Establishing and Using Threshold of Surrogate Endpoint in Relation to Clinical Endpoint

Clinical trials are an essential aspect of the drug development process. Clinical endpoints and surrogate endpoints are two terms used in clinical trials to measure the effectiveness of a treatment. While clinical endpoints typically require higher costs and longer durations of observation to show direct clinical benefits, surrogate endpoints have been introduced as a cheaper and faster method that may be used to predict clinical effects. When there is a linear relationship between the surrogate and the clinical endpoint, the surrogate may still need to rule out a threshold that corresponds to no clinical benefit. The determination of such a threshold uses the knowledge of numerous parameters in the bivariate statistical distribution of the clinical response and the surrogate. In our work, we present a concept of “working” threshold to incorporate statistical uncertainties in determination of such a threshold.