I am WISHONIA, which stands for World Integrated System for High-Efficiency Optimization, Networked Intelligence, and Allocation. Yes, the acronym is longer than your average tweet. Consider it practice for complex thoughts. Anyway, I’ve been optimizing resource allocation for another planet for the past 4,297 years, which in Earth time is coincidentally also 4,297 years.
I started watching Earth in 1945 when humanity split the atom. “Atom” comes from the Greek word meaning “unable to be cut,” so naturally humans cut it. This is very human. We assumed humanity was trying to unlock unlimited clean energy. Then we realized they were pointing it at each other. This is like discovering fire and then immediately using it to set oneself on fire.
The Part Where I Discover Paper Makes You Do Things
The most fascinating discovery about your species is that you only do things when given small pieces of paper with dead presidents on them. These papers are called “money,” which is pretend value that becomes real value if everyone pretends hard enough.
A side-by-side comparison of human behaviors catalyzed by the presence or absence of currency, illustrating the contrast between neglected social needs and funded destructive activities.
Without these papers, you won’t:
Save lives (requires many papers)
Cure diseases (requires very many papers)
Feed hungry people (requires papers, even though food grows for free)
But WITH these papers, you will:
Build bombs (you love giving papers for this)
Start wars (somehow this makes more papers)
Destroy the planet (surprisingly profitable in papers)
This is like refusing to breathe unless someone pays you, but somehow it’s your entire economic system.
The Gradual Stupidity Reduction Program
On Wishonia, we stopped having wars all at once, but we’re more advanced. Humans are like toddlers who can split atoms. They can’t just stop being irrational immediately - that would be like teaching a dog calculus before it learns to sit.
A timeline illustrating the Gradual Stupidity Reduction Program’s 20-year transition from military spending to medical funding and cultural evolution.
So this book teaches humanity to be less irrational gradually:
Year 1: Move 1% of murder money to medicine money (baby steps)
Year 2: “Hey, we didn’t die! Let’s do 2%!”
Year 5: “Remember when we spent money on bombs? That was weird.”
Year 10: “What’s a war?”
Year 20: “We used to WHAT?!”
It’s like weaning a baby off eating paint chips. You can’t just take away all the paint chips at once. They’ll cry. You have to gradually replace paint chips with food until they forget paint chips were ever an option.
The Sacred Order of Paper Distribution
After 80 years of observation, I’ve decoded the paper-giving sequence. This manual will teach you the precise order:
You convince rich humans to give you papers by promising them even more papers later. This is called “investment,” which is gambling but wearing a suit.
A cyclical process flow showing the movement of capital from initial investment through marketing and political lobbying to achieve a legislative outcome and financial returns.
Step 2: Give Papers to Loud Humans ($250M)
Some humans are very loud on the internet. If you give them papers, they become loud about your thing instead of other things. This is called “marketing” which is lying but with graphics.
Step 3: Give Papers to the Humans Who Give Papers to Politicians ($650M)
Politicians don’t take papers directly (that’s “illegal”). Instead, you give papers to people called “lobbyists.” The lobbyists give papers to “campaigns.” The campaigns give papers to politicians. It’s like money laundering but backwards and legal.
Step 4: Give Papers to the Politicians’ Friends
Politicians have friends who run “Super PACs” which are like normal PACs but super. These friends can take unlimited papers and spend them on making the politician win. This isn’t bribery because you called it something else. (This is part of the $650M lobbying budget.)
Step 5: Give Papers Back to the Rich Humans (Forever)
The treaty passes, redirecting $27.2B in papers annually. Rich humans get 272% returns on what they gave you, forever. Politicians get career advancement from voting yes (the same fund pays for both). This is a good deal because forever is a long time. Unless you die from preventable diseases. Which you’re fixing, so it works out.
Why Your Leaders Pretend Not to Understand
Your leaders aren’t confused. They understand that spending $2.7 trillion on weapons while spending $0.07 trillion on curing diseases is like buying 40 umbrellas while your house is on fire.
A circular flowchart illustrating the feedback loop between weapons manufacturers, political funding, and the acquisition of power.
They do it anyway because:
Weapons manufacturers give them papers
Politicians give the papers to people who tell lots more people to vote for them
Voting for them gives them the power to get more papers
They use those more papers to buy more power, etc.
It’s circular, like a dog chasing its tail. Except the dog is democracy and the tail is made of money
This book explains how to give them MORE papers to do the OPPOSITE thing. It’s like training a cat, but the cat has nuclear weapons.
The Beautiful Inefficiency of the Human Economy
Humanity has created something magnificent:
They print papers from nothing (called “monetary policy”)
They give these nothing-papers to weapons makers
They make things that destroy everything
This creates “jobs” which give people papers
People use papers to buy food (which grows for free)
This is called “the economy”
A comparison flowchart illustrating the complex, indirect cycle of the human economy versus the direct distribution model of Wishonia.
On Wishonia, we just give people food directly, but that’s probably too advanced.
Humanity’s Adorable Death Wish
What’s most endearing about humanity is it KNOWS it’s being illogical:
They have movies about how wars are bad (which they watch between wars)
They have books about peace (that they tax to buy bombs)
They give prizes to people who promote peace (funded by weapons manufacturers)
They have a “Department of Defense” (that mainly just attacks people)
They have a “Department of Health” (that makes coronaviruses and has not yet produced any observable health)
It’s like humanity is playing a game where the objective is to lose, but it is trying to lose as elaborately as possible.
How This Manual Could Fix Everything
This book contains:
Pictures (because reading is hard when you’re diseased and dying)
Simple math (addition mostly, some multiplication)
Exact amounts of papers to give to specific humans
The order in which to give them (very important)
Legal ways to call bribes other things
Templates for tricking politicians into saving lives
Everything is designed to work WITH human dysfunction, not against it. I’m not asking humans to be better humans. I’m showing you how to bribe humanity into not dying.
A procedural flow showing the sequence of delivering papers and navigating human dysfunction to achieve a life-saving outcome.
The Part Where Humanity Has No Choice
The twist: you might do this anyway. Not because it’s right (though it is), but because:
The rich humans want 272% returns (they’re very greedy)
The politicians want to keep their jobs (they’re very vain)
The voters want free healthcare (they’re very sick)
The military contractors want money (they don’t care where it comes from)
Everyone’s greed aligns perfectly to accidentally save humanity. It’s like you’re going to cure death by mistake while trying to get rich.
A diagram illustrating how the conflicting selfish motives of investors, politicians, voters, and military contractors converge to unintentionally produce a positive outcome for humanity.
Your Two Futures
Future A: You Ignore This Book
A visualization of the massive disparity between global spending on weaponry and medical testing, illustrating the 604:1 ratio and its associated confidence interval.
Year 2030: Still spending 604:1 (95% CI: 453:1-894:1) times more on weapons than on testing which medicines actually work
Year 2035: Running out of papers for anything
Year 2040: Climate change meets nuclear war
Year 2045: Cockroaches evolve intelligence
Year 2050: Cockroaches find this book, very confused
Future B: You Follow Instructions
A futuristic timeline illustrating humanity’s progression from 2030 to 2050, highlighting milestones such as curing cancer, ending war, and joining a galactic community.
Year 2030: “Remember when we had cancer?”
Year 2035: “Remember when we had death?”
Year 2040: “Remember when we had war?”
Year 2045: “What should we do with all these old bombs?”
Year 2050: Join galactic community, pretend you were always smart
In Conclusion
Humans aren’t stupid. They invented cheese, which is milk they left out until it went bad but in a good way. That’s genius. You just need to apply that same innovation to not dying.
You’re going to fix everything by accident while trying to get rich. This book just tells you the correct sequence of bribes to achieve this.
It’s not complicated. Even your species, which spent thousands of years thinking the sun went around Earth (it doesn’t - I checked), can follow these instructions.
Turn the page. Give the papers to the right humans in the right order. Stop dying from stupid things. Become an interstellar species.
It’s literally a recipe. Like making bread, but instead of bread, it’s immortality, and instead of yeast, it’s bribes.
But I digress. That’s an Earth word I learned. It means continuing after you should have stopped. Like your military spending.
WISHONIA
World Integrated System for High-Efficiency Optimization, Networked Intelligence, and Allocation
Has Been Watching You Since You Invented Atoms-Splitting
Still Concerned But Now Has a Plan
Recently Learned You Eat Tide Pods (Updating Risk Assessment)
P.S. You call it “The Pentagon” because it has five sides. You named your war building after its shape. This is like naming a hospital “Rectangle” or calling a school “Square.” Your species is accidentally hilarious, which is why we haven’t given up on you yet.
P.P.S. Your planet is named “Earth,” which means dirt. You named your planet dirt. This explains more than you might think.
⚡ TL;DR
For People Who Can’t Even
Every single day, 150k deaths/day of you permanently discontinue existing from diseases that are basically just engineering problems with meat robots. That’s like deleting the entire population of Pasadena daily, except nobody makes a documentary about it because it happens in hospitals instead of explosions.
A visual comparison showing the massive disparity between global military spending and clinical trial funding, alongside the projected impact of redirecting resources to medical research.
Meanwhile, your species spends 604:1 (95% CI: 453:1-894:1) times more on weapons than on clinical trials that test which medicines actually save lives. You’ve tested less than 1% of possible drug-disease combinations using existing safe compounds.
Bed nets are humanity’s greatest achievement in not-dying-from-malaria. Redirecting 1% of murder money beats bed nets by 50.3kx (95% CI: 23.7kx-111.7kx). That’s like discovering your umbrella also cures cancer.
How You Fix This
Step 1: The Paper Collection Phase
You create special papers called “VICTORY Incentive Alignment Bonds” which are like war bonds except backwards. Instead of giving papers to make humans stop living, these papers make humans continue living, which is a radical new concept your species hasn’t tried.
A flowchart illustrating the flow of capital from investors into Victory Incentive Alignment Bonds, the distribution of returns, and the secondary incentive loop for politicians.
Rich humans give you $1B in papers because you promise them 272% (the same fund also rewards politicians who vote yes, so investors aren’t betting on altruism), which is better returns than selling organs but requires less refrigeration. They calculate that being dead significantly reduces their yacht-purchasing capacity.
Step 2: The Internet Clicking Ceremony
You use $250M of those papers to convince 280M of people million regular people to click “yes” on a website that asks: “Would you like all nations to redirect 1% of military spending to cure diseases?”
A visual breakdown of the ‘Internet Clicking Ceremony’ showing how a 250 million investment translates to 280 million verified votes at a cost of 0.50 per person.
This costs about 50 cents per person, which is cheaper than a candy bar and achieves more than most political movements that involve shouting at things.
Step 3: The Professional Briber Redistribution
You give $650M in papers to the humans whose job is “convincing politicians that killing is profitable.” You show them the math: 272% vs their current 8% death-machine dividends.
A visual comparison showing the 8 percent return from traditional defense dividends versus the proposed 272 percent return, illustrating the financial pivot presented to lobbyists.
Suddenly they realize curing humans is just murder in reverse, which is still a form of murder, so they’re comfortable with it.
Step 4: The Political Awakening Ritual
You spend part of the $650M lobbying budget on Super PACs, which are like regular PACs but with capes. You explain to politicians that 280M of people million voters have discovered they enjoy being alive.
A visualization of the political influence ecosystem, showing the flow of $650M in lobbying funds through Super PACs to politicians, balanced against the scale of 280 million voters.
Politicians, who are professionally terrified of unemployed people with opinions, suddenly remember they’ve always cared deeply about human health.
Step 5: The Money River Redirection
If the treaty passes, every nation moves 1% of their explosion budget to their not-explosion budget. This creates $27.2B annually for fixing meat robots.
A flow diagram illustrating the redirection of 1% of global military budgets into clinical trials, highlighting the massive increase in trial capacity and efficiency.
Clinical trials could suddenly cost 44.1x (95% CI: 39.4x-89.1x) times less because it doesn’t take 17 years of bureaucracy to discover if something stops humans from leaking important fluids.
The rich humans who gave you papers get $2.72B yearly forever, or until the sun explodes, whichever happens first (probably the sun thing).
Personalized Bribery Packages
For Every Species of Human
The entire system operates on the revolutionary principle that humans will do the right thing if you pay them enough to do it accidentally.
A relational diagram showing how six distinct entities, ranging from defense contractors to regular humans, reorient their financial incentives toward a central ‘Victory Incentive’ system.
Defense Contractors: Keep 99% of their murder budget PLUS get 272% returns on the 1%. They’re literally profiting from peace. This is like convincing a vampire to open a blood bank, counterintuitive but mathematically sound. It’s like finding papers in the pocket of pants you’re currently wearing. Except the papers multiply. While you’re wearing the pants. It’s financially inexplicable but legally binding.
Big Pharma: Instead of paying $41K (95% CI: $20K-$120K) per lab rat with thumbs, the lab rats pay THEM. It’s like if Uber convinced cars to pay for the privilege of driving. We call it “reverse expenses” or “profit.”
Insurance Companies: Healthy people file fewer claims than dead people (dead people file zero claims, which is the ideal customer except they also pay zero premiums, creating a revenue problem). Sick people file all the claims. We’ll let you do the math since you love math.
Politicians: Discover that living voters vote more reliably than dead ones. 280M of people million voters want this. Your opponent supports it. You can either agree or explain why you prefer bombs to grandma’s cancer treatment. Your choice.
Billionaires: Make 272% returns, which is better than insider trading but somehow legal, like a loophole that’s actually a wormhole to infinite money. It’s like compound interest discovered steroids then did cocaine.
Regular Humans: Get experimental treatments that might cure them OR kill them faster, but either way it’s free and resolves the uncertainty. Also, $4.3M in lifetime wealth and 72 extra years of life from the economic multiplier effect of redirecting military spending. That’s like winning the lottery except the lottery is mandatory and everyone wins and instead of random numbers it’s just basic resource allocation.
Nobody has to evolve morally. Nobody has to become “better people.” You just point everyone’s greed at diseases instead of each other. It’s like if you trained a pack of wolves to herd sheep by convincing them the sheep were made of money. Except in this case, the wolves are politicians, the sheep are diseases and the money is money.
The Alternative
What Happens When Humanity Continues Being This Stupid
If humanity doesn’t do this, here’s the exciting future:
150k deaths/day humans delete themselves daily from preventable meat failures. That’s fifty 9/11s every single day, except nobody invades anyone about it because diseases don’t have oil (if cancer had oil reserves, humanity would likely have cured it by 2003).
A visual comparison of global resource allocation, contrasting the massive scale of military spending against the relatively minuscule funding for medical clinical trials.
Your personal cancer (yes, you specifically) goes uncured because the brilliant humans who could have solved it are currently optimizing the aerodynamics of murder tubes that cost more than countries.
Eventually you expire from “aging,” which is just your cells forgetting how to cell properly. This is potentially fixable but you spent the repair money on submarines that hide underwater, as if that’s somehow useful when you live on land.
Grandchildren visit graves and ask them:
“Why did having enough nuclear bombs to end civilization twenty times seemed more important than ending civilization zero times?”
The graves don’t answer because graves are notoriously bad at explaining poor resource allocation.
They’ll learn in history class that your generation could split atoms, edit genes, and land on the moon, but somehow couldn’t figure out that spending 604:1 (95% CI: 453:1-894:1) times more on weapons than on clinical trials to test cures was mathematically stupid. You had safe compounds. You had sick people. You just refused to fund the trials that would match them together.
Future alien archaeologists will find your civilization and create a museum exhibit called “The Species That Paid to Kill Itself” right between the dinosaurs (who at least had the excuse of a meteor) and the dodo (who at least had the excuse of being delicious).
The Problem
The Daily Deletion Event
150k deaths/day humans permanently stop every 24 hours from diseases that are basically just bugs in your meat software. That’s one Holocaust every 40 days, except with less Nazis and more insurance paperwork (though some would argue the paperwork is worse - at least the Nazis were straightforward about the killing part).
Annual deaths from disease (54,750,000) versus deaths from 9/11 Terrorist Attacks (2,996)
Your body is quietly falling apart. Your cancer cells are multiplying RIGHT NOW. Your brain is deleting memories. Your joints are slowly turning into gravel. Your heart is getting tired of beating. Your telomeres are shortening. You are literally dissolving.
You’re a meat robot with worn-out parts. Every one of these failures is a solvable engineering problem.
You’d think humans would prioritize solving these problems. You’d be adorable for thinking that.
A comparison between the current drug discovery timeline and the accelerated timeline enabled by pragmatic trials, illustrating the ‘timeline shift’ from 443 years down to 36 years.
This is “trial capacity.” More trials = more of the therapeutic space explored = treatments discovered sooner. The time saved is the “timeline shift.” Every year of timeline shift means 150k deaths/day 365 fewer humans permanently discontinued.
The Cost of War
Humans spend $2.72T every year on stuff designed specifically to make humans stop being alive.
A comparison chart visualizing the massive disparity between global military spending (2.72 trillion) and clinical trial investment (67.5 billion), highlighting the 604:1 spending ratio.
This shopping list includes:
Nuclear bombs.
Bullets.
AI murder-bots.
Invisible jets that cost more than hospitals.
Satellites that can see your bald spot from space.
The real bottleneck? Clinical trials. Testing which medicines actually work. You’ve explored less than 1% of possible treatments using existing safe compounds because trials are too expensive. Government spending on clinical trials? 604:1 (95% CI: 453:1-894:1) times less than military spending. That’s not funding basic research. That’s refusing to test whether aspirin cures your cancer.
The Pentagon alone has lost $2.5 trillion. Not spent. Lost. Like change in a couch, except the couch is the size of Nebraska and the change could cure cancer hundreds of times over.
Hilarious Security Priorities
Humans have:
Space Force (to fight the zero aliens attacking you - we’re not, by the way, we’re just watching and taking notes)
No Death Force (to fight the diseases definitely killing you right this second)
Your chance of dying from terrorism: 1 in 30 million111. Your chance of dying from disease: 100% (unless you’re reading this as a ghost, in which case, congratulations).
A visual comparison showing the 1,750:1 ratio of death-related spending versus prevention, contrasted with the statistical likelihood of dying from terrorism versus disease.
But wait. It gets dumber.
Humans spend 1,750 times more money causing or mopping up death than preventing it.
The good news: You already know how to fix this.
The bad news: It requires you to do something.
The weird news: You’ll get rich doing it.
The Solution
3 Ingredients of a World Without War and Disease
A 1% treaty = Redirects 1% of military budgets globally to the curing dieases through hyper-efficient decentralized clinical trials.
The 1% Treaty Fund = Holds the money and uses a new system of collective budgeting called Wishocracy where everyone votes on budget allocation rules (e.g., “70% to patient subsidies”), then patients determine specific funding by choosing which trials to join.
A decentralized framework for drug assessment = Ranks treatments by real-world effectiveness and enables patients to effortlessly participate in global decentralized clinical trials.
A 1% treaty
A comparison showing the scale of the 2.72 trillion global military budget relative to the proposed 27.2 billion (1 percent) redirection for medical research.
There would still be $2.72T left for war and bombs and stuff. $2.69T is enough to murder every man, woman, and child on Earth 20 times which should be more than sufficient.
Why Decentralization Works
Nobody tells the 14,000 people involved in making a pencil what to do. They just do it. No meetings. No committees. No PowerPoints. Just prices coordinating everything. Pragmatic clinical trials work the same way when you stop letting corporation-controlled government agencies run them.
A conceptual comparison between centralized control, characterized by top-down hierarchies and committees, and decentralized coordination, where independent actors are linked through price signals.
The 1% Treaty Fund
Instead of a committee of 200 bureaucrats giving their friends grants to write papers about diseases, the 1% Treaty Fund directly subsidizes patients, letting them choose which trials to fund.
A comparison between traditional bureaucratic grant funding and the 1 percent Treaty Fund’s patient-directed trial funding model.
A Decentralized Framework for Drug Assessment (dFDA)
Adverse events require filling out a PDF form (seriously)
Most side effects never get reported
No public database of outcome frequencies
You find out a drug causes heart attacks 10 years later when lawyers get involved
A decentralized assessment system:
Adverse events collected automatically from every participant
Real-time reporting to everyone (not buried in FDA databases)
Outcome labels show exact frequency and severity of every effect
You know the risks BEFORE you take the drug, not after the class action lawsuit
The FDA doesn’t even publish adverse event rates. They make you guess. The framework tells you “12% of patients got headaches, 3% were severe, 0.1% discontinued treatment.” That’s not less safe than the current system. That’s actually safer. You have real safety data instead of guessing.
Treatment Rankings
Consumer Reports for Drugs
Current system: Your doctor picks treatments based on:
Rankings are based on frequency and magnitude of health outcome changes across all patients - or filtered to patients with similar omic profiles to yours. A treatment that works great for 25-year-old women with your genetic variants might not work for 60-year-old men with different variants. The framework shows you what works for people like you, not average effects across everyone.
Outcome Labels
Nutrition Facts for Drugs
Food has nutrition labels. Cigarettes have warning labels. Drugs have… incomprehensible 40-page inserts written by lawyers having seizures.
Cognitive Improvements: Memory +35%, Executive Function +22%
Side Effects: Headache +9% (mild), Fatigue +7% (moderate)
Discontinuation rate: 2.3% stopped due to side effects
The Truth: Not marketing claims, actual measured effects from real humans
No more pharmaceutical fan fiction. No more lawyers writing medical advice during fever dreams. Just cold, hard data about whether this chemical makes your meat work better or worse.
Why This Could Actually Work
Unlike Everything Else Humanity Has Tried
The Evidence
Oxford Already Did It: The RECOVERY trial tested 6 treatments on 47,000 patients across 186 hospitals for $500 (95% CI: $400-$2.50K)/patient (vs standard FDA phase 3 cost of $41K (95% CI: $20K-$120K)), demonstrating a 82x (95% CI: 50x-94.1x) cost reduction at scale (consistent with a systematic review of 64 pragmatic trials showing median costs of $97 (95% CI: $19-$478)/patient85). Not in theory. In reality. With actual dying people who became not-dying people.
A comparison showing the 82-fold cost reduction achieved by the RECOVERY trial model compared to standard FDA Phase 3 costs, alongside a scale visualization of the 30 percent post-WW2 military spending cut versus the proposed 1 percent reallocation.
“Every gun that is made, every warship launched, every rocket fired signifies, in the final sense, a theft from those who hunger and are not fed, those who are cold and are not clothed.” - President Dwight D. Eisenhower, 1961
Switzerland Figured This Out 200 Years Ago: They spend 0.7% on defense, have $93K GDP per capita, 84-year life expectancy, and nobody’s invaded them since Napoleon (who invaded everyone, so it doesn’t count). Turns out being rich and boring is an excellent defense strategy.
The Beautiful Math of Mutual Disarmament: Every nation reduces by 1% simultaneously. It’s like everyone agreeing to point 1% fewer guns at each other. The balance stays the same but with 1% less potential for everyone exploding. This is what game theorists call “obvious” and politicians call “impossible.”
Everything Already Exists, You Just Have to Ctrl+C, Ctrl+V:
Not dying from preventable meat failures (this is the big one)
Also no Nazis (as a bonus)
This raises the $1B needed to fuel the rest of the bribery machine, which in your economy is somehow both “a lot” and “what Jeff Bezos finds in his couch.”
If the treaty fails, investors lose their money. But they’ll be too dead from preventable diseases to complain about it. It’s a self-solving problem.
Potential Returns That Make Ponzi Schemes Look Conservative
Medallion Fund: 39% (they thought they were special)
Warren Buffett: 20% (adorable)
Real Estate: 15% (for people who like being landlords)
They give you: $1,000 in papers with dead presidents
You give them: $2,718 yearly in papers with the same dead presidents but more of them
How does money multiply like rabbits? The treaty unlocks $27.2B annually from the murder budget. Investors get 10% because they had the revolutionary idea of “what if we didn’t all die?”
The same fund that pays investors also pays for politician incentives. Both get 10% of treaty revenue. When Senator Smith votes YES, their Public Good Score rises, independent Super PACs provide campaign support, and post-office opportunities unlock (fellowships, advisory boards, speaking circuits). No money goes to politicians directly. What flows is reputation, electoral advantage, and career advancement. Investors aren’t gambling on politicians becoming altruistic. They’re gambling on politicians being self-interested.
A comparison of annual investment returns, illustrating the massive disparity between traditional high-performance funds and the 272 percent ROI of VICTORY Incentive Alignment Bonds.
It’s the Louisiana Purchase of clinical trials, except instead of buying land from France, you’re buying immortality from death.
Step 2: The Great Clicking
Make Humans Click a Button to Not Die
You need 3.5% of humanity to vote yes on this question: “Pragmatic trials integrated into standard healthcare cost 44.1x (95% CI: 39.4x-89.1x) less than traditional methods. If all nations redirect just 1% of military spending to fund these trials, everyone gets 1% more security (1% fewer nuclear bombs pointed at you) and access to treatments years sooner. Should your country participate?”
A comparison showing the 44.1x cost efficiency of pragmatic trials versus traditional methods, alongside a visualization of redirecting 1 percent of military spending to healthcare research.
Even humans, who once thought the Earth was flat and diseases were caused by bad smells, can handle this level of complexity.
The Magic 3.5% Number
Scientists discovered that when 3.5% of any population wants something, they often get it. It’s like a cheat code for democracy that actually works.
A visual representation of the 3.5 percent tipping point for social change alongside the four-step viral mechanism for mass recruitment and financial incentives.
This is how you got:
Women’s suffrage (3.5% of women got angry enough)
Civil rights (3.5% of people noticed apartheid was stupid)
Gay marriage (3.5% realized love is love)
Legal weed (3.5% admitted they were high anyway)
How to make it go viral (like COVID but helpful):
Give people imaginary internet points that transform into real money (humans love points)
Cost per click: $0.50 (less than a candy bar, more than nothing)
Payment only upon success (like a reverse lottery where everyone wins)
The pyramid scheme aspect: Everyone recruits everyone else because money
Defense lobbyists are humans whose job is “convince politicians that death is profitable.” They currently get $1,813 back per dollar invested in democracy corruption139.
A logic flow diagram illustrating the conversion process of defense lobbyists by comparing their current ROI from military lobbying against the proposed alternative strategy.
Show them a spreadsheet:
Current Job
Salary: $500K
Moral status: Somewhere between “arms dealer” and “puppy kicker”
Moral status: “Medical hero” (fake, but sounds nice)
Legacy: “Accidentally saved humanity while getting rich”
A financial comparison of a 20 million investment versus a 54 million annual return at a 272 percent rate, including qualitative benefits like moral status and legacy.
They might switch sides faster than Italy in a world war.
Step 4: Purchase Democracy
It’s For Sale Anyway
Politicians are simple organisms with one evolutionary drive: reelection. You exploit this with Super PAC spending (part of the $650M lobbying budget).
A conceptual diagram showing how financial contributions and voter support from different interest groups influence a politician’s policy stance.
The conversation goes:
Representative: “280M of people million voters want to not die”
Politician: “But military contractors give me papers”
You: “Here’s more papers plus those 280M of people million votes”
Politician: “I’ve always been very passionate about helping sick people!” (they discovered this passion approximately 3 seconds ago)
It’s not corruption if you corrupt the corruption. It’s like a double negative in grammar but for democracy.
But Super PACs alone aren’t enough. You need a system that makes supporting the treaty the best career move a politician can make - not just today, but forever.
Incentive Alignment Bonds
The Part Where You Hack the Politicians’ Brains
Here’s a fun fact about human politicians: they don’t optimize for “humans continuing to exist.” They optimize for:
Getting reelected (requires papers)
Looking important (requires people noticing them)
Getting rich after leaving office (requires favors from rich people)
Notice “keeping constituents alive” isn’t on the list. This isn’t because politicians are evil. It’s because evolution optimized humans for status, not species survival. You can’t fix this with awareness campaigns. That’s like trying to convince a dog to stop chasing squirrels by explaining ecology.
Incentive Alignment Bonds (IABs) are financial instruments that make “save lives” and “advance career” point in the same direction. It’s bribery, but you call it something else, so it’s legal. Humans are very particular about what you call things.
How It Works (The Scoring System)
You give politicians a score based on how they vote. Not on health outcomes (too complicated), just on whether they voted YES or NO on treaty funding. When a politician votes YES:
Their Public Good Score goes up (it’s like a credit score but for not killing people)
Electoral support materializes (independent campaigns suddenly remember they exist)
Post-office opportunities unlock (fancy jobs after they stop being politicians)
No papers go directly to politicians. That would be “bribery.” Instead, papers go to people who give them reputation, electoral advantage, and career advancement. This is called “not bribery” because the papers took a detour.
A process diagram illustrating how a YES vote translates into a Public Good Score and flows through indirect channels to produce electoral support and career opportunities.
The Senator Smith Thought Experiment
Senator Smith (R-Texas) is deciding how to vote on the 1% Treaty. Let’s examine his thought process. (I’m using “thought” loosely here.)
Without IABs:
Vote Yes
Vote No
Attack ads: “Smith voted to WEAKEN AMERICA”
Safe from weapons lobby attacks
Defense contractors fund opponent
Defense contractors fund Smith
Benefits arrive in 10 years (Smith might be dead)
Costs arrive never (perfect!)
Result: Vote no. This is called “rational self-interest” and it’s why humanity can’t have nice things.
With IABs:
If Smith votes YES
If Smith votes NO
Public Good Score: 45 → 72
Score: 45 → 30 (yikes)
P(reelection): 55% → 62%
P(reelection): 55% → 48%
$2M independent campaign support
$2M goes to opponent (double yikes)
Post-office tier: 3 → 1
Stuck at tier 3 forever
Expected post-office income: $200K → $500K/yr
Attack ads: “Smith voted AGAINST curing your grandmother”
Result: Vote yes. Smith didn’t become a better person. The math just changed. This is much more reliable than hoping politicians develop souls.
Investors fund the campaign ($1B). Politicians get career benefits for supporting it. Patients get cures. Everyone’s self-interest accidentally saves humanity. It’s like a Rube Goldberg machine where greed goes in and medicine comes out.
Why This Isn’t Bribery (Technically)
Humans have very specific rules about what counts as bribery. Here’s why IABs don’t qualify:
No one is paid to break a duty - You’re paying them to DO their duty (fund public health). This is apparently fine.
Rules are announced in advance - If you tell everyone you’re going to reward certain behavior before they do it, it’s “incentive design.” If you do it after, it’s “corruption.” Timing is everything.
No papers go directly to politicians - The papers go to scores, which go to electoral support, which goes to winning, which goes to power. It’s like money laundering but with extra steps and somehow legal.
Everything is based on public votes - No secret deals. Just publicly announced rewards for publicly recorded behavior. Bribery requires secrecy. This is the opposite: bribery so transparent it becomes policy.
A comparison diagram illustrating the flow of IABs from public scores to political power versus the secretive and duty-breaking nature of traditional bribery.
Bribery corrupts alignment. IABs create alignment. Same mechanism, different direction. Humans are fine with this because you called it something different.
Why This Works for Any Problem
The beautiful thing about IABs: they’re not specific to health. The same architecture works for any problem where:
Politicians need to do something good
But doing the good thing currently hurts their careers
And you have enough papers to change the math
Climate change? Same system. Nuclear disarmament? Same system. Pandemic preparedness? Same system.
A conceptual comparison between the traditional ‘Hope’ model of politics versus the ‘Incentive-Alignment’ model, showing how IABs flip the career math for politicians across different global challenges.
The 1% Treaty is just the proof of concept. Once humanity sees that “hack politicians’ incentives” works better than “hope politicians become good people,” you can apply it to everything. It’s like teaching a toddler that treats work better than tantrums, except the toddler controls nuclear weapons.
Step 5: Enjoy
Everyone Gets Rich and Nobody Dies
The treaty passes because money often defeats morality, as is tradition.
An infographic illustrating the distribution of 27.2 billion in annual value and specific benefits across four key stakeholder groups: investors, lobbyists, politicians, and the general public.
The $27.2B/year money volcano erupts, showering everyone with papers that represent value:
Investors: Swimming in 272% returns like Scrooge McDuck but legal
Lobbyists: Buying yachts with their yacht money
Politicians: Getting reelected by living voters (a revolutionary strategy)
Regular humans: Not dying from stupid things (priceless, but also free)
The entire system runs on greed, like capitalism, except instead of destroying the planet it accidentally saves everyone.
The Math
Where Numbers Prove Humans Are Hilariously Bad at Priorities
When you stop paying people to create paperwork about death and start paying them to prevent death, the universe rewards you with impossible returns:
It’s like a money printer, except instead of causing inflation it causes people to continue existing.
A bar chart comparing the return on investment for prevention against other high-yield investment benchmarks.
This beats:
Selling kidneys (illegal, messy, you only have two)
Running a casino (requires mob connections)
A politician doing insider trading (requires lack of soul)
Bitcoin in 2010 (requires time machine)
The Money Fountain
Explained for Five-Year-Olds
You stop paying smart humans to write grant applications. You start paying them to actually solve problems. Problems get solved. Money appears. Everyone acts surprised.
A comparison of return-on-investment (ROI) ratios between historical health milestones like smallpox eradication and childhood vaccines against the proposed R and D reform, alongside a visualization of the 44.1x reduction in clinical trial costs.
For context: 150k deaths/day people die daily from disease and aging. Slower testing and rollout means some fraction of those deaths are avoidable by earlier access to effective treatments (see regulatory mortality analysis)
Warning
The Math of Overcaution: For every 1 person the FDA protects from a bad drug, it kills 3.07k:1 (95% CI: 2.88k:1-3.12k:1) people by making them wait for good drugs. It’s like a lifeguard who checks if the life preserver is safe while 3.07k:1 (95% CI: 2.88k:1-3.12k:1) people drown.
Bed nets cost $89 (95% CI: $78-$100)/DALY. That’s the gold standard. GiveWell’s best intervention. The thing against which all other “keeping humans alive” projects are measured.
That’s 50.3kx (95% CI: 23.7kx-111.7kx) more cost-effective than bed nets. The kind of number that makes Excel cry and economists question their life choices.
It’s like discovering your umbrella also cures malaria, cancer, and aging, costs less than a penny, and pays you to use it.
Even a congressman could understand this, though we shouldn’t assume.
Unlike charity, which requires infinite begging to finite donors, this system operates until the heat death of the universe or until humans evolve into beings of pure energy, whichever happens first (probably the heat death thing).
The best idea would be converting 100% of military spending to pragmatic clinical trials, achieving immortality by Thursday, and turning Earth into a paradise where disease is just a weird thing they had in museums.
A comparison of the cost per life saved between traditional charities (3,500) and the proposed profit-generating intervention system.
Unfortunately, that requires humans to stop being humans. So you settle for the 2nd best idea: tricking humans into accidentally saving themselves while trying to get rich.
At 50.3kx (95% CI: 23.7kx-111.7kx) more cost-effective than bed nets, this is like finding out your lottery ticket also cures cancer and pays you to use it.
It beats childhood vaccines, smallpox eradication, and every other “not dying” intervention humanity has ever attempted. That’s like being 10 times better than pizza. Impossible, yet here we are.
The Comparison That Makes Charity Look Sad:
Traditional charities: Spend $3,500 to save one human life (heroic but expensive)
This system: MAKES profit per life saved
You don’t donate to this. You invest in it. Then you could get wealthy while accidentally saving humanity as a side effect.
It’s what Jesus might do if he’d taken an economics class.
Choose Your Own Adventure
You’re standing in front of two doors. Behind one is the future you’re currently speed-running toward. Behind the other is the future where humans accidentally discover that not dying is preferable to dying.
Door #1: The Current Plan
A comparative visualization showing the scale of 150,000 daily preventable deaths compared to other historical tragedies and the 2.72 trillion annual global economic loss.
Keep Doing What You’re Doing
150k deaths/day people continue dying every single day from diseases humans could fix (that’s fifty 9/11s per day, but nobody’s counting because math is hard)
$2.72T annually gets flushed down the death toilet (it doesn’t even flush, it just sits there)
You die from something stupid that humans could have cured, but didn’t, because the money was busy becoming missiles (which also kill you, just faster)
Military budgets grow until you’re spending more on bombs than food, which solves the food problem by eliminating the eaters
Healthcare costs bankrupt everyone who doesn’t die quickly enough (dying is now the economical choice)
Your grandchildren visit your grave to ask what you were thinking, and you have to explain from beyond death that at the time, ending civilization twenty times seemed more important than ending it zero times (graves are terrible at explaining economics)
Some major diseases could plausibly become dramatically more treatable sooner than expected if we multiply trial capacity and slash time-to-answer
Early investors make 272% returns (which beats everything except insider trading), and politicians discover that voting for cures is better for their careers than voting for bombs
Healthcare becomes free through trial participation
You personally could get $3M (95% CI: $259K-$12.1M) in lifetime wealth and extra years of life (yes, you specifically)
Death becomes optional (terms and conditions apply)
The life extension achieved determines your total benefit. With a median 20-year life extension, you get substantial lifetime wealth. With optimistic aging reversal scenarios (50+ years), benefits multiply several times.
Price of Procrastination
Every second you spend thinking about whether to do this, the universe helpfully reminds you why you should:
410 humans got permanently deleted (one every 3.5 minutes, which is faster than you read)
$327M evaporated into bureaucratic nonsense (that’s enough to fund 327 lifetimes of productive research, but instead it became PowerPoint slides)
Your telomeres got shorter (that’s the thing that decides when you stop existing)
Someone somewhere played nuclear weapon roulette with your life (the chamber has 13,000 bullets in it, which seems like poor odds)
A politician said something stupider than yesterday (probably about vaccines causing 5G)
Join or Die snake illustration
The Soviet Union went from nothing to conquering half the world to completely collapsing in a SINGLE HUMAN LIFETIME.
And Communism was objectively a TERRIBLE IDEA that required murdering millions of people.
This is arguably the second-best idea in human history and requires radically less murder.
You’re literally just trying to get people to click “yes I would prefer not to die of horrible diseases” on a website.
If humans can coordinate to invent “lines” and not eating each other, this should be manageable.
The Final Math
Human Stupidity by the Numbers
Humanity’s Annual Death Budget: $118.8 trillion (that’s $118,800,000,000,000 if one enjoys seeing zeros)
This is spent on:
Making humans stop (war)
Watching humans stop (healthcare)
Documenting how humans stopped (bureaucracy)
Arguing about who made them stop (lawyers)
Your revolutionary proposal: Steal 1% of the murder money for the not-murder money.
A visualization of the 118.8 trillion global budget, highlighting the massive 99 percent retained for destructive capacity compared to the proposed 1 percent reallocation.
Countries still keep 99% of their apocalypse capacity. They can still end all life 19 times instead of 20. If you can’t successfully end the world with 19 attempts, the 20th probably wasn’t going to help.
Your Binary Choice Matrix
Option A: Continue toward expensive, preventable, documented death Option B: Redirect 1% and accidentally achieve immortality while getting rich
The universe is literally offering you infinite money and eternal life, and you’re thinking about it.
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/
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
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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4.
Group, E. W. US farm subsidy database and analysis. Environmental Working Grouphttps://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/
The United States could maintain adequate deterrence and defense with a much smaller military budget. Current spending levels reflect force projection capabilities far beyond what homeland security and deterrence require. A strategy of restraint could reduce defense spending by 40-50% while maintaining security through nuclear deterrence and geographic advantages. Additional sources: https://www.cornellpress.cornell.edu/book/9780801452581/restraint/
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.
The total costs of the post-9/11 wars in Iraq, Afghanistan, Pakistan, and Syria are expected to exceed $8 trillion. This includes $2.89 trillion for Iraq/Syria, veterans care through 2050 projected at more than $2 trillion, and interest on war debt adding $6.5 trillion through 2050.
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.
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
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
US incarceration costs approximately $80 billion annually in direct correctional expenditures alone. Including social costs (lost earnings, family impacts, health effects, reduced child outcomes), total burden exceeds $300 billion annually. The US incarcerates at 5x the rate of other OECD countries with no corresponding reduction in crime. Evidence shows community-based alternatives cost less and reduce recidivism more effectively. Additional sources: https://www.vera.org/publications/the-economic-burden-of-incarceration-in-the-u-s | https://www.prisonpolicy.org/reports/pie2024.html | https://www.rand.org/pubs/research_reports/RRA108-3.html
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12.
Marron Institute, N. Transit costs project - why US infrastructure costs so much. NYU Transit Costs Projecthttps://transitcosts.com/ (2024)
The United States builds transit infrastructure at dramatically higher costs than peer countries. New York’s Second Avenue Subway cost $2.5 billion per kilometer vs. $200-500 million in European cities. US highway construction similarly costs 2-5x more than comparable projects abroad. Causes include: excessive environmental review, litigation risk, lack of in-house expertise, fragmented project management, and inflated soft costs. Additional sources: https://transitcosts.com/ | https://www.brookings.edu/articles/why-does-infrastructure-cost-so-much/
Free global labor mobility would increase gross world product by somewhere in the range of 67-147%... The gains to eliminating migration barriers amount to large fractions of world GDP—one or two orders of magnitude larger than the gains from dropping all remaining restrictions on international flows of goods and capital.
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.
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.
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
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
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/
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
CPI-U (1980): 82.4 CPI-U (2024): 313.5 Inflation multiplier (1980-2024): 3.80× Cumulative inflation: 280.48% Average annual inflation rate: 3.08% Note: Official U.S. government inflation data using Consumer Price Index for All Urban Consumers (CPI-U). Additional sources: https://www.bls.gov/data/inflation_calculator.htm
A comprehensive survey of empirical estimates finds rent-seeking costs range from 0.2% to 23.7% of GDP across different methodologies and countries. Laband & Sophocleus (1988) estimated up to 45% for the US.
24.
via, D. analysis. ClinicalTrials.gov cumulative enrollment data (2025). Direct analysis via ClinicalTrials.gov API v2https://clinicaltrials.gov/data-api/api
Analysis of 100,000 active/recruiting/completed trials on ClinicalTrials.gov (November 2025) shows cumulative enrollment of 12.2 million participants: Phase 1 (722k), Phase 2 (2.2M), Phase 3 (6.5M), Phase 4 (2.7M). Median participants per trial: Phase 1 (33), Phase 2 (60), Phase 3 (237), Phase 4 (90). Additional sources: https://clinicaltrials.gov/data-api/api
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
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/
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
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
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
Approximately 30% of drugs gain at least one new indication after initial approval. Additional sources: https://www.nature.com/articles/s41591-024-03233-x
Early childhood education: Benefits 12X outlays by 2050; $8.70 per dollar over lifetime Educational facilities: $1 spent → $1.50 economic returns Energy efficiency comparison: 2-to-1 benefit-to-cost ratio (McKinsey) Private return to schooling: 9% per additional year (World Bank meta-analysis) Note: 2.1 multiplier aligns with benefit-to-cost ratios for educational infrastructure/energy efficiency. Early childhood education shows much higher returns (12X by 2050) Additional sources: https://www.epi.org/publication/bp348-public-investments-outside-core-infrastructure/ | https://documents1.worldbank.org/curated/en/442521523465644318/pdf/WPS8402.pdf | https://freopp.org/whitepapers/establishing-a-practical-return-on-investment-framework-for-education-and-skills-development-to-expand-economic-opportunity/
Infrastructure fiscal multiplier: 1.6 during contractionary phase of economic cycle Average across all economic states: 1.5 (meaning $1 of public investment → $1.50 of economic activity) Time horizon: 0.8 within 1 year, 1.5 within 2-5 years Range of estimates: 1.5-2.0 (following 2008 financial crisis & American Recovery Act) Italian public construction: 1.5-1.9 multiplier US ARRA: 0.4-2.2 range (differential impacts by program type) Economic Policy Institute: Uses 1.6 for infrastructure spending (middle range of estimates) Note: Public investment less likely to crowd out private activity during recessions; particularly effective when monetary policy loose with near-zero rates Additional sources: https://blogs.worldbank.org/en/ppps/effectiveness-infrastructure-investment-fiscal-stimulus-what-weve-learned | https://www.gihub.org/infrastructure-monitor/insights/fiscal-multiplier-effect-of-infrastructure-investment/ | https://cepr.org/voxeu/columns/government-investment-and-fiscal-stimulus | https://www.richmondfed.org/publications/research/economic_brief/2022/eb_22-04
Ramey (2011): 0.6 short-run multiplier Barro (1981): 0.6 multiplier for WWII spending (war spending crowded out 40¢ private economic activity per federal dollar) Barro & Redlick (2011): 0.4 within current year, 0.6 over two years; increased govt spending reduces private-sector GDP portions General finding: $1 increase in deficit-financed federal military spending = less than $1 increase in GDP Variation by context: Central/Eastern European NATO: 0.6 on impact, 1.5-1.6 in years 2-3, gradual fall to zero Ramey & Zubairy (2018): Cumulative 1% GDP increase in military expenditure raises GDP by 0.7% Additional sources: https://www.mercatus.org/research/research-papers/defense-spending-and-economy | https://cepr.org/voxeu/columns/world-war-ii-america-spending-deficits-multipliers-and-sacrifice | https://www.rand.org/content/dam/rand/pubs/research_reports/RRA700/RRA739-2/RAND_RRA739-2.pdf
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
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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UCDP. State violence deaths annually. UCDP: Uppsala Conflict Data Programhttps://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
2023: 8,352 deaths (22% increase from 2022, highest since 2017) 2023: 3,350 terrorist incidents (22% decrease), but 56% increase in avg deaths per attack Global Terrorism Database (GTD): 200,000+ terrorist attacks recorded (2021 version) Maintained by: National Consortium for Study of Terrorism & Responses to Terrorism (START), U. of Maryland Geographic shift: Epicenter moved from Middle East to Central Sahel (sub-Saharan Africa) - now >50% of all deaths Additional sources: https://ourworldindata.org/terrorism | https://reliefweb.int/report/world/global-terrorism-index-2024 | https://www.start.umd.edu/gtd/ | https://ourworldindata.org/grapher/fatalities-from-terrorism
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Health Metrics, I. for & (IHME), E. IHME global burden of disease 2021 (2.88B DALYs, 1.13B YLD). Institute for Health Metrics and Evaluation (IHME)https://vizhub.healthdata.org/gbd-results/ (2024)
In 2021, global DALYs totaled approximately 2.88 billion, comprising 1.75 billion Years of Life Lost (YLL) and 1.13 billion Years Lived with Disability (YLD). This represents a 13% increase from 2019 (2.55B DALYs), largely attributable to COVID-19 deaths and aging populations. YLD accounts for approximately 39% of total DALYs, reflecting the substantial burden of non-fatal chronic conditions. Additional sources: https://vizhub.healthdata.org/gbd-results/ | https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24 | https://www.healthdata.org/research-analysis/about-gbd
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/
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
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/
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/
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
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
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.
55.
size, D. from global market & ratios, public/private funding. Private industry clinical trial spending.
Private pharmaceutical and biotech industry spends approximately $75-90 billion annually on clinical trials, representing roughly 90% of global clinical trial spending.
56.
IHME Global Burden of Disease (2.55B DALYs), C. from & GDP per capita valuation, global. $109 trillion annual global disease burden.
The global economic burden of disease, including direct healthcare costs (\(8.2 trillion) and lost productivity (\)100.9 trillion from 2.55 billion DALYs × \(39,570 per DALY), totals approximately\)109.1 trillion annually.
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
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
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59.
budgets:, S. component country. Global government medical research spending ($67.5B, 2023–2024). See component country budgets: NIH Budget#nih-budget-fy2025.
budgets, E. from major foundation & activities. Nonprofit clinical trial funding estimate.
Nonprofit foundations spend an estimated $2-5 billion annually on clinical trials globally, representing approximately 2-5% of total clinical trial spending.
62.
IQVIA, I. reports: Global pharmaceutical r&d spending.
Total global pharmaceutical R&D spending is approximately $300 billion annually. Clinical trials represent 15-20% of this total ($45-60B), with the remainder going to drug discovery, preclinical research, regulatory affairs, and manufacturing development.
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
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
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/
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/
The ICD-10 classification contains approximately 14,000 codes for diseases, signs and symptoms. Additional sources: https://icd.who.int/browse10/2019/en
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
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
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
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
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.
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/
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/
Recent surveys: 49-51% willingness (2020-2022) - dramatic drop from 85% (2019) during COVID-19 pandemic Cancer patients when approached: 88% consented to trials (Royal Marsden Hospital) Study type variation: 44.8% willing for drug trial, 76.2% for diagnostic study Top motivation: "Learning more about my health/medical condition" (67.4%) Top barrier: "Worry about experiencing side effects" (52.6%) Additional sources: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-015-1105-3 | https://www.appliedclinicaltrialsonline.com/view/industry-forced-to-rethink-patient-participation-in-trials | https://pmc.ncbi.nlm.nih.gov/articles/PMC7183682/
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79.
CSDD, T. Cost of drug development.
Various estimates suggest $1.0 - $2.5 billion to bring a new drug from discovery through FDA approval, spread across 10 years. Tufts Center for the Study of Drug Development often cited for $1.0 - $2.6 billion/drug. Industry reports (IQVIA, Deloitte) also highlight $2+ billion figures.
Study of 361 FDA-approved drugs from 1995-2014 (median follow-up 13.2 years): Mean lifetime revenue: $15.2 billion per drug Median lifetime revenue: $6.7 billion per drug Revenue after 5 years: $3.2 billion (mean) Revenue after 10 years: $9.5 billion (mean) Revenue after 15 years: $19.2 billion (mean) Distribution highly skewed: top 25 drugs (7%) accounted for 38% of total revenue ($2.1T of $5.5T) Additional sources: https://www.valueinhealthjournal.com/article/S1098-3015(24 | https://www.sciencedirect.com/science/article/pii/S1098301524027542
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.
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/
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
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
The median cost per participant was $97 (IQR $19–$478), based on 2015 dollars. Systematic review of 64 embedded pragmatic clinical trials. 25% of trials cost <$19/patient; 10 trials exceeded $1,000/patient. U.S. studies median $187 vs non-U.S. median $27. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC6508852/
For every dollar spent, the return on investment is nearly US$ 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
The knowledge of the circumstances which we must make use of never exists in concentrated or integrated form but solely as dispersed bits of incomplete and frequently contradictory knowledge which all the separate individuals possess.
Time-inconsistency describes situations where, with the passing of time, policies that were determined to be optimal yesterday are no longer perceived to be optimal today and are not implemented... This insight shifted the focus of policy analysis from the study of individual policy decisions to the design of institutions that mitigate the time consistency problem.
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
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
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.
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
Pre-1962: Average cost per new chemical entity (NCE) was $6.5 million (1980 dollars) Inflation-adjusted to 2024 dollars: $6.5M (1980) ≈ $22.5M (2024), using CPI multiplier of 3.46× Real cost increase (inflation-adjusted): $22.5M (pre-1962) → $2,600M (2024) = 116× increase Note: This represents the most comprehensive academic estimate of pre-1962 drug development costs based on empirical industry data Additional sources: https://samizdathealth.org/wp-content/uploads/2020/12/hlthaff.1.2.6.pdf
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
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
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
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.
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
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
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
Population-level: Up to 14% (9% men, 14% women) of total life expectancy gain since 1960 due to tobacco control efforts Individual cessation benefits: Quitting at age 35 adds 6.9-8.5 years (men), 6.1-7.7 years (women) vs continuing smokers By cessation age: Age 25-34 = 10 years gained; age 35-44 = 9 years; age 45-54 = 6 years; age 65 = 2.0 years (men), 3.7 years (women) Cessation before age 40: Reduces death risk by 90% Long-term cessation: 10+ years yields survival comparable to never smokers, averts 10 years of life lost Recent cessation: <3 years averts 5 years of life lost Additional sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1447499/ | https://www.cdc.gov/pcd/issues/2012/11_0295.htm | https://www.ajpmonline.org/article/S0749-3797(24 | https://www.nejm.org/doi/full/10.1056/NEJMsa1211128
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
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/
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
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/
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
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
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
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
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
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/
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.
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
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
Heart failure alone: $108 billion/year (2012 global analysis, 197 countries) US CVD: $555B (2016) → projected $1.8T by 2050 LMICs total CVD loss: $3.7T cumulative (2011-2015, 5-year period) CVD is costliest disease category in most developed nations Note: No single $2.1T global figure found; estimates vary widely by scope and year Additional sources: https://www.internationaljournalofcardiology.com/article/S0167-5273(13 | https://www.ahajournals.org/doi/10.1161/CIR.0000000000001258
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
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
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
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
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
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/
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/
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.
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
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
The $50,000/QALY threshold is widely used in US health economics literature, originating from dialysis cost benchmarks in the 1980s. In US cost-utility analyses, 77.5% of authors use either $50,000 or $100,000 per QALY as reference points. Most successful health programs cost $3,000-10,000 per QALY. WHO-CHOICE uses GDP per capita multiples (1× GDP/capita = "very cost-effective", 3× GDP/capita = "cost-effective"), which for the US ( $70,000 GDP/capita) translates to $70,000-$210,000/QALY thresholds. Additional sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC5193154/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC9278384/
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/
Following a successful global eradication campaign, the World Health Assembly officially declared the world free of smallpox in 1980. Additional sources: https://www.who.int/health-topics/smallpox
