Meta-analysis examining impact of age on overall survival with pemetrexed for the treatment of advanced non-squamous non-small cell lung cancer.

Objective: In clinical practice, elderly patients are often undertreated relative to younger patients. This meta-analysis was designed to determine whether older patients with non-squamous non-small cell lung cancer (NSCLC) could derive an overall survival (OS) benefit from pemetrexed treatment comparable to that experienced by younger patients in the first-line, second-line, or maintenance settings.

Methods: Data from 2671 patients with non-squamous NSCLC participating in four pemetrexed phase III studies were included in a meta-analysis using a random-effects model.

Comparison of KRAS genotype: therascreen assay vs. LNA-mediated qPCR clamping assay.

Background: Kirsten rat sarcoma virus (KRAS) wild-type status determined using a locked nucleic acid (LNA)-mediated quantitative polymerase chain reaction (qPCR) clamping assay (LNA assay) predicted response to therapy in the CRYSTAL (Cetuximab Combined With Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer) study. A companion KRAS diagnostic tool has been developed for routine clinical use (QIAGEN therascreen kit) (QIAGEN Manchester Ltd, Manchester, UK). We wanted to assess the concordance between the validated US Food and Drug Administration (FDA)-approved therascreen assay and the LNA assay in determining the KRAS status of a subset of patients enrolled in the CRYSTAL study.

Subgroup identification based on differential effect search--a recursive partitioning method for establishing response to treatment in patient subpopulations.

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.

A two-stage sample size recalculation procedure for placebo- and active-controlled non-inferiority trials.

Many non-inferiority trials of a test treatment versus an active control may also, if ethical, incorporate a placebo arm. Inclusion of a placebo arm enables a direct assessment of assay sensitivity. It also allows construction of a non-inferiority test that avoids the problematic specification of an absolute non-inferiority margin, and instead evaluates whether the test treatment preserves a pre-specified proportion of the effect of the active control over placebo.

Semen and sperm reference ranges for men 45 years of age and older.

The most widely used reference values for human semen and sperm variables were developed by the World Health Organization (WHO) to help assess the fertility status of men interested in reproduction (typically a younger population). In this retrospective analysis, data from a large population of men aged 45 years or older were analyzed to derive semen and sperm reference ranges for an older population. Baseline semen samples were obtained from 1174 men with no or mild erectile dysfunction (ED) during the screening phase of two clinical trials evaluating the effects of a drug on human spermatogenesis.

A multicenter, randomized, double-blind, crossover study to evaluate patient preference between tadalafil and sildenafil.

Purpose: To assess patient preference for erectile dysfunction treatment between either sildenafil or tadalafil, each administered with their respective dosing instructions, and to evaluate preference for either sildenafil or tadalafil dosing instructions during tadalafil therapy.

Methods: We conducted a randomized, double-blind, crossover study consisting of four treatment arms. Because the dosing instructions for sildenafil and tadalafil are different, a unique methodology using sham placebo arms was employed to maintain the blind.

A multicenter, randomized, double-blind, crossover study of patient preference for tadalafil 20 mg or sildenafil citrate 50 mg during initiation of treatment for erectile dysfunction.

Background: Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor approved in >30 countries for the treatment of erectile dysfunction (ED). It has been shown to improve erectile function compared with placebo in Phase III studies, but clinical experience comparing tadalafil with the PDE5 inhibitor sildenafil citrate is lacking.

Objective: This study compared patient preference for tadalafil 20 mg or sildenafil 50 mg during initial treatment for ED.

Time course of the interaction between tadalafil and nitrates.

Objectives: This study was designed to determine the time course of nitrate interaction with tadalafil, a phosphodiesterase 5 (PDE5) inhibitor with a half-life (t(1/2)) of 17.5 h.

Background: The PDE5 inhibitors augment the blood pressure (BP)-lowering effects of nitrates, yet the time course of this interaction is unclear.

Sample-size redetermination for repeated measures studies.

Clinical trialists recently have shown interest in two-stage procedures for updating the sample-size calculation at an interim point in a trial. Because many clinical trials involve repeated measures designs, it is desirable to have available practical two-stage procedures for such designs. Shih and Gould (1995, Statistics in Medicine 14, 2239-2248) discuss sample-size redetermination for repeated measures studies but under a highly simplified setup.