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The FDA’s 1962 law requiring years of pre-approval efficacy testing was supposed to prove drugs work before allowing patient access. Instead, it made drugs more dangerous.
How? By blocking patient access during lengthy trials and forcing small, artificial studies instead of large real-world evidence, the current system:
- Tests drugs on tiny, unrepresentative populations that exclude the sick, elderly, and those with comorbidities
- Relies on passive adverse event reporting that captures less than 10% of actual problems
- Misses rare but serious side effects that only appear in larger populations
- Provides no long-term safety data beyond a few months
The result: drugs approved as “safe” based on testing 3,000 cherry-picked patients, then given to millions of real patients where problems finally emerge.
Meanwhile, the regulatory delays prevent millions from accessing treatments that could save their lives. The system doesn’t just fail to ensure safety. It actively undermines it while simultaneously killing people through delay.
The FDA employees executing this system didn’t design it. Congress did, in 1962, via the Kefauver-Harris Amendments. The FDA is implementing what Congress mandated. The problem isn’t bad people at the FDA. The problem is a bad law that makes good outcomes structurally impossible.
When this chapter says “the FDA does X,” read it as “the 1962 law requires the FDA to do X.” The humans at the agency are following the rules they were given. The rules are the problem.
This chapter relies on three tiers of evidence:
Irrefutable Facts (direct empirical data):
Strong Evidence (peer-reviewed research):
- 86.1% trial exclusion rates for real-world patients
- <10% adverse event capture rate in FAERS
- Historical life expectancy slowdown post-1962
- Publication bias (37% negative vs. 94% positive)
Model-Dependent Estimates (quantitative analysis with Monte Carlo confidence intervals):
Even if you reject all model-dependent estimates, the empirical facts alone demonstrate the system is broken.
Compare two real-world systems for testing drugs:
- The Oxford RECOVERY Trial: Tested COVID treatments on 47,000 patients for $500 (95% CI: $400-$2.50K) per patient. Found a life-saving treatment in 3 months.
- The Post-1962 System: Averages $41K (95% CI: $20K-$120K) per patient for clinical trials. Takes 9.1 years139 to approve a new drug.
The current system costs 44.1x (95% CI: 39.4x-89.1x) more and takes 42:1 (95% CI: 29.8:1-48:1) longer. Not a small difference - the difference between functional and designed-to-fail.
Here’s the breakdown of where the time goes:
The math is simple: If you die in year 5 and the drug gets approved in year 10, the regulatory process murdered you.
That’s 8.2 years (95% CI: 4.85 years-11.5 years) sitting in regulatory purgatory after we already know the drug won’t kill you.
You’re two lifetimes from applying the scientific method to medicine. That’s 0.0001% of human history - you invented science yesterday, cosmically speaking. The more clinical research you read, the more you realize you know nothing. Nearly every study ends with “more research is needed” (scientist-speak for “we have no idea what’s happening, please give us more grant money”). This would be fine except people are dying while you figure it out.
What the 1962 Efficacy Requirements Changed
The 1962 Kefauver-Harris Amendments fundamentally restructured how drugs reach patients. To understand what changed, consider the system they replaced.
For 10,000 years, life expectancy remained at 30 years. Then in 1883, doctors started sharing information through JAMA. 144k physicians physicians tested treatments on real patients and published results. Life expectancy increased by 3.82 years every decade123 (calculated from 1880-1960 data) for 80 years.
In 1938, Phase I safety testing was added after the Elixir sulfanilamide disaster. This was reasonable and didn’t slow progress. Safety regulations worked perfectly. They prevented all US deaths from thalidomide while Europe had thousands.
Then in 1962, Congress responded to this success by adding massive pre-approval efficacy requirements via the Kefauver Harris Amendment140, blocking patient access for years during testing. The new system:
- Replaced 144k physicians independent doctors with drug company-run trials
- Made trials 44.1x (95% CI: 39.4x-89.1x) more expensive
- Reduced drug approvals by 70% immediately
- Cut life expectancy growth by 60%124: from 3.82 years/decade to 1.54 years/decade
The temporal break is exact. Life expectancy growth cut in half the moment regulations changed in 1962.
The 1962 Policy Break: Measured Impact
The temporal break is exact. Every negative metric changed immediately in 1962.
The 105x (95% CI: 90.6x-119x) cost increase is rigorously documented with multiple data sources, CPI adjustments, and sensitivity analysis. See Drug Development Cost Analysis for:
- Congressional testimony and alternative data sources
- Exact inflation calculations (1962 → 2024)
- Why it’s not just inflation (timeline expansion, failure rates, trial complexity)
- Sensitivity analysis and independent validation
- Transparent methodology addressing common objections
The Modern Consequences
Even if you’re skeptical of historical analysis, the current system’s failures are undeniable. It works like this:
- Scientists discover a cure for your disease
- You wait 17 years
- You die
- The cure gets approved
- Pharmaceutical companies charge your widow $10,000 per pill
Beautiful system if you’re a mortician or bankruptcy lawyer.
You’re at the very beginning of thousands or millions of years of systematic discovery. So this decline in lifespan growth is unlikely to result from diminishing returns - you haven’t run out of things to discover.
However, validating that large-scale real-world evidence produces better health outcomes requires further validation of this experimentation method. This is why we need a decentralized framework for drug assessment.
High Costs Kill Innovation, Reward Monopoly
In the past: Genius scientist invents cure, raises a few million, tests safety. Simple.
Now: Genius scientist must convince one of three mega-corporations to spend $2.60B (95% CI: $1.50B-$4B) on a 10% chance of success. Those corporations already sell inferior drugs for the same condition.
The math for the mega-corporation:
Option 1: Spend $2.60B (95% CI: $1.50B-$4B) on trials
- 90% chance: Lose everything
- 10% chance: Succeed, then cannibalize your own profitable drug
Option 2: Buy the patent, put it on a shelf
Which would you choose if you were a rational sociopath in a suit?
The profit incentive doesn’t just fail to reward better treatments. It actively punishes them.
Off-Patent Drugs and Rare Diseases: Mathematically Doomed
The 1962 law creates a death spiral for unprofitable treatments:
- 95% of diseases are rare96: Development cost ($2.60B (95% CI: $1.50B-$4B)) ÷ patient population (~10,000 patients) = $260,000/patient
- No patent = no funding: Off-patent drugs can’t attract billion-dollar investments
- Pre-specification kills serendipity: Must predict what drug cures before testing
When something costs more, you get less of it. For 95% of diseases96 with zero treatments, this isn’t philosophy. It’s math.
The Actual Death Toll of “Drug Lag”
Economists have a term for people dying while waiting for drug approval: “drug lag.” It’s a sterile, bureaucratic phrase for a massacre. Early estimates suggested delays cost 21,000 to 120,000 American lives per decade141.
But that was just the US. And just the visible delays.
The Global Body Count
A comprehensive quantitative analysis using WHO mortality data and Monte Carlo modeling estimates the total cost of blocking patient access during the 8.2 years (95% CI: 4.85 years-11.5 years)-year post-safety efficacy delay:
416M deaths (95% CI: 225M deaths-630M deaths) eventually avoidable deaths from the efficacy lag alone.
This represents a humanitarian catastrophe larger than any war in modern history. See the full sensitivity analysis for confidence intervals and parameter uncertainty.
But deaths alone don’t capture the suffering. People don’t just die, they live for years with untreated diseases while waiting for approval.
The Morbidity Burden (DALYs)
When you account for both premature death and years lived with disability:
\[
\begin{gathered}
DALYs_{lag} = YLL_{lag} + YLD_{lag} = 7.07B + 873M = 7.94B \\[0.5em]
\text{where } YLL_{lag} \\
= Deaths_{lag} \times (LE_{global} - Age_{death,delay}) \\
= 416M \times (79 - 62) \\
= 7.07B \\[0.5em]
\text{where } Deaths_{lag} \\
= T_{lag} \times Deaths_{disease,daily} \times 338 \\
= 8.2 \times 150{,}000 \times 338 \\
= 416M \\[0.5em]
\text{where } YLD_{lag} \\
= Deaths_{lag} \times T_{suffering} \times DW_{chronic} \\
= 416M \times 6 \times 0.35 \\
= 873M \\[0.5em]
\text{where } Deaths_{lag} \\
= T_{lag} \times Deaths_{disease,daily} \times 338 \\
= 8.2 \times 150{,}000 \times 338 \\
= 416M
\end{gathered}
\]
7.94B DALYs (95% CI: 4.43B DALYs-12.1B DALYs) years of healthy human life deleted by the regulatory framework.
For comparison: The entire global pharmaceutical R&D budget is ~$300B/year. The post-safety efficacy lag costs 38× more than all drug development spending combined.
Even if you think these estimates are off by a factor of 10, the core problem remains: a system that costs 82x (95% CI: 50x-94.1x) more per patient, takes 36× longer than proven alternatives, and produces less safety data from smaller, less representative populations.
Here’s a news story from the Non-Existent Times by No One Ever without a picture of all the people who die from lack of access to life-saving treatments that might have been.
This means it’s logical for regulators to reject drug applications by default. The personal risks of approving a drug with any newsworthy side effect far outweigh the personal risk of preventing access to life-saving treatment.
Types of Error in FDA Approval Decision
| FDA Allows the Drug |
Correct Decision |
Victims are identifiable and might appear on Oprah. |
| FDA Does Not Allow the Drug |
Victims are not identifiable or acknowledged. |
Correct Decision |
The most infamous case is beta-blockers. While Europe used them to prevent heart attacks, the US regulatory process delayed. And delayed. The decade-long lag in approving them for their most common use killed an estimated 100,000 Americans138.
More Americans than died in Vietnam and Korea combined. From one drug delay. Here’s a partial list of other drugs Americans died waiting for while they were already available in other civilized countries for a year or longer:
- interleukin-2, Taxotere, vasoseal, ancrod, Glucophage, navelbine, Lamictal, ethyol, photofrin, rilutek, citicoline, panorex, Femara, ProStar, omnicath
Each name on that list represents eventually avoidable deaths.
Following the 1962 increase in US regulations, you can see a divergence from Switzerland’s growth in life expectancy, which did not introduce the same delays to availability.
Perhaps it’s coincidence, but you can see an increase in drug approvals in the ’80s. At the same time, the gap between Switzerland and the US gets smaller. Then US approvals go back down in the ’90s, and the gap expands again.
How the Incentives Work
FDA Regulator Decision Tree
Approve drug that later shows problems
- Congressional hearing (televised)
- “FDA APPROVED KILLER DRUG” headlines
- Career ends
- Pension threatened
Delay drug that could save lives
- Nothing happens
- Dead people don’t complain
- Promotion on schedule
- Retire to pharma job142
This isn’t conspiracy. It’s economics. The system literally cannot punish mistakes of commission (approving bad drugs) but imposes zero consequences for mistakes of omission (delaying good drugs).
The Math: Why Current Regulations Increase Total Harm
The regulatory system claims to prevent harm by screening out unsafe drugs (Type I errors: approving bad drugs). But this framing ignores two critical facts:
- Small trials miss more safety problems than they catch (as shown in the Safety Paradox section)
- Regulatory delays kill far more people than unsafe drugs ever did
Let’s quantify both types of harm:
Type I Harm (approving unsafe drugs):
- Even with generous overestimates, prevented harm: ~2.59M DALYs (95% CI: 1.54M DALYs-4.16M DALYs) saved (1962-2024)
- This assumes ALL drug withdrawals were prevented by the 1962 changes that blocked patient access during lengthy efficacy trials (they weren’t; Phase I safety testing already existed)
Type II Harm (delaying beneficial treatments):
\[
\begin{gathered}
Ratio_{TypeII} = \frac{DALYs_{lag}}{DALY_{TypeI}} = \frac{7.94B}{2.59M} = 3{,}070 \\[0.5em]
\text{where } DALYs_{lag} = YLL_{lag} + YLD_{lag} = 7.07B + 873M = 7.94B \\[0.5em]
\text{where } YLL_{lag} \\
= Deaths_{lag} \times (LE_{global} - Age_{death,delay}) \\
= 416M \times (79 - 62) \\
= 7.07B \\[0.5em]
\text{where } Deaths_{lag} \\
= T_{lag} \times Deaths_{disease,daily} \times 338 \\
= 8.2 \times 150{,}000 \times 338 \\
= 416M \\[0.5em]
\text{where } YLD_{lag} \\
= Deaths_{lag} \times T_{suffering} \times DW_{chronic} \\
= 416M \times 6 \times 0.35 \\
= 873M \\[0.5em]
\text{where } Deaths_{lag} \\
= T_{lag} \times Deaths_{disease,daily} \times 338 \\
= 8.2 \times 150{,}000 \times 338 \\
= 416M \\[0.5em]
\text{where } DALY_{TypeI} = DALY_{thal} \times 62 = 41{,}800 \times 62 = 2.59M \\[0.5em]
\text{where } DALY_{thal} \\
= YLD_{thal} + YLL_{thal} \\
= 13{,}000 + 28{,}800 \\
= 41{,}800 \\[0.5em]
\text{where } YLD_{thal} \\
= DW_{thal} \times N_{thal,survive} \times LE_{thal} \\
= 0.4 \times 540 \times 60 \\
= 13{,}000 \\[0.5em]
\text{where } N_{thal,survive} \\
= N_{thal,US,prevent} \times (1 - Rate_{thal,mort}) \\
= 900 \times (1 - 40\%) \\
= 540 \\[0.5em]
\text{where } N_{thal,US,prevent} \\
= N_{thal,global} \times Pct_{US,1960} \\
= 15{,}000 \times 6\% \\
= 900 \\[0.5em]
\text{where } YLL_{thal} = Deaths_{thal} \times 80 = 360 \times 80 = 28{,}800 \\[0.5em]
\text{where } Deaths_{thal} \\
= Rate_{thal,mort} \times N_{thal,US,prevent} \\
= 40\% \times 900 \\
= 360 \\[0.5em]
\text{where } N_{thal,US,prevent} \\
= N_{thal,global} \times Pct_{US,1960} \\
= 15{,}000 \times 6\% \\
= 900
\end{gathered}
\]
For every 1 unit of harm prevented by the current regulatory framework, it creates 3.07k:1 (95% CI: 2.88k:1-3.12k:1) units of harm through delay and inadequate safety monitoring.
This isn’t a trade-off. The system doesn’t reduce total harm. It massively increases it while appearing to prioritize safety.
Why Bureaucrats Are Rewarded for Letting You Die
Humans weight acts of commission (doing something bad) as worse than acts of omission (letting something bad happen) - even when omission causes more harm. Push a person in front of a trolley to save five people? Unthinkable. Let five people die by doing nothing? That’s just Monday.
The current regulatory framework operates on this principle.
Dr. Henry I. Miller ran the FDA team reviewing recombinant human insulin in the early 1980s. Mountains of evidence showed it was safe and effective. His supervisor refused to approve it. Why? If someone died from the drug, heads would roll at the FDA, including his. If people died waiting for the drug? Nothing happens.
The personal risk of approving a drug vastly exceeds the risk of rejecting it. Dead patients don’t testify before Congress.
Clinical Trial Theater: Excluding 86.1% of Reality Makes Drugs More Dangerous
The FDA requires rigorous trials to ensure safety. Then it systematically excludes the populations most at risk of adverse events.
Trials under the current system exclude2:
- Patients over 65: Most people who actually take medications (excluded due to “comorbidities”)
- Patients under 18: All children (metabolism differs from adults)
- Pregnant women: Excluded entirely (then drugs prescribed during pregnancy anyway)
- Anyone with comorbidities: The sickest patients most likely to have adverse reactions
- Anyone on other medications: Everyone elderly (can’t detect drug interactions)
- Anyone too far from trial sites: Poor and rural populations
Result: Drugs are tested on a small fraction of unusually healthy patients least likely to experience adverse events (86.1% are excluded in antidepressant trials alone), then prescribed to everyone else where safety problems finally emerge.
Why This Makes Drugs More Dangerous
When trials exclude most real patients (86.1% in antidepressant studies):
- Drug interactions go undetected: Elderly patients on multiple medications face risks never tested
- Metabolic differences are missed: Children and elderly metabolize drugs differently
- Subgroup toxicity is invisible: Rare genetic variants or comorbidities that cause severe reactions
- Real-world failure rates are hidden: Effectiveness and safety in actual sick patients remain unknown until post-market
This isn’t theoretical. Multiple drugs later withdrawn for safety issues (Vioxx, Fen-Phen, Bextra) were tested on cherry-picked populations. The cardiovascular risks, liver damage, and other serious adverse events only became apparent after millions of real-world patients (elderly, sick, on other medications) were exposed.
Testing drugs only on healthy volunteers to ensure safety is like testing parachutes only on the ground.
No Long-Term Outcome Data
Even if there’s financial incentive to research a new drug, there’s no data on long-term outcomes. Data collection for participants can be as short as several months. Under the current system, it’s not financially feasible to collect data on a participant for years or decades. So you have no idea if long-term effects of a drug are worse than initial benefits.
Pre-Specification Requirements Kill Innovation
When running an efficacy trial, the regulations require drug developers to predict exactly what a treatment will cure before collecting any human trial data.
In 2007, Dendreon submitted evidence that its immunotherapy drug Provenge significantly reduced deaths from prostate cancer. The FDA advisory committee was persuaded. But the application was rejected anyway, not because the drug didn’t work, but because Dendreon didn’t properly specify beforehand what the study would measure.
Finding a decline in deaths wasn’t enough. The paperwork wasn’t filled out in the correct order. Three more years and another large trial were required before the life-saving medication was approved.
Due to these additional costs, Dendreon ultimately filed for chapter 11 bankruptcy.
The Negative Results Black Hole
Here’s a fun fact that should be criminal:
- Negative trial results published: 37%143
- Positive trial results published: 94%143
- Money wasted repeating failed experiments: ~$100 billion annually144
Companies are literally allowed to hide when drugs don’t work.
Company: “We tested this drug!”
Regulator: “Did it work?”
Company: “…We tested this drug!”
This means humans spend billions testing the same failed drugs over and over because nobody admits they failed. It’s like playing poker where everyone claims they won but nobody shows their cards.
Pharmaceutical companies bury negative results deeper than Jimmy Hoffa. So other companies waste billions testing the same dead ends.
Your insurance premiums fund this magnificent inefficiency.
It’s like casinos only having to report when people win.
Countries That Don’t Have Our “Safety”
Japan’s Regenerative Medicine Act145:
- Conditional approval after Phase II
- Real-world data collection required
- Time to patient: 2-3 years
- Americans fly there for treatment
EU Compassionate Use146:
- Terminal patients can access experimental drugs
- Doctor’s discretion, not bureaucrat’s
- Thousands of lives extended
- FDA: “But what if they die?” (They’re already dying)
Right to Try (US)147:
- Passed despite FDA opposition
- FDA response: Made it effectively impossible to use
- Patients helped: <200 total148
- Patients who wanted help: Tens of thousands
The COVID Test Fiasco
The 1962 framework requires the FDA to approve all diagnostic tests before use. During COVID, this mandate played out as follows:
- January 2020: WHO develops COVID test, rest of world starts using it
- February 2020: FDA blocks all non-CDC tests149 to “ensure quality”
- Late February: CDC tests contaminated, completely useless150
- March: Private labs beg to help, regulatory framework says “no, approved tests only”
- Late March: FDA finally allows other tests after thousands die
- Cost: Thousands of preventable deaths151, exact number unknown
The defense: “We were ensuring quality control.”
The only approved tests didn’t work.
Ensuring quality control of broken tests is like TSA confiscating water bottles while letting actual weapons through. Except people died.
Small Trials Are Dangerous!
The FDA’s post-1962 system (requiring small, artificial efficacy trials before allowing patient access) was supposed to prove drugs work. But paradoxically, by forcing small artificial trials and excluding real-world populations, it created a system that is demonstrably more dangerous than the real-world evidence approach it replaced.
Why Small Trials Miss Safety Signals
Phase III trials test 1,000-3,000 patients. This sounds rigorous until you understand the math:
- Rare adverse events (1 in 10,000) won’t appear in trials of 3,000 patients
- Subgroup reactions (elderly, those with comorbidities) can’t be detected when these groups are systematically excluded
- Long-term effects (cancer risk, organ damage) don’t show up in 6-month trials
- Drug interactions can’t be studied when trial participants can’t be on other medications
The result: Drugs are approved as “safe” based on tiny, artificial samples, then given to millions of real patients where the actual safety problems emerge.
The Adverse Event Reporting Failure
Post-approval, the FDA relies on the FDA Adverse Event Reporting System (FAERS), a passive, voluntary system where doctors report problems they happen to notice and connect to a specific drug.
Reality:
- Estimated capture rate: Less than 10% of actual adverse events152 (empirical studies show ~6% reporting rate, meaning 94% underreported)
- Reporting burden: Voluntary, time-consuming paperwork doctors often skip
- Attribution difficulty: Hard to prove causation in individual cases
- No systematic follow-up: Most patients disappear after prescription
Examples of failures:
- Vioxx: Killed an estimated 38,000-55,000 Americans153 before voluntary reporting caught the cardiovascular risks
- Thalidomide in Europe: Thousands of birth defects before passive reporting identified the pattern
What Real-World Evidence Would Catch
A decentralized system with universal participation would:
- Detect rare events: 10 million participants catch 1-in-10,000 reactions
- Include real populations: Test on the sick, elderly, and those with comorbidities
- Track long-term outcomes: Years of follow-up data, not months
- Identify drug interactions: Real patients take multiple medications
- Provide active surveillance: Automated detection, not voluntary reporting
The safety ratio is backwards. Testing 3,000 cherry-picked patients and hoping voluntary reporting catches problems is more dangerous than testing active monitoring of adverse events with real patients.
The current system doesn’t prevent safety failures. It delays discovering them until after millions have been exposed.
Phase I safety testing works. It screens out immediately toxic compounds. But blocking patient access during the 8.2-year post-safety efficacy delay, by forcing small artificial trials and excluding real-world evidence collection, makes drugs more dangerous while simultaneously killing people through delayed access to life-saving treatments.
The Bottom Line
Phase I safety testing works. Keep it.
Blocking patient access during the 8.2-year post-safety efficacy delay kills people. Replace it with real-world evidence collection.
Many pieces already exist. The bottleneck is scale, incentives, and time-to-answer. The core idea is straightforward even if implementation is hard.
What’s missing is the political will to admit that the 1962 “reforms” were a catastrophic mistake.
P.S. - The FDA will likely object to this chapter. Estimated response time: 12-15 years, pending Phase III review and proper documentation.
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NIH Common Fund: HCS Research Collaboratory https://commonfund.nih.gov/hcscollaboratory (2025)
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8.
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US incarceration costs approximately $80 billion annually in direct correctional expenditures alone. Including social costs (lost earnings, family impacts, health effects, reduced child outcomes), total burden exceeds $300 billion annually. The US incarcerates at 5x the rate of other OECD countries with no corresponding reduction in crime. Evidence shows community-based alternatives cost less and reduce recidivism more effectively. Additional sources: https://www.vera.org/publications/the-economic-burden-of-incarceration-in-the-u-s | https://www.prisonpolicy.org/reports/pie2024.html | https://www.rand.org/pubs/research_reports/RRA108-3.html
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Marron Institute, N. Transit costs project - why US infrastructure costs so much.
NYU Transit Costs Project https://transitcosts.com/ (2024)
The United States builds transit infrastructure at dramatically higher costs than peer countries. New York’s Second Avenue Subway cost $2.5 billion per kilometer vs. $200-500 million in European cities. US highway construction similarly costs 2-5x more than comparable projects abroad. Causes include: excessive environmental review, litigation risk, lack of in-house expertise, fragmented project management, and inflated soft costs. Additional sources: https://transitcosts.com/ | https://www.brookings.edu/articles/why-does-infrastructure-cost-so-much/
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13.
Clemens, M. A.
Economics and emigration: Trillion-dollar bills on the sidewalk? Journal of Economic Perspectives 25, 83–106 (2011)
Free global labor mobility would increase gross world product by somewhere in the range of 67-147%... The gains to eliminating migration barriers amount to large fractions of world GDP—one or two orders of magnitude larger than the gains from dropping all remaining restrictions on international flows of goods and capital.
16.
Foundation, T. Tax compliance costs the US economy $546 billion annually.
https://taxfoundation.org/data/all/federal/irs-tax-compliance-costs/ (2024)
Americans will spend over 7.9 billion hours complying with IRS tax filing and reporting requirements in 2024. This costs the economy roughly $413 billion in lost productivity. In addition, the IRS estimates that Americans spend roughly $133 billion annually in out-of-pocket costs, bringing the total compliance costs to $546 billion, or nearly 2 percent of GDP.
17.
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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18.
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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19.
AARP. Unpaid caregiver hours and economic value.
AARP 2023 https://www.aarp.org/caregiving/financial-legal/info-2023/unpaid-caregivers-provide-billions-in-care.html (2023)
Average family caregiver: 25-26 hours per week (100-104 hours per month) 38 million caregivers providing 36 billion hours of care annually Economic value: $16.59 per hour = $600 billion total annual value (2021) 28% of people provided eldercare on a given day, averaging 3.9 hours when providing care Caregivers living with care recipient: 37.4 hours per week Caregivers not living with recipient: 23.7 hours per week Note: Disease-related caregiving is subset of total; includes elderly care, disability care, and child care Additional sources: https://www.aarp.org/caregiving/financial-legal/info-2023/unpaid-caregivers-provide-billions-in-care.html | https://www.bls.gov/news.release/elcare.nr0.htm | https://www.caregiver.org/resource/caregiver-statistics-demographics/
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20.
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
.
22.
Labor Statistics, U. S. B. of.
CPI inflation calculator. (2024)
CPI-U (1980): 82.4 CPI-U (2024): 313.5 Inflation multiplier (1980-2024): 3.80× Cumulative inflation: 280.48% Average annual inflation rate: 3.08% Note: Official U.S. government inflation data using Consumer Price Index for All Urban Consumers (CPI-U). Additional sources: https://www.bls.gov/data/inflation_calculator.htm
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23.
Del Rosal, I. The empirical measurement of rent-seeking costs.
Journal of Economic Surveys https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1467-6419.2009.00621.x (2011)
A comprehensive survey of empirical estimates finds rent-seeking costs range from 0.2% to 23.7% of GDP across different methodologies and countries. Laband & Sophocleus (1988) estimated up to 45% for the US.
24.
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
.
25.
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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26.
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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27.
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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28.
estimates, I. Clinical trial abandonment.
Average: 10% abandoned before completion
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32.
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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33.
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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34.
(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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35.
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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36.
EPI. Education investment economic multiplier (2.1).
EPI: Public Investments Outside Core Infrastructure https://www.epi.org/publication/bp348-public-investments-outside-core-infrastructure/ Early childhood education: Benefits 12X outlays by 2050; $8.70 per dollar over lifetime Educational facilities: $1 spent → $1.50 economic returns Energy efficiency comparison: 2-to-1 benefit-to-cost ratio (McKinsey) Private return to schooling: 9% per additional year (World Bank meta-analysis) Note: 2.1 multiplier aligns with benefit-to-cost ratios for educational infrastructure/energy efficiency. Early childhood education shows much higher returns (12X by 2050) Additional sources: https://www.epi.org/publication/bp348-public-investments-outside-core-infrastructure/ | https://documents1.worldbank.org/curated/en/442521523465644318/pdf/WPS8402.pdf | https://freopp.org/whitepapers/establishing-a-practical-return-on-investment-framework-for-education-and-skills-development-to-expand-economic-opportunity/
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37.
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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38.
Bank, W. Infrastructure investment economic multiplier (1.6).
World Bank: Infrastructure Investment as Stimulus https://blogs.worldbank.org/en/ppps/effectiveness-infrastructure-investment-fiscal-stimulus-what-weve-learned (2022)
Infrastructure fiscal multiplier: 1.6 during contractionary phase of economic cycle Average across all economic states: 1.5 (meaning $1 of public investment → $1.50 of economic activity) Time horizon: 0.8 within 1 year, 1.5 within 2-5 years Range of estimates: 1.5-2.0 (following 2008 financial crisis & American Recovery Act) Italian public construction: 1.5-1.9 multiplier US ARRA: 0.4-2.2 range (differential impacts by program type) Economic Policy Institute: Uses 1.6 for infrastructure spending (middle range of estimates) Note: Public investment less likely to crowd out private activity during recessions; particularly effective when monetary policy loose with near-zero rates Additional sources: https://blogs.worldbank.org/en/ppps/effectiveness-infrastructure-investment-fiscal-stimulus-what-weve-learned | https://www.gihub.org/infrastructure-monitor/insights/fiscal-multiplier-effect-of-infrastructure-investment/ | https://cepr.org/voxeu/columns/government-investment-and-fiscal-stimulus | https://www.richmondfed.org/publications/research/economic_brief/2022/eb_22-04
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39.
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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40.
FDA. FDA-approved prescription drug products (20,000+).
FDA https://www.fda.gov/media/143704/download There are over 20,000 prescription drug products approved for marketing. Additional sources: https://www.fda.gov/media/143704/download
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42.
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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43.
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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44.
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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45.
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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46.
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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47.
ScienceDaily. Medical research lives saved annually (4.2 million).
ScienceDaily: Physical Activity Prevents 4M Deaths https://www.sciencedaily.com/releases/2020/06/200617194510.htm (2020)
Physical activity: 3.9M early deaths averted annually worldwide (15% lower premature deaths than without) COVID vaccines (2020-2024): 2.533M deaths averted, 14.8M life-years preserved; first year alone: 14.4M deaths prevented Cardiovascular prevention: 3 interventions could delay 94.3M deaths over 25 years (antihypertensives alone: 39.4M) Pandemic research response: Millions of deaths averted through rapid vaccine/drug development Additional sources: https://www.sciencedaily.com/releases/2020/06/200617194510.htm | https://pmc.ncbi.nlm.nih.gov/articles/PMC9537923/ | https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.038160 | https://pmc.ncbi.nlm.nih.gov/articles/PMC9464102/
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48.
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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49.
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/
.
50.
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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51.
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
.
52.
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
.
53.
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
.
55.
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.
56.
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 (\(8.2 trillion) and lost productivity (\)100.9 trillion from 2.55 billion DALYs × \(39,570 per DALY), totals approximately\)109.1 trillion annually.
57.
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
.
58.
Suisse/UBS, C. Credit suisse global wealth report 2023.
Credit Suisse/UBS https://www.ubs.com/global/en/family-office-uhnw/reports/global-wealth-report-2023.html (2023)
Total global household wealth: USD 454.4 trillion (2022) Wealth declined by USD 11.3 trillion (-2.4%) in 2022, first decline since 2008 Wealth per adult: USD 84,718 Additional sources: https://www.ubs.com/global/en/family-office-uhnw/reports/global-wealth-report-2023.html
.
59.
budgets:, S. component country. Global government medical research spending ($67.5B, 2023–2024).
See component country budgets: NIH Budget #nih-budget-fy2025.
61.
budgets, E. from major foundation & activities. Nonprofit clinical trial funding estimate.
Nonprofit foundations spend an estimated $2-5 billion annually on clinical trials globally, representing approximately 2-5% of total clinical trial spending.
62.
IQVIA, I. reports: Global pharmaceutical r&d spending.
Total global pharmaceutical R&D spending is approximately $300 billion annually. Clinical trials represent 15-20% of this total ($45-60B), with the remainder going to drug discovery, preclinical research, regulatory affairs, and manufacturing development.
63.
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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64.
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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65.
NHGRI. Human genome project and CRISPR discovery.
NHGRI https://www.genome.gov/11006929/2003-release-international-consortium-completes-hgp (2003)
Your DNA is 3 billion base pairs Read the entire code (Human Genome Project, completed 2003) Learned to edit it (CRISPR, discovered 2012) Additional sources: https://www.genome.gov/11006929/2003-release-international-consortium-completes-hgp | https://www.nobelprize.org/prizes/chemistry/2020/press-release/
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66.
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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67.
WHO. ICD-10 code count ( 14,000).
WHO https://icd.who.int/browse10/2019/en (2019)
The ICD-10 classification contains approximately 14,000 codes for diseases, signs and symptoms. Additional sources: https://icd.who.int/browse10/2019/en
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68.
Wikipedia. Longevity escape velocity (LEV) - maximum human life extension potential.
Wikipedia: Longevity Escape Velocity https://en.wikipedia.org/wiki/Longevity_escape_velocity Longevity escape velocity: Hypothetical point where medical advances extend life expectancy faster than time passes Term coined by Aubrey de Grey (biogerontologist) in 2004 paper; concept from David Gobel (Methuselah Foundation) Current progress: Science adds 3 months to lifespan per year; LEV requires adding >1 year per year Sinclair (Harvard): "There is no biological upper limit to age" - first person to live to 150 may already be born De Grey: 50% chance of reaching LEV by mid-to-late 2030s; SENS approach = damage repair rather than slowing damage Kurzweil (2024): LEV by 2029-2035, AI will simulate biological processes to accelerate solutions George Church: LEV "in a decade or two" via age-reversal clinical trials Natural lifespan cap: 120-150 years (Jeanne Calment record: 122); engineering approach could bypass via damage repair Key mechanisms: Epigenetic reprogramming, senolytic drugs, stem cell therapy, gene therapy, AI-driven drug discovery Current record: Jeanne Calment (122 years, 164 days) - record unbroken since 1997 Note: LEV is theoretical but increasingly plausible given demonstrated age reversal in mice (109% lifespan extension) and human cells (30-year epigenetic age reversal) Additional sources: https://en.wikipedia.org/wiki/Longevity_escape_velocity | https://pmc.ncbi.nlm.nih.gov/articles/PMC423155/ | https://www.popularmechanics.com/science/a36712084/can-science-cure-death-longevity/ | https://www.diamandis.com/blog/longevity-escape-velocity
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69.
OpenSecrets. Lobbyist statistics for washington d.c.
OpenSecrets: Lobbying in US https://en.wikipedia.org/wiki/Lobbying_in_the_United_States Registered lobbyists: Over 12,000 (some estimates); 12,281 registered (2013) Former government employees as lobbyists: 2,200+ former federal employees (1998-2004), including 273 former White House staffers, 250 former Congress members & agency heads Congressional revolving door: 43% (86 of 198) lawmakers who left 1998-2004 became lobbyists; currently 59% leaving to private sector work for lobbying/consulting firms/trade groups Executive branch: 8% were registered lobbyists at some point before/after government service Additional sources: https://en.wikipedia.org/wiki/Lobbying_in_the_United_States | https://www.opensecrets.org/revolving-door | https://www.citizen.org/article/revolving-congress/ | https://www.propublica.org/article/we-found-a-staggering-281-lobbyists-whove-worked-in-the-trump-administration
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70.
Vaccines, M. Measles vaccination ROI.
MDPI Vaccines https://www.mdpi.com/2076-393X/12/11/1210 (2024)
Single measles vaccination: 167:1 benefit-cost ratio. MMR (measles-mumps-rubella) vaccination: 14:1 ROI. Historical US elimination efforts (1966-1974): benefit-cost ratio of 10.3:1 with net benefits exceeding USD 1.1 billion (1972 dollars, or USD 8.0 billion in 2023 dollars). 2-dose MMR programs show direct benefit/cost ratio of 14.2 with net savings of $5.3 billion, and 26.0 from societal perspectives with net savings of $11.6 billion. Additional sources: https://www.mdpi.com/2076-393X/12/11/1210 | https://www.tandfonline.com/doi/full/10.1080/14760584.2024.2367451
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73.
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.
74.
NIH. NIH budget (FY 2025).
NIH https://www.nih.gov/about-nih/organization/budget (2024)
The budget total of \(47.7 billion also includes\)1.412 billion derived from PHS Evaluation financing... Additional sources: https://www.nih.gov/about-nih/organization/budget | https://officeofbudget.od.nih.gov/
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75.
al., B. et. NIH spending on clinical trials: 3.3%.
Bentley et al. https://www.fiercebiotech.com/biotech/nih-spending-clinical-trials-reached-81b-over-decade (2023)
NIH spent $8.1 billion on clinical trials for approved drugs (2010-2019), representing 3.3% of relevant NIH spending. Additional sources: https://www.fiercebiotech.com/biotech/nih-spending-clinical-trials-reached-81b-over-decade | https://www.fiercebiotech.com/biotech/nih-spending-clinical-trials-reached-81b-over-decade
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76.
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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77.
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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78.
Trials. Patient willingness to participate in clinical trials.
Trials: Patients’ Willingness Survey https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-015-1105-3 Recent surveys: 49-51% willingness (2020-2022) - dramatic drop from 85% (2019) during COVID-19 pandemic Cancer patients when approached: 88% consented to trials (Royal Marsden Hospital) Study type variation: 44.8% willing for drug trial, 76.2% for diagnostic study Top motivation: "Learning more about my health/medical condition" (67.4%) Top barrier: "Worry about experiencing side effects" (52.6%) Additional sources: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-015-1105-3 | https://www.appliedclinicaltrialsonline.com/view/industry-forced-to-rethink-patient-participation-in-trials | https://pmc.ncbi.nlm.nih.gov/articles/PMC7183682/
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79.
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.
80.
Health, V. in. Average lifetime revenue per successful drug.
Value in Health: Sales Revenues for New Therapeutic Agents02754-2/fulltext) https://www.valueinhealthjournal.com/article/S1098-3015(24 Study of 361 FDA-approved drugs from 1995-2014 (median follow-up 13.2 years): Mean lifetime revenue: $15.2 billion per drug Median lifetime revenue: $6.7 billion per drug Revenue after 5 years: $3.2 billion (mean) Revenue after 10 years: $9.5 billion (mean) Revenue after 15 years: $19.2 billion (mean) Distribution highly skewed: top 25 drugs (7%) accounted for 38% of total revenue ($2.1T of $5.5T) Additional sources: https://www.valueinhealthjournal.com/article/S1098-3015(24 | https://www.sciencedirect.com/science/article/pii/S1098301524027542
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81.
Lichtenberg, F. R.
How many life-years have new drugs saved? A three-way fixed-effects analysis of 66 diseases in 27 countries, 2000-2013.
International Health 11, 403–416 (2019)
Using 3-way fixed-effects methodology (disease-country-year) across 66 diseases in 22 countries, this study estimates that drugs launched after 1981 saved 148.7 million life-years in 2013 alone. The regression coefficients for drug launches 0-11 years prior (beta=-0.031, SE=0.008) and 12+ years prior (beta=-0.057, SE=0.013) on years of life lost are highly significant (p<0.0001). Confidence interval for life-years saved: 79.4M-239.8M (95 percent CI) based on propagated standard errors from Table 2.
82.
Deloitte. Pharmaceutical r&d return on investment (ROI).
Deloitte: Measuring Pharmaceutical Innovation 2025 https://www.deloitte.com/ch/en/Industries/life-sciences-health-care/research/measuring-return-from-pharmaceutical-innovation.html (2025)
Deloitte’s annual study of top 20 pharma companies by R&D spend (2010-2024): 2024 ROI: 5.9% (second year of growth after decade of decline) 2023 ROI: 4.3% (estimated from trend) 2022 ROI: 1.2% (historic low since study began, 13-year low) 2021 ROI: 6.8% (record high, inflated by COVID-19 vaccines/treatments) Long-term trend: Declining for over a decade before 2023 recovery Average R&D cost per asset: $2.3B (2022), $2.23B (2024) These returns (1.2-5.9% range) fall far below typical corporate ROI targets (15-20%) Additional sources: https://www.deloitte.com/ch/en/Industries/life-sciences-health-care/research/measuring-return-from-pharmaceutical-innovation.html | https://www.prnewswire.com/news-releases/deloittes-13th-annual-pharmaceutical-innovation-report-pharma-rd-return-on-investment-falls-in-post-pandemic-market-301738807.html | https://hitconsultant.net/2023/02/16/pharma-rd-roi-falls-to-lowest-level-in-13-years/
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83.
Discovery, N. R. D. Drug trial success rate from phase i to approval.
Nature Reviews Drug Discovery: Clinical Success Rates https://www.nature.com/articles/nrd.2016.136 (2016)
Overall Phase I to approval: 10-12.8% (conventional wisdom 10%, studies show 12.8%) Recent decline: Average LOA now 6.7% for Phase I (2014-2023 data) Leading pharma companies: 14.3% average LOA (range 8-23%) Varies by therapeutic area: Oncology 3.4%, CNS/cardiovascular lowest at Phase III Phase-specific success: Phase I 47-54%, Phase II 28-34%, Phase III 55-70% Note: 12% figure accurate for historical average. Recent data shows decline to 6.7%, with Phase II as primary attrition point (28% success) Additional sources: https://www.nature.com/articles/nrd.2016.136 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6409418/ | https://academic.oup.com/biostatistics/article/20/2/273/4817524
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84.
SofproMed. Phase 3 cost per trial range.
SofproMed https://www.sofpromed.com/how-much-does-a-clinical-trial-cost Phase 3 clinical trials cost between $20 million and $282 million per trial, with significant variation by therapeutic area and trial complexity. Additional sources: https://www.sofpromed.com/how-much-does-a-clinical-trial-cost | https://www.cbo.gov/publication/57126
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85.
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 $27. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC6508852/
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86.
WHO. Polio vaccination ROI.
WHO https://www.who.int/news-room/feature-stories/detail/sustaining-polio-investments-offers-a-high-return (2019)
For every dollar spent, the return on investment is nearly US$ 39." Total investment cost of US$ 7.5 billion generates projected economic and social benefits of US$ 289.2 billion from sustaining polio assets and integrating them into expanded immunization, surveillance and emergency response programmes across 8 priority countries (Afghanistan, Iraq, Libya, Pakistan, Somalia, Sudan, Syria, Yemen). Additional sources: https://www.who.int/news-room/feature-stories/detail/sustaining-polio-investments-offers-a-high-return
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88.
Hayek, F. A.
The use of knowledge in society.
American Economic Review 35, 519–530 (1945)
The knowledge of the circumstances which we must make use of never exists in concentrated or integrated form but solely as dispersed bits of incomplete and frequently contradictory knowledge which all the separate individuals possess.
89.
Kydland, F. E. & Prescott, E. C.
Rules rather than discretion: The inconsistency of optimal plans.
Journal of Political Economy 85, 473–492 (1977)
Time-inconsistency describes situations where, with the passing of time, policies that were determined to be optimal yesterday are no longer perceived to be optimal today and are not implemented... This insight shifted the focus of policy analysis from the study of individual policy decisions to the design of institutions that mitigate the time consistency problem.
90.
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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91.
OpenSecrets.
Revolving door: Former members of congress. (2024)
388 former members of Congress are registered as lobbyists. Nearly 5,400 former congressional staffers have left Capitol Hill to become federal lobbyists in the past 10 years. Additional sources: https://www.opensecrets.org/revolving-door
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92.
Kinch, M. S. & Griesenauer, R. H.
Lost medicines: A longer view of the pharmaceutical industry with the potential to reinvigorate discovery.
Drug Discovery Today 24, 875–880 (2019)
Research identified 1,600+ medicines available in 1962. The 1950s represented industry high-water mark with >30 new products in five of ten years; this rate would not be replicated until late 1990s. More than half (880) of these medicines were lost following implementation of Kefauver-Harris Amendment. The peak of 1962 would not be seen again until early 21st century. By 2016 number of organizations actively involved in R&D at level not seen since 1914.
93.
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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94.
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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95.
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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96.
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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98.
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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99.
Museum, N. S. 11. M. &.
September 11 attack facts. (2024)
2,977 people were killed in the September 11, 2001 attacks: 2,753 at the World Trade Center, 184 at the Pentagon, and 40 passengers and crew on United Flight 93 in Shanksville, Pennsylvania.
100.
Bank, W. World bank singapore economic data.
World Bank https://data.worldbank.org/country/singapore (2024)
Singapore GDP per capita (2023): $82,000 - among highest in the world Government spending: 15% of GDP (vs US 38%) Life expectancy: 84.1 years (vs US 77.5 years) Singapore demonstrates that low government spending can coexist with excellent outcomes Additional sources: https://data.worldbank.org/country/singapore
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101.
Fund, I. M.
IMF singapore government spending data. (2024)
Singapore government spending is approximately 15% of GDP This is 23 percentage points lower than the United States (38%) Despite lower spending, Singapore achieves excellent outcomes: - Life expectancy: 84.1 years (vs US 77.5) - Low crime, world-class infrastructure, AAA credit rating Additional sources: https://www.imf.org/en/Countries/SGP
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102.
Organization, W. H.
WHO life expectancy data by country. (2024)
Life expectancy at birth varies significantly among developed nations: Switzerland: 84.0 years (2023) Singapore: 84.1 years (2023) Japan: 84.3 years (2023) United States: 77.5 years (2023) - 6.5 years below Switzerland, Singapore Global average: 73 years Note: US spends more per capita on healthcare than any other nation, yet achieves lower life expectancy Additional sources: https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-life-expectancy-and-healthy-life-expectancy
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104.
PMC. Contribution of smoking reduction to life expectancy gains.
PMC: Benefits Smoking Cessation Longevity https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1447499/ (2012)
Population-level: Up to 14% (9% men, 14% women) of total life expectancy gain since 1960 due to tobacco control efforts Individual cessation benefits: Quitting at age 35 adds 6.9-8.5 years (men), 6.1-7.7 years (women) vs continuing smokers By cessation age: Age 25-34 = 10 years gained; age 35-44 = 9 years; age 45-54 = 6 years; age 65 = 2.0 years (men), 3.7 years (women) Cessation before age 40: Reduces death risk by 90% Long-term cessation: 10+ years yields survival comparable to never smokers, averts 10 years of life lost Recent cessation: <3 years averts 5 years of life lost Additional sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1447499/ | https://www.cdc.gov/pcd/issues/2012/11_0295.htm | https://www.ajpmonline.org/article/S0749-3797(24 | https://www.nejm.org/doi/full/10.1056/NEJMsa1211128
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105.
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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106.
GAO. Annual cost of u.s. Sugar subsidies.
GAO: Sugar Program https://www.gao.gov/products/gao-24-106144 Consumer costs: $2.5-3.5 billion per year (GAO estimate) Net economic cost: $1 billion per year 2022: US consumers paid 2X world price for sugar Program costs $3-4 billion/year but no federal budget impact (costs passed directly to consumers via higher prices) Employment impact: 10,000-20,000 manufacturing jobs lost annually in sugar-reliant industries (confectionery, etc.) Multiple studies confirm: Sweetener Users Association ($2.9-3.5B), AEI ($2.4B consumer cost), Beghin & Elobeid ($2.9-3.5B consumer surplus) Additional sources: https://www.gao.gov/products/gao-24-106144 | https://www.heritage.org/agriculture/report/the-us-sugar-program-bad-consumers-bad-agriculture-and-bad-america | https://www.aei.org/articles/the-u-s-spends-4-billion-a-year-subsidizing-stalinist-style-domestic-sugar-production/
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107.
Bank, W. Swiss military budget as percentage of GDP.
World Bank: Military Expenditure https://data.worldbank.org/indicator/MS.MIL.XPND.GD.ZS?locations=CH 2023: 0.70272% of GDP (World Bank) 2024: CHF 5.95 billion official military spending When including militia system costs: 1% GDP (CHF 8.75B) Comparison: Near bottom in Europe; only Ireland, Malta, Moldova spend less (excluding microstates with no armies) Additional sources: https://data.worldbank.org/indicator/MS.MIL.XPND.GD.ZS?locations=CH | https://www.avenir-suisse.ch/en/blog-defence-spending-switzerland-is-in-better-shape-than-it-seems/ | https://tradingeconomics.com/switzerland/military-expenditure-percent-of-gdp-wb-data.html
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108.
Bank, W. Switzerland vs. US GDP per capita comparison.
World Bank: Switzerland GDP Per Capita https://data.worldbank.org/indicator/NY.GDP.PCAP.CD?locations=CH 2024 GDP per capita (PPP-adjusted): Switzerland $93,819 vs United States $75,492 Switzerland’s GDP per capita 24% higher than US when adjusted for purchasing power parity Nominal 2024: Switzerland $103,670 vs US $85,810 Additional sources: https://data.worldbank.org/indicator/NY.GDP.PCAP.CD?locations=CH | https://tradingeconomics.com/switzerland/gdp-per-capita-ppp | https://www.theglobaleconomy.com/USA/gdp_per_capita_ppp/
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109.
Economic Co-operation, O. for & Development.
OECD government spending as percentage of GDP. (2024)
OECD government spending data shows significant variation among developed nations: United States: 38.0% of GDP (2023) Switzerland: 35.0% of GDP - 3 percentage points lower than US Singapore: 15.0% of GDP - 23 percentage points lower than US (per IMF data) OECD average: approximately 40% of GDP Additional sources: https://data.oecd.org/gga/general-government-spending.htm
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110.
Economic Co-operation, O. for & Development.
OECD median household income comparison. (2024)
Median household disposable income varies significantly across OECD nations: United States: $77,500 (2023) Switzerland: $55,000 PPP-adjusted (lower nominal but comparable purchasing power) Singapore: $75,000 PPP-adjusted Additional sources: https://data.oecd.org/hha/household-disposable-income.htm
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111.
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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112.
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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113.
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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115.
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 \(19.0 million (\)12.2 million-\(33.1 million)... The clinical trials cost a median (IQR) of\)41,117 (\(31,802-\)82,362) per patient. Additional sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248200/
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116.
GBD 2019 Diseases and Injuries Collaborators.
Global burden of disease study 2019: Disability weights.
The Lancet 396, 1204–1222 (2020)
Disability weights for 235 health states used in Global Burden of Disease calculations. Weights range from 0 (perfect health) to 1 (death equivalent). Chronic conditions like diabetes (0.05-0.35), COPD (0.04-0.41), depression (0.15-0.66), and cardiovascular disease (0.04-0.57) show substantial variation by severity. Treatment typically reduces disability weights by 50-80 percent for manageable chronic conditions.
117.
WHO. Annual global economic burden of alzheimer’s and other dementias.
WHO: Dementia Fact Sheet https://www.who.int/news-room/fact-sheets/detail/dementia (2019)
Global cost: $1.3 trillion (2019 WHO-commissioned study) 50% from informal caregivers (family/friends, 5 hrs/day) 74% of costs in high-income countries despite 61% of patients in LMICs $818B (2010) → $1T (2018) → $1.3T (2019) - rapid growth Note: Costs increased 35% from 2010-2015 alone. Informal care represents massive hidden economic burden Additional sources: https://www.who.int/news-room/fact-sheets/detail/dementia | https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12901
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118.
Oncology, J. Annual global economic burden of cancer.
JAMA Oncology: Global Cost 2020-2050 https://jamanetwork.com/journals/jamaoncology/fullarticle/2801798 (2020)
2020-2050 projection: $25.2 trillion total ($840B/year average) 2010 annual cost: $1.16 trillion (direct costs only) Recent estimate: $3 trillion/year (all costs included) Top 5 cancers: lung (15.4%), colon/rectum (10.9%), breast (7.7%), liver (6.5%), leukemia (6.3%) Note: China/US account for 45% of global burden; 75% of deaths in LMICs but only 50.0% of economic cost Additional sources: https://jamanetwork.com/journals/jamaoncology/fullarticle/2801798 | https://www.nature.com/articles/d41586-023-00634-9
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120.
Care, D. Annual global economic burden of diabetes.
Diabetes Care: Global Economic Burden https://diabetesjournals.org/care/article/41/5/963/36522/Global-Economic-Burden-of-Diabetes-in-Adults 2015: $1.3 trillion (1.8% of global GDP) 2030 projections: $2.1T-2.5T depending on scenario IDF health expenditure: $760B (2019) → $845B (2045 projected) 2/3 direct medical costs ($857B), 1/3 indirect costs (lost productivity) Note: Costs growing rapidly; expected to exceed $2T by 2030 Additional sources: https://diabetesjournals.org/care/article/41/5/963/36522/Global-Economic-Burden-of-Diabetes-in-Adults | https://www.thelancet.com/journals/landia/article/PIIS2213-8587(17
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121.
World Bank, B. of E. A. US GDP 2024 ($28.78 trillion).
World Bank https://data.worldbank.org/indicator/NY.GDP.MKTP.CD?locations=US (2024)
US GDP reached $28.78 trillion in 2024, representing approximately 26% of global GDP. Additional sources: https://data.worldbank.org/indicator/NY.GDP.MKTP.CD?locations=US | https://www.bea.gov/news/2024/gross-domestic-product-fourth-quarter-and-year-2024-advance-estimate
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122.
Cardiology, I. J. of. Annual global economic burden of heart disease.
Int’l Journal of Cardiology: Global Heart Failure Burden02238-9/abstract) https://www.internationaljournalofcardiology.com/article/S0167-5273(13 (2050)
Heart failure alone: $108 billion/year (2012 global analysis, 197 countries) US CVD: $555B (2016) → projected $1.8T by 2050 LMICs total CVD loss: $3.7T cumulative (2011-2015, 5-year period) CVD is costliest disease category in most developed nations Note: No single $2.1T global figure found; estimates vary widely by scope and year Additional sources: https://www.internationaljournalofcardiology.com/article/S0167-5273(13 | https://www.ahajournals.org/doi/10.1161/CIR.0000000000001258
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123.
CSV, S. U. L. E. F. B. 1543-2019.
US life expectancy growth 1880-1960: 3.82 years per decade. (2019)
Pre-1962: 3.82 years/decade Post-1962: 1.54 years/decade Reduction: 60% decline in life expectancy growth rate Additional sources: https://ourworldindata.org/life-expectancy | https://www.mortality.org/ | https://www.cdc.gov/nchs/nvss/mortality_tables.htm
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124.
CSV, S. U. L. E. F. B. 1543-2019.
Post-1962 slowdown in life expectancy gains. (2019)
Pre-1962 (1880-1960): 3.82 years/decade Post-1962 (1962-2019): 1.54 years/decade Reduction: 60% decline Temporal correlation: Slowdown occurred immediately after 1962 Kefauver-Harris Amendment See detailed calculation: [life-expectancy-increase-pre-1962](#life-expectancy-increase-pre-1962) Additional sources: https://ourworldindata.org/life-expectancy | https://www.mortality.org/ | https://www.cdc.gov/nchs/nvss/mortality_tables.htm
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125.
Disease Control, C. for & Prevention.
US life expectancy 2023. (2024)
US life expectancy at birth was 77.5 years in 2023 Male life expectancy: 74.8 years Female life expectancy: 80.2 years This is 6-7 years lower than peer developed nations despite higher healthcare spending Additional sources: https://www.cdc.gov/nchs/fastats/life-expectancy.htm
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126.
Bureau, U. C.
US median household income 2023. (2024)
US median household income was $77,500 in 2023 Real median household income declined 0.8% from 2022 Gini index: 0.467 (income inequality measure) Additional sources: https://www.census.gov/library/publications/2024/demo/p60-282.html
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127.
Statista. US military budget as percentage of GDP.
Statista https://www.statista.com/statistics/262742/countries-with-the-highest-military-spending/ (2024)
U.S. military spending amounted to 3.5% of GDP in 2024. In 2024, the U.S. spent nearly $1 trillion on its military budget, equal to 3.4% of GDP. Additional sources: https://www.statista.com/statistics/262742/countries-with-the-highest-military-spending/ | https://www.sipri.org/sites/default/files/2025-04/2504_fs_milex_2024.pdf
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128.
Bureau, U. C. Number of registered or eligible voters in the u.s.
US Census Bureau https://www.census.gov/newsroom/press-releases/2025/2024-presidential-election-voting-registration-tables.html (2024)
73.6% (or 174 million people) of the citizen voting-age population was registered to vote in 2024 (Census Bureau). More than 211 million citizens were active registered voters (86.6% of citizen voting age population) according to the Election Assistance Commission. Additional sources: https://www.census.gov/newsroom/press-releases/2025/2024-presidential-election-voting-registration-tables.html | https://www.eac.gov/news/2025/06/30/us-election-assistance-commission-releases-2024-election-administration-and-voting
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129.
Senate, U. S. Treaties.
U.S. Senate https://www.senate.gov/about/powers-procedures/treaties.htm The Constitution provides that the president ’shall have Power, by and with the Advice and Consent of the Senate, to make Treaties, provided two-thirds of the Senators present concur’ (Article II, section 2). Treaties are formal agreements with foreign nations that require two-thirds Senate approval. 67 senators (two-thirds of 100) must vote to ratify a treaty for it to take effect. Additional sources: https://www.senate.gov/about/powers-procedures/treaties.htm
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130.
Commission, F. E.
Statistical summary of 24-month campaign activity of the 2023-2024 election cycle. (2023)
Presidential candidates raised $2 billion; House and Senate candidates raised $3.8 billion and spent $3.7 billion; PACs raised $15.7 billion and spent $15.5 billion. Total federal campaign spending approximately $20 billion. Additional sources: https://www.fec.gov/updates/statistical-summary-of-24-month-campaign-activity-of-the-2023-2024-election-cycle/
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131.
OpenSecrets.
Federal lobbying hit record $4.4 billion in 2024. (2024)
Total federal lobbying reached record $4.4 billion in 2024. The $150 million increase in lobbying continues an upward trend that began in 2016. Additional sources: https://www.opensecrets.org/news/2025/02/federal-lobbying-set-new-record-in-2024/
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132.
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.
133.
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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134.
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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136.
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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137.
Institute, I. B. Chronic illness workforce productivity loss.
Integrated Benefits Institute 2024 https://www.ibiweb.org/resources/chronic-conditions-in-the-us-workforce-prevalence-trends-and-productivity-impacts (2024)
78.4% of U.S. employees have at least one chronic condition (7% increase since 2021) 58% of employees report physical chronic health conditions 28% of all employees experience productivity loss due to chronic conditions Average productivity loss: $4,798 per employee per year Employees with 3+ chronic conditions miss 7.8 days annually vs 2.2 days for those without Note: 28% productivity loss translates to roughly 11 hours per week (28% of 40-hour workweek) Additional sources: https://www.ibiweb.org/resources/chronic-conditions-in-the-us-workforce-prevalence-trends-and-productivity-impacts | https://www.onemedical.com/mediacenter/study-finds-more-than-half-of-employees-are-living-with-chronic-conditions-including-1-in-3-gen-z-and-millennial-employees/ | https://debeaumont.org/news/2025/poll-the-toll-of-chronic-health-conditions-on-employees-and-workplaces/
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138.
FDAReview.org. Estimated deaths due to FDA delay in approving beta blockers.
FDAReview.org: FDA Harm https://www.fdareview.org/issues/theory-evidence-and-examples-of-fda-harm/ (2011)
Beta blockers approved in Europe mid-1970s, FDA didn’t approve until 1981 FDA estimated the drug could save 17,000 lives/year after approval Estimated 100,000 deaths from secondary heart attacks during 6-7 year delay Note: FDA imposed moratorium due to possible animal carcinogenicity despite human clinical evidence from 1974 Additional sources: https://www.fdareview.org/issues/theory-evidence-and-examples-of-fda-harm/ | https://www.ocregister.com/2011/02/09/walter-williams-death-by-fda-delay-denials/
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139.
Drugs.com. Time to develop one drug: 17 years.
Drugs.com https://www.drugs.com/fda-approval-process.html Time to develop one drug: 17 years Additional sources: https://www.drugs.com/fda-approval-process.html | https://www.fdareview.org/issues/the-drug-development-and-approval-process/
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140.
GovTrack. Kefauver harris amendment of 1962.
GovTrack https://www.govtrack.us/congress/bills/87/s1552 (1962)
regulating efficacy testing via the 1962 Kefauver Harris Amendment. The 1962 regulations made these large real-world efficacy trials illegal. Additional sources: https://www.govtrack.us/congress/bills/87/s1552 | https://www.fda.gov/about-fda/histories-product-regulation/promoting-safe-effective-drugs-100-years | https://pmc.ncbi.nlm.nih.gov/articles/PMC4101807/
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141.
FEE. Patients and doctors vs FDA.
FEE: Patients and Doctors vs FDA https://fee.org/articles/patients-and-doctors-vs-the-fda Dale Gieringer (1985): 21,000-120,000 lives lost per decade from FDA delay Gieringer: "Loss of life from delay alone in the hundreds of thousands" (not millions) Beta-blockers alone: William Wardell estimated "10,000 lives/year" if allowed; FDA delay 1965-1976 Sam Peltzman: Post-1962 death toll from regulatory delay "easily number in thousands per year Practolol (beta-blocker): "Could save 10,000 lives/year" (Wardell estimate) FDA allowed propranolol 1968 (3 years after Europe); for hypertension/angina not until 1978 Note: "4-10 million" figure not found in sources. Gieringer’s estimates: 21K-120K deaths per decade, "hundreds of thousands" total (not millions). Specific drug delays (beta-blockers): 100K deaths estimated Additional sources: https://fee.org/articles/patients-and-doctors-vs-the-fda | https://www.econlib.org/library/Enc/DrugLag.html | https://www.fdareview.org/issues/theory-evidence-and-examples-of-fda-harm/
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142.
CRS. Evidence of FDA regulatory capture by pharmaceutical industry.
CRS: FDA Human Medical Product User Fees https://www.congress.gov/crs-product/R44750 FY2023: User fees = 75% of PDUFA program costs (vs 7% in FY1993) FY2022: User fees = 66% ($1.4B) of human drugs program budget FY2022: User fees = 46% ($2.9B) of FDA’s total $6.2B budget Pharma finances 75% of FDA’s drug division (New York Times) Concerns: Budgetary dependence, urgency of PDUFA reauthorizations, required industry participation in negotiations Most PDUFA policy changes favor industry: decreased regulatory standards, shorter approval times, increased industry involvement FDA maintains decisions based on science, not fee collection ability Note: Regulatory capture concerns well-documented. Industry funding grew from 7% (1993) to 75% (2023) of drug review program. No evidence found for "10x government salary" claim for FDA reviewers Additional sources: https://www.congress.gov/crs-product/R44750 | https://aspe.hhs.gov/sites/default/files/documents/e4a7910607c0dd76c40aa61151d154f9/FDA-User-Fee-Issue-Brief.pdf | https://pmc.ncbi.nlm.nih.gov/articles/PMC8917050/
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143.
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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144.
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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145.
FDLI. Japan’s regenerative medicine act and conditional approval pathway.
FDLI: Japan’s Regen Med Pathways https://www.fdli.org/2019/02/global-focus-japans-regenerative-medicine-regulatory-pathways-encouraging-innovation-and-patient-access/ (2019)
Act on Safety of Regenerative Medicine (RM Act) + amended Pharmaceuticals and Medical Devices Act (PMD Act): passed Nov 2013, effective Nov 2014 Conditional and time-limited approval pathway: Obtain approval after exploratory trials demonstrate probable benefit and proven safety 7-year conditional approval period to confirm clinical benefit (e.g., using surrogate endpoints) SAKIGAKE designation (April 2015): Expedited pathway for innovative products targeting serious/life-threatening diseases without effective treatment Benefits: Prioritized consultation, accelerated review, extended re-examination period, premium pricing Examples: Terumo’s HeartSheet and Stemirac obtained conditional approval; Stemirac also SAKIGAKE-designated Additional sources: https://www.fdli.org/2019/02/global-focus-japans-regenerative-medicine-regulatory-pathways-encouraging-innovation-and-patient-access/ | https://www.insights.bio/cell-and-gene-therapy-insights/journal/article/310/Experiences-from-Japan-SAKIGAKE-Designation-System-for-Regenerative-Medical-Products | https://pmc.ncbi.nlm.nih.gov/articles/PMC6696404/
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146.
EMA. EU compassionate use program for experimental drugs.
EMA: Compassionate Use https://www.ema.europa.eu/en/human-regulatory-overview/research-development/compassionate-use Established by: Article 83 of Regulation (EC) No 726/2004 Eligibility: Life-threatening, long-lasting, or seriously debilitating illnesses Requires: No satisfactory authorized treatment; medicine in trials or approval process EMA role: CHMP provides recommendations; national authorities implement programs Pan-European programs rare: Only 6 approved by EMA in last 10 years vs hundreds of national programs Each EU member state sets own rules and procedures Note: Pan-European framework exists but rarely used due to complex navigation across varying national regulations. Most programs remain country-specific Additional sources: https://www.ema.europa.eu/en/human-regulatory-overview/research-development/compassionate-use | https://pmc.ncbi.nlm.nih.gov/articles/PMC5116859/ | https://www.eurordis.org/information-support/compassionate-use/
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148.
PMC. Number of patients helped by the u.s. Right to try act.
PMC: Understanding Right to Try https://pmc.ncbi.nlm.nih.gov/articles/PMC7416898/ (2024)
2018-2022: Supported access to only 12 products total; 4 products in 2023 Number of people treated: Not publicly reported, "likely only in the hundreds Specific documented cases: 75+ neuroendocrine cancer patients (LU-177); at least 1 ALS patient (NurOwn); 7 glioblastoma patients (Gliovac) Minimal safety reporting: Only annual basis, no requirement to publish results/outcomes Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC7416898/ | https://www.statnews.com/2024/08/02/trump-gave-patients-right-to-try-it-hasnt-helped-them/ | https://www.healio.com/news/hematology-oncology/20200303/right-to-try-a-wellintentioned-but-misguided-law
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149.
CNN. FDA delay in approving rapid COVID-19 tests.
CNN: How Government Delayed Testing https://www.cnn.com/2020/04/09/politics/coronavirus-testing-cdc-fda-red-tape-invs/index.html (2020)
Feb 16, 2020: Seattle research lab ordered to stop COVID testing without FDA approval May 2020: Gates Foundation partnership instructed to discontinue testing until authorization Feb 29, 2020: U. Nebraska finally got FDA permission after Feb 4 special permission Timeline: Critical delays measured in weeks-to-months (Feb-March 2020), not specific "6 months FDA guidance suggested EUAs needed for laboratory-developed tests (LDTs), causing delays By May 2020: 400+ test applications awaiting FDA review Note: Delays were weeks-to-months during critical Feb-March 2020 period, not continuous "6 months." FDA intervention added minimal value while contributing to deadly delays Additional sources: https://www.cnn.com/2020/04/09/politics/coronavirus-testing-cdc-fda-red-tape-invs/index.html | https://www.yalelawjournal.org/forum/deadly-delay-the-fdas-role-in-americas-covid-testing-debacle | https://oig.hhs.gov/oei/reports/OEI-01-20-00380.asp
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150.
NPR. Contamination of early CDC COVID-19 tests in 2020.
NPR: CDC Test Flawed https://www.npr.org/2020/11/06/929078678/cdc-report-officials-knew-coronavirus-test-was-flawed-but-released-it-anyway (2020)
CDC distributed flawed test kits Feb 6, 2020 - contaminated reagents caused false positives 24 of 26 public health labs found contamination, CDC recalled kits by Feb 10 Tests made in CDC lab (not manufacturing facility), violated sound manufacturing practices Contamination occurred in Respiratory Virus Diagnostic Lab during processing Note: Delays had significant consequences for early pandemic tracking and response Additional sources: https://www.npr.org/2020/11/06/929078678/cdc-report-officials-knew-coronavirus-test-was-flawed-but-released-it-anyway | https://www.cnn.com/2020/04/18/politics/cdc-coronavirus-testing-contamination/index.html
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151.
PMC. Estimated excess deaths attributed to FDA’s COVID-19 response.
PMC: EUAs vs FDA Approval Implications https://pmc.ncbi.nlm.nih.gov/articles/PMC8101583/ FDA regulations restricted clinician/patient access to COVID-19 testing, remdesivir, vaccines General drug delay estimate: 37,000-76,000 deaths per one-year delay Testing delays: By May 2020, 400+ applications awaiting FDA review Seattle lab ordered to stop testing Feb 16 for lack of FDA approval Gates Foundation partnership instructed to discontinue testing May 2020 until authorization EUA process prevented months of vaccine/testing delays Note: Specific "500,000+" figure not found in sources. Research shows FDA testing restrictions caused weeks-to-months of critical delays (Feb-March 2020). One-year drug delay = 37-76K deaths Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC8101583/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC8012986/ | https://www.yalelawjournal.org/forum/deadly-delay-the-fdas-role-in-americas-covid-testing-debacle
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152.
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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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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