It was the thalidomide disaster that first captured public attention about the risks associated with drugs and ensured that major regulatory changes in drug safety would occur throughout the world, including the UK. Paradoxically, thalidomide was initially introduced and marketed to address a serious safety concern. In the 1950s barbiturates were in widespread use. However, the toxic dose for barbiturates in children is very small, and accidental poisonings were a noted problem.
Thalidomide was serendipitously discovered in 1954, by a small German family firm called Chemie GrÃ¼nenthal, while trying to develop new antibiotics. Chemie GrÃ¼nenthal (motto â€œWe must succeed at any costâ€) already had a record of rushing drugs to market and associated drug withdrawals due to safety concerns1. After finding no beneficial effects in animal studies, they examined thalidomide use in epilepsy. No anti-epileptic activity was found, but many patients experienced a profound deep sleep and found that thalidomide produced a calming and soothing effect.
On October 1st 1957 thalidomide was marketed as the sedative Contergan in Germany. Unambiguous claims of safety led to its sale as an OTC product in Germany. A large marketing campaign, involving 50 medical journals, 50,000 therapeutic circulars and 250,000 individual letters to doctors was launched. Emphasising safety, the message was distributed that thalidomide was safe, even if used in suicide attempts. The company cited as evidence of safety in promotional material accidental overdoses of thalidomide in children.
Distillers Ltd, a UK whiskey producer who had become involved in penicillin production during World War II, sent their chief medical advisor to Germany with a view to marketing thalidomide in the UK. He returned saying, “If all the details of this are true, then it is a most remarkable drug. In short, it is impossible to give a toxic dose.” Distillers marketed thalidomide in the UK as Distaval in April of 1958, and placed a similar emphasis on the safety of thalidomide in promotional material.
In August of 1958, Chemie GrÃ¼nenthal declared the drug was suitable for use in pregnant and nursing mothers, an indication Distillers added with no supporting evidence. By 1959 Chemie GrÃ¼nenthal had received reports peripheral neuritis associated with thalidomide, though they publicly denied that such reports existed. The drug continued to be marketed as a safe drug.
In 1961, an Australian doctor called Jim McBride2 and a German doctor Dr Widukund Lenz3 independently made the connection between thalidomide and birth defects. Even after Chemie GrÃ¼nenthal were made aware of the possible connection, they posted 70,000 promotional leaflets to German doctors stating â€œContergan is a safe drugâ€. Thalidomide was eventually withdrawn in December 1961 leaving between 8,000 and 12,000 deformed children in its wake.
Like the Massengill Elixir tragedy before it, the thalidomide disaster had a major effect on the regulation of medicines, but this time the effect was worldwide. Between 1961 and 1965 Australia, Canada, Czecholovakia, Ireland, the Netherlands, New Zealand, Sweden, the UK, the US and West Germany all established spontaneous reporting systems for suspected ADRs4. The key principles of modern day pharmacovigilance systems were established. In 1968 ten countries agreed to pool all reports sent to national monitoring centres into a central database, as part of a WHO-sponsored collaboration. In the UK it led to the enactment of the Medicines Act 1968 giving the government power to license pharmaceutical companies, and individual products and clinical trials.
It also established the Medicines Commission and the Committee on the Safety of Medicines (CSM), to advise the Government on the exercise of their new powers. The spontaneous reporting system established by the CSM was the Yellow Card scheme5.
Although, it is now widely felt that a disaster of the same scale and nature of that caused by thalidomide would not excape detection by modern drug safety mechanisms, new drugs continue to be heavily marketed to physicians (and in some countries to directly to patients) before they have a established safety profile. Despite this lack of evidence, alleged safety benefits of medicines are used to boost such sales and have been a factor in a number of drug withdrawals since thalidomide.
1. Stephens T, Bryner R. Dark Remedy: The impact of thalidomide and its revival as a vital medicine. Cambridge, Massachusetts: Perseus Publishing, 2001.
2. McBride WG. Thalidomide and congenital abnormalities. The Lancet 1961;2:1358.
3. von Lenz W, Knapp K. Die thalidomid-embryopathie. Deutsche medizinische Wochenschrift 1962;87(24):1232-1242.
4. Edwards IR, Olsson S, Lindquist M, Hugman B. Global Drug Surveillance: The WHO Programme for International Drug Monitoring. In: Strom BL, ed. Pharmacoepidemiology. Chicester: John Wiley and Sons Ltd, 2005.
5. Davis D, King B, Raine JM. Spontaneous reporting – UK. In: Mann R, Andrews E, eds. Pharmacovigilance. Chichester: John Wiley and Sons Ltd, 2007: 199-216.