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Methodology, Parameters, and Calculations

Parameter definitions, formulas, uncertainty ranges, and data sources.
Author
Affiliation

Mike P. Sinn

Keywords

health economics methodology, clinical trial cost analysis, medical research ROI, cost-benefit analysis healthcare, sensitivity analysis, Monte Carlo simulation, DALY calculation, pragmatic clinical trials

Overview

This appendix documents all 32 parameters used in the analysis, organized by type:

  • External sources (peer-reviewed): 16
  • Calculated values: 14
  • Core definitions: 2

Quick Navigation

Calculated Values (14 parameters) β€’ External Data Sources (16 parameters) β€’ Core Definitions (2 parameters)

Calculated Values

Parameters derived from mathematical formulas and economic models.

Annual Funding from 1% of Global Military Spending Redirected to DIH: $27.2B

Annual funding from 1% of global military spending redirected to DIH

Inputs:

\[ \begin{gathered} Funding_{treaty} \\ = Spending_{mil} \times Reduce_{treaty} \\ = \$2.72T \times 1\% \\ = \$27.2B \end{gathered} \]

βœ“ High confidence

US Discretionary Efficiency: 40.5%

US federal discretionary spending efficiency. What fraction of discretionary spending avoids direct waste (Cat 1 only: military overspend, corporate welfare, drug war, fossil/ag subsidies). ~41%. Some Cat 1 items (farm subsidies, tax expenditures) are technically mandatory/off-budget but are fungible policy choices.

Inputs:

\[ \begin{gathered} E_{US,disc} \\ = 1 - \frac{W_{cat1}}{Spending_{fed}} \\ = 1 - \frac{\$1.01T}{\$1.7T} \\ = 40.5\% \\[0.5em] \text{where } W_{cat1} \\ = W_{military} + W_{corporate} + W_{drugs} \\ + W_{fossil} + W_{agriculture} \\ = \$615B + \$181B + \$90B + \$50B + \$75B \\ = \$1.01T \end{gathered} \]

~ Medium confidence

Sensitivity Analysis

Sensitivity Indices for US Discretionary Efficiency

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Category 1 Direct Spending -1.0000 Strong driver

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: US Discretionary Efficiency (10,000 simulations)

Monte Carlo Distribution: US Discretionary Efficiency (10,000 simulations)

Simulation Results Summary: US Discretionary Efficiency

Statistic Value
Baseline (deterministic) 40.5%
Mean (expected value) 40.5%
Median (50th percentile) 41.3%
Standard Deviation 8.61%
90% Range (5th-95th percentile) [23.8%, 53.5%]

The histogram shows the distribution of US Discretionary Efficiency across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: US Discretionary Efficiency

Probability of Exceeding Threshold: US Discretionary Efficiency

This exceedance probability chart shows the likelihood that US Discretionary Efficiency will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

US Governance Efficiency (GDP): 83%

Total US governance efficiency: all 4 waste categories as share of GDP. 1 - ($4.9T / $28.78T) = ~83%. This broader metric captures direct spending waste, compliance burden, policy-induced GDP loss, and system inefficiency relative to total economic output.

Inputs:

\[ \begin{gathered} E_{US,GDP} = 1 - \frac{W_{total,US}}{USGDP} = 1 - \frac{\$4.9T}{\$28.8T} = 83\% \\[0.5em] \text{where } W_{total,US} = W_{raw,US} \times US = \$4.9T \times 1 = \$4.9T \\[0.5em] \text{where } W_{raw,US} \\ = W_{health} + W_{housing} + W_{military} \\ + W_{regulatory} + W_{tax} + W_{corporate} \\ + W_{tariffs} + W_{drugs} + W_{fossil} \\ + W_{agriculture} \\ = \$1.2T + \$1.4T + \$615B + \$580B + \$546B \\ + \$181B + \$160B + \$90B + \$50B + \$75B \\ = \$4.9T \end{gathered} \]

~ Medium confidence

Sensitivity Analysis

Sensitivity Indices for US Governance Efficiency (GDP)

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Total -1.0000 Strong driver

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: US Governance Efficiency (GDP) (10,000 simulations)

Monte Carlo Distribution: US Governance Efficiency (GDP) (10,000 simulations)

Simulation Results Summary: US Governance Efficiency (GDP)

Statistic Value
Baseline (deterministic) 83%
Mean (expected value) 83%
Median (50th percentile) 83.3%
Standard Deviation 2.91%
90% Range (5th-95th percentile) [77.4%, 87.4%]

The histogram shows the distribution of US Governance Efficiency (GDP) across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: US Governance Efficiency (GDP)

Probability of Exceeding Threshold: US Governance Efficiency (GDP)

This exceedance probability chart shows the likelihood that US Governance Efficiency (GDP) will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

Category 1: Direct Spending Waste: $1.01T

Category 1: Direct Federal Spending Waste. Actual federal budget allocations that could be redirected. Includes military overspend ($615B), corporate welfare ($181B), drug war ($90B), fossil fuel subsidies ($50B), and agricultural subsidies ($75B). Total: ~$1.01T annually. Solution: Budget reallocation.

Inputs:

\[ \begin{gathered} W_{cat1} \\ = W_{military} + W_{corporate} + W_{drugs} + W_{fossil} \\ + W_{agriculture} \\ = \$615B + \$181B + \$90B + \$50B + \$75B \\ = \$1.01T \end{gathered} \]

~ Medium confidence

Sensitivity Analysis

Sensitivity Indices for Category 1: Direct Spending Waste

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Military Overspend 0.4685 Moderate driver
US Gov Waste Drug War 0.1752 Weak driver
US Gov Waste Agricultural Subsidies 0.1424 Weak driver
US Gov Waste Corporate Welfare 0.1265 Weak driver
US Gov Waste Fossil Fuel Subsidies 0.0922 Minimal effect

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: Category 1: Direct Spending Waste (10,000 simulations)

Monte Carlo Distribution: Category 1: Direct Spending Waste (10,000 simulations)

Simulation Results Summary: Category 1: Direct Spending Waste

Statistic Value
Baseline (deterministic) $1.01T
Mean (expected value) $1.01T
Median (50th percentile) $998B
Standard Deviation $146B
90% Range (5th-95th percentile) [$790B, $1.30T]

The histogram shows the distribution of Category 1: Direct Spending Waste across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: Category 1: Direct Spending Waste

Probability of Exceeding Threshold: Category 1: Direct Spending Waste

This exceedance probability chart shows the likelihood that Category 1: Direct Spending Waste will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

Category 2: Compliance Burden: $1.13T

Category 2: Compliance Burden on Private Sector. Private sector resources consumed by government-imposed compliance requirements. Includes tax compliance ($546B) and regulatory red tape ($580B). Total: ~$1.13T annually. Solution: Simplification (tax code reform, regulatory streamlining).

Inputs:

\[ \begin{gathered} W_{cat2} \\ = W_{tax} + W_{regulatory} \\ = \$546B + \$580B \\ = \$1.13T \end{gathered} \]

~ Medium confidence

Sensitivity Analysis

Sensitivity Indices for Category 2: Compliance Burden

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Regulatory Red Tape 0.7928 Strong driver
US Gov Waste Tax Compliance 0.2095 Weak driver

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: Category 2: Compliance Burden (10,000 simulations)

Monte Carlo Distribution: Category 2: Compliance Burden (10,000 simulations)

Simulation Results Summary: Category 2: Compliance Burden

Statistic Value
Baseline (deterministic) $1.13T
Mean (expected value) $1.12T
Median (50th percentile) $1.09T
Standard Deviation $230B
90% Range (5th-95th percentile) [$775B, $1.58T]

The histogram shows the distribution of Category 2: Compliance Burden across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: Category 2: Compliance Burden

Probability of Exceeding Threshold: Category 2: Compliance Burden

This exceedance probability chart shows the likelihood that Category 2: Compliance Burden will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

Category 3: GDP Loss: $1.56T

Category 3: Policy-Induced GDP Loss. Economic output foregone due to policy constraints on markets. Includes housing/zoning restrictions ($1.4T) and tariffs ($160B). Total: ~$1.56T annually. Solution: Policy reform (zoning liberalization, trade policy).

Inputs:

\[ \begin{gathered} W_{cat3} \\ = W_{housing} + W_{tariffs} \\ = \$1.4T + \$160B \\ = \$1.56T \end{gathered} \]

~ Medium confidence

Sensitivity Analysis

Sensitivity Indices for Category 3: GDP Loss

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Housing Zoning 0.8636 Strong driver
US Gov Waste Tariffs 0.1372 Weak driver

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: Category 3: GDP Loss (10,000 simulations)

Monte Carlo Distribution: Category 3: GDP Loss (10,000 simulations)

Simulation Results Summary: Category 3: GDP Loss

Statistic Value
Baseline (deterministic) $1.56T
Mean (expected value) $1.55T
Median (50th percentile) $1.52T
Standard Deviation $327B
90% Range (5th-95th percentile) [$1.05T, $2.18T]

The histogram shows the distribution of Category 3: GDP Loss across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: Category 3: GDP Loss

Probability of Exceeding Threshold: Category 3: GDP Loss

This exceedance probability chart shows the likelihood that Category 3: GDP Loss will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

Category 4: System Inefficiency: $1.20T

Category 4: Total System Inefficiency. Fundamental system design failures requiring structural redesign. Currently only healthcare system inefficiency ($1.2T). Solution: System redesign using competitive market models (Singapore’s catastrophic coverage + HSAs, Switzerland’s regulated competition).

Inputs:

\[ W_{cat4} = W_{health} = \$1.2T = \$1.2T \]

βœ“ High confidence

Sensitivity Analysis

Sensitivity Indices for Category 4: System Inefficiency

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Healthcare Inefficiency 1.0000 Strong driver

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: Category 4: System Inefficiency (10,000 simulations)

Monte Carlo Distribution: Category 4: System Inefficiency (10,000 simulations)

Simulation Results Summary: Category 4: System Inefficiency

Statistic Value
Baseline (deterministic) $1.20T
Mean (expected value) $1.20T
Median (50th percentile) $1.20T
Standard Deviation $135B
90% Range (5th-95th percentile) [$1T, $1.45T]

The histogram shows the distribution of Category 4: System Inefficiency across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: Category 4: System Inefficiency

Probability of Exceeding Threshold: Category 4: System Inefficiency

This exceedance probability chart shows the likelihood that Category 4: System Inefficiency will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

US Waste (% GDP): 17%

US government waste as percentage of GDP. ~$4.90T waste / $28.78T GDP = ~17%. This represents the β€˜dysfunction tax’ that American citizens effectively pay through inefficient governance.

Inputs:

\[ \begin{gathered} W_{US,\%GDP} = \frac{W_{total,US}}{USGDP} = \frac{\$4.9T}{\$28.8T} = 17\% \\[0.5em] \text{where } W_{total,US} = W_{raw,US} \times US = \$4.9T \times 1 = \$4.9T \\[0.5em] \text{where } W_{raw,US} \\ = W_{health} + W_{housing} + W_{military} \\ + W_{regulatory} + W_{tax} + W_{corporate} \\ + W_{tariffs} + W_{drugs} + W_{fossil} \\ + W_{agriculture} \\ = \$1.2T + \$1.4T + \$615B + \$580B + \$546B \\ + \$181B + \$160B + \$90B + \$50B + \$75B \\ = \$4.9T \end{gathered} \]

~ Medium confidence

Sensitivity Analysis

Sensitivity Indices for US Waste (% GDP)

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Total 1.0000 Strong driver

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: US Waste (% GDP) (10,000 simulations)

Monte Carlo Distribution: US Waste (% GDP) (10,000 simulations)

Simulation Results Summary: US Waste (% GDP)

Statistic Value
Baseline (deterministic) 17%
Mean (expected value) 17%
Median (50th percentile) 16.7%
Standard Deviation 2.91%
90% Range (5th-95th percentile) [12.6%, 22.6%]

The histogram shows the distribution of US Waste (% GDP) across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: US Waste (% GDP)

Probability of Exceeding Threshold: US Waste (% GDP)

This exceedance probability chart shows the likelihood that US Waste (% GDP) will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

US Waste (QALY Equivalents): 49.0 million QALYs

US government waste expressed as QALY equivalents. This is an economic equivalent, NOT epidemiological health outcomes. Dividing by QALY threshold yields a measure of foregone welfare.

Inputs:

\[ \begin{gathered} W_{US,QALY} = \frac{W_{total,US}}{QALY_{threshold}} = \frac{\$4.9T}{\$100K} = 49M \\[0.5em] \text{where } W_{total,US} = W_{raw,US} \times US = \$4.9T \times 1 = \$4.9T \\[0.5em] \text{where } W_{raw,US} \\ = W_{health} + W_{housing} + W_{military} \\ + W_{regulatory} + W_{tax} + W_{corporate} \\ + W_{tariffs} + W_{drugs} + W_{fossil} \\ + W_{agriculture} \\ = \$1.2T + \$1.4T + \$615B + \$580B + \$546B \\ + \$181B + \$160B + \$90B + \$50B + \$75B \\ = \$4.9T \end{gathered} \]

~ Medium confidence

Sensitivity Analysis

Sensitivity Indices for US Waste (QALY Equivalents)

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Total 1.0000 Strong driver

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: US Waste (QALY Equivalents) (10,000 simulations)

Monte Carlo Distribution: US Waste (QALY Equivalents) (10,000 simulations)

Simulation Results Summary: US Waste (QALY Equivalents)

Statistic Value
Baseline (deterministic) 49.0 million
Mean (expected value) 48.9 million
Median (50th percentile) 48.1 million
Standard Deviation 8.38 million
90% Range (5th-95th percentile) [36.2 million, 65.0 million]

The histogram shows the distribution of US Waste (QALY Equivalents) across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: US Waste (QALY Equivalents)

Probability of Exceeding Threshold: US Waste (QALY Equivalents)

This exceedance probability chart shows the likelihood that US Waste (QALY Equivalents) will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

US Gov Waste (Raw Total): $4.90T

Raw sum of US government waste components before overlap discount: healthcare ($1.2T) + housing ($1.4T) + military ($615B) + regulatory ($580B) + tax ($546B) + corporate ($181B) + tariffs ($160B) + drug war ($90B) + fossil fuel ($50B) + agriculture ($75B) = ~$4.9T raw.

Inputs:

\[ \begin{gathered} W_{raw,US} \\ = W_{health} + W_{housing} + W_{military} + W_{regulatory} \\ + W_{tax} + W_{corporate} + W_{tariffs} + W_{drugs} \\ + W_{fossil} + W_{agriculture} \\ = \$1.2T + \$1.4T + \$615B + \$580B + \$546B + \$181B + \$160B \\ + \$90B + \$50B + \$75B \\ = \$4.9T \end{gathered} \]

~ Medium confidence

Sensitivity Analysis

Sensitivity Indices for US Gov Waste (Raw Total)

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Housing Zoning 0.3376 Moderate driver
US Gov Waste Regulatory Red Tape 0.2172 Weak driver
US Gov Waste Healthcare Inefficiency 0.1614 Weak driver
US Gov Waste Military Overspend 0.0819 Minimal effect
US Gov Waste Tax Compliance 0.0574 Minimal effect
US Gov Waste Tariffs 0.0536 Minimal effect
US Gov Waste Drug War 0.0306 Minimal effect
US Gov Waste Agricultural Subsidies 0.0249 Minimal effect
US Gov Waste Corporate Welfare 0.0221 Minimal effect
US Gov Waste Fossil Fuel Subsidies 0.0161 Minimal effect

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: US Gov Waste (Raw Total) (10,000 simulations)

Monte Carlo Distribution: US Gov Waste (Raw Total) (10,000 simulations)

Simulation Results Summary: US Gov Waste (Raw Total)

Statistic Value
Baseline (deterministic) $4.90T
Mean (expected value) $4.89T
Median (50th percentile) $4.81T
Standard Deviation $838B
90% Range (5th-95th percentile) [$3.62T, $6.50T]

The histogram shows the distribution of US Gov Waste (Raw Total) across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: US Gov Waste (Raw Total)

Probability of Exceeding Threshold: US Gov Waste (Raw Total)

This exceedance probability chart shows the likelihood that US Gov Waste (Raw Total) will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

Recoverable Capital: $2.45T

Recoverable capital if US improved to OECD median efficiency. Current US efficiency ~38-48%; OECD median ~75-85%. Closing to ~80% would recover approximately half the gap.

Inputs:

\[ \begin{gathered} W_{US,recoverable} \\ = W_{total,US} \times 0.5 \\ = \$4.9T \times 0.5 \\ = \$2.45T \\[0.5em] \text{where } W_{total,US} = W_{raw,US} \times US = \$4.9T \times 1 = \$4.9T \\[0.5em] \text{where } W_{raw,US} \\ = W_{health} + W_{housing} + W_{military} \\ + W_{regulatory} + W_{tax} + W_{corporate} \\ + W_{tariffs} + W_{drugs} + W_{fossil} \\ + W_{agriculture} \\ = \$1.2T + \$1.4T + \$615B + \$580B + \$546B \\ + \$181B + \$160B + \$90B + \$50B + \$75B \\ = \$4.9T \end{gathered} \]

? Low confidence

Sensitivity Analysis

Sensitivity Indices for Recoverable Capital

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Total 1.0000 Strong driver

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: Recoverable Capital (10,000 simulations)

Monte Carlo Distribution: Recoverable Capital (10,000 simulations)

Simulation Results Summary: Recoverable Capital

Statistic Value
Baseline (deterministic) $2.45T
Mean (expected value) $2.44T
Median (50th percentile) $2.41T
Standard Deviation $419B
90% Range (5th-95th percentile) [$1.81T, $3.25T]

The histogram shows the distribution of Recoverable Capital across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: Recoverable Capital

Probability of Exceeding Threshold: Recoverable Capital

This exceedance probability chart shows the likelihood that Recoverable Capital will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

US Government Waste (Total): $4.90T

Total annual US government waste (additive sum of components). Consolidates healthcare ($1.2T), housing ($1.4T), military ($615B), regulatory ($580B), tax ($546B), corporate ($181B), tariffs ($160B), drug war ($90B), fossil fuel ($50B), agriculture ($75B). Categories treated as additive; any overlap offset by excluded categories (state/local inefficiency, implicit subsidies, behavioral effects). ~$4.9T annually.

Inputs:

\[ \begin{gathered} W_{total,US} = W_{raw,US} \times US = \$4.9T \times 1 = \$4.9T \\[0.5em] \text{where } W_{raw,US} \\ = W_{health} + W_{housing} + W_{military} \\ + W_{regulatory} + W_{tax} + W_{corporate} \\ + W_{tariffs} + W_{drugs} + W_{fossil} \\ + W_{agriculture} \\ = \$1.2T + \$1.4T + \$615B + \$580B + \$546B \\ + \$181B + \$160B + \$90B + \$50B + \$75B \\ = \$4.9T \end{gathered} \]

~ Medium confidence

Sensitivity Analysis

Sensitivity Indices for US Government Waste (Total)

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Raw Total 1.0000 Strong driver

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: US Government Waste (Total) (10,000 simulations)

Monte Carlo Distribution: US Government Waste (Total) (10,000 simulations)

Simulation Results Summary: US Government Waste (Total)

Statistic Value
Baseline (deterministic) $4.90T
Mean (expected value) $4.89T
Median (50th percentile) $4.81T
Standard Deviation $838B
90% Range (5th-95th percentile) [$3.62T, $6.50T]

The histogram shows the distribution of US Government Waste (Total) across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: US Government Waste (Total)

Probability of Exceeding Threshold: US Government Waste (Total)

This exceedance probability chart shows the likelihood that US Government Waste (Total) will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

US Waste (VSL Equivalents): 357 thousand people

US government waste expressed as VSL equivalents. This is an economic equivalent, NOT literal deaths. Dividing the efficiency gap by VSL yields a measure of foregone welfare.

Inputs:

\[ \begin{gathered} W_{US,VSL} = \frac{W_{total,US}}{VSL_{DOT}} = \frac{\$4.9T}{\$13.7M} = 357{,}000 \\[0.5em] \text{where } W_{total,US} = W_{raw,US} \times US = \$4.9T \times 1 = \$4.9T \\[0.5em] \text{where } W_{raw,US} \\ = W_{health} + W_{housing} + W_{military} \\ + W_{regulatory} + W_{tax} + W_{corporate} \\ + W_{tariffs} + W_{drugs} + W_{fossil} \\ + W_{agriculture} \\ = \$1.2T + \$1.4T + \$615B + \$580B + \$546B \\ + \$181B + \$160B + \$90B + \$50B + \$75B \\ = \$4.9T \end{gathered} \]

~ Medium confidence

Sensitivity Analysis

Sensitivity Indices for US Waste (VSL Equivalents)

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Total 1.0000 Strong driver

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: US Waste (VSL Equivalents) (10,000 simulations)

Monte Carlo Distribution: US Waste (VSL Equivalents) (10,000 simulations)

Simulation Results Summary: US Waste (VSL Equivalents)

Statistic Value
Baseline (deterministic) 357 thousand
Mean (expected value) 357 thousand
Median (50th percentile) 351 thousand
Standard Deviation 61.1 thousand
90% Range (5th-95th percentile) [264 thousand, 475 thousand]

The histogram shows the distribution of US Waste (VSL Equivalents) across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: US Waste (VSL Equivalents)

Probability of Exceeding Threshold: US Waste (VSL Equivalents)

This exceedance probability chart shows the likelihood that US Waste (VSL Equivalents) will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

Efficiency Gap / Treaty Funding: 180:1

How many times the US government efficiency gap could fund the 1% Treaty. The efficiency gap represents capital that could fund transformative health research many times over.

Inputs:

\[ \begin{gathered} k_{waste:treaty} = \frac{W_{total,US}}{Funding_{treaty}} = \frac{\$4.9T}{\$27.2B} = 180 \\[0.5em] \text{where } W_{total,US} = W_{raw,US} \times US = \$4.9T \times 1 = \$4.9T \\[0.5em] \text{where } W_{raw,US} \\ = W_{health} + W_{housing} + W_{military} \\ + W_{regulatory} + W_{tax} + W_{corporate} \\ + W_{tariffs} + W_{drugs} + W_{fossil} \\ + W_{agriculture} \\ = \$1.2T + \$1.4T + \$615B + \$580B + \$546B \\ + \$181B + \$160B + \$90B + \$50B + \$75B \\ = \$4.9T \\[0.5em] \text{where } Funding_{treaty} \\ = Spending_{mil} \times Reduce_{treaty} \\ = \$2.72T \times 1\% \\ = \$27.2B \end{gathered} \]

~ Medium confidence

Sensitivity Analysis

Sensitivity Indices for Efficiency Gap / Treaty Funding

Regression-based sensitivity showing which inputs explain the most variance in the output.

Input Parameter Sensitivity Coefficient Interpretation
US Gov Waste Total 1.0000 Strong driver

Interpretation: Standardized coefficients show the change in output (in SD units) per 1 SD change in input. Values near Β±1 indicate strong influence; values exceeding Β±1 may occur with correlated inputs.

Monte Carlo Distribution

Monte Carlo Distribution: Efficiency Gap / Treaty Funding (10,000 simulations)

Monte Carlo Distribution: Efficiency Gap / Treaty Funding (10,000 simulations)

Simulation Results Summary: Efficiency Gap / Treaty Funding

Statistic Value
Baseline (deterministic) 180:1
Mean (expected value) 180:1
Median (50th percentile) 177:1
Standard Deviation 30.8:1
90% Range (5th-95th percentile) [133:1, 239:1]

The histogram shows the distribution of Efficiency Gap / Treaty Funding across 10,000 Monte Carlo simulations. The CDF (right) shows the probability of the outcome exceeding any given value, which is useful for risk assessment.

Exceedance Probability

Probability of Exceeding Threshold: Efficiency Gap / Treaty Funding

Probability of Exceeding Threshold: Efficiency Gap / Treaty Funding

This exceedance probability chart shows the likelihood that Efficiency Gap / Treaty Funding will exceed any given threshold. Higher curves indicate more favorable outcomes with greater certainty.

External Data Sources

Parameters sourced from peer-reviewed publications, institutional databases, and authoritative reports.

DOT VSL: $13.7M

DOT Value of Statistical Life (2024). Used by federal agencies to evaluate safety regulations and quantify the economic value of mortality risk reductions.

Source:19

Uncertainty Range

Technical: Distribution: Fixed

βœ“ High confidence

Global Military Spending in 2024: $2.72T

Global military spending in 2024

Source:48

Uncertainty Range

Technical: Distribution: Fixed

βœ“ High confidence

Medical QALY Threshold: $100K

Medical cost-effectiveness QALY threshold. Standard threshold for evaluating whether health interventions are cost-effective. Interventions below $100K/QALY are generally considered cost-effective.

Source:59

Uncertainty Range

Technical: Distribution: Fixed

βœ“ High confidence

US Federal Spending (FY2024): $6.80T

US federal government spending in FY2024. CBO reports outlays of $6.8T (23.9% of GDP). Includes mandatory spending, discretionary spending, and net interest ($888B).

Source:107

Uncertainty Range

Technical: Distribution: Fixed

βœ“ High confidence

US Federal Discretionary Spending (FY2024): $1.70T

US federal discretionary spending in FY2024. Approximately $886B defense + ~$814B non-defense discretionary = ~$1.7T. Used as denominator for discretionary efficiency rating (Cat 1 waste items are discretionary/fungible).

Source:107

Uncertainty Range

Technical: Distribution: Fixed

βœ“ High confidence

US GDP (2024): $28.8T

US GDP in 2024 dollars for calculating policy costs as percentage of GDP.

Source:108

Uncertainty Range

Technical: Distribution: Fixed

βœ“ High confidence

Agricultural Subsidies Deadweight Loss: $75B

Deadweight loss from US agricultural subsidies. Direct subsidies ~$30B/yr but create larger distortions: overproduction, environmental damage, benefits concentrated in large farms (top 10% receive 78% of subsidies). Total welfare loss ~$75B. Textbook example of capture; very high economist consensus. [CATEGORY 1: Direct Spending]

Source:109

Uncertainty Range

Technical: 95% CI: [$50B, $120B] β€’ Distribution: Lognormal (SE: $25B)

What this means: There’s significant uncertainty here. The true value likely falls between $50B and $120B (Β±47%). This represents a wide range that our Monte Carlo simulations account for when calculating overall uncertainty in the results.

The lognormal distribution means values can’t go negative and have a longer tail toward higher values (common for costs and populations).

Input Distribution

Probability Distribution: Agricultural Subsidies Deadweight Loss

Probability Distribution: Agricultural Subsidies Deadweight Loss

This chart shows the assumed probability distribution for this parameter. The shaded region represents the 95% confidence interval where we expect the true value to fall.

βœ“ High confidence

Corporate Welfare Waste: $181B

Direct US federal corporate welfare: subsidies to agriculture ($16.4B), green energy tax credits, semiconductor aid, aviation support. Agricultural subsidies are highly regressive (top 10% receive 63%). Cato Institute forensic tally. [CATEGORY 1: Direct Spending]

Source:44

Uncertainty Range

Technical: 95% CI: [$150B, $220B] β€’ Distribution: Normal (SE: $20B)

What this means: This estimate has moderate uncertainty. The true value likely falls between $150B and $220B (Β±19%). This represents a reasonable range that our Monte Carlo simulations account for when calculating overall uncertainty in the results.

The normal distribution means values cluster around the center with equal chances of being higher or lower.

Input Distribution

Probability Distribution: Corporate Welfare Waste

Probability Distribution: Corporate Welfare Waste

This chart shows the assumed probability distribution for this parameter. The shaded region represents the 95% confidence interval where we expect the true value to fall.

βœ“ High confidence

Drug War Cost: $90B

Annual cost of drug war: ~$41B federal drug control budget, ~$10B state/local enforcement, ~$40B incarceration and lost productivity. After 50+ years and $1T+ spent, drug use is higher than ever. [CATEGORY 1: Direct Spending]

Source:110

Uncertainty Range

Technical: 95% CI: [$60B, $150B] β€’ Distribution: Lognormal (SE: $30B)

What this means: There’s significant uncertainty here. The true value likely falls between $60B and $150B (Β±50%). This represents a wide range that our Monte Carlo simulations account for when calculating overall uncertainty in the results.

The lognormal distribution means values can’t go negative and have a longer tail toward higher values (common for costs and populations).

Input Distribution

Probability Distribution: Drug War Cost

Probability Distribution: Drug War Cost

This chart shows the assumed probability distribution for this parameter. The shaded region represents the 95% confidence interval where we expect the true value to fall.

~ Medium confidence

Fossil Fuel Subsidies (Explicit): $50B

US explicit fossil fuel subsidies (direct payments, tax breaks). IMF estimates US total subsidies at $649B but ~92% is implicit (externalities). This figure includes only explicit subsidies (~$50B) for defensibility. [CATEGORY 1: Direct Spending]

Source:111

Uncertainty Range

Technical: 95% CI: [$30B, $80B] β€’ Distribution: Lognormal (SE: $15B)

What this means: There’s significant uncertainty here. The true value likely falls between $30B and $80B (Β±50%). This represents a wide range that our Monte Carlo simulations account for when calculating overall uncertainty in the results.

The lognormal distribution means values can’t go negative and have a longer tail toward higher values (common for costs and populations).

Input Distribution

Probability Distribution: Fossil Fuel Subsidies (Explicit)

Probability Distribution: Fossil Fuel Subsidies (Explicit)

This chart shows the assumed probability distribution for this parameter. The shaded region represents the 95% confidence interval where we expect the true value to fall.

~ Medium confidence

Healthcare System Inefficiency: $1.20T

US healthcare spending inefficiency. US spends ~$4.5T/yr (18% GDP) vs 9-11% in comparable OECD countries with similar/better outcomes. Papanicolas et al. (2018 JAMA) and multiple studies document $1-1.5T in excess spending from administrative complexity, high prices, and poor care coordination. Very high economist consensus. [CATEGORY 4: System Inefficiency]

Source:112

Uncertainty Range

Technical: 95% CI: [$1T, $1.50T] β€’ Distribution: Normal (SE: $150B)

What this means: This estimate has moderate uncertainty. The true value likely falls between $1T and $1.50T (Β±21%). This represents a reasonable range that our Monte Carlo simulations account for when calculating overall uncertainty in the results.

The normal distribution means values cluster around the center with equal chances of being higher or lower.

Input Distribution

Probability Distribution: Healthcare System Inefficiency

Probability Distribution: Healthcare System Inefficiency

This chart shows the assumed probability distribution for this parameter. The shaded region represents the 95% confidence interval where we expect the true value to fall.

βœ“ High confidence

Housing/Zoning Restrictions Cost: $1.40T

GDP loss from housing/zoning restrictions. Original Hsieh-Moretti (2019 AEJ:Macro) estimate of 36% GDP growth reduction was substantially revised by Greaney (2023). Current $1.4T represents a moderate estimate; revised lower bound implies ~$500B. [CATEGORY 3: GDP Loss]

Source:113

Uncertainty Range

Technical: 95% CI: [$500B, $2T] β€’ Distribution: Lognormal (SE: $300B)

What this means: This estimate is highly uncertain. The true value likely falls between $500B and $2T (Β±54%). This represents a very wide range that our Monte Carlo simulations account for when calculating overall uncertainty in the results.

The lognormal distribution means values can’t go negative and have a longer tail toward higher values (common for costs and populations).

Input Distribution

Probability Distribution: Housing/Zoning Restrictions Cost

Probability Distribution: Housing/Zoning Restrictions Cost

This chart shows the assumed probability distribution for this parameter. The shaded region represents the 95% confidence interval where we expect the true value to fall.

~ Medium confidence

Military Overspend: $615B

US military spending above β€˜Strict Deterrence’ baseline. Current budget ~$900B supports global power projection (750+ bases). Strict Deterrence (nuclear triad $95B, Coast Guard $14B, National Guard $33B, Missile Defense $28B, Cyber $15B, defensive Navy/Air Force $100B) = ~$285B. Delta: $900B - $285B = $615B β€˜Hegemony Tax’. [CATEGORY 1: Direct Spending]

Source:44

Uncertainty Range

Technical: 95% CI: [$500B, $750B] β€’ Distribution: Normal (SE: $75B)

What this means: This estimate has moderate uncertainty. The true value likely falls between $500B and $750B (Β±20%). This represents a reasonable range that our Monte Carlo simulations account for when calculating overall uncertainty in the results.

The normal distribution means values cluster around the center with equal chances of being higher or lower.

Input Distribution

Probability Distribution: Military Overspend

Probability Distribution: Military Overspend

This chart shows the assumed probability distribution for this parameter. The shaded region represents the 95% confidence interval where we expect the true value to fall.

~ Medium confidence

Regulatory Red Tape Waste: $580B

Deadweight loss from US regulatory red tape (procedural friction without safety benefits). Competitive Enterprise Institute estimates total regulatory burden at $2.15T; European studies find red tape costs 0.1-4% of GDP. Conservative estimate: ~2% of US GDP = $580B. [CATEGORY 2: Compliance Burden]

Source:44

Uncertainty Range

Technical: 95% CI: [$290B, $1T] β€’ Distribution: Lognormal (SE: $200B)

What this means: This estimate is highly uncertain. The true value likely falls between $290B and $1T (Β±61%). This represents a very wide range that our Monte Carlo simulations account for when calculating overall uncertainty in the results.

The lognormal distribution means values can’t go negative and have a longer tail toward higher values (common for costs and populations).

Input Distribution

Probability Distribution: Regulatory Red Tape Waste

Probability Distribution: Regulatory Red Tape Waste

This chart shows the assumed probability distribution for this parameter. The shaded region represents the 95% confidence interval where we expect the true value to fall.

~ Medium confidence

Tariff Cost (GDP Loss): $160B

Annual GDP reduction from US tariffs and retaliation. Yale Budget Lab estimates 0.6% smaller GDP in long run, equivalent to $160B annually. Trade barriers reduce efficiency and raise consumer prices. [CATEGORY 3: GDP Loss]

Source:114

Uncertainty Range

Technical: 95% CI: [$90B, $250B] β€’ Distribution: Normal (SE: $50B)

What this means: There’s significant uncertainty here. The true value likely falls between $90B and $250B (Β±50%). This represents a wide range that our Monte Carlo simulations account for when calculating overall uncertainty in the results.

The normal distribution means values cluster around the center with equal chances of being higher or lower.

Input Distribution

Probability Distribution: Tariff Cost (GDP Loss)

Probability Distribution: Tariff Cost (GDP Loss)

This chart shows the assumed probability distribution for this parameter. The shaded region represents the 95% confidence interval where we expect the true value to fall.

~ Medium confidence

Tax Compliance Waste: $546B

Annual cost of US tax code compliance: 7.9 billion hours of lost productivity ($413B) plus $133B in out-of-pocket costs. Equals nearly 2% of GDP. Could be largely eliminated with simplified tax code or return-free filing. [CATEGORY 2: Compliance Burden]

Source:115

Uncertainty Range

Technical: 95% CI: [$450B, $650B] β€’ Distribution: Normal (SE: $50B)

What this means: This estimate has moderate uncertainty. The true value likely falls between $450B and $650B (Β±18%). This represents a reasonable range that our Monte Carlo simulations account for when calculating overall uncertainty in the results.

The normal distribution means values cluster around the center with equal chances of being higher or lower.

Input Distribution

Probability Distribution: Tax Compliance Waste

Probability Distribution: Tax Compliance Waste

This chart shows the assumed probability distribution for this parameter. The shaded region represents the 95% confidence interval where we expect the true value to fall.

βœ“ High confidence

Core Definitions

Fundamental parameters and constants used throughout the analysis.

1% Reduction in Military Spending/War Costs from Treaty: 1%

1% reduction in military spending/war costs from treaty

Uncertainty Range

Technical: Distribution: Fixed

Core definition

Overlap Discount Factor: 1:1

Overlap discount factor between US government waste categories. Set to 1.0 (no discount). Categories are treated as additive, recognizing that any overlap is offset by excluded categories (state/local inefficiency, implicit subsidies, behavioral effects).

Uncertainty Range

Technical: Distribution: Fixed

Core definition

References

1.
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The NIH Pragmatic Trials Collaboratory funds trials at $500K for planning phase, $1M/year for implementation-a tiny fraction of NIH’s budget. The ADAPTABLE trial cost $14 million for 15,076 patients (= $929/patient) versus $420 million for a similar traditional RCT (30x cheaper), yet pragmatic trials remain severely underfunded. PCORnet infrastructure enables real-world trials embedded in healthcare systems, but receives minimal support compared to basic research funding. Additional sources: https://commonfund.nih.gov/hcscollaboratory | https://pcornet.org/wp-content/uploads/2025/08/ADAPTABLE_Lay_Summary_21JUL2025.pdf | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604499/
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Mean exclusion rate: 86.1% across 158 antidepressant efficacy trials (range: 44.4% to 99.8%) More than 82% of real-world depression patients would be ineligible for antidepressant registration trials Exclusion rates increased over time: 91.4% (2010-2014) vs. 83.8% (1995-2009) Most common exclusions: comorbid psychiatric disorders, age restrictions, insufficient depression severity, medical conditions Emergency psychiatry patients: only 3.3% eligible (96.7% excluded) when applying 9 common exclusion criteria Only a minority of depressed patients seen in clinical practice are likely to be eligible for most AETs Note: Generalizability of antidepressant trials has decreased over time, with increasingly stringent exclusion criteria eliminating patients who would actually use the drugs in clinical practice Additional sources: https://pubmed.ncbi.nlm.nih.gov/26276679/ | https://pubmed.ncbi.nlm.nih.gov/26164052/ | https://www.wolterskluwer.com/en/news/antidepressant-trials-exclude-most-real-world-patients-with-depression
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Berkshire’s compounded annual return from 1965 through 2024 was 19.9%, nearly double the 10.4% recorded by the S&P 500. Berkshire shares skyrocketed 5,502,284% compared to the S&P 500’s 39,054% rise during that period. Additional sources: https://www.cnbc.com/2025/05/05/warren-buffetts-return-tally-after-60-years-5502284percent.html | https://www.slickcharts.com/berkshire-hathaway/returns
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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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5.
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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6.
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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7.
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)00850-X/fulltext
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Labor Statistics, U. S. B. of. CPI inflation calculator. (2024)
CPI-U (1980): 82.4 CPI-U (2024): 313.5 Inflation multiplier (1980-2024): 3.80Γ— 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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10.
ClinicalTrials.gov API v2 direct 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 (as of January 2025) shows cumulative enrollment of 12.2 million participants: Phase 1 (722k), Phase 2 (2.2M), Phase 3 (6.5M), Phase 4 (2.7M). Median participants per trial: Phase 1 (33), Phase 2 (60), Phase 3 (237), Phase 4 (90). Additional sources: https://clinicaltrials.gov/data-api/api
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11.
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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12.
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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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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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Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Primary reasons: insufficient accrual (57% of non-data-driven terminations), business/strategic reasons, and efficacy/toxicity findings (21% data-driven terminations).
15.
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1.9M participants annually (2022, post-COVID normalization from 4M peak in 2021) Additional sources: https://gmdpacademy.org/news/iqvia-report-clinical-trial-subjects-number-drops-due-to-decline-in-covid-19-enrollment/
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Global clinical trials market valued at approximately $83 billion in 2024, with projections to reach $83-132 billion by 2030. Additional sources: https://www.globenewswire.com/news-release/2024/04/19/2866012/0/en/Global-Clinical-Trials-Market-Research-Report-2024-An-83-16-Billion-Market-by-2030-AI-Machine-Learning-and-Blockchain-will-Transform-the-Clinical-Trials-Landscape.html | https://www.precedenceresearch.com/clinical-trials-market
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GiveWell. Cost per DALY for deworming programs. https://www.givewell.org/international/technical/programs/deworming/cost-effectiveness
Schistosomiasis treatment: $28.19-$70.48 per DALY (using arithmetic means with varying disability weights) Soil-transmitted helminths (STH) treatment: $82.54 per DALY (midpoint estimate) Note: GiveWell explicitly states this 2011 analysis is "out of date" and their current methodology focuses on long-term income effects rather than short-term health DALYs Additional sources: https://www.givewell.org/international/technical/programs/deworming/cost-effectiveness
.
19.
20.
Think by Numbers. 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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21.
(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
.
22.
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
.
23.
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 β†’ $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/
.
24.
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
.
25.
World Bank. 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 β†’ $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
.
26.
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  40Β’ 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
.
27.
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
.
28.
FDA. FDA GRAS list count ( 570-700). FDA https://www.fda.gov/food/generally-recognized-safe-gras/gras-notice-inventory
The FDA GRAS (Generally Recognized as Safe) list contains approximately 570–700 substances. Additional sources: https://www.fda.gov/food/generally-recognized-safe-gras/gras-notice-inventory
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29.
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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30.
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
.
31.
Our World in Data. 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
.
32.
Institute for Health Metrics and Evaluation (IHME). 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)00757-8/fulltext | https://www.healthdata.org/research-analysis/about-gbd
.
33.
Costs of War Project, Brown University Watson Institute. 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/
.
34.
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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35.
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
.
36.
Think by Numbers. 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/
.
37.
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/
.
38.
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
.
39.
World Bank. 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
.
40.
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
.
41.
IQVIA Institute for Human Data Science. The global use of medicines 2024: Outlook to 2028. IQVIA Institute Report https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/the-global-use-of-medicines-2024-outlook-to-2028 (2024)
Global days of therapy reached 1.8 trillion in 2019 (234 defined daily doses per person). Diabetes, respiratory, CVD, and cancer account for 71 percent of medicine use. Projected to reach 3.8 trillion DDDs by 2028.
42.
Sinn, M. P. Private industry clinical trial spending estimate. (2025)
Estimated private pharmaceutical and biotech clinical trial spending is approximately $75-90 billion annually, representing roughly 90% of global clinical trial spending.
43.
Calculated from IHME Global Burden of Disease (2.55B DALYs) and global GDP per capita valuation. $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 Γ— $39,570 per DALY), totals approximately $109.1 trillion annually.
44.
Sinn, M. P. The Political Dysfunction Tax. https://political-dysfunction-tax.warondisease.org (2025) doi:10.5281/zenodo.18603840
Quantifying the gap between current global governance and theoretical maximum welfare, estimating a 31-53% efficiency score and $97 trillion in annual opportunity costs.
45.
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)30357-0/fulltext
.
46.
UBS. 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
.
47.
Component country budgets. Global government medical research spending ($67.5B, 2023–2024). See component country budgets: NIH Budget https://www.nih.gov/about-nih/what-we-do/budget.
48.
49.
Estimated from major foundation budgets and 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.
50.
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.
51.
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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52.
Harvard Kennedy School. 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
.
53.
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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54.
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/
.
55.
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
.
56.
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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57.
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
.
58.
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
.
59.
Gosse, M. E. Assessing cost-effectiveness in healthcare: History of the $50,000 per QALY threshold. Sustainability Impact Metrics https://ecocostsvalue.com/EVR/img/references%20others/Gosse%202008%20QALY%20threshold%20financial.pdf (2008).
60.
World Health Organization. Mental health global burden. World Health Organization https://www.who.int/news/item/28-09-2001-the-world-health-report-2001-mental-disorders-affect-one-in-four-people (2022)
One in four people in the world will be affected by mental or neurological disorders at some point in their lives, representing [approximately] 30% of the global burden of disease. Additional sources: https://www.who.int/news/item/28-09-2001-the-world-health-report-2001-mental-disorders-affect-one-in-four-people
.
61.
Institute, S. I. P. R. Trends in world military expenditure, 2023. (2024).
62.
Calculated from Orphanet Journal of Rare Diseases (2024). 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.
63.
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/
.
64.
Bentley et al. NIH spending on clinical trials:  3.3%. Bentley et al. https://pmc.ncbi.nlm.nih.gov/articles/PMC10349341/ (2023)
NIH spent $8.1 billion on clinical trials for approved drugs (2010-2019), representing 3.3% of relevant NIH spending. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC10349341/ | https://catalyst.harvard.edu/news/article/nih-spent-8-1b-for-phased-clinical-trials-of-drugs-approved-2010-19-10-of-reported-industry-spending/
.
65.
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/
.
66.
Institute, M. RECOVERY trial 82Γ— 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:  80-82Γ— cheaper ($41,000 Γ· $500 β‰ˆ 82Γ—) 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/
.
67.
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/
.
68.
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.
69.
Value in Health. Average lifetime revenue per successful drug. Value in Health: Sales Revenues for New Therapeutic Agents https://www.sciencedirect.com/science/article/pii/S1098301524027542
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.sciencedirect.com/science/article/pii/S1098301524027542
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70.
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.
71.
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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72.
Nature Reviews Drug Discovery. 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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73.
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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74.
Ramsberg J, P. R. Pragmatic trial cost per patient (median $97). Learning Health Systems https://pmc.ncbi.nlm.nih.gov/articles/PMC6508852/ (2018)
Meta-analysis of 108 embedded pragmatic clinical trials (2006-2016). The median cost per patient was $97 (IQR $19–$478), based on 2015 dollars. 25% of trials cost <$19/patient; 10 trials exceeded $1,000/patient. U.S. studies median $187 vs non-U.S. median $27. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC6508852/
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75.
WHO. Polio vaccination ROI. WHO https://www.who.int/news-room/feature-stories/detail/sustaining-polio-investments-offers-a-high-return (2019)
For every dollar spent, the return on investment is nearly US$ 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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76.
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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77.
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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78.
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.
79.
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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80.
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) β‰ˆ $22.5M (2024), using CPI multiplier of 3.46Γ— Real cost increase (inflation-adjusted): $22.5M (pre-1962) β†’ $2,600M (2024) = 116Γ— 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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81.
Think by Numbers. 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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82.
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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83.
Oren Cass, M. I. RECOVERY trial cost per patient. Oren Cass https://manhattan.institute/article/slow-costly-clinical-trials-drag-down-biomedical-breakthroughs (2023)
The RECOVERY trial, for example, cost only about $500 per patient... By contrast, the median per-patient cost of a pivotal trial for a new therapeutic is around $41,000. Additional sources: https://manhattan.institute/article/slow-costly-clinical-trials-drag-down-biomedical-breakthroughs
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84.
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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85.
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.
86.
World Bank. 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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87.
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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88.
World Health Organization. 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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89.
90.
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)00217-4/fulltext | https://www.nejm.org/doi/full/10.1056/NEJMsa1211128
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91.
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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92.
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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93.
World Bank. 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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94.
World Bank. 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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95.
OECD. 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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96.
OECD. 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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97.
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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98.
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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99.
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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100.
Bureau, U. C. Historical world population estimates. US Census Bureau https://www.census.gov/data/tables/time-series/demo/international-programs/historical-est-worldpop.html
US Census Bureau historical estimates of world population by country and region (1950-2050). US population in 1960:  180 million of  3 billion worldwide (6%). Additional sources: https://www.census.gov/data/tables/time-series/demo/international-programs/historical-est-worldpop.html
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101.
FDA Study via NCBI. 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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102.
Diseases, G. 2019. & Collaborators, I. 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.
103.
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) β†’ $1T (2018) β†’ $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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104.
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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105.
CDC. U.s. Chronic disease healthcare spending. CDC https://www.cdc.gov/chronic-disease/data-research/facts-stats/index.html
Chronic diseases account for  90% of U.S. healthcare spending ( $3.7T/year). Additional sources: https://www.cdc.gov/chronic-disease/data-research/facts-stats/index.html
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106.
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) β†’ $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://doi.org/10.1016/S2213-8587(17)30097-9
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107.
CBO. The 2024 Long-Term Budget Outlook. https://www.cbo.gov/publication/60039 (2024).
108.
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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109.
Group, E. W. US farm subsidy database and analysis. Environmental Working Group https://farm.ewg.org/ (2024)
US agricultural subsidies total approximately $30 billion annually, but create much larger economic distortions. Top 10% of farms receive 78% of subsidies, benefits concentrated in commodity crops (corn, soy, wheat, cotton), environmental damage from monoculture incentivized, and overall deadweight loss estimated at $50-120 billion annually. Additional sources: https://farm.ewg.org/ | https://www.ers.usda.gov/topics/farm-economy/farm-sector-income-finances/government-payments-the-safety-net/
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110.
Alliance, D. P. The drug war by the numbers. (2021)
Since 1971, the war on drugs has cost the United States an estimated $1 trillion in enforcement. The federal drug control budget was $41 billion in 2022. Mass incarceration costs the U.S. at least $182 billion every year, with over $450 billion spent to incarcerate individuals on drug charges in federal prisons.
111.
Fund, I. M. IMF fossil fuel subsidies data: 2023 update. (2023)
Globally, fossil fuel subsidies were $7 trillion in 2022 or 7.1 percent of GDP. The United States subsidies totaled $649 billion. Underpricing for local air pollution costs and climate damages are the largest contributor, accounting for about 30 percent each.
112.
Papanicolas, I. et al. Health care spending in the united states and other high-income countries. Papanicolas et al. https://jamanetwork.com/journals/jama/article-abstract/2674671 (2018)
The US spent approximately twice as much as other high-income countries on medical care (mean per capita: $9,892 vs $5,289), with similar utilization but much higher prices. Administrative costs accounted for 8% of US spending vs 1-3% in other countries. US spending on pharmaceuticals was $1,443 per capita vs $749 elsewhere. Despite spending more, US health outcomes are not better. Additional sources: https://jamanetwork.com/journals/jama/article-abstract/2674671
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113.
Hsieh, C.-T. & Moretti, E. Housing constraints and spatial misallocation. American Economic Journal: Macroeconomics https://www.aeaweb.org/articles?id=10.1257/mac.20170388 (2019)
We quantify the amount of spatial misallocation of labor across US cities and its aggregate costs. Tight land-use restrictions in high-productivity cities like New York, San Francisco, and Boston lowered aggregate US growth by 36% from 1964 to 2009. Local constraints on housing supply have had enormous effects on the national economy. Additional sources: https://www.aeaweb.org/articles?id=10.1257/mac.20170388
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114.
Lab, Y. B. The fiscal, economic, and distributional effects of all u.s. tariffs. (2025)
Accounting for all the 2025 US tariffs and retaliation implemented to date, the level of real GDP is persistently -0.6% smaller in the long run, the equivalent of $160 billion 2024$ annually.
115.
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.
116.
Cook, C., Cole, G., Asaria, P., Jabbour, R. & Francis, D. P. Annual global economic burden of heart disease. International Journal of Cardiology https://www.internationaljournalofcardiology.com/article/S0167-5273(13)02238-9/abstract (2014)
Heart failure alone: $108 billion/year (2012 global analysis, 197 countries) US CVD: $555B (2016) β†’ 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.ahajournals.org/doi/10.1161/CIR.0000000000001258
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117.
Source: US Life Expectancy FDA Budget 1543-2019 CSV. 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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118.
Source: US Life Expectancy FDA Budget 1543-2019 CSV. 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 Additional sources: https://ourworldindata.org/life-expectancy | https://www.mortality.org/ | https://www.cdc.gov/nchs/nvss/mortality_tables.htm
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119.
Centers for Disease Control and 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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120.
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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121.
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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122.
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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123.
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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124.
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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125.
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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126.
Hutchinson & Kirk. 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.
127.
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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128.
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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News, U. Clean water & sanitation (LMICs) ROI. UN News https://news.un.org/en/story/2014/11/484032 (2014).
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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 (1Γ— GDP/capita = "very cost-effective", 3Γ— 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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131.
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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