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Real-World Evidence Historical Success (Pre-1962)

Keywords

war-on-disease, 1-percent-treaty, medical-research, public-health, peace-dividend, decentralized-trials, dfda, dih, victory-bonds, health-economics, cost-benefit-analysis, clinical-trials, drug-development, regulatory-reform, military-spending, peace-economics, decentralized-governance, wishocracy, blockchain-governance, impact-investing

Historical Evidence: Why Real-World Evidence Works Better

Large-scale efficacy trials based on real-world evidence produce better health outcomes. They beat current pharmaceutical industry-driven randomized controlled trials.

Trials run in the real world with real patients produce better health outcomes than trials run by pharmaceutical companies with carefully selected patients. Reality is more helpful than theater.

Trials run in the real world with real patients produce better health outcomes than trials run by pharmaceutical companies with carefully selected patients. Reality is more helpful than theater.

10,000 Years of Dying at 30

For over 99% of human history, average life expectancy was 30 years136.

Ancient Rome: 30 years. Medieval Europe: 30 years. Renaissance: Still 30 years.

Kings, peasants, philosophers, farmers - everyone died embarrassingly young.

10,000 years. Zero progress.

Life expectancy over time. It goes up. Then in 1962 it stops going up as fast. Something happened in 1962.

Life expectancy over time. It goes up. Then in 1962 it stops going up as fast. Something happened in 1962.

1883 – The Year You Figured It Out

Then something changed.

In 1883, doctors started sharing notes. Doctor sees something, writes it down, other doctors check the notes, JAMA says ‘Yes, this is real.’ Collaboration was invented.

In 1883, doctors started sharing notes. Doctor sees something, writes it down, other doctors check the notes, JAMA says ‘Yes, this is real.’ Collaboration was invented.

In 1883, doctors founded the Journal of the American Medical Association (JAMA)137. They did something novel: they shared information. After 10,000 years someone thought “what if we told each other what works?”

144 thousand physicians across America (see reference83) tried treatments on real patients. They wrote down what happened. “This drug helped.” “This drug killed the patient.” “This drug did nothing but made the patient smell funny.”

Leading experts reviewed these case reports. They compiled them into studies and published results. If a medicine worked and didn’t kill people, JAMA gave it a seal of approval.

Crowdsourced, observational, objective, peer-reviewed clinical research. And it worked.

The Result

After 10,000 years of zero progress, life expectancy suddenly shot up. It increased by 3.82 years every decade119 (calculated from 1880-1960 data). For 80 years straight.

The most linear relationship in medical history. Suspiciously perfect. It lasted from 1883 to 1960.

1938 – The FDA Requires Phase 1 Safety Trials

Elixir sulfanilamide killed over 100 people138 in 1937.

Congress reacted139. They required all new drugs to include:

“adequate tests by all methods reasonably applicable to show whether or not such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof.”

These requirements evolved into the Phase 1 Safety Trial140. This was reasonable. Test if a compound kills people before giving it to patients. Makes sense.

The 3.82 years per decade gain119 stayed the same. It held steady before and after the new safety regulations. Safety testing worked without slowing medical progress.

Life expectancy before and after the FDA required safety trials. The line goes up both times but at different speeds. Safety has a speed limit.

Life expectancy before and after the FDA required safety trials. The line goes up both times but at different speeds. Safety has a speed limit.

The regulations had no measurable impact on developing life-saving treatments. Not positive. Not negative.

1950s – Thalidomide: When Safety Regulations Actually Worked

Thalidomide hit European markets in 1957141 for morning sickness. Doctors thought it was safe in pregnancy. It wasn’t. It caused thousands of horrific congenital disabilities142.

Existing FDA safety regulations prevented any birth defects in the US143. The 1938 safety framework worked as intended. Zero American babies harmed.

The safety regulations succeeded. But newspaper stories like the one below created public outcry for more regulation. They targeted efficacy testing.

Thalidomide babies. This is what happens when you don’t test drugs on pregnant women. So now we test nothing on pregnant women and they take untested drugs.

Thalidomide babies. This is what happens when you don’t test drugs on pregnant women. So now we test nothing on pregnant women and they take untested drugs.

1962 – The Year You Decided to Make Everything Worse

Effective safety regulations already existed. They worked. America had zero Thalidomide deaths. Europe had thousands. Safety testing succeeded.

Before 1962: doctors tested if drugs worked. After 1962: drug companies tested if drugs worked. Costs went up. Time went up. Asking the seller if the product works costs more than asking the buyer.

Before 1962: doctors tested if drugs worked. After 1962: drug companies tested if drugs worked. Costs went up. Time went up. Asking the seller if the product works costs more than asking the buyer.

So naturally, the government responded to this success by adding massive efficacy regulations. The 1962 Kefauver Harris Amendment144 changed everything.

Safety testing wasn’t the problem. That worked fine. The problem? They took efficacy testing away from 144 thousand physicians independent doctors. They gave it to drug companies. It got 82x times more expensive. It got 32.8x times slower.

What Changed

Before 1962:

  • Drug companies spent $24.7M (inflation-adjusted) to prove safety (see reference22)
  • Once the FDA approved a drug as safe, 144 thousand physicians independent doctors tested efficacy on real patients (see reference83)
  • The AMA compiled results and published findings

After 1962:

  • The FDA took over efficacy testing
  • They made the old system illegal144
  • They required small, controlled trials run by… the drug companies themselves

The irony: Regulations meant to ensure drugs work did this by:

  1. Banning large real-world trials
  2. Requiring small artificial trials
  3. Letting drug companies run their own tests

Before 1962: doctors in charge, cheap, simple. After 1962: drug companies in charge, expensive, complicated. We replaced the people who use the product with the people who sell it.

Before 1962: doctors in charge, cheap, simple. After 1962: drug companies in charge, expensive, complicated. We replaced the people who use the product with the people who sell it.

What Happened to Efficacy Data

After 1962, trials got smaller, patients got less representative, and conflicts of interest got bigger. Making trials more rigorous made them worse at everything except paperwork.

After 1962, trials got smaller, patients got less representative, and conflicts of interest got bigger. Making trials more rigorous made them worse at everything except paperwork.

The 1962 regulations were about ensuring efficacy. They massively reduced the quantity and quality of efficacy data:

  • Trials Got Smaller: Fewer patients, less data
  • Patients Got Less Representative: They excluded sick people, old people, and people with other conditions. (You know, the people who actually need medicine.)
  • Conflicts of Interest Exploded: Drug companies ran their own trials. Independent doctors lost control.

What Happened to New Treatments

The new regulations immediately reduced new drug approvals by 70% (see reference81).

Not gradually. Immediately.

New treatments per year. The line goes up until 1962. Then it goes down. Regulating medicine made less medicine.

New treatments per year. The line goes up until 1962. Then it goes down. Regulating medicine made less medicine.

What Happened to Costs

Since 1962, the cost of bringing a new treatment to market exploded. It went from $24.7M to over $1 billion145 (inflation-adjusted).

A 105x increase. For worse results.

Cost to develop one new drug has exploded under FDA regulations (1950-2000)

Cost to develop one new drug has exploded under FDA regulations (1950-2000)

This chart shows the exponential increase in the cost to develop a single new drug from 1960-2019, adjusted for inflation to 2020 dollars. The vertical line marks the 1962 efficacy amendment (Kefauver-Harris Amendment).

Drug development costs were relatively stable before 1962, then exploded exponentially after the efficacy requirement was added. Costs increased 52x from $74M (1960) to $3,861M (2019), making innovation increasingly expensive and inaccessible.

What Happened to Drug Patents

The new regulations created massive delays. The pharmaceutical industry complained about a “drug lag.”

In 1984, patents got extended to encourage innovation. Prices went up. Availability went down. Safety went down. The incentive to innovate became an incentive to charge more for less.

In 1984, patents got extended to encourage innovation. Prices went up. Availability went down. Safety went down. The incentive to innovate became an incentive to charge more for less.

Congress “fixed” this by extending drug patent monopolies146 in 1984.

Kefauver’s amendments aimed to make drugs safer and cheaper. Instead they made them:

  • More dangerous (smaller trials, less real-world data to spot dangerous side effects)
  • More expensive (monopolies extended)
  • Less available (70% fewer approvals)

Decreased Ability to Determine Comparative Efficacy

The placebo-controlled randomized controlled trial helped gauge individual drug efficacy. But it makes comparative effectiveness harder to judge.

Drug A beats placebo. Drug B beats placebo. No one compares Drug A to Drug B. You know they both work better than nothing. You don’t know which one works better than the other.

Drug A beats placebo. Drug B beats placebo. No one compares Drug A to Drug B. You know they both work better than nothing. You don’t know which one works better than the other.

What Happened to Life Expectancy (The Part That Matters)

Remember that suspiciously linear 3.82-year increase119 every decade from 1883 to 1960?

Here’s what happened in 1962:

It strangely quickly dropped by 60%120. To 1.54 years per decade.

Average Life Expectancy Over Time

Average Life Expectancy Over Time

From 1880 to 1960: 3.82 years per decade119.

From 1962 onward: 1.54 years per decade120.

The break is so clean. You can see the exact year Congress decided to “help.”

Before 1962: gaining 3.82 years per decade. After 1962: gaining 1.54 years per decade. The line breaks exactly at 1962. Coincidences are supposed to be less precise than this.

Before 1962: gaining 3.82 years per decade. After 1962: gaining 1.54 years per decade. The line breaks exactly at 1962. Coincidences are supposed to be less precise than this.

The detailed chart showing this break over time is presented in the main FDA chapter.

The “Diminishing Returns” Excuse

Some claim “diminishing returns explain the slowdown.”

Diminishing returns produce a smooth curve. It flattens over time.

This is what diminishing returns look like when you smooth out all the noise and variables. A gentle curve. Reality is not a gentle curve. Reality is a sharp break in 1962.

This is what diminishing returns look like when you smooth out all the noise and variables. A gentle curve. Reality is not a gentle curve. Reality is a sharp break in 1962.

This isn’t what happened.

What happened was a straight line. It instantly changed slope in 1962 when the regulations changed.

Diminishing returns don’t produce sudden linear breaks. Regulatory changes do.

The “Correlation Is Not Causation” Excuse

True. Correlation alone proves nothing.

How to prove something caused something else: it happened at the same time, there’s a reason it would happen, and the timing is suspiciously exact. 1962 has all three.

How to prove something caused something else: it happened at the same time, there’s a reason it would happen, and the timing is suspiciously exact. 1962 has all three.

But correlation + mechanism + temporal precision is how science works.

Here’s what you have:

  1. Temporal correlation: Life expectancy growth dropped by half right after 1962 regulations
  2. Mechanism: Regulations reduced new treatments by 70%. They increased costs 105x. They banned real-world efficacy trials.
  3. Alternative explanations: Yes, they exist (increasing disease complexity, higher safety standards). But the timing, magnitude, and linearity of the slope change all point to one event: the 1962 regulations. Other causes would produce gradual change, not a clean break.

This is how clinical trials work. Temporal correlation + mechanism of action = inference of causation.

If you don’t trust this method, you can’t trust any clinical research. Or science generally.

Impact of Innovative Medicines on Life Expectancy

A three-way fixed-effects analysis147 studied 66 diseases in 27 countries. Without new drugs launched after 1981, people would have lost 2.16 times more years of life. The cost? $2,837 per life-year saved147.

More treatments lead to more survivors. There’s a strong correlation between new cancer treatments and cancer survival over 30 years.

More cancer treatments invented, more people survive cancer. Turns out medical research works. Who knew.

More cancer treatments invented, more people survive cancer. Turns out medical research works. Who knew.

The Summary

  • 10,000 years: Zero progress
  • 1880-1960: Decentralized real-world trials, 3.82 years/decade progress119
  • 1962: Kefauver-Harris passes. Progress drops 60%120 to 1.54 years/decade
  • Today: Still stuck with the broken system

Humanity solved medical progress in 1883. Congress broke it in 1962.

Medical progress: 3.82 years gained per decade. Then 1962 happens. Medical progress: 1.54 years gained per decade. We cut medical progress in half with good intentions and paperwork.

Medical progress: 3.82 years gained per decade. Then 1962 happens. Medical progress: 1.54 years gained per decade. We cut medical progress in half with good intentions and paperwork.