Ubiquitous Pragmatic Trial Impact Analysis: How to Prevent a Year of Death and Suffering for 84 Cents

Website: https://manual.warondisease.org/knowledge/appendix/dfda-impact-paper.html Abstract: Of 9.5 million combinations plausible drug-disease pairings, only 0.342% (95% CI: 0%-1%) have been clinically tested. At the current discovery rate of 15 diseases/year (95% CI: 8 diseases/year-30 diseases/year), clearing this backlog would take ~443 years (95% CI: 324 years-712 years). A decentralized FDA integrating pragmatic clinical trials into standard healthcare at \$929 (95% CI: \$97-\$3K)/patient (vs. \$41K (95% CI: \$20K-\$120K) traditional) increases trial capacity 12.3x (95% CI: 4.2x-61.4x), reducing backlog clearance to 36 years (95% CI: 11.6 years-77.1 years). Combined with eliminating the 8.2 years (95% CI: 4.85 years-11.5 years) post-safety efficacy delay through opt-in trial participation after Phase I, treatments arrive 212 years (95% CI: 135 years-355 years) earlier on average. This timeline shift saves 10.7 billion deaths (95% CI: 7.4 billion deaths-16.2 billion deaths), averts 565 billion DALYs (95% CI: 361 billion DALYs-877 billion DALYs), and eliminates 1.93 quadrillion hours (95% CI: 1.36 quadrillion hours-2.62 quadrillion hours) of suffering (YLD portion of 565 billion DALYs (95% CI: 361 billion DALYs-877 billion DALYs) converted to hours) at \$0.842 (95% CI: \$0.242-\$1.75)/DALY, competitive with bed nets (\$89 (95% CI: \$78-\$100)/DALY) at vastly greater scale. Using standard health economic valuation (\$150K (95% CI: \$100K-\$199K)/DALY, the US cost-effectiveness threshold; conservative relative to EPA/DOT Value of Statistical Life estimates), full impact yields \$84.8 quadrillion (95% CI: \$62.4 quadrillion-\$97.3 quadrillion) in cumulative value (565 billion DALYs (95% CI: 361 billion DALYs-877 billion DALYs) cumulative DALYs over the 212 years (95% CI: 135 years-355 years) timeline shift, not annual; 178k (95% CI: 110k-421k):1 ROI). Summary: Only 15 diseases/year get their first treatment each year. With 6.65 thousand diseases lacking effective treatments, the backlog would take 443 years to clear. Integrating pragmatic trials into standard healthcare increases trial capacity 12.3x, cutting that timeline from 443 years to 36 years. The average untreated disease gets a treatment 212 years earlier, saving 10.7 billion deaths at \$0.842 per year of healthy life saved.