Surrogate marker

Surrogate Marker

A surrogate marker or surrogate endpoint is a measure used in clinical trials that is intended to substitute for a direct and clinically meaningful endpoint. Surrogate markers are used when the primary endpoint is undesired (e.g., death), or when the number of events is very small, thus making it impractical to conduct a clinical trial to gather a statistically significant number of endpoints. The use of surrogate markers has the potential to considerably reduce the time required to bring a new treatment to market.

Definition[edit | edit source]

The Food and Drug Administration (FDA) defines a surrogate endpoint as a "laboratory measurement or physical sign that is used in therapeutic trials as a substitute for a clinically meaningful endpoint that is a direct measure of how a patient feels, functions, or survives and is expected to predict the effect of the therapy".

Types of Surrogate Markers[edit | edit source]

Surrogate markers can be classified into three types: biomarkers, intermediate clinical endpoints, and substitute endpoints. Biomarkers are biological parameters that can be objectively measured and evaluated, and are indicators of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Intermediate clinical endpoints are clinical events that reflect improvement or progression of disease. Substitute endpoints are expected to predict clinical benefit (or harm, or lack of benefit or harm) based on epidemiologic, therapeutic, pathophysiologic, or other scientific evidence.

Use in Clinical Trials[edit | edit source]

Surrogate markers are often used in clinical trials to reduce the time required to see the effects of a treatment. For example, in trials of antiretroviral therapy for HIV, the primary endpoint of interest is usually the time to development of AIDS or death. However, because these events take a long time to occur, surrogate markers like CD4 cell count and viral load are used instead.

Controversies and Criticisms[edit | edit source]

The use of surrogate markers in clinical trials is not without controversy. Critics argue that surrogate markers may not accurately reflect the clinical outcomes they are supposed to predict. For example, a drug might lower a patient's cholesterol (a surrogate marker), but not actually reduce the risk of heart disease (the clinical outcome). Despite these criticisms, surrogate markers continue to be used in clinical trials due to their potential to speed up the drug development process.