Harms are assessed inconsistently and reported inadequately Part 2: nonsystematic adverse events

Abstract

Objective: We examined nonsystematic adverse events (AEs) in Part 2 (of 2) of a study describing the assessment and reporting AEs in clinical trials.Study Design and Setting: We examined 21 trials of gabapentin for neuropathic pain (52 sources) and seven trials of quetiapine for bipolar depression (80 sources) using data from the Multiple Data Sources study. We extracted and compared information about nonsystematic AEs (i.e., AEs that were not assessed for every participant), including AEs categorized as ''serious.'' We recorded whether AEs were grouped by anatomic or physiological system.Results: Trials of the same drug reported information about different AEs. Information in public sources was inadequate for decisionmaking. No public source reported all AEs, or all serious AEs, identified in nonpublic sources about the same trial. Of trials with only public sources, 2/15 (13%) gabapentin and 0/3 (0%) quetiapine trials grouped AEs by anatomic or physiological system.Conclusion: Public sources contained little information about nonsystematic AEs, including serious AEs. Grouping might make nonsystematic AEs easier to detect; however, most public sources did not report grouped AEs. Standards are needed to improve the collection and reporting of nonsystematic AEs so that stakeholders can use trials to assess the balance of potential benefits and harms.

Those who control evidence control evidence based medicine

“…These reviews frequently ignore the fact that unfavourable findings are sometimes unpublished and that studies are often designed to favour the sponsored product (15,16). Indeed, overstating treatment benefits and understating risks in published research is standard practice (17)(18)(19). For instance, Turner et al examined the RCTs used for regulatory approval of all 12 antidepressant drugs approved by the Food and Drug Administration (FDA) from 1987 to 2004.…”

Mapping outcome reporting bias in published non-pharmacological randomized trials: a protocol for a cross-sectional study

“…Because of this, an outcome may be considered only fully specified when all 5 elements are present (10). Given the five possible elements that constitute an outcome and a difference in criteria required by international standards (3 elements), it can be considered an adequately reported outcome one that is partially defined (with a domain, measure and time point) or even fully specified (if all 5 possible elements are present) being defined in the registry in a retrospective manner (6,8,9,(11)(12)(13)(14)(15)(16). In this example, "mean change from baseline of Beck Depression Inventory score 12-month post randomization", stated in the primary outcome section in a registry (done prospectively -before the initiation of the clinical trial) in clinicaltrials.gov platform (or other platform) with a registry number (13), would be considered a fully specified outcome (10) and hence adequately reported (13).…”

“…Different methods give different results when assessing the frequency of outcomes partially defined in samples of published RCTs (6). Multiple outcome definitions and multiple methods of analysis create opportunities to select results and this can also compromise meta-analysis, because outcomes need to be standardized in the literature to be synthesized when appropriate (12,15,17). A single outcome with a same domain can be reported differently according to other elements, for example, method of aggregation or specific measure in clinical trials assessing similar questions (12).…”

Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for nonsystematic adverse events

“…Although previously non-public sources are becoming available for some trials [8][9][10]-including through data sharing services such as Vivli [ 11], Yale Open Data Access (YODA) [ 12,13], and clinicalstudydatarequest.com-clinical study reports (CSRs) and individual patient datasets (IPD) remain unavailable for many trials. Consequently, the results of many trials are available only in public sources [ 14,15], which are often incomplete [15][16][17][18][19][20][21][22][23][24]. Reporting bias, which is the selective reporting of research results, occurs when reporting is influenced by the nature of results (e.g., the direction, magnitude, statistical significance of results).…”

“…Reporting bias, which is the selective reporting of research results, occurs when reporting is influenced by the nature of results (e.g., the direction, magnitude, statistical significance of results). Reporting bias may lead to overestimating potential benefits of an intervention [15][16][17][18][19][20] and underestimating potential AEs [ 22,[25][26][27][28][29][30][31][32].…”