Reporting of adverse effects in clinical trials, systematic reviews, and guidelines: How events are lost along the evidence chain

Knowledge about adverse effects of a medication is essential to assess treatment benefits versus risks. Several researchers have found that not all adverse effects are included when results from clinical trials are published. Consequently, evaluations of risk profiles may result in conflicting conclusions. Differences in what is counted as an adverse effect, and what is mentioned in publications, may influence the risk assessments that are presented to doctors and patients. The researchers found that adverse effects observed in clinical trials are not always presented in study publications or reflected in systematic reviews and guidelines. The aims of this thesis were to assess how adverse effects in clinical trials are identified and communicated, and how adverse effects are described in therapy guidelines. The researchers addressed two model areas: Risk of gastrointestinal bleeding due to corticosteroid therapy, and risk of adverse effects from antidepressants in children and adolescents. The researchers found that use of corticosteroids was associated with increased risk of gastrointestinal bleeding in hospitalized patients. There were few cases of gastrointestinal bleeding in ambulant patients. What was counted as a gastrointestinal bleeding differed considerably between trials. Many trial publications did not fulfil all international criteria for reporting of harms. Risk of adverse effects from antidepressants in children and adolescents has not been extensively studied. The researchers found that adverse effects from treatment in a pivotal trial had been incompletely reported. The publications on adverse effects focused on suicidality, and did not describe other adverse reactions for treatment lasting more than 12 weeks. Therapy guidelines on depression in children and adolescents mention adverse effects to a varying degree. All the assessed guidelines mentioned risk of suicidality, but many guidelines did not mention other types of adverse effects