Assessing Risk Thresholds in Controlled Human Infection Models (CHIM)
Alexa Nord-Bronzyk1, Barnaby Young2, Jerry Menikoff1
1Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore, Singpaore, Singapore.
Bioethics
|March 24, 2026
Summary
Controlled Human Infection Models (CHIMs) offer benefits for vaccine and therapeutic development but raise ethical concerns. This study proposes three frameworks for evaluating risk thresholds in CHIMs to guide future research.
Area of Science:
- Medical Ethics
- Infectious Disease Research
- Clinical Trial Design
Background:
- Controlled Human Infection Models (CHIMs) accelerate vaccine and therapeutic development by deliberately exposing volunteers to pathogens.
- CHIMs present unique ethical challenges, particularly regarding acceptable risk levels for participants, especially in high-risk scenarios.
- Existing ethical guidelines for CHIMs are well-established for low-risk pathogens but require re-evaluation for emerging threats and pandemic preparedness.
Purpose of the Study:
- To address the ethical considerations surrounding risk thresholds in Controlled Human Infection Models (CHIMs).
- To propose a taxonomy of approaches for evaluating and setting ethical risk limits in CHIMs.
- To provide a resource for researchers navigating the ethical permissibility of current and future CHIM studies.
Main Methods:
- The study reviews the ethical landscape of CHIMs, contrasting them with other early-phase clinical trials.
- It analyzes the unique ethical considerations posed by CHIMs, particularly concerning participant risk.
- A proposed taxonomy outlines three distinct approaches to determining risk thresholds: consistency, community engagement, and no risk threshold.
Main Results:
- The paper identifies a critical need for frameworks to ethically evaluate higher-risk CHIMs, especially in the context of future pandemic preparedness.
- Three distinct approaches—consistency, engaging community perspectives, and no risk threshold—are presented as potential models for setting ethical risk boundaries.
- The strengths and weaknesses of each proposed approach are explored to inform ethical decision-making.
Conclusions:
- Establishing clear ethical guidelines and risk thresholds for CHIMs is crucial for advancing medical research while protecting participants.
- The proposed taxonomy offers a structured method for the research community to deliberate on the ethical permissibility of CHIMs with varying risk levels.
- Future CHIM research, particularly for pandemic response, necessitates careful consideration of participant safety and societal values when defining acceptable risks.
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