Trust is like a piece of china,
Precious, raw, and rare.
When it’s broken, it can be mended,
But the crack is always there.
Most everyone agrees that trust in our public health leadership has gone, and the confidence in our public health system needs to be rebuilt- although there are few ideas about how to do that. Let’s visit some past leaders who did engender trust, emblazoning their work with integrity to search for some lessons.
Tripping over phocomelia
Some years ago, when vacationing in Spain, I visited the outdoor shopping mall near our hotel (as I am wont to do). Beckoned by the inviting shop displays, I almost tripped. Looking down, I saw what looked like a young boy, as the person was quite small. He wasn’t. He was a wizened older man with limbs like olive-colored busted balloons. Scraps of flesh, like pierced balloon latex, hung from his shoulder and hip sockets like flippers. Indeed, that is what the man’s condition is called: “phocomelia,” - meaning seal-like.
These malformed or misshapen limbs can be caused by a drug called “Thalidomide,” widely available in Europe between 1957 and 1961 – an OTC-- over the counter –as an aid to sleep, preventing morning sickness in pregnant women, and to counter anxiety. Instead of helping, the drug killed some 10,000 children and injured thousands of others.
This is not a common sight in America - mainly due to the efforts of Dr. Frances Kelsey, who worked for the now much-maligned FDA. Thalidomide had been approved in Canada and 20 European countries, but Dr. Kelsey, charged with issuing FDA approval, noticed the drug reacted differently from others of similar chemical nature. She became suspicious.
“All they wanted was a good night's sleep, and a drug called thalidomide gave it to them. It brought a quick, natural sleep for millions of people who had trouble drifting off, and it also gave pregnant women relief from morning sickness. The drug's German manufacturer claimed it was non-addictive, caused no hangover, and was safe for pregnant women. And, unlike barbiturates, its lack of toxicity made it a poor choice for a suicide attempt.”
Dr. Kelsey demanded more data from the American manufacturer, the Richardson-Merrell Company, who promptly went over her head to her superiors and complained. “Dr. Joseph Murray, Richardson-Merrell's representative, grew increasingly frustrated. He made repeated phone calls and personal visits to Kelsey, and complained to her superiors that she was unreasonable and nit-picking, and that she was delaying the drug's approval unnecessarily.” Kelsey refused to bow to pressure, withholding approval for the drug, and requested further studies.
"I think I always accepted the fact that one was going to get bullied and pressured by industry. It was understandable that the companies were very anxious to get their drugs approved."
-- Dr. Frances Kelsey
Despite continuous pressure, Kelsey demanded additional information to explain an English study documenting peripheral neuritis, a nervous system side-effect. By May of 1960, she had enough information to reason that if thalidomide caused paralysis of the peripheral nerves, it probably caused greater damage to the developing embryo and asked for more safety assurances. Despite this, the company continued to seek product approval by appealing to her superiors. They backed Kelsey up.
Dr. Kelsey’s suspicions were soon vindicated. By November, a German scientist's report determined that the phocomelia epidemic in his country was associated with Thalidomide.
“Merrell withdrew its application and, in March 1962, withdrew the drug from experimental use” – a term under the laws then in effect, allowing “the use of the drug while approval for marketing was being sought.”
Due to Dr. Kelsey’s efforts, in October of 1962, the Kefauver Harris Amendment, or the Drug Efficacy Amendment, was unanimously passed by Congress. Now, in addition to safety, companies would be required to demonstrate the efficacy of new drugs before receiving FDA approval. Among its other provisions:
- Reporting of adverse reactions to the FDA.
- Stricter testing and patient consent before participation in clinical trials.
- Companies were required to disclose accurate information about side effects on labels and in advertising.
- Cheap generic drugs being marketed as expensive drugs under new trade names as new "breakthrough" medications were banned.
- The Drug Efficacy Study Implementation (DESI) program was begun to classify all pre-1962 drugs already on the market as either effective, ineffective, or needing further study. Of the roughly 3500 drugs evaluated, 30% were found to be ineffective.
The actions of Dr. Kelsey, the FDA, Congress, and the mainstream scientific community were a triumph, resulting in both immediate and long-range drug product safety for all of us. How come we can’t find that kind of leadership today?
More on other historical leaders in public health to come. In the meantime, dear reader, how would you suggest we invigorate trust in our public health leadership? What kind of leaders would you want? Who (what type of credentials, expertise, training) would be able to persuade you to accept views that are contrary to your own – especially if you aren’t trained in medicine, public health law, or science?
I’m looking forward to your responses.
