A Translational Research-Program for Compound Race Pathology: Five Framework-Distinct Trial-Design Templates

Abstract

A Hypothesis & Theory research programme proposing five clinical trial-design templates for compound, multi-mechanism disease. It draws on established adaptive-platform, sequential multiple-assignment (SMART), N-of-1, and biomarker-enrichment methodology, and its distinct proposals — consolidation-window scheduling with sleep protection, within-patient combination-effect testing against independent-action benchmarks, and a reversibility-based (A1/A2/A3) stratification for immune-reset durability (Sullivan et al. 2018) — are offered as a curated programme of tests, not as claimed results. v3 (August 2026). This version corrects the description of the CASTLE basket trial in the abstract region: a reversibility gradient across the trial's arms that had been described as an observed 24-week outcome is restated as a predicted future gradient, with all arms drug-free at 24 weeks, aligning the abstract with the body's treatment of the same trial — the reversibility gradient is read from substrate types (cellular versus fibrotic), not from the uniformly-positive 24-week outcomes. Editorial pass. Earlier versions remain in the version history.