Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo‐controlled clinical trials. Issue 7 (7th February 2017)

• Record Type: Journal Article
• Authors: Mahr, Alfred; Golmard, Clara; Pham, Emilie; Iordache, Laura; Deville, Laure; Faure, Pierre
• Is Part Of: Pharmacoepidemiology and drug safety. Volume 26:Issue 7(2017)
• Page Start: 731
• Page End: 741
• Publication Date: 2017-02-07
• Subjects: adverse events -- placebo -- nocebo -- randomized controlled trial -- adverse drug reaction -- pharmacoepidemiology; Pharmacoepidemiology -- Periodicals; Chemotherapy -- Periodicals; Epidemiology -- Periodicals; 615.705
• DOI: 10.1002/pds.4169
• Languages: English
• ISSNs: 1053-8569

Abstract

Abstract: Purpose: Scarce studies analyzing adverse event (AE) data from randomized placebo‐controlled clinical trials (RPCCTs) of selected illnesses suggested that a substantial proportion of collected AEs are unrelated to the drug taken. This study analyzed the nonspecific AEs occurring with active‐drug exposure in RPCCTs for a large range of medical conditions. Methods: Randomized placebo‐controlled clinical trials published in five prominent medical journals during 2006–2012 were searched. Only trials that evaluated orally or parenterally administered active drugs versus placebo in a head‐to‐head setting were selected. For AEs reported from ≥10 RPCCTs, Pearson's correlation coefficients ( r ) were calculated to determine the relationship between AE rates in placebo and active‐drug recipients. Random‐effects meta‐analyses were used to compute proportions of nonspecific AEs, which were truncated at a maximum of 100%, in active‐drug recipients. Results: We included 231 trials addressing various medical domains or healthy participants. For the 88 analyzed AE variables, AE rates for placebo and active‐drug recipients were in general strongly correlated ( r > 0.50) or very strongly correlated ( r > 0.80). The pooled proportions of nonspecific AEs for the active‐drug recipients were 96.8% (95%CI: 95.5–98.1) for any AEs, 100% (97.9–100) for serious AEs, and 77.7% (72.7–83.2) for drug‐related AEs. Results were similar for individual medical domains and healthy participants. The pooled proportion of nonspecificity of 82 system organ class and individual AE types ranged from 38% to 100%. Conclusion: The large proportion of nonspecific AEs reported in active‐drug recipients of RPCCTs, including serious and drug‐related AEs, highlights the limitations of clinical trial data to determine the tolerability of drugs. Copyright © 2017 John Wiley & Sons, Ltd.