Cobra Effect · Evidence in medicine

The reviewer who asked for more

How one reviewer's demand for better evidence kept thalidomide off American shelves.

7 cards, read aloud in 2:60, with a test and sources.

A pill bottle with pills spilling out beside it

In the late 1950s, a new sedative called thalidomide was selling in many countries.

It was first sold in West Germany in 1957. It was sold as a gentle way to calm nerves and help people sleep. Doctors also gave it to pregnant women for morning sickness. In Germany, you could buy it without a prescription.

In 1960, a company asked to sell it in the United States.

The application landed with Frances Kelsey, a doctor and pharmacologist who had just joined the Food and Drug Administration. It was one of her first cases. She found the evidence that the drug was safe too thin, and asked for more.

The company pushed hard, and Kelsey kept asking questions.

She came under heavy pressure from the company, and from within her own agency. In December 1960, a British doctor reported nerve damage in some patients taking the drug. Kelsey wanted to know what else it might do, including to a baby developing in the womb. She would not approve it without better answers.

In late 1961, doctors linked thalidomide to terrible harm before birth.

In Germany and in Australia, doctors noticed babies born with severely shortened or missing limbs. Their mothers had taken thalidomide early in pregnancy. The drug was pulled from sale, but thousands of children around the world had already been affected.

In America, Kelsey’s refusal meant it had never gone on sale.

The company withdrew its application in March 1962. But the drug had already been handed out to thousands of American patients to try, some of them pregnant. A small number of American babies were born with its injuries. Far more would have been, had it been approved.

The near miss changed the rules for new medicines.

In August 1962, President Kennedy gave Kelsey a top award for public service. That October, a new law required companies to show that a drug works, not just that it is safe. It also tightened the rules for testing drugs on people, including asking for their consent. Kelsey worked at the agency for decades, and died in 2015, aged a hundred and one.

So when you are pressed to approve something quickly, ask what the evidence really shows.

Kelsey did not know that thalidomide harmed unborn babies. She knew only that the evidence it was safe was not good enough. Today the drug is still used, under strict controls, to treat some cancers. Holding out for better evidence can look like stubbornness, until the day it looks like wisdom.

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