We propose a novel recursive partitioning method for identifying subgroups of subjects with enhanced treatment effects based on a differential effect search algorithm. The idea is to build a collection of subgroups by recursively partitioning a database into two subgroups at each parent group, such that the treatment effect within one of the two subgroups is maximized compared with the other subgroup. The process of data splitting continues until a predefined stopping condition has been satisfied. The method is similar to 'interaction tree' approaches that allow incorporation of a treatment-by-split interaction in the splitting criterion. However, unlike other tree-based methods, this method searches only within specific regions of the covariate space and generates multiple subgroups of potential interest. We develop this method and provide guidance on key topics of interest that include generating multiple promising subgroups using different splitting criteria, choosing optimal values of complexity parameters via cross-validation, and addressing Type I error rate inflation inherent in data mining applications using a resampling-based method. We evaluate the operating characteristics of the procedure using a simulation study and illustrate the method with a clinical trial example.
OBJECTIVE
To provide an update on the efficacy and safety of tadalafil, a phosphodiesterase‐5 inhibitor, in the treatment of erectile dysfunction (ED).
PATIENTS AND METHODS
In all, 2102 men (mean age 56 years) with mild‐to‐severe ED of various causes were randomized to placebo or tadalafil, taken as needed with no food restrictions, at fixed ‘on‐demand’ doses of 10 or 20 mg in 11 randomized, double‐blind, placebo‐controlled trials lasting 12 weeks. The three co‐primary outcomes were changes from baseline in the erectile function domain of the International Index of Erectile Function (IIEF) and the proportion of ‘yes’ responses to questions 2 and 3 of the Sexual Encounter Profile (SEP). Additional efficacy instruments included a Global Assessment Question (GAQ).
RESULTS
Compared with placebo, tadalafil gave significantly better outcomes. Patients receiving either dose of tadalafil had a significant mean improvement of 6.5 and 8.6, respectively, in the IIEF erectile function domain score from baseline (P < 0.001 vs placebo). At both doses the mean success rate for intercourse attempts (SEP‐Q3) was 58% and 68%, respectively, compared with 31% in the placebo group (P < 0.001), and 71% and 84% reported improved erections at the endpoint (GAQ), vs 33% on placebo (P < 0.001). Tadalafil was effective up to 36 h after dosing and was effective regardless of disease severity and causes, and in patients of all ages. The most frequent adverse events were headache, dyspepsia, back pain and myalgia.
CONCLUSION
Tadalafil was an effective and well‐tolerated treatment for ED.
Aims/hypothesis. A retrospective analysis of pooled data from twelve placebo-controlled trials was conducted to characterise the efficacy and safety of tadalafil for the treatment of erectile dysfunction in men with diabetes compared with that in men without diabetes. Methods. Patients were randomly allocated to tadalafil 10 mg, 20 mg, or placebo, taken as needed for 12 weeks. The study population comprised 637 men with diabetes (mean age 57 years) and 1681 men without diabetes (mean age 56 years). Results. At baseline, patients with diabetes had more severe erectile dysfunction than patients without diabetes, with mean International Index of Erectile Function (IIEF) erectile function domain scores of 12.6 and 15.0 respectively (p<0.001). Compared with placebo, tadalafil 10 mg and 20 mg improved all primary efficacy outcomes in both patient groups (p<0.001). Men with diabetes receiving tadalafil 20 mg experienced a mean improvement of 7.4 in their IIEF erectile function domain score against baseline versus 0.9 for placebo (p<0.001). This group reported on average that 53% of their attempts at intercourse were successful, compared with 22% for placebo (p<0.001 for the change from baseline). Baseline IIEF erectile function domain scores correlated inversely with baseline HbA 1 c levels. The responses to tadalafil were similar regardless of levels of baseline glycaemic control, diabetic therapy received, or previous use of sildenafil. Conclusions/interpretation. Despite more severe baseline erectile dysfunction in men with diabetes, tadalafil was efficacious and well tolerated in this population. As reported for other phosphodiesterase 5 inhibitors, the response to tadalafil was slightly lower in men with diabetes than in men without diabetes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.