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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
.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/
.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/
.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/
.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
.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
.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
.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
.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
.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
.11.
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
.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
.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/
.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
.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
.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/
.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
.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
.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
.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/
.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/
.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
.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
.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
.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
.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
.34.
SIPRI. Global military spending ($2.72T, 2024).
SIPRI https://www.sipri.org/publications/2025/sipri-fact-sheets/trends-world-military-expenditure-2024
(2025).
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
.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
.37.
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/
.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/
.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
.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
.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
.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
.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
.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
.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/
.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
.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
.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/
.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/
.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/
.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
.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/
.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
.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/
.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/
.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
.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/
.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
.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
.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/
.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
.67.
Institute, S. I. P. R. Trends
in world military expenditure, 2023. (2024).
68.
CSIS. Smallpox eradication ROI. CSIS
https://www.csis.org/analysis/smallpox-eradication-model-global-cooperation.
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/
.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/
.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/
.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
.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
.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/
.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
.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
.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
.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
.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
.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
.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
.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
.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
.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/
.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/
.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
.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
.