Dr. Frances Kelsey and Thalidomide: Standing up for evidence based medicine

July 24 marked Dr. Frances Kelsey’s 98th birthday. Dr. Kelsey is a true medical hero from North America (‘North America’ is more befitting as I consider her a true Canadian hero and inspiration while my American colleagues refer to her as an American hero since she moved to the United States and currently resides in the suburbs of Washington).

Organizations/regulatory bodies such as Health Canada and the US’s Food and Drug Administration (FDA) exist for a reason. They are there to safeguard the public through regulations and measures overseeing medications, health products, foods and devices. Researchers and industry may at times be too eager to market a drug that has shown potential and/or may find it too tiring to continuously go over regulations ensuring all the T's are crossed and I's are dotted. However, the experiences of Dr. Kelsey remind us why these regulations are vital.

Dr. Kelsey was born in Vancouver Island, British Columbia (Canada). She completed her undergraduate and master’s degrees in pharmacology from McGill University. She later obtained a Ph.D. in Pharmacology from the University of Chicago and her M.D. from Chicago medical school. Dr. Kelsey then joined the Food and Drug Administration (FDA) in 1960. Within her first month of service at the FDA, she was asked to review the application for a drug called Kevadon, which was manufactured in West Germany and known there by its more popular and generic name, Thalidomide. This appeared to be a quick and easy assignment of approving a drug which was popularly prescribed in Europe and Canada for insomnia and was hailed as a wonder drug, providing a ‘safe and sound sleep’. It had already received approval in over a dozen countries. However, Dr. Kelsey was alarmed by the evidence supporting the drug’s safety claims and rejected approval until further clinical evidence was provided. She was particularly concerned about what harmful effects it might have during pregnancy.

The manufacturer grew frustrated and pressured Kelsey and her superiors for approval, but Kelsey stuck to her principles and stood her ground. Around that time, physicians in Europe began to notice an increase in birth defects and in November 1961, Dr. Lenz, a German pediatrician determined that thalidomide was the cause. It was estimated that around 10,000-12,000 children worldwide were born with deformities associated with thalidomide. However, thanks to the efforts of Dr. Kelsey, America was spared such a disaster, having less than 50 cases of Thalidomide related birth defects. These U.S exposures to thalidomide had occurred because the manufacturer had already distributed more than 2.5 million tablets to more than a thousand doctors across the USA on an ‘investigational basis’. These tablets in turn were given out to more than 20,000 patients which included pregnant women (this would make doctors think twice before freely handing out samples to patients). By 1962, Thalidomide was withdrawn from the world market. In more recent times Thalidomide has been studied and approved in certain countries for the treatment of leprosy and multiple myeloma but under strict control due to its teratogenic effects.

On July 15, 1962, the front page of the Washington Post noted “‘Heroine’ of FDA keeps Bad Drug Off Market” recognizing and honouring Dr. Kelsey’s efforts in saving thousands. As a result of Dr. Kelsey’s commendable act of not bowing to pressure, steps were taken towards stricter measures and amendments of drug regulations. The thalidomide incident as a whole also made women and physicians more aware and cautious about various medications taken during pregnancy. Today, organizations such as the world renowned Motherisk Program founded by Dr. Gideon Koren at Toronto’s Hospital for Sick Children serve as a valuable resource of information providing evidence-based information and guidance about the safety or risks to the developing fetus/infant of maternal exposure to various drugs, diseases and agents (this can be accessed by doctors and parents from all over the world).

Dr. Frances Kelsey has since received several awards and honours which includes the President's Award for Distinguished Federal Civilian Service awarded in 1962 by President John F. Kennedy; she has had a school named after her in British Columbia (Canada); and in 2010 the FDA named an award after her called the ‘Dr. Frances O. Kelsey Award for Excellence and Courage in Protecting Public Health’. The FDA also announced the first recipient of this award was none other than Dr. Frances Kelsey herself at the age of 96.

About the author: Dr. Farhan M. Asrar is Chief Resident in the Dual Public Health & Preventive Medicine and Family Medicine Program at McMaster University (Canada). He is also the recipient of the 2012 Royal College of Physicians and Surgeons of Canada Resident Leadership Award. Dr. Asrar is passionate about the history of medicine and is a keen collector of original art, antiques and collectibles pertaining to the history of medicine, medical pioneers and Nobel prize winners in medicine. The original autograph of Dr. Frances Kelsey on a U.S. postal first day cover is from his personal collection.