Estimating health related quality of life effects in vitiligo. Mapping EQ-5D-5 L utilities from vitiligo specific scales: VNS, VitiQoL and re-pigmentation measures using data from the HI-Light trial.

Background: Vitiligo is reported to affect 2% of the world's population and has a significant impact on health related quality of life (HRQoL). The relationship between HRQoL and clinical outcomes used in vitiligo require further examination. Mapping condition specific measures of HRQoL: vitiligo specific quality of life instrument (VitiQoL), vitiligo noticeability scale (VNS) and vitiligo re-pigmentation scores (RPS) to the EQ-5D have not yet been reported.

Bridging disconnected networks of first and second lines of biologic therapies in rheumatoid arthritis with registry data: bayesian evidence synthesis with target trial emulation.

Objectives: We aim to use real-world data in evidence synthesis to optimize an evidence base for the effectiveness of biologic therapies in rheumatoid arthritis to allow for evidence on first-line therapies to inform second-line effectiveness estimates.

Study Design And Setting: We use data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis to supplement randomized controlled trials evidence obtained from the literature, by emulating target trials of treatment sequences to estimate treatment effects in each line of therapy. Treatment effects estimates from the target trials inform a bivariate network meta-analysis (NMA) of first-line and second-line treatments.

Methods for the inclusion of real-world evidence in network meta-analysis.

Background: Network Meta-Analysis (NMA) is a key component of submissions to reimbursement agencies world-wide, especially when there is limited direct head-to-head evidence for multiple technologies from randomised controlled trials (RCTs). Many NMAs include only data from RCTs. However, real-world evidence (RWE) is also becoming widely recognised as a valuable source of clinical data.

Comparative effectiveness analysis between entrectinib clinical trial and crizotinib real-world data in + NSCLC.

Generating direct comparative evidence in prospective randomized trials is difficult for rare diseases. Real-world cohorts may supplement control populations. Entrectinib-treated adults with advanced fusion-positive NSCLC (n = 94) from Phase I/II trials (ALKA-372-001 [EudraCT2012-00148-88], STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]) were compared with a real-world crizotinib-treated cohort (n = 65).

Stress Hyperglycemia Is Independently Associated with Persistent Organ Failure in Acute Pancreatitis.

Background/aims: Stress hyperglycemia is common in critical illness but it has not been clearly studied in patients with acute pancreatitis (AP). This study aimed to investigate the specific blood glucose (BG) level that defines stress hyperglycemia and to determine the impact of stress hyperglycemia on clinical outcomes in AP patients.

Methods: AP patients admitted ≤ 48 h after abdominal pain onset were retrospectively analyzed.

An adaptive randomized clinical trial in interstitial cystitis/bladder pain syndrome evaluating efficacy of ASP3652 and the relationship between disease characteristics and Hunner's lesions.

Purpose: The primary purpose of this study was to evaluate the effect of the fatty acid amide hydrolase (FAAH) inhibitor ASP3652 on efficacy and safety in patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). The secondary purpose was to evaluate phenotyping based on Hunner's lesions (HL).

Methods: In this randomized trial, adult female patients with moderate/severe IC/BPS received 12 weeks of treatment with an oral dose of ASP3652 (50, 150, or 300 mg twice daily) or placebo.

A combined proof of concept and dose finding study with multiple endpoints: A Bayesian adaptive design in chronic prostatitis/chronic pelvic pain syndrome.

There is a need for identifying effective drugs or terminating ineffective drugs as early as possible to optimize efficient and cost effective drug development. The aim of the proposed trial was to simultaneously establish Proof of Concept (PoC) and dose finding (DF) for a new drug with a novel mode of action in a new indication. We simulated and executed an adaptive allocation design to investigate the effects of a drug on male patients suffering from chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

The inclusion of real world evidence in clinical development planning.

Background: When designing studies it is common to search the literature to investigate variability estimates to use in sample size calculations. Proprietary data of previously designed trials in a particular indication are also used to obtain estimates of variability. Estimates of treatment effects are typically obtained from randomised controlled clinical trials (RCTs).

Comparative effectiveness from a single-arm trial and real-world data: alectinib versus ceritinib.

Aim: To compare the overall survival of anaplastic lymphoma kinase-positive non-small-cell lung cancer patients who received alectinib with those who received ceritinib.

Materials & Methods: Two treatment arms (alectinib [n = 183] and ceritinib [n = 67]) were extracted from clinical trials and an electronic health record database, respectively. Propensity scores were applied to balance baseline characteristics.

qSOFA, SIRS and NEWS for predicting inhospital mortality and ICU admission in emergency admissions treated as sepsis.

Background: The third international consensus definition for sepsis recommended use of a new prognostic tool, the quick Sequential Organ Failure Assessment (qSOFA), based on its ability to predict inhospital mortality and prolonged intensive care unit (ICU) stay in patients with suspected infection. While several studies have compared the prognostic accuracy of qSOFA to the Systemic Inflammatory Response Syndrome (SIRS) criteria in suspected sepsis, few have compared qSOFA and SIRS to the widely used National Early Warning Score (NEWS).

Methods: This was a retrospective cohort study carried out in a UK tertiary centre.

Fatty Acid Amide Hydrolase Inhibitor Treatment in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: An Adaptive Double-blind, Randomized Controlled Trial.

Objective: To examine the effect of a peripherally active fatty acid amide hydrolase (FAAH) inhibitor ASP3652 on safety and efficacy outcomes in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Inhibition of FAAH is hypothesized to reduce the excitability of urinary tract afferents including nociceptors.

Materials And Methods: In this adaptive, randomized, double-blind, placebo-controlled study, adult male patients with moderate to severe CP/CPPS were treated for 12 weeks with an oral dose of ASP3652 (25, 75, 150, or 300 mg twice daily, or 300 mg once daily), or placebo.

Electronic bladder diaries of differing duration versus a paper diary for data collection in overactive bladder.

Aims: This observational study compared data values, reliability, consistency and compliance collected by electronic and paper diaries of differing durations.

Methods: Subjects ≥18 years with overactive bladder (OAB) on stable antimuscarinic treatment for ≥12 weeks were assigned to one of five, 15-week diary schedules in this randomized, parallel-group observational study. Sample size was sufficient to assess reliability and consistency of diary data with adequate precision.

A clinical perspective on the analysis and presentation of the number of incontinence episodes following treatment for OAB.

Aims: To provide a clinical view and interpretation on the methods for analysis of incontinence in patients with overactive bladder.

Methods: Results are analyzed using the total number of incontinence episodes in a 3-day diary period, using fixed and random effect Poisson regression models to calculate ratio of event rates and 95% confidence interval (CI) together with P-values and are compared with the analysis of the mean number of incontinence episodes/24 hr using analysis of covariance models to calculate P-values and 95% CI for the difference between treatments.

Results: Using random effects Poisson regression models demonstrated that the number of incontinence episodes was reduced by 26% more with mirabegron 50 mg than with placebo.

Combination treatment with mirabegron and solifenacin in patients with overactive bladder: efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (Symphony).

Background: Combining the β3-adrenoceptor agonist mirabegron and the antimuscarinic (AM) agent solifenacin may improve efficacy in the treatment of overactive bladder (OAB) while reducing the AM side effects.

Objective: The primary objective was to evaluate the efficacy of combinations of solifenacin/mirabegron compared with solifenacin 5mg monotherapy. The secondary objective was to explore the dose-response relationship and the safety/tolerability compared with placebo and monotherapy.

The effect of intravenous infusion of adenosine on electrically evoked hyperalgesia in a healthy volunteer model of central sensitization.

Human pain models invoking central sensitization, one of the key mechanisms of chronic pain, may be useful for characterizing new analgesics. A new model of electrical hyperalgesia can detect the efficacy of several analgesic mechanisms. Because IV adenosine can alleviate neuropathic pain, we investigated its effect on experimental sensitization.