Endpoints for geroscience clinical trials: health outcomes, biomarkers, and biologic age

Abstract

Treatments that target fundamental processes of aging are expected to delay several aging-related conditions simultaneously. Testing the efficacy of these treatments for potential anti-aging benefits will require clinical trials with endpoints that reflect the potential benefits of slowing processes of aging. There are several potential types of endpoints to capture the benefits of slowing a process of aging, and a consensus is needed to standardize and compare the results of these trials and to guide the analysis of observational data to support trial planning. Using biomarkers instead of clinical outcomes would substantially reduce the size and the duration of clinical trials. This requires validation of surrogate markers showing that treatment induced change in the marker reliably predicts the magnitude of change in the clinical outcome. The surrogate marker must also reflect the biological mechanism for the effect of treatment on the clinical outcome. “Biological age” is a superficially attractive marker for such trials. However, it is essential to establish that treatment induced change in biological age reliably predict the magnitude of benefits in the clinical outcome. Reaching consensus on clinical outcomes for geroscience trials and then validating potential surrogate biomarkers requires time, effort, and coordination that will be worthwhile to develop surrogate outcomes that can be trusted to efficiently test the value of many anti-aging treatments under development.