In the 1950’s, a Pharmaceutical company in Germany developed the drug Thalidomide for convulsion, however it was found to make the patients relaxed and sleepy. It subsequently entered the market as a wonder drug for insomnia, cough, cold and headache. Pre-clinical testing of this drug had proven that the drug could not kill a rat even at high doses and thus the drug was deemed safe and marketed and sold over the counter widely based on its safety profile, thus becoming very popular. Thalidomide first entered the German market around 1957 and by 1960, it was marketed in 46 countries. It was also discovered that Thalidomide was very effective in controlling the morning sickness in pregnant women and because of its safety profile it was widely consumed by pregnant women with morning sickness. However, in late 1950’s and early 1960’s there were increasing reports of babies that were born with deformed limbs and several reports linking the consumption of thalidomide to the abnormal increase in the birth defects in the children whose mothers has consumed thalidomide during pregnancy. It is estimated that, in Germany alone, 10,000 babies were born affected by Thalidomide. Subsequently the drug was banned and withdrawn from the market.
This disaster was averted in the US by then FDA inspector Ms. Frances Kelsey who prevented the drug’s approval within the United States. Kelsey felt the application for thalidomide contained incomplete and insufficient data on its safety and effectiveness. Dr. Frances Kelsey later received President’s award and was praised by then President of USA John. F. Kennedy who regarded her as heroine for averting the disaster.
Thalidomide tragedy is no doubt one of the darkest episodes of modern medicine which taught us several lessons about pharmaceutical prescriptions. Few critical ones are that:
- Medications could pass the placenta and cause deformities in the fetus.
- Drugs could have differential effects in animals and humans.
- Approval of marketing the medication has to be thoroughly regulated.
- Elaborate preclinical and clinical testing has to be performed prior to approval of medications.
- A continuous monitoring system has to be established after marketing a medicine to identify any harms or adverse effects that may be detected post marketing the medication which may have not been initially detected.
In the view of the last mentioned point, a Pharmacovigilance program was established by WHO for International Drug Monitoring in response to the thalidomide disaster along with a Collaborating Centre for International Drug Monitoring, Uppsala. Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. By the end of 2010, 134 countries were part of the WHO Pharmacovigilance program. The aims of Pharmacovigilance are to enhance patient care and patient safety in relation to the use of medicines; and to support public health programs by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines.
Ever since its inception, Pharmacovigilance has played a key role in identifying some expected (Augmented) and Unexpected (Bizzare) drug reactions to medications thus altering their safety profile, approval status, warnings and precautions, and labelling. This has also given us a better insight into the various mechanisms and interactions of a drug in human body resulting in a betterment of the science of drug development by the manufacturers and prescription by the physicians. It has also corroborated the stance of the regulatory authorities in implementing and adhering to stricter policies in approval of medications for use.
One of the notable instances which resulted in withdrawal of a drug is the case of Rofecoxib (Marketed as Vioxx). Rofecoxib a nonsteroidal anti-inflammatory drugs, was hoped to be safer than previous nonsteroidal anti-inflammatory drugs, due to its lower risk of GI bleeding was approved by the FDA in 1999. Rofecoxib gained widespread acceptance among physicians treating patients with arthritis and other conditions causing chronic or acute pain. On September 30, 2004, the manufacturer withdrew Rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use.
ADRs are one of the leading causes of morbidity and mortality in health care. Several studies conducted on hospitalized patient populations estimate that there are more than 2,216,000 serious ADRs in hospitalized patients, causing over 106,000 deaths annually. If true, then ADRs are the 4th leading cause of death—ahead of pulmonary disease, diabetes, AIDS, pneumonia, accidents, and automobile deaths. These statistics do not include the number of ADRs that occur in ambulatory settings. Also, it is estimated that over 350,000 ADRs occur in U.S. nursing homes each year (1). It is the onus of the healthcare professionals to spread awareness and to council the patients and other stakeholders to always be vigilant of any reaction caused during to the consumption of a medication and report the same to the health authorities appropriately in a timely fashion so that burden of the disease can be minimalized.