CONTROLLED HUMAN INFECTION STUDIES

• Recently, the Indian Council of Medical Research (ICMR) Bioethics Unit published a consensus policy statement for the ethical conduct of Controlled Human Infection Studies (CHIS), commonly known as human challenge studies.
• These studies involve exposing human participants to diseases intentionally to gain insights into pathogenesis, infection, and potential medical interventions.
• India is venturing into this domain to complement traditional clinical trials and expedite the discovery of safe and effective drugs and vaccines.
• The public consultation on the policy statement is open until August 16, 2023.

2. Reasons for Venturing into Human Challenge Studies

• While human challenge studies have been conducted worldwide for centuries, India has not undertaken such trials before.
• The decision to engage in these studies stems from the country's high disease burden and mortality rate from infectious diseases, which stands at around 30%.
• Human challenge studies can provide valuable information on well-studied pathogens, infection transmission, pathogenesis, and prevention.
• With many infectious diseases endemic in developing nations and drug resistance on the rise, these studies may offer crucial benefits to the population.

3. Fundamental Differences from Traditional Clinical Trials

• The primary distinction between human clinical trials and human challenge studies lies in participants' exposure to pathogens.
• In traditional trials, participants try to avoid infection, leaving exposure to chance, while human challenge studies intentionally expose volunteers to disease-causing agents.
• Additionally, traditional clinical trials focus on assessing drug and vaccine safety and efficacy, whereas human challenge studies aim to explore various facets of infection and disease pathogenesis.
• Moreover, while both studies assess drug/vaccine safety in humans for the first time, human challenge studies involve an additional risk as participants are deliberately exposed to pathogens.
• These studies typically focus on "less deadly diseases," such as influenza, dengue, typhoid, cholera, and malaria.

4. Safeguards to Reduce Harm to Participants

• To minimize harm to participants, human challenge studies generally use well-known and studied infectious agents.
• Weaker or less virulent forms of the pathogen are employed to reduce risks.
• Furthermore, a "rescue remedy" is available to prevent disease progression to a severe stage.
• However, the reliance on a rescue remedy, such as remdesivir during SARS-CoV-2 studies, raises ethical concerns, especially when its substantial mortality benefit is unknown.

5. Ethical Challenges of Human Challenge Studies

• Human challenge studies pose ethical challenges due to the deliberate exposure of participants to pathogens.
• The ICMR consensus statement limits participation to healthy individuals aged 18-45, excluding pregnant or lactating women and those with pre-existing medical conditions.
• However, medical examinations are essential to exclude unknown conditions.
• Transparent disclosure of payment for participation is required in the consent form, but the exact amount is only revealed after consent.
• Ensuring informed consent in studies involving specific age or disadvantaged groups remains a concern.
• Additionally, unpredictable disease outcomes even with less infectious agents necessitate the availability of effective rescue remedies.

6. The Way Forward

• India's entry into human challenge studies marks a significant step in advancing medical research and understanding infectious diseases.
• However, the ethical complexities surrounding these studies demand stringent safeguards and transparent informed consent processes.
• By adhering to high ethical standards, India can contribute valuable insights to global scientific knowledge while prioritizing the well-being and safety of its research participants.