When someone takes a medicine, it is generally in the hope that it will do some good. However, whether it does or doesn’t is only half of the story: even the seemingly most innocuous of drugs can have adverse effects on health. In an editorial in the Archives of Internal Medicine, Dr John Ioannidis of University of Ioannina School of Medicine in Greece, makes the point that adverse effects from drugs are neglected, restricted, distorted, and silenced .
Dr Ioannidis’ editorial starts by making the point that new drugs often offer little in the way of benefit over existing treatments. This means that knowledge of their risk profile is essential to be able to make informed choices regarding therapy.
The editorial focuses on an analysis of relevant studies which appears in the same edition of the journal . In this analysis 133 studies published in ‘high-impact’ journals (the most widely-read and respected journals) were assessed in terms of the adverse effect reporting. This analysis showed that some trials gave absolutely no information on harms, severity was often undefined or vaguely defined, and half the trials reported no information on withdrawal of patients owing to harms. Only 13% reported the reasons why patients withdrew owing to adverse events, information that is of prime clinical relevance.
Dr Ioannidis also makes the point some trials limit their reporting of adverse effects to ‘statistically significant’ results. The problem is, the most serious adverse effects are generally very rare, and studies may not be large (powered) enough to define serious adverse effects as ‘statistically significant’. Dr Ioannidis claims that the statements such as no significant differences were found are misleading. I made a similar point some time ago in the blog post here.
Dr Ioannidis draws our attention to the fact that randomised controlled trials on drugs are primarily used to assess effectiveness, not risk. He asks whether this is perhaps the accepted norm as a result of conflicts of interest and marketing. Dr Ioannidis ends by suggesting that the mission of randomised control trials may need to change to include better understanding of the potential harms of medication.
1. Ioannidis JPA. Adverse Events in Randomized Trials: Neglected, Restricted, Distorted, and Silenced. Arch Intern Med 2009;169(19):1737-1739
2. Pitrou I, et al. Reporting of Safety Results in Published Reports of Randomized Controlled Trials. Arch Intern Med 2009;169(19):1756-1761