Surrogate outcomes: experiences at the Common Drug Review.

Area of Science:

• Health Technology Assessment (HTA)
• Drug Evaluation
• Regulatory Science

Background:

• Surrogate outcomes present significant challenges in drug evaluation for HTA agencies.
• The Common Drug Review (CDR) in Canada faces complexities in assessing surrogate endpoints.
• International comparisons of surrogate endpoint evaluation are crucial for harmonization.

Purpose of the Study:

• To identify factors influencing surrogate use and acceptability within CDR recommendations.
• To compare the CDR's approach to surrogate concerns with other international HTA and regulatory bodies.

Main Methods:

• Analysis of CDR recommendations from inception to December 2010.
• Classification of outcomes as surrogate, final, or other, and assessment of surrogate acceptability.
• Statistical analysis of factors associated with surrogate use and acceptance, and review of international agency stances on surrogates.

Main Results:

• 68% of 156 final recommendations involved surrogate outcomes.
• Non-accepted surrogates were significantly associated with higher 'do not list' rates (64% vs. 25%).
• Clinical uncertainty, economic evidence use, and premium pricing correlated with non-accepted surrogates; regulatory agencies frequently accepted surrogates.

Conclusions:

• The CDR largely accepted surrogate outcomes, but non-accepted surrogates were linked to clinical uncertainty and negative recommendations.
• Inconsistent surrogate acceptability was observed across international agencies.
• Collaborative development of guidelines for surrogate use, validation, and acceptance is recommended.