Surrogate Endpoints for the accelerated approval and Statistical Considerations

by | May 6, 2019 |

A surrogate endpoint or surrogate marker is any physical sign or laboratory measurement that can be used as a substitute (or surrogate) for a target outcome (or primary endpoint) of the clinical study. When the measurement of the target outcome is time-consuming and requires a larger number of patients, then, surrogate endpoints are decided, which are of higher precision and can be measured earlier with lesser patients and cost. As per the Food and Drug Administration (FDA), numerous dugs may get quicker approval for the treatment of severe or life-threatening diseases, such as cancer, through the Accelerated Approval regulations by adopting the surrogate endpoints in the clinical studies.

Sometimes, the surrogate endpoints may be responsible for disease progression or make life-threating issues in the patient’s life. Therefore, statistical rigor is required to check the qualification of the surrogate endpoint or marker in the clinical study. For evaluating surrogate endpoints as a potential substitute for clinical endpoints, it is important to emphasize on the relation of the surrogate endpoint to the mechanism of action of the drug for which statistical analysis helps. Nowadays, an analysis of covariance (ANCOVA) model is considered as an effective approach for assessing the effectiveness of the drug with respect to the target endpoint. For the development of valid surrogate endpoints, a clinical study is required with a given treatment analyzing both the target endpoint and surrogate endpoint. If the result came out to be similar, then the surrogate endpoints can be adopted for that particular disease in the future.

This way, surrogate endpoints can replace other endpoints and are useful as they can be measured quickly, more conveniently or more frequently than true endpoints to help provide regulatory approval. However, surrogate endpoints should be avoided if they are invalid.

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