The history of medication safety started 169 years ago, on Jan 29, 1848, when a young girl (Hannah Greener) from the north of England died after receiving chloroform anesthetic before removal of an infected toenail. Sir James Simpson had discovered that chloroform was a safer and powerful anesthetic, and he had introduced it in clinical practice.
The cause of Hannah’s death was investigated to understand what happened to Hannah, but it was impossible to identify what killed her. Probably she died of a lethal arrhythmia or pulmonary aspiration. As a result of other deaths and alerts raised by the clinicians and the public about the safety of anesthesia, The Lancet Journal established a commission to take on this problem. The commission exhorted English doctors, including the doctor in colonies, to report deaths caused by the anesthesia. The results were published in The Lancet in 1893.
In the United States of America (USA) an experience for more than a century in the field of the safety of medications, and the use of these drugs led to creation of new acts or changes to the existing ones. The US Federal Food and Drug Act was formed on June 30, 1906, and it established that drugs must be pure and free of any contamination.
In October 1937, the use of the antibiotic sulfanilamide caused the death of more than 100 people in the USA. These deaths were not due to the active ingredient itself; rather, they were caused by the addition of diethylene glycol (DEG), the excipient used as a solvent for the active drug. DEG was supposed to be inert, with no therapeutic benefits; however, it was the toxic substance that led to those fatal side effects. The company claimed they did not foresee these side effects, which was true, as they did not commit animal studies before they marketed the drug. Because of this incident, the U.S. Food and Drug Administration (FDA) approved an act to ensure the safety of any drug by conducting non-clinical and clinical studies before the drugs are marketed for public use (Geiling and Cannon, 1938, Young, 1984, Wax, 1995).
Of course, the problems arising from drugs and their side effects did not stop occurring. A severe worldwide crisis was initiated by the use of the drug thalidomide, which was used as an antiemetic agent for pregnant women in many countries. In the early 1960s, the use of thalidomide during the first trimester of pregnancy led to teratogenic effects manifested by the birth of infants with severe deformities known as “Phocomelia”. Babies would be born lacking extremities (hands and legs) or with only very short ones. Many infants died because of this “medication” as well. Overall, more than 10,000 children in 46 countries were victims of thalidomide. It is important to mention that this drug was not authorized or approved for use in the United States because of some concerns that arose during non-clinical studies (animal studies) due to the existence of cases of deformities on animal embryos. Note that those animal studies were conducted according to the act that was initiated following the sulfanilamide incident in the USA; therefore the public was protected and avoided from this crisis.
In 1961, a big change of European Pharmacovigilance happened following the tragedy of Thalidomide. Dr. McBride, an Australian doctor, wrote a letter to the editor of the Lancet Journal, in which he suggested a connection between congenital malformation of babies and thalidomide. In fact, he observed that the incidence of congenital malformations of babies (1.5%) had increased up to 20% in women who had taken thalidomide during pregnancy . At the same time, during a Pediatric Convention in Germany Dr. Lenz suggested a correlation between malformations and thalidomide and his suspect was published in a German Journal.
Over the years drug safety studies have provided key information that has prevented deaths and human tragedies. There’s been a lot of progress in developing a scalable and sustainable pharmacovigilance operating model for the industry. Companies are creating solutions that apply AI across the entire information value chain for end-to-end case processing, aggregate reporting, and signal detection/ evaluation automation. Current WHO regulations requires that all medicines and vaccines undergo rigorous testing for safety and efficacy through clinical trials before they are authorized for use.
