Through the looking glass: understanding non-inferiority

Non-inferiority trials test whether a new product is not unacceptably worse than a product already in use. This paper introduces concepts related to non-inferiority, and discusses the regulatory views of both the European Medicines Agency and the United States Food and Drug Administration

In‐treatment HDL cholesterol levels and development of new diabetes mellitus in hypertensive patients: The LIFE Study

Aims Although hypertensive patients with low baseline HDL cholesterol levels have a higher incidence of diabetes mellitus, whether changing levels of HDL over time are more strongly related to the risk of new diabetes in hypertensive patients has not been examined. Methods Incident diabetes mellitus was examined in relation to baseline and in‐treatment HDL levels in 7485 hypertensive patients with no history of diabetes randomly assigned to losartan‐ or atenolol‐based treatment. Results During 4.7 ± 1.2 years follow‐up, 520 patients (6.9%) developed new diabetes. In univariate Cox analyses, compared with the highest quartile of HDL levels (> 1.78 mmol/l), baseline and in‐treatment HDL in the lowest quartile ( 5‐fold and > 9 fold higher risks of new diabetes, respectively; patients with baseline or in‐treatment HDL in the 2nd and 3rd quartiles had intermediate risk of diabetes. In multivariable Cox analyses, adjusting for randomized treatment, age, sex, race, prior anti‐hypertensive therapy, baseline uric acid, serum creatinine and glucose entered as standard covariates, and in‐treatment non‐ HDL cholesterol, Cornell product left ventricular hypertrophy, diastolic and systolic pressure, BMI , hydrochlorothiazide and statin use as time‐varying covariates, the lowest quartile of in‐treatment HDL remained associated with a nearly 9‐fold increased risk of new diabetes (hazard ratio 8.7, 95%  CI 5.0–15.2), whereas the risk of new diabetes was significantly attenuated for baseline HDL < 1.21 mmol/l (hazard ratio 3.9, 95%  CI 2.8–5.4). Conclusions Lower in‐treatment HDL is more strongly associated with increased risk of new diabetes than baseline HDL level.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108303/1/dme12213.pd

Risk of HIV acquisition among circumcised and uncircumcised young men with penile human papillomavirus infection

OBJECTIVES: There are very few data from men on the risk of HIV acquisition associated with penile human papillomavirus (HPV) infection and no data on the potential modifying effect of male circumcision. Therefore, this study evaluated whether HPV is independently associated with risk of HIV. DESIGN: A cohort study of HPV natural history nested within a randomized control trial of male circumcision to reduce HIV incidence in Kisumu, Kenya. METHODS: Prospective data from 2519 men were analyzed using 6-month discrete-time Cox models to determine if HIV acquisition was higher among circumcised or uncircumcised men with HPV compared to HPV-uninfected men. RESULTS: Risk of HIV acquisition was nonsignificantly increased among men with any HPV [adjusted hazard ratio (aHR) 1.72; 95% confidence interval (CI) 0.94–3.15] and high-risk HPV (aHR 1.92; 95% CI 0.96–3.87) compared to HPV-uninfected men, and estimates did not differ by circumcision status. Risk of HIV increased 27% with each additional HPV genotype infection (aHR 1.27; 95% CI 1.09–1.48). Men with persistent (aHR 3.27; 95% CI 1.59–6.72) or recently cleared (aHR 3.05; 95% CI 1.34–6.97) HPV had a higher risk of HIV acquisition than HPV-uninfected men. CONCLUSIONS: Consistent with the findings in women, HPV infection, clearance, and persistence were associated with an increased risk of HIV acquisition in men. Given the high prevalence of HPV in populations at risk of HIV, consideration of HPV in future HIV-prevention studies and investigation into mechanisms through which HPV might facilitate HIV acquisition are needed