Surrogate outcomes: experiences at the Common Drug Review.

Angela Rocchi,Rob Hopkins,Ron Goeree,Shoghag Khoudigian

doi:10.1186/1478-7547-11-31

Abstract

BackgroundSurrogate outcomes are a significant challenge in drug evaluation for health technology assessment (HTA) agencies. The research objectives were to: identify factors associated with surrogate use and acceptability in Canada’s Common Drug Review (CDR) recommendations, and compare the CDR with other HTA or regulatory agencies regarding surrogate concerns.MethodsFinal recommendations were identified from CDR inception (September 2003) to December 31, 2010. Recommendations were classified by type of outcome (surrogate, final, other) and acceptability of surrogates (determined by the presence/absence of statements of concern regarding surrogates). Descriptive and statistical analyses examined factors related to surrogate use and acceptability. For thirteen surrogate-based submissions, recommendations from international HTA and regulatory agencies were reviewed for statements about surrogate acceptability.ResultsOf 156 final recommendations, 68 (44%) involved surrogates. The overall ‘do not list’ (DNL) rate was 48%; the DNL rate for surrogates was 41% (p = 0.175). The DNL rate was 64% for non-accepted surrogates (n = 28) versus 25% for accepted surrogates (odds ratio 5.4, p = 0.002). Clinical uncertainty, use of economic evidence over price alone, and a premium price were significantly associated with non-accepted surrogates. Surrogates were used most commonly for HIV, diabetes, rare diseases, cardiovascular disease and cancer. For the subset of drugs studied, other HTA agencies did not express concerns for most recommendations, while regulatory agencies frequently stated surrogate acceptance.ConclusionsThe majority of surrogates were accepted at the CDR. Non-accepted surrogates were significantly associated with clinical uncertainty and a DNL recommendation. There was inconsistency of surrogate acceptability across several international agencies. Stakeholders should consider collaboratively establishing guidelines on the use, validation, and acceptability of surrogates.

Highlights

Surrogate outcomes are a significant challenge in drug evaluation for health technology assessment (HTA) agencies
A comparison of recommendations from Canada, Australia and the UK found that clinical uncertainty was a key issue, with uncertainty typically arising from inadequate study design, inappropriate comparators or unvalidated surrogate endpoints [5]
This research has shown that surrogate acceptability was closely aligned with clinical uncertainty – a predictable association, but important to establish as a preface to more in-depth analysis

Summary

Introduction

Surrogate outcomes are a significant challenge in drug evaluation for health technology assessment (HTA) agencies. The research objectives were to: identify factors associated with surrogate use and acceptability in Canada’s Common Drug Review (CDR) recommendations, and compare the CDR with other HTA or regulatory agencies regarding surrogate concerns. In 2003, the Common Drug Review (CDR) was created to provide a single national process to review the comparative clinical evidence and cost-effectiveness of new drugs, and to make formulary listing recommendations to Canadian publicly funded federal, provincial and territorial drug benefit plans (excluding Quebec) [1]. That study concluded that all three agencies “face common issues with respect to the quality and strength of experimental evidence in support of a clinically meaningful effect”. Chairs of the CDR’s expert advisory panel have noted that clinical uncertainty, and surrogate outcomes, remain one of their greatest challenges [6]

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