Biography as the Missing Variable in Drug Development: A Case for Bio-Biographical Mechanistic Profiling.

Most clinical trial failures reflect unmeasured biological heterogeneity. Biography - chronic stress, adversity, trauma, and social isolation-is a neglected source of that heterogeneity, operating through the same molecular pathways drugs engage. Independent studies in non-small cell lung cancer and melanoma have demonstrated that pretreatment biographical measurement predicts immune checkpoint inhibitor response through measurable immunological intermediaries, providing existence proof that this axis of heterogeneity is both detectable and pharmacologically consequential. Bio-biographical mechanistic profiling (BBMP) is the prospective, mechanism-matched measurement of biographical factors alongside standard biomarkers, designed to identify patients in whom biography has modified the pathway a drug is intended to engage. Matching treatment to pathway is not the same as matching treatment to a person in whom that pathway has been constituted by biography. BBMP is designed to close that gap.