The use of evidence in pharmacovigilance - Case reports as the reference source for drug withdrawals

Objective: Withdrawal of a drug from the market for safety reasons is a ser ious and sometimes complex decision. The scientific evidence supporting dru g withdrawals in the past years is critically appraised, Methods: With data provided by the Spanish Medicines Agency, all drugs with drawn from the Spanish market for safety reasons from January 1990 to Decem ber 1999 were identified. The adverse drug reactions (ADRs) were classified by the year of withdrawal, by the organ/system affected and by the alleged type of reaction (Rawlins and Thompson classification). A systematic revie w of the literature was performed. Results: A total of 22 drugs were withdrawn from the market due to safety r easons. In 18 of 22 cases (82%), the evidence supporting the drug withdrawa l came from individual case reports, cases series or the combination of dat a provided by randomised clinical trials and case reports. Hepatic (eight c ases) and cardiac (five cases) reactions accounted for 59% (13 of 22) of th e total withdrawals. In 10 of 22 (45%) cases, drug withdrawal was clearly d ue to type-B reactions. Only four withdrawals were based on evidence from o bservational studies inducting a comparison group. Conclusion: Case reports are the main source of information used to withdra w a drug from the market for safety reasons. It is necessary to improve the quality of evidence supporting the withdrawal process of drugs linked to u nexpected and severe ADRs. The use of large databases to perform cohort or nested case-control analyses is the most efficient and reliable method to s tudy type-A class effect ADRs, The implementation of such databases in diff erent countries could increase the quality of the information on ADRs by al lowing researchers to conduct efficiently these type of studies.