of CHIS in India is a pointer towards India actively considering allowing CHIS for biomedical research. The policy document needs to be well publicised for comprehensive scrutiny by experts and other public stakeholders to ensure that no ethical issue related to CHIS is left unaddressed in the final draft. The ICMR has posted the document on its website for public consultation, with the last date for receiving comments, suggestions, and feedback being August 16. The ‘WHO Guidance on the Ethical Conduct of Controlled Human Infection Studies can be a useful document for the public consultation process and guide stakeholders who wish to give their comments and suggestions on the ICMR draft. The WHO document points out the fundamental difference between deliberate infection studies like the ones conducted in Germany and Japan during World War II by infecting thousands of subjects with pathogens, including anthrax, plague, tetanus, and tuberculosis; deliberate infection of intellectually challenged children in the United States when no consent was taken or it was ill-informed; and CHIS, which require informed consent and the maintenance of the highest ethical standards. WHO insists that “CHIS should only be conducted in sites that have the infrastructure, facilities, personnel, and processes required to rigorously and safely conduct such research.” The ICMR claims that its Bioethics Unit has formulated a consensus policy statement to address the ethical concerns related to the conduct of CHIS in India through a process of rigorous engagement with experts in the last few months. “However, being a very specialised type of research involving deliberately infecting healthy volunteers with a specific pathogen under controlled conditions, this may have a lot of ethical challenges, and an attempt has been made to address these issues in this document”, it adds. The document mentions that though many countries have conducted CHIS on various infectious diseases such as malaria, influenza, dengue fever, typhoid, and cholera, India has yet to apply CHIS for biomedical research on any infectious disease. The apex body for biomedical research in India cites the high burden of morbidity and mortality from infectious diseases, which contributes to about 30% of the disease burden of the country, to justify pushing for CHIS. Two key objectives of policy are to identify the ethical considerations related to CHIS that would guide the protection of safety, rights, and the well-being of research participants and to provide an ethical framework and a systematic approach for conducting an ethics committee review of CHIS-related proposals. The general consideration outlined in the policy document is that CHIS offers accelerated, cost-effective, and efficient outcomes using smaller sample sizes in comparison to large clinical trials, and its social value includes potential contributions to public health response to diseases of concern, healthcare decision-making, policies and economic benefits, improved pandemic preparedness, and community empowerment. Viewed in the context of the health emergency triggered by the COVID-19 pandemic and successful clinical trials leading to the development of vaccines within a short period, the adoption of CHIS merits careful consideration by the government, provided adequate safeguards are included in it without any ambiguity. Some of the ethical safeguards proposed by the ICMR include: Participants should be provided with detailed information about the rationale and nature of the study, the potential risks and benefits, the expected endpoints, the treatment plan, the duration of infection clearance, and measures to minimise harm. To minimise harm, the study should be conducted for self-limiting infections and/or those that can be resolved with known medications and treatment protocols. The document proposes that the reason for participation should be evaluated and should include altruism as a genuine desire to contribute to public health advancement. It also insists that participants should preferably be graduates so that they have the capacity to comprehend the research purpose, potential benefits, and possible harm, allowing them to make an informed decision regarding their participation. The document lists dos and don’ts regarding informed consent and mentions that as the study involves deliberate harm and higher risk, it is an ethical requirement that these aspects be clearly explained to the participant in a simple form and manner and in a language in which the participant has a full understanding of the research. Monitoring and oversight mechanisms must be robust to ensure that there is no deviation from ethical standards. India must evaluate its biomedical research ecosystem to assess anticipated risks and the capacity to manage those while opening the door for CHIS.