The Innovative Evaluation Schema of Validating Putative Surrogate Endpoints

• Activity Number: 113
• Type: Topic Contributed
• Date/Time: Monday, August 2, 2010 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Marissa Nichole Lassere*+
• Companies: St George Hospital and University of New South Wales
• Keywords: surrogates

Abstract

There are advantages to using surrogate endpoints, but concerns about clinical and statistical validity and systematic methods of evaluation impede their efficient application and interpretation. A criterion-based, multi-dimensional, hierarchical level of evidence schema is proposed. The schema incorporates the following independent domains: Study Design, Target Outcome, Statistical Evaluation and Generalizability. The domains have items ranked from zero to three, the higher the rank the better the evidence of surrogacy. The total rank across domains determines the level of evidence. Statistical Evaluation requires calculation of coefficient of determination at the trial and patient level as well as the surrogate threshold effect proportion (STEP) ranked by different cut-off values. Surrogacy ranks can be compared to guide drug development, registration and reimbursement decisions.