Uniting Discovery and Care: The Role of Pharmaceutical Companies in Research, Clinical Studies, and Patient Care.

In an era of increased complexity of clinical research, a demand for personalized medicine, an increasing value of diversity, a focus on digital health, and a call for patient centricity, the discovery and development of new medicines, more than ever, is dependent on collaboration between multiple stakeholders.

An evaluation of semen characteristics in men 45 years of age or older after daily dosing with tadalafil 20mg: results of a multicenter, randomized, double-blind, placebo-controlled, 9-month study.

OBJECTIVES: Assess the effects on spermatogenesis of daily tadalafil 20mg over three spermatogenesis cycles in men >or= 45 yr. METHODS: In this double-blind, placebo-controlled, noninferiority study, healthy men (or with mild erectile dysfunction) were randomized to receive tadalafil 20mg (n=125) or placebo (n=128) for 9 mo followed by a 6-mo, treatment-free period. Semen and serum samples were provided at baseline and every 10-12 wk. The primary outcome was the proportion of subjects with >or= 50% reduction in sperm concentration at end point. Secondary outcomes included sperm concentration, number per ejaculate, motility and morphology; serum concentrations of testosterone, luteinizing and follicle-stimulating hormones; and tolerability. RESULTS: Of 253 men enrolled, 191 (75%) completed treatment phase: 2 of 96 (2.1%, placebo) and 12 of 95 (12.6%, tadalafil) subjects had >or= 50% reduction in sperm concentration. Tadalafil was noninferior to placebo because the upper 95% confidence interval for the difference in proportions of tadalafil and placebo subjects with a >or= 50% reduction in sperm concentration was 17.5%, significantly less than the prespecified noninferiority margin of 20% (p=0.015). Ninety-four percent (179 of 191) of men completed the 6-mo, treatment-free period: Baseline sperm concentration levels were restored in 8 of 12 (tadalafil) and 1 of 2 (placebo) men. There were no significant differences between groups in secondary end points. Common treatment-emergent adverse events were headache, back pain, dyspepsia, gastroesophageal reflux disease, and myalgia. Twelve (9.6%) tadalafil and seven (5.5%) placebo subjects discontinued because of adverse events. CONCLUSIONS: This study demonstrated no deleterious effects of 9 mo of daily tadalafil 20mg on spermatogenesis or hormones related to testicular function in men >or= 45 yr.

The pathobiology of biliary epithelia.

The morbidity and mortality from chronic biliary diseases (i.e., the cholangiopathies) remains substantial. End-stage liver disease from biliary causes of cirrhosis (e.g., primary biliary cirrhosis [PBC], and primary sclerosing cholangitis) account for approximately one third of patients referred for liver transplantation. A single-topic conference sponsored by the American Association for the Studies of Liver Diseases entitled "The Pathobiology of Biliary Epithelia" brought together investigators to review the status of the field of cholangiocyte pathobiology, identify new areas of interest, and propose future directions. This information was presented in 6 sessions: "Structural and Functional Characteristics of the Bile Duct System," "Biological Topics from Nonbiliary Epithelia," "Malignant Transformation of Cholangiocytes," "Cholangiocyte Proliferation and Death," "Transport Mechanisms in Bile Duct Epithelia," and "Pathobiology of Biliary Epithelia." In the 7 years since the first symposium on this topic, major advances have been made in our understanding of ductal bile formation, including, greater insight into the hormones, intracellular signaling mechanisms, and effector proteins responsible for bile secretion and absorption. More sophisticated imaging technologies have increased our understanding of the polarity of cholangiocytes, their embryology and ultrastructural anatomy, and in vivo human secretory responses to current medical therapy. Information on mediators of inflammation permeated many sessions, having potentially important roles in malignant transformation of cholangiocytes, cholangiocyte apoptosis, fluid and electrolyte transport, and have begun to be specifically characterized for certain biliary diseases, e.g., acquired immunodeficiency syndrome (AIDS) cholangiopathy and graft-versus-host disease (GVHD).