Abstract
BackgroundPrescribing pharmacologic therapies for critically ill patients requires a careful balancing of risks and benefits. Defining, monitoring, and reporting harms that occur in clinical trials conducted in critically ill populations, however, is challenging given that the natural history of most critical illnesses includes progressive multiple organ failure and death. In this study, we assessed harms reporting in clinical trials performed in critically ill populations.MethodsRandomized, non-industry-sponsored, human clinical trials of pharmacologic interventions in adult critically ill populations published between 2015 and 2018 in high-impact journals were included in this systematic review. Harms data, adherence to Consolidated Standards of Reporting Trials (CONSORT) harms reporting guidelines, and restrictions on harms reporting were recorded.ResultsA total of 707 abstracts were screened with 40 trials ultimately being included in the analysis. Included trials represent 28,636 randomized patients with a median of 292 (IQR 100–546) patients per trial. The most common disease states were general critical care (33%) and sepsis (28%). Of 18 included CONSORT items, the median number met was 12 (IQR 9, 14). The most commonly missed items were adverse event (AE) severity grading definitions and AE attribution (relationship of AE to study drug), which were only reported in 35 and 38% of manuscripts, respectively. Half of the manuscripts (48%) provided definitions for recorded AEs. There were 5 studies investigating the effects of corticosteroids in sepsis, with the number of AEs reported per analyzed patient ranging from 0.01 to 1.89. AE definitions in studies of similar/equivalent interventions often varied substantially. Study protocols were available for 30/40 (75%) of studies, with 13 (43%) of those not providing any guidance regarding AE attribution.ConclusionsRandomized trials of pharmacologic interventions conducted in critically ill populations and published in high impact journals often fail to adequately describe AE definitions, severity, attribution, and collection procedures. Among trials of similar interventions in comparable populations, variation in AE collection and reporting procedures is substantial. These factors may limit a clinician’s ability to accurately balance the potential benefits and harms of an intervention.
Highlights
Prescribing pharmacologic therapies for critically ill patients requires a careful balancing of potential efficacy against potential harm
Randomized trials of pharmacologic interventions conducted in critically ill populations and published in high impact journals often fail to adequately describe adverse event (AE) definitions, severity, attribution, and collection procedures
Randomized clinical trials (RCT) are a crucial research tool, which allow investigators and clinicians insight into the risk/benefit ratio of medical therapies and promote informed decision-making in the intensive care unit (ICU)
Summary
Prescribing pharmacologic therapies for critically ill patients requires a careful balancing of potential efficacy against potential harm. The published results of clinical trials, frequently focus on the potential efficacy of the intervention with limited (if any) discussion of potential harms [1] The reason for this is multifactorial and likely includes investigator excitement regarding the studied intervention and the difficulty in accurately identifying, collecting, and reporting adverse events (AEs; any adverse outcomes potentially related to the active intervention) [2]. The latter is challenging in clinical trials conducted in critically ill populations where the distinction between a suspected adverse drug reaction (in which there is a reasonable possibility that the AE was related to the study drug) and the natural history of the critical illness is often difficult to determine [3]. We assessed harms reporting in clinical trials performed in critically ill populations
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