Adverse reaction signal detection methodology in pharmacoepidemiology

Excerpt

In the nineteenth century, the toxicity of chloroform led to its withdrawal from clinical use [1] and in the period 1920–1940, hepatic injury by cinchophen [2] and agranulocytosis by amidopyrine and related agents [3] were recognized. But from the point of view of detection of important unknown adverse reactions, the thalidomide disaster with its thousands of fatal and non-fatal cases of congenital malformations was an absolute hallmark [4]. As a direct consequence, it was made mandatory in the early sixties of the preceding century to perform extensive toxicological, preclinical, and clinical studies before marketing of a drug in Western countries, and national spontaneous monitoring systems were set up. These systems in concert with the medical literature, proved to be the most effective and efficient system for recognizing new adverse reactions since then [5]. In the years thereafter, several drugs were recognized as the cause of serious disease, such as chronic active hepatitis by oxyphenisatin [6], sclerosing peritonitis by practolol [7] and many more since then. Such monitoring consists of manual review of adverse reaction reports by medical professionals and is relatively cheap and flexible but suffers from substantial underreporting, potential false-positive reporting and absence of reliable usage figures. Also, case-by-case assessments may lead to a loss of overview when large numbers of reports are involved and rests heavily on the quality of the professional. …