Background: The US Food and Drug Administration defines a surrogate as ‘a laboratory measurement or physical sign that is used in therapeutic trials as a substitute for a clinically meaningful end point that is a direct measure of how a patient feels, functions, or survives. Surrogate markers are expected to predict the effect of therapy’. Examples of surrogate markers are LDL cholesterol, glycated hemoglobin, and blood pressure. Despite their frequent use in healthcare intervention research, surrogate markers are not always useful as efficacy measures and can be misleading. Surrogate marker evidence appears in many Cochrane Reviews but is not always critically assessed.

Objectives: To provide an understanding of the logic and systematic framework that is required to critically assess surrogate markers when used as measures of efficacy in healthcare intervention reviews.

Methods: This presentation will introduce the concept of falsifiability (i.e. looking for ‘black swans’) and the logic required to assess the relationship between surrogate markers and the risk of morbidity and/or mortality as it relates to healthcare intervention efficacy. Participants will be given practical exercises to help answer the following questions when faced with surrogate marker evidence in the process of conducting a Cochrane Review: does a ‘worsening’ surrogate marker (e.g increasing LDL cholesterol) indicate an increased risk of morbidity and mortality?; is it universally true that ‘improving’ the surrogate marker (e.g. lowering LDL) with a intervention leads to an improvement in a clinical condition or a decreased risk of M/M?; can we use surrogate markers to monitor the effect of interventions (i.e. if a surrogate marker is ‘improving’, does that mean the medication is working)? Participants will then be given guidance on including critical assessments of all surrogate marker evidence in their Cochrane Reviews. For readers of reviews, guidance will be given on interpreting this type of assessment.