Scientific Publications by FDA Staff

Ther Innov Regul Sci 2016 Mar;50(2):241-52

Validation of prognostic marker tests: statistical lessons learned from regulatory experience.

Tang R, Pennello G

Despite concerted efforts to discover and validate prognostic biomarkers or signatures, few medical tests indicated for prognostic uses have been widely accepted by the clinical community. Even fewer, perhaps, are covered by public or private health plans. We were able to identify 6 prognostic marker tests that have been approved or cleared by the US Food and Drug Administration. The pivotal clinical studies for these prognostic marker tests exhibited a wide variety of designs and statistical analyses. From these experiences, we develop statistical points to consider for design, conduct, and analysis of successful clinical validation studies of prognostic tests. In particular, we review broad themes regarding prospective and retrospective study designs, sample size, clinical performance evaluation, and handling of missing data. Our review emphasizes the distinction between a prognostic biomarker and the medical test used to measure it. For this purpose, a section on test measurement validation is also provided.