A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four

Mark, Lonneke B van der; Lyklema, P H Edo; Geskus, Ronald B.; Mohrs, Jacob; Bindels, Patrick J E; Aalderen, W. M. C. van; Riet, Gerben ter

doi:10.1186/1471-2466-12-63

Cited by 4 publications

(8 citation statements)

References 48 publications

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“…Two systematic reviews in asthma began with the goal of conducting an NMA; only one was successful. The first study evaluated the effectiveness of the various inhalation regimens on FEV1 improvement [ 18 ]. The systematic review revealed large variations in the way the 23 trials measured and reported FEV1.…”

Section: Discussionmentioning

confidence: 99%

Network meta-analysis: users’ guide for pediatricians

et al. 2018

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BackgroundNetwork meta-analysis (NMA) is a powerful analytic tool that allows simultaneous comparison between several management/treatment alternatives even when direct comparisons of the alternatives (such as the case in which treatments are compared against placebo and have not been compared against each other) are unavailable. Though there are still a limited number of pediatric NMAs published, the rapid increase in NMAs in other areas suggests pediatricians will soon be frequently facing this new form of evidence summary.DiscussionEvaluating the NMA evidence requires serial judgments on the creditability of the process of NMA conduct, and evidence quality assessment. First clinicians need to evaluate the basic standards applicable to any meta-analysis (e.g. comprehensive search, duplicate assessment of eligibility, risk of bias, and data abstraction). Then evaluate specific issues related to NMA including precision, transitivity, coherence, and rankings.ConclusionsIn this article we discuss how clinicians can evaluate the credibility of NMA methods, and how they can make judgments regarding the quality (certainty) of the evidence. We illustrate the concepts using recent pediatric NMA publications.

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Section: Discussionmentioning

confidence: 99%

Network meta-analysis: users’ guide for pediatricians

et al. 2018

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“…Specifically in mild-to-moderate pediatric asthma, we have several comparative studies for different add-on strategies such as increasing the doses of ICS ( 64 ), adding LABA, LAMA, or montelukast [reviewed in Vogelberg et al ( 65 )]. The comparisons among the aforementioned drugs and chromones or methylxanthines received less attention; however, a systematic review of asthma therapy for 5–18 year olds concluded that, although direct comparisons are lacking, there is no reason for considering theophylline inferior to LABA or LTRA ( 66 ). Although the paucity of further studies still makes it impossible to establish direct comparisons, indirect comparisons may be performed when planning an individual treatment.…”

Section: Methodsmentioning

confidence: 99%

Doxofylline for Pediatric Asthma Steps 1–4. Pediatric Asthma: New Role for an Old Drug

et al. 2022

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The panoply of anti-asthma drugs for children between 6 and 18 years is not limited to those reported in the guidelines. In this review, we will re-assess the role of doxofylline, a xanthine characterized by a much higher handling than that of theophylline, as add-on treatment in pediatric asthma grade 1–4. Ten studies evaluated doxofylline in the treatment of asthma of patients non-responsive to the first-line inhaled corticosteroids. Of these, two included children and one was exclusively pediatric. According to their results, doxofylline exerts a powerful bronchodilator and anti-inflammatory activity, which can be exploited when the inhaled oral corticosteroids are not sufficient to get the desired effect of reducing symptoms. Unlike theophylline, doxofylline does not require blood testing. It can be administered together with or as an alternative to a series of other drugs considered in additional therapy.

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“…Moreover, a series of other issues make the interpretation and generalisability of the results of this NMA difficult. There is a lack of complete overlapping of the included studies compared with the previous Cochrane reviews 15 16 and previous planned NMA 18 —only seven RCTs are in common across the two NMAs. 17 18 Two other weak points are represented by the lack of analyses focussing on outcomes of importance and relevance to patients and the lack of analyses comparing different drugs (ICS, LABA, LTRA), doses and types of inhalation devices within ICS and LABA classes.…”

Section: Introductionmentioning

confidence: 99%

“…The considerable variation in and the incomplete reporting of outcome measurements across RCTs prevented a formal NMA and assessment of relative efficacies of treatments in one NMA of 23 RCTs (4129 patients). 18 In 2015, Zhao et al 17 conducted a formal NMA consisting of 35 RCTs with 12 010 children. These authors suggested that combined ICS and LABA treatments were most effective in preventing exacerbations and that treatments with medium-dose or high-dose ICS, combined ICS/LTRA and low-dose ICS seem to be equally effective.…”

Section: Introductionmentioning

confidence: 99%

EstablishINg the best STEp-up treatments for children with uncontrolled asthma despite INhaled corticosteroids (EINSTEIN): protocol for a systematic review, network meta-analysis and cost-effectiveness analysis using individual participant data (IPD)

et al. 2021

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IntroductionAsthma affects millions of children worldwide—1.1 million children in the UK. Asthma symptoms cannot be cured but can be controlled with low-dose inhaled corticosteroids (ICSs) in the majority of individuals. Treatment with a low-dose ICS, however, fails to control asthma symptoms in around 10%–15% of children and this places the individual at increased risk for an asthma attack. At present, there is no clear preferred treatment option for a child whose asthma is not controlled by low-dose ICS and international guidelines currently recommend at least three treatment options. Herein, we propose a systematic review and individual participant data network meta-analysis (IPD-NMA) aiming to synthesise all available published and unpublished evidence from randomised controlled trials (RCTs) to establish the clinical effectiveness of pharmacological treatments in children and adolescents with uncontrolled asthma on ICS and help to make evidence-informed treatment choices. This will be used to parameterise a Markov-based economic model to assess the cost-effectiveness of alternative treatment options in order to inform decisions in the context of drug formularies and clinical guidelines.Methods and analysisWe will search in MEDLINE, the Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, NICE Technology Appraisals and the National Institute for Health Research (NIHR) Health Technology Assessment series for RCTs of interventions in patients with uncontrolled asthma on ICS. All studies where children and adolescents were eligible for inclusion will be considered, and authors or sponsors will be contacted to request IPD on patients aged <18. The reference lists of existing clinical guidelines, along with included studies and relevant reviews, will be checked to identify further relevant studies. Unpublished studies will be located by searching across a range of clinical trial registries, including internal trial registers for pharmaceutical companies. All studies will be appraised for inclusion against predefined inclusion and exclusion criteria by two independent reviewers with disagreements resolved through discussion with a third reviewer. We will perform an IPD-NMA—eventually supplemented with aggregate data for the RCTs without IPD—to establish both the probability that a treatment is best and the probability that a particular treatment is most likely to be effective for a specific profile of the patient. The IPD-NMA will be performed for each outcome variable within a Bayesian framework, using the WinBUGS software. Also, potential patient-level characteristics that may modify treatment effects will be explored, which represents one of the strengths of this study.Ethics and disseminationThe Committee on Research Ethics, University of Liverpool, has confirmed that ethics review is not required. The dissemination plan consists of publishing the results in an open-access medical journal, a plain-language summary available for parents and children, dissemination via local, national and international meetings and conferences and the press offices of our Higher Education Institutions (HEIs). A synopsis of results will be disseminated to NICE and British Thoracic Society/Scottish Intercollegiate Guidelines Network (SIGN) as highly relevant to future clinical guideline updates.PROSPERO registration numberCRD42019127599.

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A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four

Cited by 4 publications

References 48 publications

Network meta-analysis: users’ guide for pediatricians

Network meta-analysis: users’ guide for pediatricians

Doxofylline for Pediatric Asthma Steps 1–4. Pediatric Asthma: New Role for an Old Drug

EstablishINg the best STEp-up treatments for children with uncontrolled asthma despite INhaled corticosteroids (EINSTEIN): protocol for a systematic review, network meta-analysis and cost-effectiveness analysis using individual participant data (IPD)

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