Health, Law and Bioethics 2014 By: Ana Granadeiro 1.

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THALIDOMIDEHealth, Law and Bioethics 2014

By: Ana Granadeiro

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BACKGROUND

The release of thalidomide in the 1950s and 1960s led to the world’s most publicised pharmaceutical disaster.

Thalidomide was invented in the early 1950s by scientists working for a German pharmaceutical company Chemie Grünenthal, who believed the drug could succeed as a sleeping pill and sedative and it was marketed in 1957, first in Germany and then throughout Europe.

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POPULARITY

Thalidomide first entered the German market in 1957 as an over-the-counter remedy, based on the maker’s safety claims. They advertised their product as “completely safe” for everyone, including mother and child, “even during pregnancy,” as its developers “could not find a dose high enough to kill a rat.” By 1960, thalidomide was marketed in 46 countries, with sales nearly matching those of aspirin.

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THALIDOMIDE BABIES Australian obstetrician Dr. William

McBride discovered that the drug also alleviated morning sickness. He started recommending this off-label use of the drug to his pregnant patients, setting a worldwide trend.

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McBride began to associate this so-called harmless compound with severe birth defects in the babies he delivered. The drug interfered with the babies normal development, more than 10,000 children in 46 countries were born with deformities such as phocomelia as a consequence of thalidomide use.

Other effects included deformed eyes and hearts, deformed alimentary and urinary tracts, blindness and deafness.

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REMOVAL FROM MARKET It took some time before the increasing number of babies being born with

malformations was connected with thalidomide, despite the existence of reports of birth defects associated with the drug.

Initially he phenomenon was blamed on nuclear weapon testing and lack of healthy nutrition and behavior of the mothers.

When a German newspaper published that 161 babies were adversely affected by thalidomide, marked he beginning of the end, leading the makers of the drug to finally stop distribution within Germany. Other countries followed and, by March of 1962, the drug was banned in most countries where it was previously sold.

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THALIDOMIDE IN THE COMMONWEALTH

The British pharmaceutical company The Distillers Company (Biochemicals) Ltd, who marketed thalidomide under the brand name Distavel throughout the United Kingdom, Australia and New Zealand.

Their advertisement claimed that: "Distavel can be given with complete safety to pregnant women and nursing mothers without adverse effect on mother or child...Outstandingly safe Distavel has been prescribed for nearly three years in this country." 

8THALIDOMIDE IN THE U.S.A.

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FDA REFUSAL Chemie Grünenthal approached Smith, Kline & French (SKF), with a request

to market and distribute the drug in the United States, however said marketing and distribution of the drug were denied by the FDA.

FDA inspector Frances Kelsey considered the application for thalidomide contained incomplete data on its safety and effectiveness. Chemie Grünenthal applied for its approval 6 more times, through different distributors and manufacturers, and 6 more times Frances Kelsey refused.

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THALIDOMIDE DISTRIBUTION IN THE U.S. Clinical trials were not under supervision nor needed aproval by the FDA at

the time, which resulted in about 2,5 million doses being distributed in the United States.

Smith, Kline and French and other pharmaceutical companies conducted animal tests and ran clinical trials of the drug in the United States involving about 20,000 people, including pregnant women.

A total of 17 children in the United States were born with thalidomide-induced malformations.

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TIME FOR A CHANGE FDA inspector Frances Kelsey, who prevented the

drug’s approval within the United States was praised as a hero and received the President's Award for Distinguished Federal Civilian Service by John F. Kennedy.

The tragedy surrounding thalidomide helped motivate profound changes in the FDA. By passing the Kefauver-Harris Drug Amendments Act in 1962, legislators tightened restrictions surrounding the surveillance and approval process for drugs to be sold in the United States, requiring that manufacturers prove they are both safe and effective before they are marketed.

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DRUG TESTS BEFORE THALIDOMIDE The procedures for drug testing at that time were much less rigid and

therefore the tests on thalidomide revealed no teratogenic effects. The tests in rodents, which metabolized drugs differently than humans do, did not show problems. Later, the same tests were performed in rabbits and primates, which produced the same horrible effects that he drug caused in human fetuses.

The drug was never tested on pregnant animals to check the effect on the embryos, and no follow-up was made to see what effect the drug had had on the children of pregnant women who had taken it once the drug was on the market.

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CHANGE IN DRUG REGULATIONS The need for the testing and approval of the toxins in certain

pharmaceutical drugs became more important after the disaster.

Thalidomide brought changes in the way drugs are tested, what type of drugs are used during pregnancy, and increased the awareness of potential side effects of drugs.

 The negative effects of thalidomide also led to the development of more structured drug regulations and control over drug use and development.

Kefauver Harris Amendment (U.S.) Directive 65/65/EEC1 (E.U.)

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LEGAL ACTION In 1968, a large criminal trial began in Germany, charging several Grünenthal

officials with negligent homicide and injury. After Grünenthal settled with the victims in April 1970, the trial ended in December 1970 with no finding of guilt.

In 2011, a class action commenced against Chemie Grünenthal and the British company The Distillers Company (Biochemicals) Ltd, who marketed thalidomide under the brand name Distavel throughout the United Kingdom, Australia and New Zealand on behalf of Australians born between January 1, 1958 and December 31, 1970. The lead plaintiff in the court case was Ms Lynette Rowe, a victim of thalidomide who was born without arms and legs.

On July 18, 2012 it was announced that Ms Rowe had settled her case (believed to be) in the millions of dollars, opening the way for class action victims to receive further compensation.

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THALIDOMIDE TODAY For a long time, thalidomide was associated with one

of the most horrific medical accidents of history. Slowly new studies began being made regarding thalidomide treatments for diseases like cancer or leprosy.

Was found useful in treating diseases such as lupus, relieving symptoms of HIV patients, decreased risk of bone marrow transplant rejection and rheumatoid arthritis, thalidomide is today indicated in about 60 treatments.

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THE END

by: Ana Granadeiro