Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas

JAMA. 2001 Jan;285(4):437-43. doi: 10.1001/jama.285.4.437.

Abstract

Context: Randomized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting; however, generalizable 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 = 130074 patients). Trial reports were identified from comprehensive meta-analyses in 7 medical areas.

Main outcome measures: Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects; article space allocated to safety reporting and predictors of such reporting.

Results: Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39% and 29% of trial reports, respectively. Only 46% of trials stated the frequency of specific reasons for discontinuation 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). Overall, the median space allocated 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% smaller in trials reporting statistically significant results for efficacy outcomes (P =.047).

Conclusions: The quality and quantity of safety reporting vary across medical areas, study designs, and settings but they are largely inadequate. Current standards for safety reporting in randomized trials should be revised to address this inadequacy.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adverse Drug Reaction Reporting Systems* / standards
  • Drug Evaluation* / standards
  • Humans
  • Quality Control
  • Quality of Health Care*
  • Randomized Controlled Trials as Topic* / standards
  • Regression Analysis