Equipoise: asking the right questions for clinical trial design

Area of Science:

• Clinical Research Ethics
• Evidence-Based Medicine
• Health Policy Research

Background:

• Randomized controlled trials (RCTs) are crucial for evidence-based decisions but present ethical dilemmas regarding physician and investigator obligations.
• Clinical equipoise, while intended to resolve these dilemmas, faces practical and conceptual challenges.
• Existing frameworks struggle to balance therapeutic norms with the scientific goals of research.

Approach:

• This perspective critically examines the limitations of clinical equipoise in the context of RCTs.
• It explores the difficulties in establishing and maintaining equipoise.
• An alternative risk-benefit assessment framework is proposed.

Key Points:

• Clinical equipoise imposes therapeutic norms on research, hindering scientific progress.
• Determining the existence of equipoise is challenging and prone to bias.
• Equipoise is insufficient for generating evidence needed for health policy.
• Expert judgment in equipoise can be influenced by weak evidence and bias.

Conclusions:

• A revised risk-benefit assessment aligned with the scientific aims of RCTs is necessary.
• This alternative approach offers a more robust ethical framework for evaluating clinical trials.
• Rethinking ethical guidelines can better support evidence generation for clinical and policy decisions.