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LETTERS: Godfrey Oakley, Jr Lessons from the withdrawal of rofecoxib: Observational studies should not be forgotten BMJ 2004; 329: 1342 [Full text]

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Sentinel systems for long-term adverse drug reactions

Torbjörn Callréus   (13 December 2004)

Sentinel systems for long-term adverse drug reactions 13 December 2004
Torbjörn Callréus, Research fellow in Pharmacoepidemiology Institute of Public Health, University of Southern Denmark, DK-5000 Odense C, Denmark Send response to journal: Re: Sentinel systems for long-term adverse drug reactions	Editor—In the wake of the withdrawal of rofecoxib (Vioxx), the limitation of the present system for pharmacovigilance is once again discussed. With its focus on spontaneous reports, unexpected and rare reactions occurring shortly after exposure are usually detected with reasonable sensitivity. However, adverse effects are not readily identified if they occur after long-time exposure, or manifest themselves as an increase of a common disease. The cardiovascular events caused by rofecoxib belong to the latter group. While theoretically attractive, the proposal of Dieppe et al 1 to require independent, large scale, randomised trials before definitive drug licensing, is associated with some problems. As Oakley 2 points out, the sample sizes needed to investigate rare adverse reactions in traditional randomised controlled trials would significantly increase costs for clinical development and ultimately raise drug prices. Furthermore, over time, treatment switches and discontinuations often transforms large and simple randomised trials into observational cohort studies. Instead, Oakley wants to promote the use of cost-effective case-control studies. In selected cases, when there is a clear hypothesis about the nature of the reaction, and some idea of the suspected drugs, the case-control study can provide important information. However, as a strategy for continuous post- marketing surveillance of unexpected effects, it is less suitable. In recent years, large databases originating from routine healthcare procedures have become widely available. Although collected for other purposes, the information in these data sources could play an important role as a cost-effective sentinel system for long-term adverse drug reactions. However, the abundance of information in health care databases require techniques for research to move beyond traditional epidemiologic study designs, inherited from an era when data collection was expensive and yielded only a relatively small number of facts for each study subject. 3 Torbjörn Callréus Research fellow in Pharmacoepidemiology, Institute of Public Health, IPH Research Unit of Clinical Pharmacology, University of Southern Denmark, Winslowparken 19, 3rd floor, DK-5000 Odense C Denmark E-mail : torbjorncallreus@hotmail.com References 1. Dieppe PA, Ebrahim S, Martin RM, Jüni P. Lessons from the withdrawal of rofecoxib. BMJ 2004;329: 867-8. (16 October) 2. Oakley G Jr. Lessons from the withdrawal of rofecoxib: Observational studies should not be forgotten. BMJ 2004;329: 1342. (4 December) 3. Walker AM. Pattern recognition in health insurance claims databases. Pharmacoepidemiol Drug Saf. 2001;10: 393-7. Competing interests: As a former employee of AstraZeneca, TC has dividends that currently are in the process of being divested.