Surrogate outcomes: experiences at the Common Drug Review

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.

Association Between the Use of Surrogate Measures in Pivotal Trials and Health Technology Assessment Decisions: A Retrospective Analysis of NICE and CADTH Reviews of Cancer Drugs

“…Using surrogate measures in cancer trials has several benefits, as they allow for shorter study durations, smaller sample sizes, 2 lower costs, and earlier approval of new drugs for cancer patients. 3,4 In recent years, PFS and response rates have become increasingly popular surrogate measures used in cancer trials. 5 Nevertheless, evidence shows that such surrogate measures may be an unpredictable marker of OS 6 and QoL benefit.…”

“…8 Licensing agencies such as the European Medicines Agency (EMA) focus on a drug's benefit-risk profile for granting marketing authorizations. 1,4 Nevertheless, health technology assessment (HTA) bodies, such as the National Institute of Health and Care Excellence (NICE) in England and the Canadian Agency for Drugs and Technologies in Health (CADTH) in Canada, are concerned with long-term comparative clinical effectiveness and costeffectiveness in addition to efficacy and safety. HTA decision making is a multidisciplinary process that includes many factors that may differ across individual agencies.…”

Economic Evaluation of an Alternative Drug to Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment of Malaria in Pregnancy

“…The choice of the outcomes used in this economic analysis was based on their public health impact as well as the statistically significant difference found between intervention groups. Intermediate health outcomes are generally used in economic evaluations when final health ones have not been measured [ 58 ]. However, final health outcomes are preferred when available from the study [ 25 , 59 ].…”

21st Century Cures Act and similar policy efforts: at what cost?:

“…1 Moreover, the UK, Canada, Germany, and many other countries require higher standards for health plan coverage than for regulatory approval. 2 Since Medicare and US insurance companies usually pay for FDA approved indications, 21st Century Cures is likely to have more effect on prescriptions in the US than in other countries.…”