Adverse event assessment methods in published trials of psychotropic drugs: Poor reporting and neglect of emerging safety concerns.

BACKGROUND: Actual assessment methods for identifying adverse events (AEs) in clinical trials have received less scrutiny than underreporting of AEs.

OBJECTIVE: To investigate whether AE assessment has changed over time for three psychotropic drugs with turbulent histories of safety concerns since their U.S. approval.

METHODS: From industry-funded published trials of atomoxetine, duloxetine, and olanzapine retrieved from PubMed for 1996-2004 (n = 33) and 2009-2014 (n = 40), verbatim AE assessment and numbers of words describing efficacy and safety assessment were extracted.

RESULTS: Closest to drug approval (1996-2004), 77.8% of atomoxetine trials used open-ended questioning only, 50% of duloxetine trials used spontaneous self-report or clinician observation only, and 66.7% of olanzapine trials used a scale (primarily for extrapyramidal symptoms) and one former method. Recent studies (2009-2014) showed less rigor and transparency: 35.3% of atomoxetine and 64.7% of duloxetine studies reported no AE assessment method and 50% of olanzapine studies no longer used scales. Overall, the mean number of words describing efficacy assessment increased from 202 to 309 but decreased from 83 to 63 for safety.

CONCLUSION: Trial methodology for assessing psychotropic drug safety remains an underdeveloped area with major public health implications.