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Source Quotes and References

Keywords

war-on-disease, 1-percent-treaty, medical-research, public-health, peace-dividend, decentralized-trials, dfda, dih, victory-bonds, health-economics, cost-benefit-analysis, clinical-trials, drug-development, regulatory-reform, military-spending, peace-economics, decentralized-governance, wishocracy, blockchain-governance, impact-investing

1.
School, H. K. 3.5% participation tipping point. Harvard Kennedy School https://www.hks.harvard.edu/centers/carr/publications/35-rule-how-small-minority-can-change-world (2020)
The research found that nonviolent campaigns were twice as likely to succeed as violent ones, and once 3.5% of the population were involved, they were always successful. Chenoweth and Maria Stephan studied the success rates of civil resistance efforts from 1900 to 2006, finding that nonviolent movements attracted, on average, four times as many participants as violent movements and were more likely to succeed. Key finding: Every campaign that mobilized at least 3.5% of the population in sustained protest was successful (in their 1900-2006 dataset) Note: The 3.5% figure is a descriptive statistic from historical analysis, not a guaranteed threshold. One exception (Bahrain 2011-2014 with 6%+ participation) has been identified. The rule applies to regime change, not policy change in democracies. Additional sources: https://www.hks.harvard.edu/centers/carr/publications/35-rule-how-small-minority-can-change-world | https://www.hks.harvard.edu/sites/default/files/2024-05/Erica%20Chenoweth_2020-005.pdf | https://www.bbc.com/future/article/20190513-it-only-takes-35-of-people-to-change-the-world | https://en.wikipedia.org/wiki/3.5%25_rule
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2.
GAO. 95% of diseases have 0 FDA-approved treatments. GAO https://www.gao.gov/products/gao-25-106774 (2025)
95% of diseases have no treatment Additional sources: https://www.gao.gov/products/gao-25-106774 | https://globalgenes.org/rare-disease-facts/
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3.
ACLED. Active combat deaths annually. ACLED: Global Conflict Surged 2024 https://acleddata.com/2024/12/12/data-shows-global-conflict-surged-in-2024-the-washington-post/ (2024)
2024: 233,597 deaths (30% increase from 179,099 in 2023) Deadliest conflicts: Ukraine (67,000), Palestine (35,000) Nearly 200,000 acts of violence (25% higher than 2023, double from 5 years ago) One in six people globally live in conflict-affected areas Additional sources: https://acleddata.com/2024/12/12/data-shows-global-conflict-surged-in-2024-the-washington-post/ | https://acleddata.com/media-citation/data-shows-global-conflict-surged-2024-washington-post | https://acleddata.com/conflict-index/index-january-2024/
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4.
PMC, S. et al. |. FAERS adverse event underreporting rate. PubMed: Empirical estimation of under-reporting in FAERS https://pubmed.ncbi.nlm.nih.gov/28447485/ (2017)
Empirical estimation: Average reporting rate approximately 6%, meaning  94% of adverse events are underreported Variability: 0.01% to 44% for statin events; 0.002% to >100% for biological drugs; 20% to >100% for narrow therapeutic index (NTI) drugs Selective reporting: Serious, unusual events more likely reported than mild or expected ones Newly marketed drugs: Higher reporting rates due to heightened awareness Older drugs: Events often under-reported Note: FAERS voluntary reporting system captures only "tip of the iceberg" of drug safety problems. Under-reporting introduces inherent biases and limitations in pharmacovigilance data Additional sources: https://pubmed.ncbi.nlm.nih.gov/28447485/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12393772/
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5.
NIH. Antidepressant clinical trial exclusion rates. Zimmerman et al. https://pubmed.ncbi.nlm.nih.gov/26276679/ (2015)
Mean exclusion rate: 86.1% across 158 antidepressant efficacy trials (range: 44.4% to 99.8%) More than 82% of real-world depression patients would be ineligible for antidepressant registration trials Exclusion rates increased over time: 91.4% (2010-2014) vs. 83.8% (1995-2009) Most common exclusions: comorbid psychiatric disorders, age restrictions, insufficient depression severity, medical conditions Emergency psychiatry patients: only 3.3% eligible (96.7% excluded) when applying 9 common exclusion criteria Only a minority of depressed patients seen in clinical practice are likely to be eligible for most AETs Note: Generalizability of antidepressant trials has decreased over time, with increasingly stringent exclusion criteria eliminating patients who would actually use the drugs in clinical practice Additional sources: https://pubmed.ncbi.nlm.nih.gov/26276679/ | https://pubmed.ncbi.nlm.nih.gov/26164052/ | https://www.wolterskluwer.com/en/news/antidepressant-trials-exclude-most-real-world-patients-with-depression
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6.
(BIO), B. I. O. BIO clinical development success rates 2011-2020. Biotechnology Innovation Organization (BIO) https://go.bio.org/rs/490-EHZ-999/images/ClinicalDevelopmentSuccessRates2011_2020.pdf (2021)
Phase I duration: 2.3 years average Total time to market (Phase I-III + approval): 10.5 years average Phase transition success rates: Phase I→II: 63.2%, Phase II→III: 30.7%, Phase III→Approval: 58.1% Overall probability of approval from Phase I: 12% Note: Largest publicly available study of clinical trial success rates. Efficacy lag = 10.5 - 2.3 = 8.2 years post-safety verification. Additional sources: https://go.bio.org/rs/490-EHZ-999/images/ClinicalDevelopmentSuccessRates2011_2020.pdf
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7.
Bloom, C. I. J., Nicholas & Webb, M. Research productivity declining over time. Bloom https://www.aeaweb.org/articles?id=10.1257/aer.20180338 (2020)
Research productivity is falling sharply everywhere we look. Averaging across industries, research productivity declines at a rate that averages about 5% per year. For example, the number of researchers required to achieve a constant level of Moore’s Law has risen by a factor of 18 since 1971. Note: This finding reflects innovation productivity in traditional research models; dFDA targets trial execution efficiency (cost per patient), not fundamental idea generation Additional sources: https://www.aeaweb.org/articles?id=10.1257/aer.20180338
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8.
Institute, C. Chance of dying from terrorism statistic. Cato Institute: Terrorism and Immigration Risk Analysis https://www.cato.org/policy-analysis/terrorism-immigration-risk-analysis
Chance of American dying in foreign-born terrorist attack: 1 in 3.6 million per year (1975-2015) Including 9/11 deaths; annual murder rate is 253x higher than terrorism death rate More likely to die from lightning strike than foreign terrorism Note: Comprehensive 41-year study shows terrorism risk is extremely low compared to everyday dangers Additional sources: https://www.cato.org/policy-analysis/terrorism-immigration-risk-analysis | https://www.nbcnews.com/news/us-news/you-re-more-likely-die-choking-be-killed-foreign-terrorists-n715141
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9.
Reymond, J. L. Total drug-like chemical space (10^23 - 10^60). Reymond https://pubs.acs.org/doi/10.1021/ar500432k (2015)
Estimated 10^23 to 10^60 drug-like molecules exist in chemical space, dwarfing the number of compounds ever synthesized. Additional sources: https://pubs.acs.org/doi/10.1021/ar500432k
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10.
MMWR, C. Childhood vaccination economic benefits. CDC MMWR https://www.cdc.gov/mmwr/volumes/73/wr/mm7331a2.htm (1994)
US programs (1994-2023): $540B direct savings, $2.7T societal savings ( $18B/year direct,  $90B/year societal) Global (2001-2020): $820B value for 10 diseases in 73 countries ( $41B/year) ROI: $11 return per $1 invested Measles vaccination alone saved 93.7M lives (61% of 154M total) over 50 years (1974-2024) Additional sources: https://www.cdc.gov/mmwr/volumes/73/wr/mm7331a2.htm | https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24
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CDC. Childhood vaccination (US) ROI. CDC https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6316a4.htm (2017).
12.
News, U. Clean water & sanitation (LMICs) ROI. UN News https://news.un.org/en/story/2014/11/484032 (2014).
13.
estimates, I. Clinical trial abandonment.
Average:  10% abandoned before completion
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14.
Arena, C. T. Clinical trial enrollment timelines. Clinical Trials Arena https://www.clinicaltrialsarena.com/marketdata/featureclinical-trial-patient-recruitment/.
15.
CAN, A. Clinical trial patient participation rate. ACS CAN: Barriers to Clinical Trial Enrollment https://www.fightcancer.org/policy-resources/barriers-patient-enrollment-therapeutic-clinical-trials-cancer
Only 3-5% of adult cancer patients in US receive treatment within clinical trials About 5% of American adults have ever participated in any clinical trial Oncology: 2-3% of all oncology patients participate Contrast: 50-60% enrollment for pediatric cancer trials (<15 years old) Note:  20% of cancer trials fail due to insufficient enrollment; 11% of research sites enroll zero patients Additional sources: https://www.fightcancer.org/policy-resources/barriers-patient-enrollment-therapeutic-clinical-trials-cancer | https://hints.cancer.gov/docs/Briefs/HINTS_Brief_48.pdf
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16.
PMC. Only  12% of human interactome targeted. PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC10749231/ (2023)
Mapping 350,000+ clinical trials showed that only  12% of the human interactome has ever been targeted by drugs. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC10749231/
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17.
via, D. analysis. ClinicalTrials.gov cumulative enrollment data (2025). Direct analysis via ClinicalTrials.gov API v2 https://clinicaltrials.gov/data-api/api
Analysis of 100,000 active/recruiting/completed trials on ClinicalTrials.gov (November 2025) shows cumulative enrollment of 12.2 million participants: Phase 1 (722k), Phase 2 (2.2M), Phase 3 (6.5M), Phase 4 (2.7M). Median participants per trial: Phase 1 (33), Phase 2 (60), Phase 3 (237), Phase 4 (90). Additional sources: https://clinicaltrials.gov/data-api/api
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18.
GiveWell. Cost per DALY for deworming programs. https://www.givewell.org/international/technical/programs/deworming/cost-effectiveness
Schistosomiasis treatment: $28.19-$70.48 per DALY (using arithmetic means with varying disability weights) Soil-transmitted helminths (STH) treatment: $82.54 per DALY (midpoint estimate) Note: GiveWell explicitly states this 2011 analysis is "out of date" and their current methodology focuses on long-term income effects rather than short-term health DALYs Additional sources: https://www.givewell.org/international/technical/programs/deworming/cost-effectiveness
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19.
IHME Global Burden of Disease (2.55B DALYs), C. from & GDP per capita valuation, global. $109 trillion annual global disease burden.
The global economic burden of disease, including direct healthcare costs (8.2trillion)andlostproductivity(100.9 trillion from 2.55 billion DALYs × 39, 570perDALY), totalsapproximately109.1 trillion annually.
20.
ScienceDaily. Global prevalence of chronic disease. ScienceDaily: GBD 2015 Study https://www.sciencedaily.com/releases/2015/06/150608081753.htm (2015)
2.3 billion individuals had more than five ailments (2013) Chronic conditions caused 74% of all deaths worldwide (2019), up from 67% (2010) Approximately 1 in 3 adults suffer from multiple chronic conditions (MCCs) Risk factor exposures: 2B exposed to biomass fuel, 1B to air pollution, 1B smokers Projected economic cost: $47 trillion by 2030 Note: 2.3B with 5+ ailments is more accurate than "2B with chronic disease." One-third of all adults globally have multiple chronic conditions Additional sources: https://www.sciencedaily.com/releases/2015/06/150608081753.htm | https://pmc.ncbi.nlm.nih.gov/articles/PMC10830426/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC6214883/
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21.
Orphanet Journal of Rare Diseases (2024), C. from. Diseases getting first effective treatment each year. Calculated from Orphanet Journal of Rare Diseases (2024) https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03398-1 (2024)
Under the current system, approximately 10-15 diseases per year receive their FIRST effective treatment. Calculation: 5% of 7,000 rare diseases ( 350) have FDA-approved treatment, accumulated over 40 years of the Orphan Drug Act =  9 rare diseases/year. Adding  5-10 non-rare diseases that get first treatments yields  10-20 total. FDA approves  50 drugs/year, but many are for diseases that already have treatments (me-too drugs, second-line therapies). Only  15 represent truly FIRST treatments for previously untreatable conditions.
22.
SIPRI. 36:1 disparity ratio of spending on weapons over cures. SIPRI: Military Spending https://www.sipri.org/commentary/blog/2016/opportunity-cost-world-military-spending (2016)
Global military spending: $2.7 trillion (2024, SIPRI) Global government medical research:  $68 billion (2024) Actual ratio: 39.7:1 in favor of weapons over medical research Military R&D alone:  $85B (2004 data, 10% of global R&D) Military spending increases crowd out health: 1% ↑ military = 0.62% ↓ health spending Note: Ratio actually worse than 36:1. Each 1% increase in military spending reduces health spending by 0.62%, with effect more intense in poorer countries (0.962% reduction) Additional sources: https://www.sipri.org/commentary/blog/2016/opportunity-cost-world-military-spending | https://pmc.ncbi.nlm.nih.gov/articles/PMC9174441/ | https://www.congress.gov/crs-product/R45403
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23.
DOT. DOT value of statistical life ($13.6M). DOT: VSL Guidance 2024 https://www.transportation.gov/office-policy/transportation-policy/revised-departmental-guidance-on-valuation-of-a-statistical-life-in-economic-analysis (2024)
Current VSL (2024): $13.7 million (updated from $13.6M) Used in cost-benefit analyses for transportation regulations and infrastructure Methodology updated in 2013 guidance, adjusted annually for inflation and real income VSL represents aggregate willingness to pay for safety improvements that reduce fatalities by one Note: DOT has published VSL guidance periodically since 1993. Current $13.7M reflects 2024 inflation/income adjustments Additional sources: https://www.transportation.gov/office-policy/transportation-policy/revised-departmental-guidance-on-valuation-of-a-statistical-life-in-economic-analysis | https://www.transportation.gov/regulations/economic-values-used-in-analysis
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24.
CSDD, T. Cost of drug development.
Various estimates suggest $1.0 - $2.5 billion to bring a new drug from discovery through FDA approval, spread across  10 years. Tufts Center for the Study of Drug Development often cited for $1.0 - $2.6 billion/drug. Industry reports (IQVIA, Deloitte) also highlight $2+ billion figures.
25.
Medicine, N. Drug repurposing rate ( 30%). Nature Medicine https://www.nature.com/articles/s41591-024-03233-x (2024)
Approximately 30% of drugs gain at least one new indication after initial approval. Additional sources: https://www.nature.com/articles/s41591-024-03233-x
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26.
Ramsberg J, P. R. Opportunities and barriers for pragmatic embedded trials: Triumphs and tribulations. Harvard Medical School/Harvard Pilgrim Health Care Institute https://pmc.ncbi.nlm.nih.gov/articles/PMC6508852/ (2018)
**Meta-analysis of 108 embedded pragmatic clinical trials** (2006-2016). The median cost per patient was **$97** (mean $478) across all trials reviewed. 25% of studies cost less than $19 per patient. US studies had higher median costs ($187 vs $27 non-US). Registry-based trials were less expensive than EHR-based trials. Traditional RCT comparison: **$16,600/patient** (Berndt & Cockburn 2014). The 108 trials had median enrollment of 5,540 patients with broad eligibility criteria. 81% used cluster randomization. Trials spanned 15 countries, infectious diseases (25%), cardiovascular (18%), diabetes (12%). Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC6508852/
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27.
War, B. W. C. of. Environmental cost of war ($100B annually). Brown Watson Costs of War: Environmental Cost https://watson.brown.edu/costsofwar/costs/social/environment
War on Terror emissions: 1.2B metric tons GHG (equivalent to 257M cars/year) Military: 5.5% of global GHG emissions (2X aviation + shipping combined) US DoD: World’s single largest institutional oil consumer, 47th largest emitter if nation Cleanup costs: $500B+ for military contaminated sites Gaza war environmental damage: $56.4B; landmine clearance: $34.6B expected Climate finance gap: Rich nations spend 30X more on military than climate finance Note: Military activities cause massive environmental damage through GHG emissions, toxic contamination, and long-term cleanup costs far exceeding current climate finance commitments Additional sources: https://watson.brown.edu/costsofwar/costs/social/environment | https://earth.org/environmental-costs-of-wars/ | https://transformdefence.org/transformdefence/stats/
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28.
FDA. FDA sentinel initiative. FDA: Sentinel Initiative https://www.fda.gov/safety/fdas-sentinel-initiative
Launched: May 2008 in response to FDAAA 2007; transitioned to full system Feb 2016 Purpose: Active post-market risk identification and analysis (ARIA) for medical products Scale: World’s largest multisite distributed database for medical product safety; 128.7M members Data sources: Insurance claims, electronic health records, patient reports Privacy: Distributed data approach - data remains with owners, patient identifiers removed Structure (2019): 3 coordinating centers - Operations, Innovation, Community Building/Outreach Real-World Evidence: RWE Data Enterprise (RWE-DE) - 25.5M lives (21M commercial + 4.5M academic) 2008-2014: FDA mandated 657 studies under FDAAA authority Note: Major advancement in post-market surveillance. "Limited Transparency and Bureaucratic Constraints" may refer to challenges, but system represents significant FDA capability improvement Additional sources: https://www.fda.gov/safety/fdas-sentinel-initiative | https://pmc.ncbi.nlm.nih.gov/articles/PMC9667154/ | https://en.wikipedia.org/wiki/Sentinel_Initiative
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29.
FDA. FDA trial patient exclusion criteria. FDA: Evaluating Inclusion & Exclusion Criteria https://www.fda.gov/media/134754/download
Most frequent exclusions: Pregnancy, lactation/breastfeeding, renal/hepatic abnormalities, specific infectious diseases Pregnant/lactating women: >90% of trials exclude Older adults:  27% exclude based on age (arbitrary upper limits) Patients with organ dysfunction: Excluded due to adverse impact concerns from comorbidities/concomitant meds Multiple chronic conditions: Often exclusion criterion despite being common in target population Children/adolescents: Excluded due to ethical considerations High-risk patients: Prior malignancy history, active brain metastases, suboptimal hepatic/renal function, HIV+ FDA guidance: Working to broaden eligibility; "exclusions based on age alone rarely appropriate Note: Exclusion criteria often eliminate patients who would actually use the drug, reducing real-world applicability of trial results Additional sources: https://www.fda.gov/media/134754/download | https://www.sciencedirect.com/science/article/abs/pii/S1551714421002512 | https://ascopubs.org/doi/10.1200/EDBK_155880
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30.
GiveWell. GiveWell cost per life saved for top charities (2024). GiveWell: Top Charities https://www.givewell.org/charities/top-charities
General range: $3,000-$5,500 per life saved (GiveWell top charities) Helen Keller International (Vitamin A): $3,500 average (2022-2024); varies $1,000-$8,500 by country Against Malaria Foundation: $5,500 per life saved New Incentives (vaccination incentives): $4,500 per life saved Malaria Consortium (seasonal malaria chemoprevention):  $3,500 per life saved VAS program details:  $2 to provide vitamin A supplements to child for one year Note: Figures accurate for 2024. Helen Keller VAS program has wide country variation ($1K-$8.5K) but $3,500 is accurate average. Among most cost-effective interventions globally Additional sources: https://www.givewell.org/charities/top-charities | https://www.givewell.org/charities/helen-keller-international | https://ourworldindata.org/cost-effectiveness
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31.
Research & Markets. Global clinical trials market 2024. Research and Markets https://www.globenewswire.com/news-release/2024/04/19/2866012/0/en/Global-Clinical-Trials-Market-Research-Report-2024-An-83-16-Billion-Market-by-2030-AI-Machine-Learning-and-Blockchain-will-Transform-the-Clinical-Trials-Landscape.html (2024)
Global clinical trials market valued at approximately $83 billion in 2024, with projections to reach $83-132 billion by 2030. Additional sources: https://www.globenewswire.com/news-release/2024/04/19/2866012/0/en/Global-Clinical-Trials-Market-Research-Report-2024-An-83-16-Billion-Market-by-2030-AI-Machine-Learning-and-Blockchain-will-Transform-the-Clinical-Trials-Landscape.html | https://www.precedenceresearch.com/clinical-trials-market
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32.
budgets:, S. component country. Global government medical research spending ($67.5B, 2023–2024). See component country budgets: NIH Budget #nih-budget-fy2025.
33.
Trials, A. C. Global government spending on interventional clinical trials:  $3-6 billion/year. Applied Clinical Trials https://www.appliedclinicaltrialsonline.com/view/sizing-clinical-research-market
Estimated range based on NIH ( $0.8-5.6B), NIHR ($1.6B total budget), and EU funding ( $1.3B/year). Roughly 5-10% of global market. Additional sources: https://www.appliedclinicaltrialsonline.com/view/sizing-clinical-research-market | https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(20
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35.
C&EN. Annual number of new drugs approved globally:  50. C&EN https://cen.acs.org/pharmaceuticals/50-new-drugs-received-FDA/103/i2 (2025)
50 new drugs approved annually Additional sources: https://cen.acs.org/pharmaceuticals/50-new-drugs-received-FDA/103/i2 | https://www.fda.gov/drugs/development-approval-process-drugs/novel-drug-approvals-fda
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36.
UN. Global population reaches 8 billion. UN: World Population 8 Billion Nov 15 2022 https://www.un.org/en/desa/world-population-reach-8-billion-15-november-2022 (2022)
Milestone: November 15, 2022 (UN World Population Prospects 2022) Day of Eight Billion" designated by UN Added 1 billion people in just 11 years (2011-2022) Growth rate: Slowest since 1950; fell under 1% in 2020 Future: 15 years to reach 9B (2037); projected peak 10.4B in 2080s Projections: 8.5B (2030), 9.7B (2050), 10.4B (2080-2100 plateau) Note: Milestone reached Nov 2022. Population growth slowing; will take longer to add next billion (15 years vs 11 years) Additional sources: https://www.un.org/en/desa/world-population-reach-8-billion-15-november-2022 | https://www.un.org/en/dayof8billion | https://en.wikipedia.org/wiki/Day_of_Eight_Billion
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Report, I. Global trial capacity. IQVIA Report: Clinical Trial Subjects Number Drops Due to Decline in COVID-19 Enrollment https://gmdpacademy.org/news/iqvia-report-clinical-trial-subjects-number-drops-due-to-decline-in-covid-19-enrollment/
1.9M participants annually (2022, post-COVID normalization from 4M peak in 2021) Additional sources: https://gmdpacademy.org/news/iqvia-report-clinical-trial-subjects-number-drops-due-to-decline-in-covid-19-enrollment/
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38.
Talk, A. Grant writing time for top researchers (50%). Acquisition Talk https://acquisitiontalk.com/2021/12/top-researchers-spend-50-of-their-time-writing-grants-how-to-fix-it-and-what-it-means-for-dod/ (2021)
Top researchers can spend up to 50% of their time writing grants. Additional sources: https://acquisitiontalk.com/2021/12/top-researchers-spend-50-of-their-time-writing-grants-how-to-fix-it-and-what-it-means-for-dod/
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39.
Data, O. W. in. Terror attack deaths (8,300 annually). Our World in Data: Terrorism https://ourworldindata.org/terrorism (2024)
2023: 8,352 deaths (22% increase from 2022, highest since 2017) 2023: 3,350 terrorist incidents (22% decrease), but 56% increase in avg deaths per attack Global Terrorism Database (GTD): 200,000+ terrorist attacks recorded (2021 version) Maintained by: National Consortium for Study of Terrorism & Responses to Terrorism (START), U. of Maryland Geographic shift: Epicenter moved from Middle East to Central Sahel (sub-Saharan Africa) - now >50% of all deaths Additional sources: https://ourworldindata.org/terrorism | https://reliefweb.int/report/world/global-terrorism-index-2024 | https://www.start.umd.edu/gtd/ | https://ourworldindata.org/grapher/fatalities-from-terrorism
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40.
PMC. Healthcare investment economic multiplier (1.8). PMC: California Universal Health Care https://pmc.ncbi.nlm.nih.gov/articles/PMC5954824/ (2022)
Healthcare fiscal multiplier: 4.3 (95% CI: 2.5-6.1) during pre-recession period (1995-2007) Overall government spending multiplier: 1.61 (95% CI: 1.37-1.86) Why healthcare has high multipliers: No effect on trade deficits (spending stays domestic); improves productivity & competitiveness; enhances long-run potential output Gender-sensitive fiscal spending (health & care economy) produces substantial positive growth impacts Note: "1.8" appears to be conservative estimate; research shows healthcare multipliers of 4.3 Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC5954824/ | https://cepr.org/voxeu/columns/government-investment-and-fiscal-stimulus | https://ncbi.nlm.nih.gov/pmc/articles/PMC3849102/ | https://set.odi.org/wp-content/uploads/2022/01/Fiscal-multipliers-review.pdf
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41.
ICRC. International campaign to ban landmines (ICBL) - ottawa treaty (1997). ICRC https://www.icrc.org/en/doc/resources/documents/article/other/57jpjn.htm (1997)
ICBL: Founded 1992 by 6 NGOs (Handicap International, Human Rights Watch, Medico International, Mines Advisory Group, Physicians for Human Rights, Vietnam Veterans of America Foundation) Started with ONE staff member: Jody Williams as founding coordinator Grew to 1,000+ organizations in 60 countries by 1997 Ottawa Process: 14 months (October 1996 - December 1997) Convention signed by 122 states on December 3, 1997; entered into force March 1, 1999 Achievement: Nobel Peace Prize 1997 (shared by ICBL and Jody Williams) Government funding context: Canada established $100M CAD Canadian Landmine Fund over 10 years (1997); International donors provided $169M in 1997 for mine action (up from $100M in 1996) Additional sources: https://www.icrc.org/en/doc/resources/documents/article/other/57jpjn.htm | https://en.wikipedia.org/wiki/International_Campaign_to_Ban_Landmines | https://www.nobelprize.org/prizes/peace/1997/summary/ | https://un.org/press/en/1999/19990520.MINES.BRF.html | https://www.the-monitor.org/en-gb/reports/2003/landmine-monitor-2003/mine-action-funding.aspx
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42.
ICER. ICER QALY methodology and standards. ICER https://icer.org/our-approach/methods-process/cost-effectiveness-the-qaly-and-the-evlyg/ (2024)
The quality-adjusted life year (QALY) is the academic standard for measuring how well all different kinds of medical treatments lengthen and/or improve patients’ lives, and therefore the metric has served as a fundamental component of cost-effectiveness analyses in the US and around the world for more than 30 years. ICER’s health benefit price benchmark (HBPB) will continue to be reported using the standard range from $100,000 to $150,000 per QALY and per evLYG. Additional sources: https://icer.org/our-approach/methods-process/cost-effectiveness-the-qaly-and-the-evlyg/ | https://icer.org/wp-content/uploads/2024/02/Reference-Case-4.3.25.pdf
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43.
Health Metrics, I. for & (IHME), E. IHME global burden of disease 2021 (2.88B DALYs, 1.13B YLD). Institute for Health Metrics and Evaluation (IHME) https://vizhub.healthdata.org/gbd-results/ (2024)
In 2021, global DALYs totaled approximately 2.88 billion, comprising 1.75 billion Years of Life Lost (YLL) and 1.13 billion Years Lived with Disability (YLD). This represents a 13% increase from 2019 (2.55B DALYs), largely attributable to COVID-19 deaths and aging populations. YLD accounts for approximately 39% of total DALYs, reflecting the substantial burden of non-fatal chronic conditions. Additional sources: https://vizhub.healthdata.org/gbd-results/ | https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24 | https://www.healthdata.org/research-analysis/about-gbd
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44.
size, D. from global market & ratios, public/private funding. Private industry clinical trial spending.
Private pharmaceutical and biotech industry spends approximately $75-90 billion annually on clinical trials, representing roughly 90% of global clinical trial spending.
45.
Wikipedia. Journal of the american medical association (JAMA) founded in 1883. Wikipedia: JAMA https://en.wikipedia.org/wiki/JAMA
Founded: 1883 by American Medical Association Founding editor: Nathan Smith Davis Superseded: Transactions of the American Medical Association 1960: Obtained current title "JAMA: The Journal of the American Medical Association Evolution: Late 1800s resembled general journalism; 1910s-1920s "turndown era" began rejecting submissions based on quality; routine peer review instituted after WWII Current: Peer-reviewed medical journal published 48 times/year covering all aspects of biomedicine Additional sources: https://en.wikipedia.org/wiki/JAMA | https://jamanetwork.com/journals/jama/fullarticle/291201 | https://onlinebooks.library.upenn.edu/webbin/serial?id=jama
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46.
Statecraft, R. Lobbying ROI calculation ($1,813 per $1). Responsible Statecraft https://responsiblestatecraft.org/2021/09/02/top-military-firms-see-2t-return-on-1b-investment-in-afghan-war/ (2021).
47.
OpenSecrets. Lobbying spend (defense). OpenSecrets https://www.opensecrets.org/federal-lobbying/industries/summary?cycle=2024\&id=D (2024).
48.
Numbers, T. by. Lost human capital due to war ($270B annually). Think by Numbers: War Costs $74 <https://thinkbynumbers.org/military/war/the-economic-case-for-peace-a-comprehensive-financial-analysis/> (2021)
Lost human capital from war: $300B annually (economic impact of losing skilled/productive individuals to conflict) Broader conflict/violence cost: $14T/year globally 1.4M violent deaths/year; conflict holds back economic development, causes instability, widens inequality, erodes human capital 2002: 48.4M DALYs lost from 1.6M violence deaths = $151B economic value (2000 USD) Economic toll includes: commodity prices, inflation, supply chain disruption, declining output, lost human capital Additional sources: <https://thinkbynumbers.org/military/war/the-economic-case-for-peace-a-comprehensive-financial-analysis/> | https://www.weforum.org/stories/2021/02/war-violence-costs-each-human-5-a-day/ | https://pubmed.ncbi.nlm.nih.gov/19115548/
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49.
Mercatus. Military spending economic multiplier (0.6). Mercatus: Defense Spending and Economy https://www.mercatus.org/research/research-papers/defense-spending-and-economy
Ramey (2011):  0.6 short-run multiplier Barro (1981): 0.6 multiplier for WWII spending (war spending crowded out  40¢ private economic activity per federal dollar) Barro & Redlick (2011): 0.4 within current year, 0.6 over two years; increased govt spending reduces private-sector GDP portions General finding: $1 increase in deficit-financed federal military spending = less than $1 increase in GDP Variation by context: Central/Eastern European NATO: 0.6 on impact, 1.5-1.6 in years 2-3, gradual fall to zero Ramey & Zubairy (2018): Cumulative 1% GDP increase in military expenditure raises GDP by  0.7% Additional sources: https://www.mercatus.org/research/research-papers/defense-spending-and-economy | https://cepr.org/voxeu/columns/world-war-ii-america-spending-deficits-multipliers-and-sacrifice | https://www.rand.org/content/dam/rand/pubs/research_reports/RRA700/RRA739-2/RAND_RRA739-2.pdf
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50.
Murphy, K. M. & Topel, R. H. The value of health and longevity. Journal of Political Economy 114, 871–904 (2006).
51.
NIH. NIH centralized decision-making structure. NIH Almanac https://www.nih.gov/about-nih/what-we-do/nih-almanac
NIH structure: 27 Institutes and Centers, each with own research agenda Office of the Director: Sets policy, plans/manages/coordinates all NIH components Location: 9000 Rockville Pike, Bethesda, Maryland Total NIH employees:  20,000 Leadership structure: Director + 27 Institute/Center directors + division chiefs + council members Specific count of "key decision-makers" varies by definition; centralized funding decisions flow through Office of Director and IC leadership Additional sources: https://www.nih.gov/about-nih/what-we-do/nih-almanac | https://www.nih.gov/about-nih/what-we-do/nih-almanac/nih-organization
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52.
PMC. Pragmatic trial cost per patient (median $97). PMC: Costs of Pragmatic Clinical Trials https://pmc.ncbi.nlm.nih.gov/articles/PMC6508852/
The median cost per participant was $97 (IQR $19–$478), based on 2015 dollars. Systematic review of 64 embedded pragmatic clinical trials. 25% of trials cost <$19/patient; 10 trials exceeded $1,000/patient. U.S. studies median $187 vs non-U.S. median $27. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC6508852/
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53.
Fund, N. C. NIH pragmatic trials: Minimal funding despite 30x cost advantage. NIH Common Fund: HCS Research Collaboratory https://commonfund.nih.gov/hcscollaboratory (2025)
The NIH Pragmatic Trials Collaboratory funds trials at **$500K for planning phase, $1M/year for implementation**—a tiny fraction of NIH’s budget. The ADAPTABLE trial cost **$14 million** for **15,076 patients** (= **$929/patient**) versus **$420 million** for a similar traditional RCT (30x cheaper), yet pragmatic trials remain severely underfunded. PCORnet infrastructure enables real-world trials embedded in healthcare systems, but receives minimal support compared to basic research funding. Additional sources: https://commonfund.nih.gov/hcscollaboratory | https://pcornet.org/wp-content/uploads/2025/08/ADAPTABLE_Lay_Summary_21JUL2025.pdf | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604499/
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54.
Patsopoulos, N. A. Pragmatic vs. Explanatory trials. Patsopoulos https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181997/ (2011)
Pragmatic trials evaluate the effectiveness of interventions in real-life routine practice conditions, whereas explanatory trials determine the efficacy of interventions under ideal situations. Pragmatic trials produce results that can be generalized and applied in routine practice settings. Note: Pragmatic trials often find smaller effect sizes than explanatory trials but have higher external validity (generalizability to real-world populations) Additional sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181997/
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55.
Baily, M. N. Pre-1962 drug development costs (baily 1972). Baily (1972) https://samizdathealth.org/wp-content/uploads/2020/12/hlthaff.1.2.6.pdf (1972)
Pre-1962: Average cost per new chemical entity (NCE) was $6.5 million (1980 dollars) Inflation-adjusted to 2024 dollars: $6.5M (1980) ≈ $22.5M (2024), using CPI multiplier of 3.46× Real cost increase (inflation-adjusted): $22.5M (pre-1962) → $2,600M (2024) = 116× increase Note: This represents the most comprehensive academic estimate of pre-1962 drug development costs based on empirical industry data Additional sources: https://samizdathealth.org/wp-content/uploads/2020/12/hlthaff.1.2.6.pdf
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56.
Numbers, T. by. Pre-1962 drug development costs and timeline (think by numbers). Think by Numbers: How Many Lives Does FDA Save? https://thinkbynumbers.org/health/how-many-net-lives-does-the-fda-save/ (1962)
Historical estimates (1970-1985): USD $226M fully capitalized (2011 prices) 1980s drugs:  $65M after-tax R&D (1990 dollars),  $194M compounded to approval (1990 dollars) Modern comparison: $2-3B costs, 7-12 years (dramatic increase from pre-1962) Context: 1962 regulatory clampdown reduced new treatment production by 70%, dramatically increasing development timelines and costs Note: Secondary source; less reliable than Congressional testimony Additional sources: https://thinkbynumbers.org/health/how-many-net-lives-does-the-fda-save/ | https://en.wikipedia.org/wiki/Cost_of_drug_development | https://www.statnews.com/2018/10/01/changing-1962-law-slash-drug-prices/
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57.
Numbers, T. by. Pre-1962 physician-led clinical trials. Think by Numbers: How Many Lives Does FDA Save? https://thinkbynumbers.org/health/how-many-net-lives-does-the-fda-save/ (1966)
Pre-1962: Physicians could report real-world evidence directly 1962 Drug Amendments replaced "premarket notification" with "premarket approval", requiring extensive efficacy testing Impact: New regulatory clampdown reduced new treatment production by 70%; lifespan growth declined from  4 years/decade to  2 years/decade Drug Efficacy Study Implementation (DESI): NAS/NRC evaluated 3,400+ drugs approved 1938-1962 for safety only; reviewed >3,000 products, >16,000 therapeutic claims FDA has had authority to accept real-world evidence since 1962, clarified by 21st Century Cures Act (2016) Note: Specific "144,000 physicians" figure not verified in sources Additional sources: https://thinkbynumbers.org/health/how-many-net-lives-does-the-fda-save/ | https://www.fda.gov/drugs/enforcement-activities-fda/drug-efficacy-study-implementation-desi | http://www.nasonline.org/about-nas/history/archives/collections/des-1966-1969-1.html
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58.
PubMed. Psychological impact of war cost ($100B annually). PubMed: Economic Burden of PTSD https://pubmed.ncbi.nlm.nih.gov/35485933/
PTSD economic burden (2018 U.S.): $232.2B total ($189.5B civilian, $42.7B military) Civilian costs driven by: Direct healthcare ($66B), unemployment ($42.7B) Military costs driven by: Disability ($17.8B), direct healthcare ($10.1B) Exceeds costs of other mental health conditions (anxiety, depression) War-exposed populations: 2-3X higher rates of anxiety, depression, PTSD; women and children most vulnerable Note: Actual burden $232B, significantly higher than "$100B" claimed Additional sources: https://pubmed.ncbi.nlm.nih.gov/35485933/ | https://news.va.gov/103611/study-national-economic-burden-of-ptsd-staggering/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC9957523/
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59.
AllTrials. Publication rate of clinical trial results. AllTrials: Half of Trials Unreported https://www.alltrials.net/news/half-of-all-trials-unreported/ (2013)
 50.0% of clinical trials never publish results (NHS-funded systematic review, 2010) Schmucker et al (2014): 53% of trials published (analyzing 39 studies, >20,000 trials) Munch et al (2014): 46% of pain treatment trials published Chang et al (2015): 49% of high-risk cardiac device trials published Positive findings: 3X more likely to be published than negative results Antidepressant example: Published literature showed 94% positive trials; FDA analysis showed only 51% positive Additional sources: https://www.alltrials.net/news/half-of-all-trials-unreported/ | https://www.nature.com/articles/nature.2013.14286 | https://pmc.ncbi.nlm.nih.gov/articles/PMC8276556/
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60.
ICER. Value per QALY (standard economic value). ICER https://icer.org/wp-content/uploads/2024/02/Reference-Case-4.3.25.pdf (2024)
Standard economic value per QALY: $100,000–$150,000. This is the US and global standard willingness-to-pay threshold for interventions that add costs. Dominant interventions (those that save money while improving health) are favorable regardless of this threshold. Additional sources: https://icer.org/wp-content/uploads/2024/02/Reference-Case-4.3.25.pdf
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61.
Rare Diseases (2024), O. J. of. Rare disease treatment gap. Orphanet Journal of Rare Diseases (2024) https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03398-1 (2024)
Most patients wait 5 to 10 years to get an accurate diagnosis - and only about 5% of rare diseases have an FDA-approved treatment. Over the 40 years of the ODA, 6,340 orphan drug designations were granted, representing drug development for 1,079 rare diseases out of 7,000-10,000 known rare conditions.
62.
International, R. D. 300 million people with rare diseases globally. Rare Diseases International: 300 Million Worldwide https://www.rarediseasesinternational.org/new-scientific-paper-confirms-300-million-people-living-with-a-rare-disease-worldwide/ (2019)
Conservative estimate: 300 million people (3.5-5.9% of world population of 7.5B) Range: 263-446 million people globally Based on Orphanet database analysis of 3,585 rare diseases Note: Excludes rare cancers and infectious diseases, so actual number likely higher Additional sources: https://www.rarediseasesinternational.org/new-scientific-paper-confirms-300-million-people-living-with-a-rare-disease-worldwide/ | https://sciencedaily.com/releases/2019/10/191024075007.htm | https://pmc.ncbi.nlm.nih.gov/articles/PMC9632971/
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63.
Oren Cass, M. I. RECOVERY trial cost per patient. Oren Cass https://manhattan.institute/article/slow-costly-clinical-trials-drag-down-biomedical-breakthroughs (2023)
The RECOVERY trial, for example, cost only about 500perpatient...Bycontrast, themedianper − patientcostofapivotaltrialforanewtherapeuticisaround41,000. Additional sources: https://manhattan.institute/article/slow-costly-clinical-trials-drag-down-biomedical-breakthroughs
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64.
al., N. E. Á. et. RECOVERY trial global lives saved ( 1 million). NHS England: 1 Million Lives Saved https://www.england.nhs.uk/2021/03/covid-treatment-developed-in-the-nhs-saves-a-million-lives/ (2021)
Dexamethasone saved  1 million lives worldwide (NHS England estimate, March 2021, 9 months after discovery). UK alone: 22,000 lives saved. Methodology: Águas et al. Nature Communications 2021 estimated 650,000 lives (range: 240,000-1,400,000) for July-December 2020 alone, based on RECOVERY trial mortality reductions (36% for ventilated, 18% for oxygen-only patients) applied to global COVID hospitalizations. June 2020 announcement: Dexamethasone reduced deaths by up to 1/3 (ventilated patients), 1/5 (oxygen patients). Impact immediate: Adopted into standard care globally within hours of announcement. Additional sources: https://www.england.nhs.uk/2021/03/covid-treatment-developed-in-the-nhs-saves-a-million-lives/ | https://www.nature.com/articles/s41467-021-21134-2 | https://pharmaceutical-journal.com/article/news/steroid-has-saved-the-lives-of-one-million-covid-19-patients-worldwide-figures-show | https://www.recoverytrial.net/news/recovery-trial-celebrates-two-year-anniversary-of-life-saving-dexamethasone-result
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65.
Institute, M. RECOVERY trial 82× cost reduction. Manhattan Institute: Slow Costly Trials https://manhattan.institute/article/slow-costly-clinical-trials-drag-down-biomedical-breakthroughs
RECOVERY trial:  $500 per patient ($20M for 48,000 patients = $417/patient) Typical clinical trial:  $41,000 median per-patient cost Cost reduction:  80-82× cheaper ($41,000 ÷ $500 ≈ 82×) Efficiency: $50 per patient per answer (10 therapeutics tested, 4 effective) Dexamethasone estimated to save >630,000 lives Additional sources: https://manhattan.institute/article/slow-costly-clinical-trials-drag-down-biomedical-breakthroughs | https://pmc.ncbi.nlm.nih.gov/articles/PMC9293394/
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66.
News, O. U. RECOVERY trial summary quote. Oxford University News https://www.ox.ac.uk/news/features/recovery-trial-two-years
One trial. Over 47,000 participants. Nearly 200 hospital sites, across six countries. Ten results. Four effective COVID-19 treatments... Through discovering four treatments that effectively reduce deaths from COVID-19, it is certain that the study has saved thousands – if not millions – of lives worldwide. Additional sources: https://www.ox.ac.uk/news/features/recovery-trial-two-years
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67.
Institute, S. I. P. R. Trends in world military expenditure, 2023. (2024).
68.
69.
PMC. Standard medical research ROI ($20k-$100k/QALY). PMC: Cost-effectiveness Thresholds Used by Study Authors https://pmc.ncbi.nlm.nih.gov/articles/PMC10114019/ (1990)
Typical cost-effectiveness thresholds for medical interventions in rich countries range from $50,000 to $150,000 per QALY. The Institute for Clinical and Economic Review (ICER) uses a $100,000-$150,000/QALY threshold for value-based pricing. Between 1990-2021, authors increasingly cited $100,000 (47% by 2020-21) or $150,000 (24% by 2020-21) per QALY as benchmarks for cost-effectiveness. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC10114019/ | https://icer.org/our-approach/methods-process/cost-effectiveness-the-qaly-and-the-evlyg/
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70.
Orphanet, C. estimate based on. Average time to cure under current system.
Queue-based calculation:  7,000 diseases without effective treatment ÷  15 diseases getting first treatment per year =  467 years for the average disease to receive a cure under the status quo system. This is consistent with the fact that only 5% of rare diseases have treatments after 40+ years of the Orphan Drug Act. Well-funded diseases may take 30-50 years; underfunded diseases 100-500+ years; and neglected diseases effectively never within human planning horizons.
71.
FDA. Thalidomide caused thousands of birth defects. FDA https://www.fda.gov/about-fda/fda-history-exhibits/frances-oldham-kelsey-medical-reviewer-famous-averting-public-health-tragedy
it resulted in thousands of horrific congenital disabilities. Additional sources: https://www.fda.gov/about-fda/fda-history-exhibits/frances-oldham-kelsey-medical-reviewer-famous-averting-public-health-tragedy | https://www.smithsonianmag.com/science-nature/woman-who-stood-between-america-and-epidemic-birth-defects-180963165/
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72.
FDA. FDA dr. Kelsey prevented widespread thalidomide birth defects in the US. FDA: Frances Oldham Kelsey https://www.fda.gov/about-fda/fda-history-exhibits/frances-oldham-kelsey-medical-reviewer-famous-averting-public-health-tragedy
Dr. Frances Kelsey (FDA reviewer) resisted pressure to approve thalidomide September 1960-November 1961 Worldwide:  8,000 infants born with missing/malformed limbs; 5,000-7,000 perished in utero United States: 17 confirmed phocomelia cases + 9 likely cases (vs.  8,000 worldwide) Kelsey insisted on hard evidence, refused to be browbeaten; repeatedly requested more information every 60 days Merrell complained to her bosses, calling her "petty bureaucrat" - she persisted Recognition: President’s Award for Distinguished Federal Civilian Service (JFK, 1962) Led to 1962 Kefauver-Harris Amendments requiring drugs prove both safety AND effectiveness Additional sources: https://www.fda.gov/about-fda/fda-history-exhibits/frances-oldham-kelsey-medical-reviewer-famous-averting-public-health-tragedy | https://www.uchicagomedicine.org/forefront/biological-sciences-articles/courageous-physician-scientist-saved-the-us-from-a-birth-defects-catastrophe | https://www.smithsonianmag.com/science-nature/woman-who-stood-between-america-and-epidemic-birth-defects-180963165/
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73.
Wikipedia. Thalidomide scandal: Worldwide cases and mortality. Wikipedia https://en.wikipedia.org/wiki/Thalidomide_scandal
The total number of embryos affected by the use of thalidomide during pregnancy is estimated at 10,000, of whom about 40% died around the time of birth. More than 10,000 children in 46 countries were born with deformities such as phocomelia. Additional sources: https://en.wikipedia.org/wiki/Thalidomide_scandal
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74.
One, P. Health and quality of life of thalidomide survivors as they age. PLOS One https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210222 (2019)
Study of thalidomide survivors documenting ongoing disability impacts, quality of life, and long-term health outcomes. Survivors (now in their 60s) continue to experience significant disability from limb deformities, organ damage, and other effects. Additional sources: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210222
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75.
NCBI, F. S. via. Trial costs, FDA study. FDA Study via NCBI https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248200/
Overall, the 138 clinical trials had an estimated median (IQR) cost of 19.0million(12.2 million-33.1million)...Theclinicaltrialscostamedian(IQR)of41,117 (31, 802−82,362) per patient. Additional sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248200/
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76.
UCDP. State violence deaths annually. UCDP: Uppsala Conflict Data Program https://ucdp.uu.se/
Uppsala Conflict Data Program (UCDP): Tracks one-sided violence (organized actors attacking unarmed civilians) UCDP definition: Conflicts causing at least 25 battle-related deaths in calendar year 2023 total organized violence: 154,000 deaths; Non-state conflicts: 20,900 deaths UCDP collects data on state-based conflicts, non-state conflicts, and one-sided violence Specific "2,700 annually" figure for state violence not found in recent UCDP data; actual figures vary annually Additional sources: https://ucdp.uu.se/ | https://en.wikipedia.org/wiki/Uppsala_Conflict_Data_Program | https://ourworldindata.org/grapher/deaths-in-armed-conflicts-by-region
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77.
UNHCR. UNHCR forcibly displaced people 2023. UNHCR https://www.unhcr.org/global-trends-report-2023 (2023)
At the end of 2023, 117.3 million people worldwide were forcibly displaced. Additional sources: https://www.unhcr.org/global-trends-report-2023
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78.
CGDev. UNHCR average refugee support cost. CGDev https://www.cgdev.org/blog/costs-hosting-refugees-oecd-countries-and-why-uk-outlier (2024)
The average cost of supporting a refugee is $1,384 per year. This represents total host country costs (housing, healthcare, education, security). OECD countries average $6,100 per refugee (mean 2022-2023), with developing countries spending $700-1,000. Global weighted average of  $1,384 is reasonable given that 75-85% of refugees are in low/middle-income countries. Additional sources: https://www.cgdev.org/blog/costs-hosting-refugees-oecd-countries-and-why-uk-outlier | https://www.unhcr.org/sites/default/files/2024-11/UNHCR-WB-global-cost-of-refugee-inclusion-in-host-country-health-systems.pdf
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79.
Bureau, U. C. Historical world population estimates. US Census Bureau https://www.census.gov/data/tables/time-series/demo/international-programs/historical-est-worldpop.html
US Census Bureau historical estimates of world population by country and region (1950-2050). US population in 1960:  180 million of  3 billion worldwide (6%). Additional sources: https://www.census.gov/data/tables/time-series/demo/international-programs/historical-est-worldpop.html
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80.
Wikipedia. US military spending reduction after WWII. Wikipedia https://en.wikipedia.org/wiki/Demobilization_of_United_States_Armed_Forces_after_World_War_II (2020)
Peaking at over $81 billion in 1945, the U.S. military budget plummeted to approximately $13 billion by 1948, representing an 84% decrease. The number of personnel was reduced almost 90%, from more than 12 million to about 1.5 million between mid-1945 and mid-1947. Defense spending exceeded 41 percent of GDP in 1945. After World War II, the US reduced military spending to 7.2 percent of GDP by 1948. Defense spending doubled from the 1948 low to 15 percent at the height of the Korean War in 1953. Additional sources: https://en.wikipedia.org/wiki/Demobilization_of_United_States_Armed_Forces_after_World_War_II | https://www.americanprogress.org/article/a-historical-perspective-on-military-budgets/ | https://www.stlouisfed.org/on-the-economy/2020/february/war-highest-military-spending-measured | https://www.usgovernmentspending.com/defense_spending_history
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81.
Kirk (2011), H. &. Valley of death in drug development. (2011)
The overall failure rate of drugs that passed into Phase 1 trials to final approval is 90%. This lack of translation from promising preclinical findings to success in human trials is known as the "valley of death." Estimated 30-50% of promising compounds never proceed to Phase 2/3 trials primarily due to funding barriers rather than scientific failure. The late-stage attrition rate for oncology drugs is as high as 70% in Phase II and 59% in Phase III trials.
82.
VA. Veteran healthcare cost projections. VA https://department.va.gov/wp-content/uploads/2025/06/2026-Budget-in-Brief.pdf (2026)
VA budget: $441.3B requested for FY 2026 (10% increase). Disability compensation: $165.6B in FY 2024 for 6.7M veterans. PACT Act projected to increase spending by $300B between 2022-2031. Costs under Toxic Exposures Fund: $20B (2024), $30.4B (2025), $52.6B (2026). Additional sources: https://department.va.gov/wp-content/uploads/2025/06/2026-Budget-in-Brief.pdf | https://www.cbo.gov/publication/45615 | https://www.legion.org/information-center/news/veterans-healthcare/2025/june/va-budget-tops-400-billion-for-2025-from-higher-spending-on-mandated-benefits-medical-care
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83.
Graham, D. (FDA). |. L. Vioxx cardiovascular deaths (rofecoxib). PMC: FDA incapable of protecting against another Vioxx https://pmc.ncbi.nlm.nih.gov/articles/PMC534432/ (2007)
Graham testimony (2004): 88,000-139,000 U.S. heart attacks/strokes from Vioxx; up to 55,000 deaths (40% fatality rate) Lancet study estimate: 88,000 Americans had heart attacks from Vioxx; 38,000 died FDA memo (2004): Vioxx contributed to  27,785 heart attacks and sudden cardiac deaths (1999-2003) High-dose Vioxx: Tripled risk of heart attacks and sudden cardiac death Prescriptions: 92.8 million U.S. prescriptions 1999-2003 Withdrawn: September 30, 2004 after APPROVE trial showed cardiovascular risks Note: Vioxx case demonstrates failure of passive post-market surveillance (FAERS) to detect safety signals in time. Voluntary reporting missed cardiovascular risks for years despite millions of prescriptions Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC534432/ | https://www.npr.org/2007/11/10/5470430/timeline-the-rise-and-fall-of-vioxx | https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05
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84.
ONE, P. Cost per DALY for vitamin a supplementation. PLOS ONE: Cost-effectiveness of "Golden Mustard" for Treating Vitamin A Deficiency in India (2010) https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012046 (2010)
India: $23-$50 per DALY averted (least costly intervention, $1,000-$6,100 per death averted) Sub-Saharan Africa (2022): $220-$860 per DALY (Burkina Faso: $220, Kenya: $550, Nigeria: $860) WHO estimates for Africa: $40 per DALY for fortification, $255 for supplementation Uganda fortification: $18-$82 per DALY (oil: $18, sugar: $82) Note: Wide variation reflects differences in baseline VAD prevalence, coverage levels, and whether intervention is supplementation or fortification Additional sources: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012046 | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266495
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85.
CNBC. Warren buffett’s career average investment return. CNBC https://www.cnbc.com/2025/05/05/warren-buffetts-return-tally-after-60-years-5502284percent.html (2025)
Berkshire’s compounded annual return from 1965 through 2024 was 19.9%, nearly double the 10.4% recorded by the S&P 500. Berkshire shares skyrocketed 5,502,284% compared to the S&P 500’s 39,054% rise during that period. Additional sources: https://www.cnbc.com/2025/05/05/warren-buffetts-return-tally-after-60-years-5502284percent.html | https://www.slickcharts.com/berkshire-hathaway/returns
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86.
Science/AAAS. Estimated annual cost of repeating failed experiments due to non-publication of results. Science/AAAS https://www.science.org/content/article/study-claims-28-billion-year-spent-irreproducible-biomedical-research (2020)
Up to 50.0% of published preclinical research is irreproducible, with an estimated annual cost of $28 billion in the U.S. alone. This is based on $56B annual spending on preclinical research × 50.0% irreproducibility rate. Main causes: reagents/materials (36%), study design (28%), data analysis (25%), protocols (11%). Additional sources: https://www.science.org/content/article/study-claims-28-billion-year-spent-irreproducible-biomedical-research | https://www.idbs.com/2020/11/replicating-science-28-billion-is-wasted-every-year-in-the-us-alone/
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87.
PMC. Cost-effectiveness threshold ($50,000/QALY). PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC5193154/
The $50,000/QALY threshold is widely used in US health economics literature, originating from dialysis cost benchmarks in the 1980s. In US cost-utility analyses, 77.5% of authors use either $50,000 or $100,000 per QALY as reference points. Most successful health programs cost $3,000-10,000 per QALY. WHO-CHOICE uses GDP per capita multiples (1× GDP/capita = "very cost-effective", 3× GDP/capita = "cost-effective"), which for the US ( $70,000 GDP/capita) translates to $70,000-$210,000/QALY thresholds. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC5193154/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC9278384/
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88.
Organization, W. H. WHO global health estimates 2024. World Health Organization https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates (2024)
Comprehensive mortality and morbidity data by cause, age, sex, country, and year Global mortality:  55-60 million deaths annually Lives saved by modern medicine (vaccines, cardiovascular drugs, oncology):  12M annually (conservative aggregate) Leading causes of death: Cardiovascular disease (17.9M), Cancer (10.3M), Respiratory disease (4.0M) Note: Baseline data for regulatory mortality analysis. Conservative estimate of pharmaceutical impact based on WHO immunization data (4.5M/year from vaccines) + cardiovascular interventions (3.3M/year) + oncology (1.5M/year) + other therapies. Additional sources: https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates
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89.
Bank, W. World bank trade disruption cost from conflict. World Bank https://www.worldbank.org/en/topic/trade/publication/trading-away-from-conflict
Estimated $616B annual cost from conflict-related trade disruption. World Bank research shows civil war costs an average developing country 30 years of GDP growth, with 20 years needed for trade to return to pre-war levels. Trade disputes analysis shows tariff escalation could reduce global exports by up to $674 billion. Additional sources: https://www.worldbank.org/en/topic/trade/publication/trading-away-from-conflict | https://www.nber.org/papers/w11565 | http://blogs.worldbank.org/en/trade/impacts-global-trade-and-income-current-trade-disputes
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