A new review article in JAMA on the use of surrogate biomarkers (eg by FDA in clinical trials) takes a grim position. Wallach et al. take all the surrogate biomarkers for non-cancer conditions, as listed by FDA, and perform a systematic literature review. Their main index is whether there are systematic meta-analyses of each marker, and if so, how many.
They note they exclude cancer surrogate markers (like progression-free survival) while dropping a quick comment they view that data as poor (as "weakly associated" with clinical outcomes.)
- Expert Tip: Although not identical, there are many conceptual parallels between saying (a biomarker is weakly associated with an outcome, its use as a surrogate decision tool is weak) and saying (a biomarker is not proving to have clinical utility for health outcomes, is not payable.)
Their table 1 lists all 37 FDA surrogate biomarkers (see also their 241-page online supplement.) 17 are viewed by FDA as s strong enough for traditional approval (when not so honored, surrogates would generally be for accelerated approval.)
Their bottom line - "Most surrogate markers used as primary end points in clinical trials to support FDA approval of drugs treating nononcologic chronic diseases lacked high-strength evidence of associations with clinical outcomes from published meta-analyses."
(Most surrogate biomarkers are lab tests, though some are physiological or functional, like forced expiratory air volume or progression-free survival or blood pressure.)
