With the Bioethics Unit of the Indian Council of Medical Research (ICMR) Submission of a Consensus Policy Statement on Controlled Human Infection Studies (CHIS) For comments, India has taken the first step towards paving the way for such studies to take place in India. CHIS, also called human challenge studies, where healthy volunteers are intentionally exposed to a disease-causing microbe in a highly controlled and monitored environment, has been done for hundreds of years, for example in the early 1900s yellow fever studies to establish that mosquitoes transmit the virus. Generally, less virulent strains of the microbe are used to study less lethal diseases for which proven drugs are available. These are often performed on small numbers of volunteers, in order to understand different aspects of infection and disease, and, sometimes, to accelerate the development process of medical interventions. When used as part of vaccine development, these studies are initiated only when the safety and immune response of candidate vaccines are known through the early stages of clinical trials. Importantly, human challenge studies are not performed as a substitute for Phase-3 efficacy trials, but rather to help select the best candidate for testing in a traditional Phase-3 clinical trial. Phase-3 clinical trials often require fewer volunteers after human challenge studies, thereby speeding up the development process. Over the past 50 years, CHIS studies have been conducted with thousands of people to accelerate the development of vaccines against typhoid and cholera. During the COVID-19 pandemic, Imperial College London used 36 volunteers to study aspects of SARS-CoV-2 infection. In 2020, the World Health Organization approved the use of CHIS to accelerate COVID-19 vaccine development.
There are many ethical challenges with human exposure studies, which require well-trained and robust systems. While collaboration with accomplished institutions and scientists is essential in conducting such studies, navigating the ethical minefield is a challenge. Several clinical trials, which have been conducted by or involved ICMR, have been mired in ethical breaches, such as the Human Papillomavirus (HPV) vaccine trial in Andhra Pradesh in 2010. The ethical challenges when conducting CHIS are of greater magnitude, the scope for abuse is wider, and the consequences are severe. Given the monetary dimension associated with volunteering, there is potential for exploitation. If this becomes a reality, India should use CHIS to study diseases with safe and effective treatments. The use of CHIS to study novel pathogens/disease with limited medical intervention should wait until Indian scientists gain expertise, and strong institutional structures and mechanisms are in place.