Comment on ‘Measuring the impact of medicines regulatory interventions – systematic review and methodological considerations’ by Goedecke et al.

Abstract

We read with interest the recent systematic review of studies that examined the impact of pharmacovigilance regulatory interventions worldwide by Goedecke et al.[1] and aimed to highlight methodological challenges.We agree that policies such as pharmacovigilance regulatory actions can have intended and unintended consequences. Monitoring the outcomes of such policies is an important [2] public health issue because they often affect tens of millions of people. However, we were surprised that Goedecke et al. included studies using weak research designs (for example, cross-sectional studies) that are typically excluded by international standards, i.e., Cochrane Systematic Reviews [3]. Secondly, their search and review omitted one of the most important studies in the field, our paper [4] published by BMJ in 2014 reporting an interrupted time series analysis of changes in antidepressant use and suicidal behaviour after safety FDA warnings from the US Food and Drug Administration (FDA) and media coverage.Weak research designs include single observations before and after (pre-post) an intervention without any controls and simple cross-sectional designs that correlate the exposure to an intervention with outcomes at a single point in time [5]. These designs are excluded by Cochrane systematic reviews of effects of health policies or programmes [6]. They rarely provide trustworthy evidence of policy effects because they do not control for common biases (e.g., secular trends or history bias and selection bias). Instead, interrupted time series (ITS) with and without a control series are one of the strongest quasi-experimental designs for evaluating policy effects. Based on Cochrane review standards, of the 153 articles included by Goedecke et al., only 48 ITS studies can provide credible evidence.Goedecke et al. included 27 articles that examined regulatory actions related to antidepressants. Interestingly, our interrupted times series study [4] on this topic was not identified by their search, and therefore, it was not included in their review. Our study of 10 years of health care data among 7 million people investigated if the widely publicized 2004 warnings from the FDA about possible suicidality risk with antidepressants in youth were associated with changes in antidepressant use and suicidal behaviour. We found that safety warnings and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts (as measured by psychotropic drug poisonings) among youth, which might be one consequence of under-treatment of mood disorders.Importantly, drug safety warnings or regulatory actions generally have little or no effect on health behaviour except those widely reported by media [3]. For instance, the antidepressant warnings were widely publicized by media reports [7]. It is possible that the warnings and extensive media attention led to unexpected and unintended population-level reductions in treatment for depression and subsequent increases in suicide attempts among young peo...

Response to ‘Comment on ‘Measuring the impact of medicines regulatory interventions – systematic review and methodological considerations’ by Goedecke et al.’

“…We would like to thank Christine Lu and Stephen Soumerai for their comments [1] on our systematic review of studies measuring the impact of medicines regulatory interventions [2].…”