Nearly a third of clinical trials don’t adequately report adverse events

Medical libraryA study published in Archives of Internal Medicine has found that almost a third of clinical trials reported in top medical journals don’t adequately report the side effects of the intervention being tested.

Pitrou et al. assessed the reporting of safety data in 133 randomised controlled trials published between January 2006 and January 2007 in five high impact factor medical journals: New England Journal of Medicine, Lancet, Journal of the American Medical Association, British Medical Journal and Annals of Internal Medicine. PLoS Medicine was included in the search for relevant papers, but no trials from this journal were assessed.

Although 88.7% of published trials mentioned at some point the adverse effects of the study intervention – that is, the drug or non-pharmacological treatment being investigated – 32.6% of all trials didn’t properly report the adverse events data. For example, 17 articles only provided a description of the most common adverse events, whereas 16 reported just severe adverse events.

Thirty-six articles (27.1%) did not give any information the severity of the adverse events reported.  In addition, 63 reports (47.4%) did not give any data on the number of patients who withdrew from the trial owing to adverse events.

So why is this research important?  As the authors say, “the reporting of harm is as important as the reporting of efficacy in publications of clinical trials.”  Insufficient reporting of side effects affects the interpretation of the trial results and distorts the picture of the drug for both clinicians and patients – the drug seems effective but without full adverse effect data no-one can properly assess the risks and benefits of using it.

Writing in an Editorial in the same issue of Arch Intern Med, John PA Ioannidis discusses this issue further. “Accurate information on harms of medical interventions is essential for evidence-based practice”, he says. “Most newly introduced treatments usually have small, incremental benefits, if any, against already available interventions, and differences in the profile of harms should play a key role on treatment choice.”

In addition, this research raises the issue of reported research focusing on the benefits of the intervention being investigated and playing down the negative aspects – the dreaded publication bias.

Guidelines like the Consolidated Standards of Reporting Trials (CONSORT) statement have been put together to try to make sure that researchers report their trials in a complete and transparent way. The CONSORT Statement is a set of 22 recommendations for reporting randomised controlled trials that provides a standard way for authors to prepare reports of trial findings, thus aiding critical appraisal and interpretation of the results.

Granted, the CONSORT statement was only published in 2001 and thus it’s not entirely suprising that trial reporting wasn’t completely up to scratch in the 2006 papers analysed by Pitrou et al.

However, several journals, including BMJ, currently insist that authors fill in the CONSORT checklist and provide a flow chart before the paper can be accepted.  Let’s hope that researchers and publishers are now taking seriously the issue of thoroughly reporting adverse effects.

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Pitrou I, Boutron I, Ahmad N & Ravaud P (2009) Reporting of safety results in published reports of randomized controlled trials. Archives of Internal Medicine 169 (19): 1756-61. PMID: 19858432

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