151 – Enrichment Clinical Trials: Novel Designs, Statistical Inferences, and Case Studies
Assessment of Utility of Total Kidney Volume for Trial Enrichment
John Lawrence
US Food and Drug Administration
A consortium recently submitted an application to qualify Total Kidney Volume (TKV) as a biomarker for enriching trials of patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). TKV, in combination with patient age and baseline estimated glomerular filtration rate (eGFR), was qualified as a prognostic enrichment biomarker for ADPKD subjects at high risk for a progressive decline in renal function, defined as a confirmed 30% decline in eGFR. Risk scores can be derived from datasets to select patients to enrich future trials. The utility of this approach is discussed. We used a model from the historical datasets to define a risk score and applied it to a hypothetical trial. In the hypothetical trial, we simulated data according to a model that was fit to an independent dataset. We found the risk score may not select the higher risk patients very well. The R package SurvDisc can be used to try out different assumptions and enrichment criteria. This will be illustrated in the presentation.