BackgroundThis meta-analysis assessed the efficacy of duloxetine versus other oral treatments used after failure of acetaminophen for management of patients with osteoarthritis.MethodsA systematic literature review of English language articles was performed in PUBMED, EMBASE, MedLine In-Process, Cochrane Library, and ClinicalTrials.gov between January 1985 and March 2013. Randomized controlled trials of duloxetine and all oral non-steroidal anti-inflammatory drugs and opioids were included if treatment was ≥12 weeks and the Western Ontario and McMaster Universities Index (WOMAC) total score was available. Studies were assessed for quality using the assessment tool from the National Institute for Health and Clinical Excellence guidelines for single technology appraisal submissions.WOMAC baseline and change from baseline total scores were extracted and standardized. A frequentist meta-analysis, meta-regression, and indirect comparison were performed using the DerSimonian-Laird and Bucher methods. Bayesian analyses with and without adjustment for study-level covariates were performed using noninformative priors.ResultsThirty-two publications reported 34 trials (2 publications each reported 2 trials) that met inclusion criteria. The analyses found all treatments except oxycodone (frequentist) and hydromorphone (frequentist and Bayesian) to be more effective than placebo. Indirect comparisons to duloxetine found no significant differences for most of the compounds. Some analyses showed evidence of a difference with duloxetine for etoricoxib (better), tramadol and oxycodone (worse), but without consistent results between analyses. Forest plots revealed positive trends in overall efficacy improvement with baseline scores. Adjusting for baseline, the probability duloxetine is superior to other treatments ranges between 15% to 100%.Limitations of this study include the low number of studies included in the analyses, the inclusion of only English language publications, and possible ecological fallacy associated with patient level characteristics.ConclusionsThis analysis suggests no difference between duloxetine and other post-first line oral treatments for osteoarthritis (OA) in total WOMAC score after approximately 12 weeks of treatment. Significant results for 3 compounds (1 better and 2 worse) were not consistent across performed analyses.

The available evidence shows that there does not seem to be any difference in efficacy between duloxetine and other oral pharmacological therapies, providing a valuable alternative for this disabling condition.

These data from the APTOR study provide key information on current European ACS patient care management from hospitalization through 1 year. Even with European Society of Cardiology (ESC) guidelines, variations in practice patterns exist among ACS patients treated with PCI between the 14 European countries studied, including the use of proven therapies, as well as appropriate duration and dosing of antiplatelet regimens. Efforts are needed to further explain why such variation exists and to continue to improve adherence to ESC guidelines to improve patient care.

Introduction The International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) assess efficacy of phosphodiesterase type 5 (PDE5) inhibitor treatment of erectile dysfunction (ED). Aims To determine the degree that multiplicity of satisfaction questions in ED treatment evaluation instruments are congruent, to better understand the concept of sexual “satisfaction,” and to identify factors that correlate with improvement. Methods Questionnaire data from 4,174 placebo- or tadalafil-treated patients with ED were analyzed. Principal component analysis (PCA) was performed on IIEF and SEP satisfaction questions. Spearman correlation coefficients were determined. Data from 431 of the 4,174 patients who completed EDITS questionnaires were analyzed. Logistic regression was used to investigate improvement of each IIEF satisfaction question. Results PCA rotated on three factors explained 91% of total variance and separated IIEF Q6 (intercourse frequency) from a SEP and a remaining IIEF factor. All correlations between and among questions were close (ρ = 0.62–0.98; P < 0.0001), except for those with IIEF Q6 (ρ = 0.28–0.34; P < 0.0001). In a sub-sample, PCA of five IIEF, two SEP, and three EDITS questions identified four factors that explained 90% of all variance: EDITS questions, IIEF questions except Q6, SEP questions, and IIEF Q6. Greater improvement in IIEF-EF domain score was consistently and positively associated with satisfaction measures (P < 0.0001). Conclusions Factor analysis detected close relationships among satisfaction questions in IIEF, SEP, and EDITS instruments, each of which, apart from IIEF Q6 (intercourse frequency), appeared to be an independent measure of satisfaction. Cultural differences may explain different satisfaction correlations with baseline ED severity in different regions. Clinicians may make use of the correlation between intercourse frequency (Q6) and satisfaction when prescribing a PDE5 inhibitor for ED, by explaining that the inhibitor should enable more frequent intercourse.

dSubgroup analysis is an integral part of access and reimbursement dossiers, in particular health technology assessment (HTA), and their HTA recommendations are often limited to subpopulations. HTA recommendations for subpopulations are not always clear and without controversies. In this paper, we review several HTA guidelines regarding subgroup analyses. We describe good statistical principles for subgroup analyses of clinical effectiveness to support HTAs and include case examples where HTA recommendations were given to subpopulations only. Unlike regulatory submissions, pharmaceutical statisticians in most companies have had limited involvement in the planning, design and preparation of HTA/payers submissions. We hope to change this by highlighting how pharmaceutical statisticians should contribute to payers' submissions. This includes early engagement in reimbursement strategy discussions to influence the design, analysis and interpretation of phase III randomized clinical trials as well as meta-analyses/network meta-analyses. The focus on this paper is on subgroup analyses relating to clinical effectiveness as we believe this is the first key step of statistical involvement and influence in the preparation of HTA and reimbursement submissions.