Ethics, ambiguity aversion, and the review of complex translational clinical trials

Area of Science:

• Bioethics
• Clinical Trial Ethics
• Neuroscience Research Ethics

Background:

• Clinical trials for novel agents present complex ethical challenges.
• Limited resources for ethical and safety reviews necessitate careful attention allocation.
• Investigator, Institutional Review Board (IRB), and regulatory attention to safety dimensions is a critical ethical consideration.

Purpose of the Study:

• To examine how attention allocation during ethical review can be influenced by risk ambiguity.
• To demonstrate how ambiguous risks might divert focus from known risks in clinical trial ethics.
• To propose strategies for mitigating attention biases in ethical review processes for novel agent trials.

Main Methods:

• Analysis of ethical challenges in clinical trials using a Parkinson's disease gene transfer trial as a case study.
• Exploration of how ambiguity in risk probabilities or outcomes affects reviewer attention.
• Proposal of cognitive aids and structured discussion for ethical review.

Main Results:

• Risks with unknown probabilities or outcomes (ambiguity) may capture reviewer attention disproportionately.
• This attention bias can detract from the systematic analysis of known risks during ethical review.
• The goal of systematic and nonarbitrary risk analysis may be undermined by such biases.

Conclusions:

• Reviewers should develop cognitive aids, such as checklists, to ensure comprehensive risk assessment.
• Dedicated time for discussing non-ambiguous risks is recommended to counteract attention biases.
• Further research is needed to understand the interplay of attention, emotion, and ambiguity in ethical decision-making for clinical trials.