Increasing the power of surrogate endpoint biomarkers: the aggregation of predictive factors.

A variable that predicts an outcome with sufficient accuracy is called a predictive factor. Predictive factors can be divided into three types based on the outcomes to be predicted and on the accuracy with which they can be predicted. These three types include risk factors, where the main outcome of interest is incidence and the predictive accuracy is less than 100%; diagnostic factors, where the main outcome of interest is also incidence but the predictive accuracy is almost 100%; and prognostic factors, where the main outcome of interest is death and the predictive accuracy is variable. Surrogate outcomes are predictive factors that are used for a purpose beyond the prediction of an outcome--surrogate outcomes are predictive factors that are substituted for the true outcome in order to determine the effectiveness of an intervention. Surrogate outcomes used in clinical trials are called intermediate endpoints and surrogate endpoints. Predictive factors used as surrogate outcomes have a poor accuracy rate in predicting the true outcome; aggregating risk factors increases predictive accuracy. Artificial neural networks effectively combine predictive factors. Aggregating predictive factors increases the degree of linkage of the surrogate outcome to the true outcome. The resulting increase in predictive accuracy allows enrollment of people most likely to benefit from intervention. This increases the trial's efficiency, reducing the number of people required to assess a chemopreventive agent.