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Sally Hollis,1 Carin Jorup,2 Dan Lythgoe,3 Gunnar Martensson,2 Pontus Regnell,2 Göran Eckerwall2 1AstraZeneca R&D, Alderley Park, Macclesfield, UK; 2AstraZeneca R&D, Gothenburg, Sweden; 3Phastar, Chiswick, London, UK Background: Concerns have been raised that treatment of COPD with inhaled corticosteroids may increase pneumonia risk. Responding to a request from the European Medicines Agency Pharmacovigilance Risk Assessment Committee, a pooled analysis of interventional studies compared pneumonia risk with inhaled budesonide-containing versus non-budesonide-containing treatments and the impact of other clinically relevant factors.Methods: AstraZeneca-sponsored, parallel-group, double-blind, randomized controlled trials meeting the following criteria were included: >8 weeks’ duration; ≥60 patients with COPD; inhaled budesonide treatment arm (budesonide/formoterol or budesonide); and non-budesonide-containing comparator arm (formoterol or placebo). Primary and secondary outcomes were time to first pneumonia treatment-emergent serious adverse event (TESAE) and treatment-emergent adverse event (TEAEs), respectively, analyzed using Cox regression models stratified by study.Results: Eleven studies were identified; 10,570 out of 10,574 randomized patients receiving ≥1 dose of study treatment were included for safety analysis (budesonide-containing, n=5,750; non-budesonide-containing, n=4,820). Maximum exposure to treatment was 48 months. The overall pooled hazard ratio (HR), comparing budesonide versus non-budesonide-containing treatments, was 1.15 for pneumonia TESAEs (95% confidence interval [CI]: 0.83, 1.57) and 1.13 for pneumonia TEAEs (95% CI: 0.94, 1.36). The annual incidence of pneumonia TESAEs was 1.9% and 1.5% for budesonide-containing and non-budesonide-containing treatments, respectively. Comparing budesonide/formoterol with non-budesonide-containing treatment, the HRs for pneumonia TESAEs and TEAEs were 1

David M Kern,1 Jill Davis,2 Setareh A Williams,3 Ozgur Tunceli,1 Bingcao Wu,1 Sally Hollis,4 Charlie Strange,5 Frank Trudo2 1HealthCore, Inc., Wilmington, DE, 2AstraZeneca Pharmaceuticals, Wilmington, DE, 3AstraZeneca Pharmaceuticals, Gaithersburg, MD, USA; 4AstraZeneca Pharmaceuticals, Cheshire, UK; 5Department of Medicine, Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC, USA Objective: To estimate the accuracy of claims-based pneumonia diagnoses in COPD patients using clinical information in medical records as the reference standard.Methods: Selecting from a repository containing members’ data from 14 regional United States health plans, this validation study identified pneumonia diagnoses within a group of patients initiating treatment for COPD between March 1, 2009 and March 31, 2012. Patients with ≥1 claim for pneumonia (International Classification of Diseases Version 9-CM code 480.xx–486.xx) were identified during the 12 months following treatment initiation. A subset of 800 patients was randomly selected to abstract medical record data (paper based and electronic) for a target sample of 400 patients, to estimate validity within 5% margin of error. Positive predictive value (PPV) was calculated for the claims diagnosis of pneumonia relative to the reference standard, defined as a documented diagnosis in the medical record.Results: A total of 388 records were reviewed; 311 included a documented pneumonia diagnosis, indicating 80.2% (95% confidence interval [CI]: 75.8% to 84.0%) of claims-identified pneumonia diagnoses were validated by the medical charts. Claims-based diagnoses in inpatient or emergency departments (n=185) had greater PPV versus outpatient settings (n=203), 87.6% (95% CI: 81.9%–92.0%) versus 73.4% (95% CI: 66.8%–79.3%), respectively. Claims-diagnoses verified with paper-based charts had similar PPV as the overall study sample, 80.2% (95% CI:&a

Context: Meta-analyses are regularly used to inform healthcare decisions. Concerns have been expressed about the quality of meta-analyses and, in particular, about those supported by the pharmaceutical industry. Objective: The objective of this study is to compare the quality of pharmaceutical-industry-supported meta-analyses with academic meta-analyses and of meta-analyses published before and after companies started to disclose their data. Data Sources: We identified industry-supported meta-analyses by searching the Scopus bibliographic database, using author affiliations. We matched each industry-supported meta-analysis with an academic meta-analysis using high-level MeSH terms in PubMed. Study Selection: We included meta-analyses of randomized trials assessing the efficacy or safety of any pharmaceutical intervention in humans, published in 2002–2004 or 2008–2009. Cochrane reviews were excluded. Two individuals independently selected papers, with discrepancies resolved by two further individuals. Assessment: We developed and piloted a quality-assessment tool, consisting of 43 questions in four domains, with a key summary question covering each domain. Two individuals independently assessed each meta-analysis. Results: We examined 126 meta-analysis publications in 63 matched pairs. The average quality was low, with fewer than 50% adequate in three of the four domains. Industry-supported meta-analyses less often

Background: Because meta-analyses are increasingly prevalent and cited in the medical literature, it is important that tools are available to assess their methodological quality. When performing an empirical study of the quality of published meta-analyses, we found that existing tools did not place a strong emphasis on statistical and interpretational issues. Methods: We developed a quality-assessment tool using existing materials and expert judgment as a starting point, followed by multiple iterations of input from our working group, piloting, and discussion. After having used the tool for our empirical study, agreement for four key items in the tool was measured using weighted kappa coefficients. Results: Our tool contained 43 items divided into four key areas (data sources, analysis of individual studies, meta-analysis methods, and interpretation), and each area ended with a summary question. We also produced guidance for completing the tool. Agreement between raters was fair to moderate. Conclusions: The tool should usefully inform subsequent initiatives to develop quality-assessment tools for meta-analysis. We advocate use of consensus between independent raters when assessing statistical appropriateness and adequacy of interpretation in meta-analyses.

Bullous pemphigoid is the most common autoimmune bullous disease in the West. Oral steroids are considered the standard treatment.