Interpretation and inference in noninferiority randomized controlled trials in drug research.

Noninferiority (NI) trials in drug research are used for the purpose of demonstrating that a new treatment is not worse than a proven active comparator, thereby indirectly showing that the treatment is effective. This article explains and addresses the complications in the interpretation of NI trials that arise from the indirect comparison. On the basis of our review of 232 trials, we conclude that the interpretation and inference of NI trials are complicated, partly because of the incompleteness of the information.

Hemoglobin and atherosclerosis in patients with manifest arterial disease. The SMART-study.

BACKGROUND: Decreased hemoglobin levels are known to be associated with an increased risk of coronary mortality and morbidity. This is largely thought to result from the development of left ventricular hypertrophy. Similar remodeling mechanisms of the vessel wall that may result in atherosclerosis are likely to be present. We studied whether hemoglobin levels are related to different vascular indicators of atherosclerosis. METHODS AND RESULTS: This cross-sectional study was performed in the first consecutive 2514 patients with manifest arterial disease enrolled in the SMART-study (Second Manifestations of ARTerial disease). The relation of hemoglobin levels with common carotid IMT (CIMT), presence of a>/=50% internal carotid artery stenosis (ICAS) and prevalent peripheral arterial disease (PAD) was assessed with linear and logistic regression analyses. Each mmol/l increase in hemoglobin was associated with a lower CIMT (-0.03 mm [95% CI: -0.04; -0.01]) and a lower prevalence of >/=50% ICAS (odds ratio: 0.84 [95% CI: 0.73; 0.97]) after adjustment for age, gender and potential confounders. Hemoglobin was not related to prevalence of peripheral arterial disease (1.02 [95% CI: 0.89; 1.16]). CONCLUSIONS: This study shows that in patients with manifest arterial disease, increasing hemoglobin levels are associated with reduced severity of atherosclerosis.