What is clearance worth? Patients' stated risk tolerance for psoriasis treatments.

Purpose: The purpose of this study was to provide quantitative evidence of patients' tolerance for therapeutic risks associated with psoriasis treatments that could offer psoriasis improvements beyond the PASI 75 benchmark.

Materials And Methods: We used a discrete-choice experiment in which respondents chose between competing psoriasis treatments characterized by benefits (i.e.

Effective Partnering in Conducting Benefit-Risk Patient Preference Studies: Perspectives From a Patient Advocacy Organization, a Pharmaceutical Company, and Academic Stated-Preference Researchers.

Background: Formal incorporation of patients' perspectives is becoming increasingly important in medical product development and decision making. This article shares practical advice regarding how patient advocacy organizations, the pharmaceutical industry, and academic experts in stated-preference research can effectively partner on benefit-risk patient preference studies.

Methods: The authors partnered on a benefit-risk patient preference study related to the treatment of psoriasis.

Patient Engagement at a Tipping Point-The Need for Cultural Change Across Patient, Sponsor, and Regulator Stakeholders: Insights From the DIA Conference, "Patient Engagement in Benefit Risk Assessment Throughout the Life Cycle of Medical Products".

Benefit-risk assessment is the foundation for decision making throughout the life cycle of medical products. Because patients are the beneficiaries of the efficacy of medical treatments and also bear their possible risks, their perspectives and judgments about value and the relative importance of benefits and risks should be at the heart of the medical decision-making process. Patient engagement is now at a tipping point; there have been a growing number of patient engagement initiatives over the past several years, but there remains the need for a common language, alignment on engagement approaches and best practices, and a shared vision regarding a desired future state.

Implementing Benefit-Risk Assessment for the Periodic Benefit-Risk Evaluation Report.

Background: In 2012, the International Conference on Harmonisation (ICH) E2C (R1) guideline for periodic safety update reporting (PSUR) for medicines was revised. Several new concepts that expanded the scope of the report were added, including a new section focused on benefits and an additional section focused on integrated benefit-risk (B-R) assessment. These changes are reflected in the new title of the report, namely, the Periodic Benefit-Risk Evaluation Report (PBRER).

Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): a 26-week double-blind study.

Objective: To test the safety and efficacy of exenatide once weekly (EQW) compared with metformin (MET), pioglitazone (PIO), and sitagliptin (SITA) over 26 weeks, in suboptimally treated (diet and exercise) drug-naive patients with type 2 diabetes.

Research Design And Methods: Patients were randomized to subcutaneous (SC) EQW 2.0 mg + oral placebo (n = 248), MET 2,000 mg/day + SC placebo (n = 246), PIO 45 mg/day + SC placebo (n = 163), or SITA 100 mg/day + SC placebo (n = 163) for 26 weeks.

Oral protein kinase c β inhibition using ruboxistaurin: efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy in the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study 2.

Purpose: To evaluate efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with moderately severe to very severe nonproliferative diabetic retinopathy from the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and Protein Kinase C β Inhibitor-Diabetic Retinopathy Study 2 ruboxistaurin (RBX) protein kinase C β inhibitor trials.

Methods: Patients in these 3-year, randomized, placebo-controlled, double-masked, Phase 3 trials had best-corrected Early Treatment Diabetic Retinopathy Study visual acuity ≥45 letters (∼20/125 Snellen), Early Treatment Diabetic Retinopathy Study retinopathy level 47A/B-53E, and no previous panretinal photocoagulation in ≥1 eye. Patients received placebo (N = 401) or RBX 32 mg/day (N = 412).

Safety, tolerability, pharmacokinetics, and pharmacodynamics of exenatide once weekly in Japanese patients with type 2 diabetes.

This randomized, placebo-controlled, double-blind, parallel study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of exenatide once weekly (QW) in 30 Japanese patients with type 2 diabetes (T2D) suboptimally controlled by diet and exercise alone or combined with biguanide, sulfonylurea, thiazolidinedione, or combinations of these agents (58.6% male; 58+/-9 years; body mass index 26.3+/-2.

Effects of once-daily tadalafil on erectile function in men with erectile dysfunction and signs and symptoms of benign prostatic hyperplasia.

Background: Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH; BPH-LUTS) may be associated with erectile dysfunction (ED).

Objective: To evaluate the effects of once-daily tadalafil on erectile function in men with ED and BPH-LUTS.

Design, Setting, And Participants: Post hoc analysis of a phase 2-3, multinational, randomized, double-blind, placebo-controlled, parallel-group study of men with ED and moderate-to-severe LUTS secondary to BPH who reported being sexually active.

Exenatide exhibits dose-dependent effects on glycemic control over 12 weeks in Japanese patients with suboptimally controlled type 2 diabetes.

This study assessed the dose-dependent efficacy and safety of exenatide over 12 weeks in Japanese patients with type 2 diabetes suboptimally controlled despite therapeutic doses of sulfonylurea (SU), SU plus biguanide, or SU plus thiazolidinedione. Patients were randomly assigned to placebo (N = 40), 2.5 microg (N = 38), 5 microg (N = 37), or 10 microg (N = 38) exenatide administered subcutaneously twice daily (BID).

Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study.

Background: Evaluation of exenatide monotherapy in patients with type 2 diabetes may be of clinical interest based on improvements in glycemic control and weight that have been reported with the use of exenatide in combination with oral antidiabetic agents.

Objective: The aim of this study was to evaluate the efficacy and tolerability of exenatide monotherapy in patients with type 2 diabetes naive to antidiabetic agents and whose disease was inadequately controlled with diet and exercise alone.

Methods: This 24-week, double-blind, placebo-controlled, parallel-group study was conducted at 23 centers across the United States, Puerto Rico, Romania, Russia, and India.

Long-term safety and efficacy of tadalafil 5 mg dosed once daily in men with erectile dysfunction.

Introduction: With once-daily administration of tadalafil, dosing and sexual activity would no longer need to be temporally linked for patients with erectile dysfunction (ED).

Aim: To evaluate long-term safety and efficacy of tadalafil 5 mg dosed once daily for the treatment of ED.

Methods: Patients > or = 18 years of age with ED of any functional severity or etiology received tadalafil 5 mg once daily for 1 (N = 234) or 2 (N = 238) years during the open-label extensions of two previously reported studies.

A 6-month, randomized, double-masked, placebo-controlled study evaluating the effects of the protein kinase C-beta inhibitor ruboxistaurin on skin microvascular blood flow and other measures of diabetic peripheral neuropathy.

Objective: Diabetes leads to protein kinase C (PKC)-beta overactivation and microvascular dysfunction, possibly resulting in disordered skin microvascular blood flow (SkBF) and other changes observed in diabetic peripheral neuropathy (DPN) patients. We investigate the effects of the isoform-selective PKC-beta inhibitor ruboxistaurin mesylate on neurovascular function and other measures of DPN.

Research Design And Methods: Endothelium-dependent and C fiber-mediated SkBF, sensory symptoms, neurological deficits, nerve fiber morphometry, quantitative sensory and autonomic function testing, nerve conduction studies, quality of life (using the Norfolk Quality-of-Life Questionnaire for Diabetic Neuropathy [QOL-DN]), and adverse events were evaluated for 20 placebo- and 20 ruboxistaurin-treated (32 mg/day) DPN patients (aged > or =18 years; with type 1 or type 2 diabetes and A1C < or =11%) during a randomized, double-masked, single-site, 6-month study.

Effect of growth hormone dose on bone maturation and puberty in children with idiopathic short stature.

Context: GH at 0.22 mg/kg.wk has been shown to have no effect on pubertal onset or pace, whereas GH at 0.

Safety of growth hormone treatment in pediatric patients with idiopathic short stature.

Context: Recombinant human GH was approved by the United States Food and Drug Administration in 2003 for the treatment of idiopathic short stature (ISS). However, to date, the safety of GH in this patient population has not been rigorously studied.

Objective: The objective of this study was to address the safety of GH treatment in children with ISS compared with GH safety in patient populations for which GH has been approved previously: Turner syndrome (TS) and GH deficiency (GHD).

The interaction of the penetration enhancer DDAIP with a phospholipid model membrane.

Differential scanning calorimetry (DSC) was used to investigate the mechanism of action of a proprietary skin penetration enhancer, dodecyl-2-(N,N-dimethylamino)propionate (DDAIP) in dipalmitoylphosphatidylcholine (DPPC) liposomes. Furthermore, the effect of enhancer concentration on lipid thermotropic transitions was investigated. With increasing concentrations of DDAIP (from 5 to 50 mol%), the main transition peak shifted to lower temperatures and became more broad.

Pain and the blood-brain barrier: obstacles to drug delivery.

Delivery of drugs across the blood-brain barrier has been shown to be altered during pathological states involving pain. Pain is a complex phenomenon involving immune and centrally mediated responses, as well as activation of the hypothalamic-pituitary-adrenal axis. Mediators released in response to pain have been shown to affect the structure and function of the blood-brain barrier in vitro and in vivo.