Adverse event assessment, analysis, and reporting in recent published analgesic clinical trials: ACTTION review and checklist

      The development of valid information about treatment risks and benefits requires consistent and comprehensive data about adverse event assessment and participants’ adverse events during randomized clinical trials (RCTs). Despite a 2004 extension of the Consolidated Standards of Reporting Trials (CONSORT) statement recommending the specific harms (i.e., adverse events) information that investigators should report, there is little evidence that published analgesic RCTs adequately adhere to these recommendations. This systematic review builds on prior recommendations by describing a comprehensive checklist for adverse event reporting developed to capture clinically important adverse event information (e.g., the severity of each adverse event causing withdrawal per arm; the duration of adverse events per arm). Using this checklist, we coded adverse event assessment methods and reporting in all 80 double-blind RCTs of non-invasive pharmacologic treatments published in European Journal of Pain, Journal of Pain, and Pain between 2006 and 2011. Across all trials, adverse event reporting was frequently incomplete, inconsistent across trials, and in some cases missing. For example, > 50% of RCTs reported an arbitrarily selected subset of adverse events occurring in the trial and > 40% of trials failed to report any information on serious adverse events [SAEs]. Two specific study characteristics (participant type and sponsor) previously shown to be associated with variability in adverse event reporting were examined. Trials of participants with acute or chronic pain conditions and industry-sponsored trials typically provided more and better quality adverse event data than trials involving healthy volunteers or trials that were not industry sponsored. The results of this review suggest that improved adverse event reporting is needed in analgesic RCTs. We developed an ACTTION adverse event reporting checklist that is intended to assist investigators thoroughly and consistently capture and report these critically important data in publications.