Safety analysis of new medications in clinical trials: a simulation study to assess the differences between cause-specific and subdistribution frameworks in the presence of competing events.

Safety is an essential part of the evaluation of new medications and competing risks that occur in most clinical trials are a well identified challenge in the analysis of adverse events. Two statistical frameworks exist to consider competing risks: the cause-specific and the subdistribution framework. To date, the application of the cause-specific framework is the standard practice in safety analyses. Here we analyze how the safety analysis results of new medications would be affected if instead of the cause-specific the subdistribution framework was chosen. We conducted a simulation study with 600 participants, equally allocated to verum and control groups and a 30 months follow-up period. Simulated trials were analyzed for safety in a competing risk (death) setting using both the cause-specific and subdistribution frameworks. Results show that comparing safety profiles in a subdistribution setting is always more pessimistic than in a cause-specific setting. For the group with the longest survival and a safety advantage in a cause-specific setting, the advantage either disappeared or a disadvantage was found in the subdistribution analysis setting. These observations are not contradictory but show different perspectives. To evaluate the safety of a new medication over its comparator, one needs to understand the origin of both the risks and the benefits associated with each therapy. These requirements are best met with a cause-specific framework. The subdistribution framework seems better suited for clinical prediction, and therefore more relevant for providers or payers, for example.

Self-reported cardiovascular health of teachers: results from the 5-year follow-up of the Gutenberg Health Study cohort.

OBJECTIVES: Following an exploratory approach, we examined cardiovascular disease risk factors at baseline and the 5-year incidence proportion of self-reported doctor-diagnosed cardiovascular diseases (CVD) in teachers and other occupational groups of the Gutenberg Health Study. METHODS: Study participants lived in the region of Mainz, Germany. Data from 6510 working participants without prevalent CVD at baseline (2007-2012) were analyzed. Participants were teachers (n = 215), other professionals from the health, social or educational (HSE) fields (n = 1061) or worked outside the HSE fields (n = 5234). For occupational comparisons, we estimated prevalence ratios (PR) for each CVD risk factor at baseline with robust Poisson regression analyses. We calculated crude CVD incidence rates based on the observed 5-year CVD cumulative incidence at follow-up and estimated age-weighted incidence proportions. All analyses were stratified by sex. RESULTS: Male non-HSE workers showed a higher prevalence of smoking and physical inactivity than male teachers (PR 2.26; 95%-CI: 1.06-4.82/PR 1.89; 95%-CI: 1.24-2.87). In contrast, non-HSE workers and other HSE professionals were less likely to have reported an unhealthy alcohol intake than teachers. Differences were attenuated after SES-adjustment. We did not detect occupational group-specific differences in CVD incidence. However, there were only two cases of CVD among the teachers. CONCLUSION: Particularly male teachers showed a healthier lifestyle regarding physical inactivity and smoking. Nevertheless, occupational-medical care practitioners and researchers need to be aware of the relatively heightened prevalence of unhealthy alcohol intake in female and male teachers, and in absolute terms, the high hypertension prevalence in male teachers.