Attention must be paid: adverse event reporting needs improvement

Abstract

The insightful review by Russell and Colevas discusses various tools used in the reporting of adverse events, highlighting the need for consistent adverse event reporting guidelines [1]. With clinical trial data being larger and more complex than ever, accurate toxicity reporting is necessary to assess a drug’s efficacy and safety profile – the two factors that serve as an integral base for regulatory decision making. Both in and out of clinical trial settings, reporting rates are low and adverse event reports are often incomplete. To date there is no standard approach for adverse event reporting. The Common Terminology Criteria for Adverse Events (CTCAE) serves as a lexicon used to define an adverse event and its severity. In clinical trials, reports are graded in terms of the CTCAE v4.0 terminology – this system uses definitions from the Medical Dictionary for Regulatory Activities (MedDRA). To improve medication safety initiatives, established reporting guidelines are needed. In oncology trials, adverse events may arise from iatrogenic causes or from an underlying disease. The CTCAE v4.0 defines an adverse event as “any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medical treatment or procedure.” Adverse events can be symptoms, exam finding, abnormal laboratory values, or irregular radiology reports. A serious adverse event is life threatening, requires hospitalization, results in disability, or results in an abnormality or birth defect. In the CTCAE v4.0, adverse events are organized into System Organ Classes. These groups are based on anatomical, physiological or etiological criteria and are easily mapable to the MedDRA. The terminology was agreed upon by the National Cancer Institute and the European Medicines Agency. The severity of the adverse event is ranked on a 1–5 scale; one being the least severe and five resulting in death. This scale is not included in the MedDRA definitions – as it is unique to the CTCAE. Adverse event categories cover a wide array of laboratory values and clinical findings. Russell et al. examine adverse event reporting in clinical trials and provided eight recommendations for clinical investigators [1]: ■ Collect all serious adverse events without regard to causality;