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Östermalm, Sweden

Jansen J.P.,Mapi | Jansen J.P.,Tufts University | Naci H.,The London School of Economics and Political Science
BMC Medicine | Year: 2013

Background: In the last decade, network meta-analysis of randomized controlled trials has been introduced as an extension of pairwise meta-analysis. The advantage of network meta-analysis over standard pairwise meta-analysis is that it facilitates indirect comparisons of multiple interventions that have not been studied in a head-to-head fashion. Although assumptions underlying pairwise meta-analyses are well understood, those concerning network meta-analyses are perceived to be more complex and prone to misinterpretation.Discussion: In this paper, we aim to provide a basic explanation when network meta-analysis is as valid as pairwise meta-analysis. We focus on the primary role of effect modifiers, which are study and patient characteristics associated with treatment effects. Because network meta-analysis includes different trials comparing different interventions, the distribution of effect modifiers cannot only vary across studies for a particular comparison (as with standard pairwise meta-analysis, causing heterogeneity), but also between comparisons (causing inconsistency). If there is an imbalance in the distribution of effect modifiers between different types of direct comparisons, the related indirect comparisons will be biased. If it can be assumed that this is not the case, network meta-analysis is as valid as pairwise meta-analysis.Summary: The validity of network meta-analysis is based on the underlying assumption that there is no imbalance in the distribution of effect modifiers across the different types of direct treatment comparisons, regardless of the structure of the evidence network. © 2013 Jansen and Naci; licensee BioMed Central Ltd. Source

Buckley F.,Mapi | Finckh A.,University of Geneva | Huizinga T.W.J.,Leiden University | Dejonckheere F.,Hoffmann-La Roche | Jansen J.P.,Tufts University
Journal of Managed Care Pharmacy | Year: 2015

BACKGROUND: Given the availability of a number of alternative biologic treatment options and other novel disease-modifying antirheumatic drugs (DMARDs) for the treatment of patients with rheumatoid arthritis (RA), clinicians are faced with an increasingly challenging choice regarding optimal treatment. Biologics are usually combined with traditional DMARDs, primarily methotrexate (MTX), but some biologics and tofacitinib (together referred to in this article as novel DMARDs) have been shown to be efficacious as monotherapy as well. In real-world practice, approximately one-third of RA patients receiving biologics are on monotherapy, primarily because of intolerance of, or noncompliance with, MTX. Limited data, however, are available analyzing the effectiveness of monotherapy compared with combination therapy across novel DMARDs. OBJECTIVE: To compare American College of Rheumatology (ACR) responses to approved novel DMARDs used as monotherapy or as combination therapy with methotrexate (MTX) at 24 weeks in RA patients who have shown inadequate response to conventional DMARDs (DMARD-IR). METHODS: Through a systematic review of the literature, we identified randomized controlled trials that assessed approved novel DMARDs used as monotherapy or as combination therapy with MTX in DMARD-IR RA patients. Twenty-eight RCTs were identified that evaluated abatacept, anakinra, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, tocilizumab, or tofacitinib. ACR responses at 24 weeks were extracted and combined by means of Bayesian network meta-analyses. RESULTS: With the exception of anakinra plus MTX, which was less efficacious, most novel DMARDs, when used in combination with MTX, demonstrated comparable ACR responses. When novel DMARDs were used as monotherapies, greater ACR20/50/70 responses were observed with tocilizumab than with anti-tumor necrosis factor agents (aTNF) or tofacitinib. Furthermore, ACR20/50/70 responses with tocilizumab plus MTX were similar to those with tocilizumab monotherapy (odds ratio [OR] for the indirect comparison = 1.08, 95% credible interval [CrI] = 0.40-2.84; OR = 1.24, CrI = 0.44-3.61; OR = 0.95, CrI = 0.33-2.72, respectively), whereas greater responses were observed with aTNF plus MTX than with aTNF monotherapy (OR = 2.41, CrI = 0.51-11.61; OR = 2.85, CrI = 0.51-17.67; OR = 1.28, CrI = 0.21- 8.42, respectively). Relative efficacy estimates for the indirect comparison of tofacitinib plus MTX with tofacitinib monotherapy were very uncertain. CONCLUSIONS: Results suggest that in combination with MTX most of the available novel DMARDs have similar levels of efficacy in DMARD-IR patients. As monotherapy, however, tocilizumab displayed higher ACR responses than aTNF or tofacitinib. ACR responses with tocilizumab plus MTX were similar to those with tocilizumab as monotherapy, whereas aTNF in combination with MTX demonstrated greater ACR responses than aTNF as monotherapy. © 2015, Academy of Managed Care Pharmacy. Source

Jansen J.P.,Redwood Outcomes | Jansen J.P.,Tufts University | Vieira M.C.,Previously at Mapi | Cope S.,Mapi
Statistics in Medicine | Year: 2015

Network meta-analysis of randomized controlled trials (RCTs) are often based on one treatment effect measure per study. However, many studies report data at multiple time points. Furthermore, not all studies measure the outcomes at the same time points. As an alternative to a network meta-analysis based on a synthesis of the results at one time point, a network meta-analysis method is presented that allows for the simultaneous analysis of outcomes at multiple time points. The development of outcomes over time of interventions compared in an RCT is modeled with fractional polynomials, and the differences between the parameters of these polynomials within a trial are synthesized across studies with a Bayesian network meta-analysis. The proposed models are illustrated with an analysis of RCTs evaluating interventions for osteoarthritis of the knee. Fixed and random effects second order fractional polynomials were applied to the case study. Network meta-analysis with models that represent the treatment effects in terms of several parameters using fractional polynomials can be considered a useful addition to models for network meta-analysis of repeated measures previously proposed. When RCTs report treatment effects at multiple follow-up times, these models can be used to synthesize the results even if reporting times differ across the studies. © 2015 John Wiley & Sons, Ltd. Source

Dominiak-Felden G.,Sanofi S.A. | Cohet C.,Sanofi S.A. | Atrux-Tallau S.,Sanofi S.A. | Gilet H.,Mapi | And 2 more authors.
BMC Public Health | Year: 2013

Background: Data on the psychosocial burden of human papillomavirus (HPV)-related diseases other than cervical cancer are scarce. The objectives of this study were to measure and compare the psychosocial burden and the impact on health-related quality of life (HRQoL) of HPV-related lower genital tract diseases and genital warts (GW) using several generic and disease-specific instruments. Methods. Overall, 842 individuals with normal cervical cytology (n = 241), borderline nuclear abnormalities and/or mild dyskaryosis (n = 23), cervical intraepithelial neoplasia (CIN)1 (n = 84), CIN2/3 (n = 203), vulval intraepithelial neoplasia (VIN)2/3 (n = 43), GW (n = 186) and a history of GW (non-current) (n = 62) were included. The generic European Quality of Life Index Version 5D (EQ-5D) questionnaire was completed by patients with GW and VIN2/3. Sexual functioning was evaluated using the Change in Sexual Functioning Questionnaire (CSFQ). Psychosocial impact was measured in women using the HPV Impact Profile (HIP) questionnaire. HRQoL was assessed using a GW-specific questionnaire, the Cuestionario Especifico en Condilomas Acuminados (CECA) (completed by patients with GW and history of GW). For each instrument, scores were compared between groups using the Student's t-test. In addition, utility loss due to GW and VIN2/3 was evaluated by comparing mean EQ-5D scores weighted by age and sex with the UK general population normal values. Results: A significant psychosocial impact was found in women diagnosed with HPV-related genital diseases, particularly in those with GW. The health state of younger adults with GW was significantly impaired compared with UK normal values (mean EQ-5D index score 0.86 vs 0.94, p < 0.001 for 18-24-year-olds; 0.87 vs 0.93, p = 0.030 for 25-34-year-olds). VIN2/3 was found to have a significant negative impact on sexual functioning, and women with VIN2/3 had a highly impaired health state compared with women in the UK general population (weighted mean EQ-5D index score 0.72 vs 0.89, p < 0.001; weighted mean Visual Analogue Scale score 62 vs 85, p < 0.001). Conclusions: HPV-related lower genital tract lesions and GW significantly impair psychosocial wellbeing and HRQoL. The psychosocial aspects of HPV-related diseases need to be considered when evaluating the potential benefit of HPV vaccination. © 2013 Dominiak-Felden et al.; licensee BioMed Central Ltd. Source

Santagostino E.,Angelo Bianchi Bonomi Hemophilia and Thrombosis Center | Lentz S.R.,University of Iowa | Busk A.K.,Novo Nordisk AS | Regnault A.,Mapi | Iorio A.,McMaster University
Haemophilia | Year: 2014

Haemophilia and its treatment interfere with patients' life, so health-related quality of life (HRQoL) should be assessed when evaluating treatments. This study investigated the HRQoL of patients with haemophilia A treated prophylactically with a new recombinant factor VIII. Two phase 3 trials investigated turoctocog alfa in patients with severe haemophilia A: one in children, one in adults and adolescents. HRQoL was a secondary endpoint assessed by the HAEMO-QOL age-specific, self-administered questionnaires. Parent-completed versions were also included for parents of children and adolescents. All HAEMO-QOL questionnaires allow the calculation of domain-specific and total scores ranging from 0 to 100, lower scores indicating better HRQoL. Mean change in all scores was described for 25 children aged 4-7 years, 21 children aged 8-12 years, 18 adolescents aged 13-18 years and 129 adults, overall, and according to the treatment regimen received prior to the study (on-demand; prophylaxis; mixed). Mean changes in HAEMO-QOL total score were 1.4 for children aged 4-7 years, -2.6 for children aged 8-12 years, -5.8 for adolescents and -1.6 for adults. In parent-completed versions, mean changes in total score were -6.0 for children aged 4-7 years, -4.7 for children aged 8-12 years, and -10.0 for adolescents. Patients receiving on-demand treatment before the trial showed greater improvement in HRQoL scores than patients already on prophylaxis. HRQoL of patients remained fairly stable over the course of the trials. However, improvements were observed for adolescents. Switching to prophylaxis was identified as a potential driver of improvement of HRQoL in patients with haemophilia A. © 2014 The Authors. Haemophilia published by John Wiley & Sons Ltd. Source

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