Thalidomide in the U.S.

If you’re old enough, you should remember the epidemic of babies born in the 1960s—mostly in European countries—with shortened limbs and other serious medical conditions.

A German drug company had developed a new non-addictive sedative—a supposedly safe wonder drug. It was the second-best seller in Germany, right behind Aspirin. Active ingredient: thalidomide. People used it to get a good night’s sleep. For pregnant women, it helped with morning sickness. Because the drug was such a big moneymaker in Germany, Merrell, a U.S. drug manufacturer, got a license to make and sell it in the U.S.

On September 8, 1960, Merrell submitted the drug application to the FDA for approval. Because it was already so popular in Europe, Merrell thought it would be a shoo-in for approval. Just let the new girl rubber stamp it. The “new girl” was Frances Kelsey, an MD with a PhD in pharmacology who had joined the FDA a month before the application was submitted. She was in charge of reviewing the clinical trials portion of the application, which was the size of four phone books bound together.

Kelsey had 60 days from the date of submission to respond to the application. If she did not, the drug would automatically be put on the market. To deny it, she had to prove it was unsafe. She was disturbed by the lack of details about the clinical trials, such as the participants’ age, sex, dosages, how long they were on the drug, adverse effects, and so forth. The company had never performed randomized, placebo-controlled studies over a sufficient period of time. In order to reject the application, Kelsey needed data proving the drug wasn’t safe—data she didn’t have.

Fortunately, there’s a loophole allowing reviewers to delay action by calling the application incomplete. You can just ask for more information and stall, which Kelsey did. In the meantime, Merrell was ready to go ahead. Even without approval, Merrell was already distributing the drug to thousands of patients across the U.S. They’d sent millions of thalidomide pills to doctors in so-called clinical trials. They’d already had brochures printed and enough raw material to make 15 million pills. They’d also lined up dozens of sales representatives to start hawking the drug in hospitals.

Kelsey kept stalling. The old-boy network was furious. In November 1961, the shit hit the fan. A doctor in Scotland, as well as other sleuths in Europe, had found a side effect of thalidomide, which was reported in a letter in The British Medical Journal. It turns out that the drug is safe in late pregnancy but harms an early embryo by blocking the development of blood vessels.

Thalidomide had been on the market for four years at this point. Thousands of babies had been affected. In the U.S., the official FDA count was 17 affected babies, nine of them born to mothers who took the samples; eight who had obtained the drug in other countries. But approximately 150 others in the U.S. have self-identified as thalidomide survivors. Absent Kelsey, it could have been much worse.

The scandal led to the Kefauver Harris Amendments of 1962, which required manufacturers to provide data from animal experiments and human trials to prove that a drug is safe before it can be sold. Ya think?

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