Biases in reporting of adverse effects in clinical trials, and potential impact on safety assessments in systematic reviews and therapy guidelines.

ABSTRACT

BACKGROUND: Clinical trials are an important source of adverse effects data, including analyses in systematic reviews and recommendations in therapy guidelines. Trial publication bias may have profound effects on safety perceptions. This MiniReview presents and discusses biases in reporting of safety data in clinical trials and the implications for systematic reviews and guidelines. OBJECTIVES: The objectives of this work are to analyse risk of gastrointestinal bleeding in systemic corticosteroid trials and to assess adverse effects reporting in a fluoxetine trial in depression (Treatment for Adolescents With Depression Study [TADS]) and descriptions of adverse effects in adolescent depression therapy guidelines. METHODS: We performed literature reviews and descriptive analyse of clinical trials with corticosteroids, and publications from the TADS trial. Risk of gastrointestinal bleeding from corticosteroids was analysed by meta-analysis. FINDINGS: Gastrointestinal bleeding definitions varied considerably between trials. The incidence was significantly increased in hospitalized, but not in ambulant, patients compared to placebo. We identified several biases concerning TADS safety reporting, including severity thresholds and nonpublication of most adverse effects data beyond the initial 12 weeks. Therapy guidelines on adolescent depression mentioned suicidality risk, but many failed to mention other adverse effects. CONCLUSIONS: We identified several pitfalls in adverse effects reporting in clinical trials. These include heterogeneous disease definitions, reporting thresholds, and incomplete reporting. Trial bias may have great impact on risk assessments in systematic reviews and meta-analyses.