Completeness of safety reporting in randomized trials - An evaluation of 7medical areas

Context Randomized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting; however, gen eralizable data on drug safety reporting are sparse, Objective To scrutinize the completeness of safety reporting in randomized trials. Design, Setting, and Patients Survey of safety reporting in 192 randomized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm (N =130 074 patients). Trial reports w ere identified from comprehensive meta-analyses in 7 medical areas. Main Outcome Measures Adequate reporting of specific adverse effects and fr equency and reasons for withdrawals due to toxic effects; article space all ocated to safety reporting and predictors of such reporting. Results Severity of clinical adverse effects and laboratory-determined toxi city was adequately defined in only 39% and 29% of trial reports, respectiv ely. Only 46% of trials stated the frequency of specific reasons for discon tinuation of study treatment due to toxicity. For these 3 parameters, there was significant heterogeneity in rates of adequate reporting across topics (P=.003, P<.001, and P=.02, respectively). Over all, the median space allo cated to safety results was 0.3 page. A similar amount of space was devoted to contributor names and affiliations (P=.16). On average, the percentage of space devoted to safety in the results section was 9.3% larger in trials involving dose comparisons than in those that did not (P<.001) and 3.8% sm aller in trials reporting statistically significant results for efficacy ou tcomes (P=.047), Conclusions The quality and quantity of safety reporting vary across medica l areas, study designs, and settings but they are largely inadequate. Curre nt standards for safety reporting in randomized trials should be revised to address this inadequacy.