The Human Variable 

Clinical trials for ME/CFS have consistently failed not because therapies were inherently ineffective, but because the system was never built for conditions like ME/CFS and related IACCs. FDA gold-standard trial design assumes predictable progression, uniform subtypes, and tolerance for interventions — none of which apply to ME/CFS The CYNAERA Thesis asserts that repurposed drugs can work for ME/CFS if trials account for post-exertional malaise (PEM),(MCAS), and POTS

The Va-IRI™ (Vaccination Immune Readiness Index) provides a structured 0–100 readiness score derived from common labs, symptom baselines, and patient function. Built on the STAIR Stable Method™ (Stabilization, Tolerance, And Immune Readiness), Va-IRI™ adapts low-and-slow principles pioneered by patients and refined through collaboration with leading researchers.

Using CYNAERA’s recalibrated US-CCUC™ prevalence models, which place the U.S. burden between 8.7 million (conservative) and 21.5 million (realistic), the annual economic impact rises to $243–817 billion.

Using CYNAERA’s US-CCUC™ model, we present a corrected demographic landscape grounded in published science, epidemiological data, and terrain-calibrated prevalence modeling. For the first time, undocumented immigrant populations and ancestral dietary biology are incorporated as visible drivers of disease prevalence. Our analysis demonstrates that half of Americans with ME/CFS are non-white, and that prevalence in certain groups is likely higher when adjusted for baseline into

Using CYNAERA’s US-CCUC™ (U.S. Chronic Condition Undercount Correction – Pediatric Edition) methodology, we estimate 1.5–3 million U.S. children and adolescents and 10–20 million globally meet ME/CFS criteria in 2025.

Using CYNAERA’s recalibrated tiered prevalence model, weighted for environmental exposure, access to paid sick leave, and diagnostic inequity, we estimate that around 14.4 million Americans currently meet the diagnostic criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).