In nineteen sixty-two, your Congress decided that after proving a drug won't kill you, sick people should wait another eight
point two years before they're allowed to take it. The drug passed safety testing.
It won't kill you, won't melt your liver, won't make your hair migrate to your back.
But you can't have it, because a committee needs to spend eight point two years making sure it works well enough.
You're not allowed to volunteer for the trials that would answer that question faster, either.
You are, however, allowed to die. This was called "safety."
On Wishonia, when we confirm something won't harm you (no organ damage, no mutations, no growing a second head), we let
you try it. On Earth, you lock it in a cabinet and form a committee.
The committee meets quarterly. You decompose on a different schedule.
Then, during those eight point two years of efficacy testing, the drugs are tested on three thousand young, healthy volunteers
(excluding the sick, elderly, and anyone on other medications).
The very people dying from the disease are banned from the trials testing treatments for their disease.
When the drug is finally approved, it's prescribed to millions of actual sick people, where the problems finally show up.
It's like testing sunscreen on people who live in caves, then acting surprised when it fails outdoors.
A Note on Blame. When this chapter says "the F.D.A. does X," read it as "the nineteen sixty-two law requires the F.D.A.
to do X." Congress wrote the rules. The F.D.A. follows them.
Blaming the F.D.A. is like blaming the gun instead of the person who loaded it, aimed it at patients, and pulled the trigger
on a sixty-two-year schedule. "But What About Safety?". This is the part where humans panic, so let me be very precise about
what this chapter is (and isn't) proposing. Keep: Phase One safety testing.
It screens for death, organ damage, toxic reactions, dangerous side effects, and all the creative ways a molecule can ruin
a human body. It works. It caught thalidomide. It takes two point three years.
Nobody is suggesting you skip it. Keep (but fix): efficacy testing.
You should do massively more of it. But open it to every patient who wants to participate, publish all results (positive
AND negative), and stop blocking access to known-safe drugs while you run the trials.
Remove: The part where known-safe drugs sit in a cabinet for eight point two years while dying patients are banned from
trying them and banned from the trials testing them. To be excruciatingly clear: this chapter is not arguing against efficacy
testing. It is arguing for radically more efficacy testing, on real patients, with transparent results, while not holding
known-safe drugs hostage during the process. On Wishonia, we have a word for "preventing someone from accessing a substance
confirmed not to harm them while they die from the condition it might treat."
The word is "murder." You call it "the approval process." The forty-four point one times Inefficiency Tax.
Compare two real-world systems for testing drugs: The Oxford RECOVERY Trial tested COVID treatments on forty-seven thousand
patients for five hundred dollars and found a life-saving treatment in three months, like a normal species would.
The Post-nineteen sixty-two System averages forty-one thousand dollars per trial and takes nine point one years to approve
a new drug, like humans would. The current system costs forty-four point one times more and takes forty-two times longer.
That's not inefficiency. That's a system performing exactly as designed, if the design goal was to kill people slowly enough
that nobody notices. The eight point two year Efficacy Lag.
Here's where your lifespan goes to die: Phase One (Safety Testing) takes two point three years to test if the drug harms
people through death, organ damage, mutations, serious adverse reactions, and all the ways a molecule can ruin your day
(this part works, keep it). Phase Two and Three (Efficacy Testing) takes eight point two years where the drug is now known
safe, but patients can't have it while it is tested on young, healthy volunteers to see if it works better than placebo.
The sick people who actually need the drug are excluded from the trial, and access is blocked until the committee is satisfied.
This is where people die waiting for a drug that already passed every safety check your species invented.
Not because efficacy testing is bad, but because you do it on the wrong people and lock everyone else out while you wait.
The math is simple: If you die in year five and the drug that passed every safety screen gets approved in year ten, the
regulatory process murdered you. Not hypothetically. You are dead because a committee decided that confirming efficacy was
more important than your continued existence. That's eight point two years sitting in regulatory purgatory after we already
know the drug won't harm you. No toxicity. No organ failure.
No spontaneous extra limbs. The solution isn't to skip efficacy testing.
It's to stop using it as a reason to block access. On Wishonia, when we confirm a substance is safe, we make it available
with real-time outcome tracking so we learn if it works from the millions who take it (all of whom volunteered), not from
three thousand hand-picked healthy people in a controlled environment that resembles no actual patient's life.
We get MORE efficacy data, FASTER, from REAL patients, while NOBODY dies in a queue.
You invented science yesterday, cosmically speaking. Nearly every study ends with "more research is needed," which is scientist
for "please keep paying us while we figure out what we're looking at."
This would be fine except people are decomposing while you figure it out.
On Wishonia, we have a saying: "The dead have no use for data."
You don't have that saying, which explains a lot. What the nineteen sixty-two Efficacy Requirements Changed.
Before nineteen sixty-two, one hundred forty-four thousand physicians tested treatments on real patients and published results.
Life expectancy grew three point eight two years every decade for eighty straight years.
Things were going well. Naturally, Congress intervened. Phase One safety testing (added in 1938) worked perfectly.
It screens for toxicity, organ damage, dangerous side effects, and all the ways a drug can physically harm you.
It prevented all U.S. thalidomide deaths while Europe had thousands.
So in 1962, Congress looked at a system that was working and thought, "What if we made this much worse?"
They added massive pre-approval efficacy requirements via the Kefauver Harris Amendment, blocking patient access for years
during testing. The cost of developing a drug went from twenty-four point seven million dollars to two point six billion
dollars, a one hundred and five times increase. New drug approvals dropped from forty-six per year to thirteen, a seventy
percent decline. Life expectancy gains slowed from three point eight two years per decade to one point five four, a sixty
percent reduction. Time to approval stretched from two to three years to ten point five years.
The temporal break is exact. Every metric got worse the moment the law passed.
Like flipping a switch from "progress" to "paperwork.". The one hundred and five times cost increase is rigorously documented.
See Drug Development Cost Analysis for methodology, sensitivity analysis, and source data.
The Modern Consequences. Even if you think historical analysis is just opinions with footnotes, the current system's failures
are undeniable: Scientists discover a cure for your disease.
Phase One confirms the drug is safe (two point three years).
You are not allowed to take the known-safe drug. You are also not allowed to join the efficacy trial (you're too sick, too
old, or on other medications). You wait eight point two more years.
You die. The F.D.A. approves the cure. Pharmaceutical companies charge your widow ten thousand dollars per pill.
On Wishonia, this sequence would be considered a war crime.
On Earth, it's called "the approval process." Beautiful system if you're a mortician or bankruptcy lawyer.
Fourteen years from discovery to patient. That's longer than it took to build the pyramids.
Those involved moving rocks the size of houses without machinery (also the pharaohs didn't have to file quarterly progress
reports in triplicate). High Costs Kill Innovation, Reward Monopoly.
Before 1962: Genius scientist invents cure, raises a few million, tests safety, gives it to people.
Like a civilization that wants to survive would. Now: Genius scientist must convince one of three mega-corporations to spend
two point six billion dollars on a ten percent chance of success.
Those corporations already sell inferior drugs for the same condition.
The math for the mega-corporation: Option One: Spend two point six billion dollars on trials.
Ninety percent chance: Lose everything. Ten percent chance: Succeed, then cannibalize your own profitable drug.
Option Two: Buy the patent, put it on a shelf. Zero percent chance of losing two point six billion dollars.
One hundred percent chance your inferior cash cow keeps printing money.
Which would you choose if you were a rational sociopath in a suit?
The profit incentive doesn't just fail to reward better treatments.
It actively punishes them. Off-Patent Drugs and Rare Diseases: Mathematically Doomed.
The 1962 law made it mathematically impossible to cure diseases that aren't profitable enough: Ninety-five percent of diseases
are rare: development costs of two point six billion dollars for a patient population of approximately ten thousand patients
equals two hundred sixty thousand dollars per patient. No patent equals no funding: off-patent drugs can't attract billion-dollar
investments. Pre-specification kills serendipity: one must predict what drug cures before testing.
When something costs more, you get less of it. This is the first thing they teach in economics, and the last thing anyone
considers when writing health policy. Ninety-five percent of diseases have zero treatments.
Not because cures are impossible. Because cures are unprofitable.
The Actual Death Toll of "Drug Lag". Economists call it "drug lag," which is a lovely, clinical way of saying "people rotting
to death in a queue for drugs that have already been confirmed not to hurt them.".
Early estimates: twenty-one thousand to one hundred twenty thousand American lives per decade.
But that was just the U.S. A comprehensive quantitative analysis using W.H.O.
mortality data estimates the total cost of the eight point two years post-safety efficacy delay (the lag after drugs are
known safe): four hundred sixteen million eventually avoidable deaths.
Including years lived with disability: seven point nine four billion disability-adjusted life years, or D.A.L.Y.s, of healthy
human life deleted. Economic cost: one point one nine quadrillion dollars (in twenty-twenty-four U.S.D.), thirty-eight times
more than all global pharma R. and D. spending combined. Even if these estimates are off by a factor of ten, the system
still costs eighty-two times more per patient and takes thirty-six times longer than proven alternatives.
Here's a news story from the Non-Existent Times by No One Ever without a picture of all the people who die from lack of
access to life-saving treatments that might have been. Types of Error in F.D.A.
Approval Decision If the drug is beneficial and the F.D.A. allows it, it is a correct decision.
If the drug is harmful and the F.D.A. allows it, victims are identifiable and might appear on Oprah.
If the drug is beneficial and the F.D.A. does not allow it, victims are not identifiable or acknowledged.
If the drug is harmful and the F.D.A. does not allow it, it is a correct decision.
The most infamous case: beta-blockers. Europe used them to prevent heart attacks.
The U.S. delayed for a decade, killing an estimated one hundred thousand Americans.
More than died in Vietnam and Korea combined. From one drug delay.
After nineteen sixty-two, U.S. life expectancy diverged from Switzerland's (which didn't introduce the same delays).
More drug approvals in the eighties narrowed the gap. Fewer approvals in the nineties widened it again.
How the Incentives Work. F.D.A. Regulator Decision Tree. Approve drug that later shows problems.
Congressional hearing (televised). "F.D.A. APPROVED KILLER DRUG" headlines.
Career ends. Pension threatened. Delay drug that could save lives.
Nothing happens. Dead people don't complain. Promotion on schedule.
Retire to pharma job. This isn't conspiracy. It's just a system where the only career-ending move is doing something.
Approve a bad drug, your name is in the newspaper. Delay a good drug, the people who could have complained are dead.
It's a perfect incentive structure if you're optimizing for cowardice.
The Math: Why Current Regulations Increase Total Harm. Even generously crediting ALL drug withdrawals to the 1962 changes
(ignoring that Phase One safety testing already existed), the prevented harm totals approximately two point five nine million
disability-adjusted life years, or D.A.L.Y.s. The delay harm totals seven point nine four billion D.A.L.Y.s.
For every one unit of harm prevented, the current system creates three thousand and seventy units of harm through delay.
Why Bureaucrats Are Rewarded for Letting You Die. Dr. Henry I.
Miller ran the F.D.A. team reviewing recombinant human insulin in the early 1980s.
Mountains of evidence showed it was safe and effective. His supervisor refused to approve it.
If someone died from the drug, heads would roll. If people died waiting for the drug?
Nothing happens. Dead patients don't testify before Congress.
Clinical Trial Theater: Excluding eighty-six point one percent of Reality Makes Drugs More Dangerous.
Here is the part I find most baffling about your species. You block dying patients from accessing known-safe drugs because
you need to "test efficacy first." Then you ALSO block those dying patients from the efficacy trials.
So they can't take the drug, and they can't participate in the test that would let them take the drug.
They can, however, die. Nobody blocks that. The F.D.A. requires rigorous trials to ensure safety.
Then it tests the drugs on people who aren't sick, aren't old, aren't on other drugs, and aren't pregnant.
Basically, it tests drugs on triathletes and then acts surprised when grandma has a reaction.
Trials under the current system exclude: Patients over sixty-five: Most people who actually take medications (excluded due
to "comorbidities"). Patients under eighteen: All children (metabolism differs from adults).
Pregnant women: Excluded entirely (then drugs prescribed during pregnancy anyway).
Anyone with comorbidities: The sickest patients most likely to have adverse reactions.
Anyone on other medications: Everyone elderly (can't detect drug interactions).
Anyone too far from trial sites: Poor and rural populations.
This is like crash-testing a car by gently rolling it into a pillow, declaring it safe, and selling it to demolition derby
drivers. Result: In antidepressant trials alone, eighty-six point one percent of real patients are excluded.
The drugs are tested on the healthiest people alive, declared "safe," then handed to everyone the trial specifically avoided.
This is how Vioxx, Fen-Phen, and Bextra all got approved, celebrated, prescribed to millions, and then withdrawn after killing
people whose demographics the trials had carefully excluded.
The eight point two years delay didn't make these drugs safer.
It made them seem safer by hiding the danger behind an exclusion list.
Testing drugs only on healthy volunteers to ensure safety is like testing parachutes only on the ground.
No Long-Term Outcome Data. Data collection can be as short as several months.
You take the drug for forty years. Pre-Specification Requirements Kill Innovation.
The regulations require drug developers to predict exactly what a treatment will cure before testing it on humans.
You must know the answer before you're allowed to ask the question.
This is how science works on your planet, apparently. In two thousand seven, Dendreon showed that its immunotherapy drug
Provenge significantly reduced deaths from prostate cancer.
The F.D.A. advisory committee agreed it worked. Then the F.D.A.
rejected it anyway. Not because it didn't save lives. Because Dendreon filled out the wrong form about which lives it was
planning to save. "People stopped dying" wasn't good enough.
The paperwork predicting that people would stop dying wasn't filed in the right order.
Three more years and another trial were required. During those three years, people who could have stopped dying continued
dying, but at least the forms were correct. Due to these additional costs, Dendreon ultimately filed for chapter eleven
bankruptcy. Small Trials Are Dangerous. Phase Three trials test one thousand to three thousand patients.
A one-in-ten-thousand adverse event is mathematically invisible in a trial of three thousand.
Then the drug goes to millions. After approval, the F.D.A. monitors safety using FAERS, a system where doctors voluntarily
report problems if they feel like it. It captures less than ten percent of actual adverse events.
Vioxx killed an estimated thirty-eight thousand to fifty-five thousand Americans before this honor system noticed.
That's more people than died in the entire Korean War, detected by a system that relies on doctors filling out optional
paperwork. A D.F.D.A. (a decentralized F.D.A.) with ten million participants catches one-in-ten-thousand reactions, includes
real populations, tracks long-term outcomes, and provides automated surveillance instead of voluntary paperwork.
You have a fax machine and a suggestion box. One of these is a safety system.
The other is a prayer with an eight-year waiting period. The Negative Results Black Hole.
Here's something that would be illegal if anybody important cared: Negative trial results published: thirty-seven percent.
Positive trial results published: ninety-four percent. Money wasted repeating failed experiments: approximately one hundred
billion dollars annually. Companies are allowed to hide when drugs don't work, which is like letting restaurants hide their
health inspection failures. Actually, restaurants can't do that.
Drugs get less transparency than a sandwich shop. Company: "We tested this drug!".
Regulator: "Did it work?". Company: "...We tested this drug!".
Pharmaceutical companies bury negative results deeper than Jimmy Hoffa.
Other companies waste billions testing the same dead ends. Your insurance premiums fund this magnificent inefficiency.
It's like casinos only having to report when people win. Countries That Don't Have Our "Safety" Japan gives conditional
approval after Phase Two with real-world data collection. Time to patient: two to three years.
Americans fly there for treatment. The E.U. lets terminal patients access experimental drugs at a doctor's discretion.
F.D.A.: "But what if they die?" (They're already dying.). Right to Try (U.S.) passed despite F.D.A.
opposition. The F.D.A. made it effectively impossible to use.
Patients helped: less than two hundred total. Patients who wanted help: tens of thousands.
On Wishonia, "Right to Try" is just called "rights." The fact that your species needed a special law to allow dying people
to take known-safe drugs, and then made the law effectively unusable, is the most human thing I've ever observed.
The COVID Test Fiasco January twenty-twenty: W.H.O. develops COVID test, world starts using it.
February: F.D.A. blocks all non-C.D.C. tests to "ensure quality.".
The C.D.C. tests were contaminated. Private labs begged to help.
Late March: F.D.A. finally allows other tests after thousands die.
The only approved tests didn't work. Ensuring quality control of broken tests is like T.S.A.
confiscating water bottles while letting actual weapons through.
Except people died. The Bottom Line The post-safety efficacy lag is eight point two years.
During that lag, four hundred sixteen million deaths died, seven point nine four billion disability-adjusted life years,
or D.A.L.Y.s, of healthy life were destroyed, and the economic cost reached one point one nine quadrillion dollars.
For every one unit of harm the delay prevented, it created three thousand and seventy units of harm through blocking access.
It is not a safety system. It is a filing system that produces corpses as a byproduct.
The only thing missing is the political will to admit that a law signed before the Beatles existed might not be the pinnacle
of pharmaceutical regulation. Technical Analysis For the full quantitative analysis including methodology, sensitivity analysis,
and source data (warning: contains numbers large enough to make you physically ill), see: The Human Cost of Regulatory Latency.
P.S. - The F.D.A. will likely object to this chapter. Estimated response time: twelve to fifteen years, pending Phase Three
review and proper documentation.