Network Meta-analysis Of Data Research Articles

P623 Network meta-analysis to evaluate the comparative efficacy of advanced therapies as first line for maintenance treatment of adult patients with moderate-to-severe Crohn’s disease

Abstract Background Subcutaneous (SC) CT-P13 provides patients and physicians with a new opportunity for maintenance treatment of Crohn’s disease (CD).1 Given the rapidly expanding therapeutic armamentarium for CD and lack of direct comparative evidence,2 an updated network meta-analysis (NMA) of data from Phase 3 randomised controlled trials (RCTs) was performed to evaluate the comparative efficacy of advanced CD therapies licensed in Europe or the US. Methods Eligible studies, identified by systematic literature review (PROSPERO no.: CRD42023413752), evaluated the efficacy of maintenance therapy using intravenous (IV) or SC infliximab, SC adalimumab, IV or SC vedolizumab, SC ustekinumab, SC risankizumab or oral upadacitinib, in patients with moderate-to-severe CD who responded to induction therapy. Head-to-head studies (including with treat-through designs) comparing licensed advanced therapies were also eligible. Studies were placebo- (PBO) or active-controlled and included 52–64 weeks of follow-up. Patients had not received prior tumour necrosis factor inhibitors, other biologics or Janus kinase inhibitors, thus each drug was received as first-line advanced therapy. Clinical remission and endoscopic response rates achieved with maintenance treatment were synthesised and analysed in a frequentist NMA random-effects model. Results There were 9 eligible RCTs (ACCENT I, LIBERTY-CD, CHARM, SEAVUE, GEMINI 2, VISIBLE 2, IM-UNITI, FORTIFY, U-ENDURE). Among 14 compared treatment arms, SC infliximab 120 mg every 2 weeks (Q2W) showed the highest risk difference (RD) versus PBO for achieving clinical remission during the maintenance phase (0.38 [95% confidence interval (CI): 0.23, 0.53]), followed by SC adalimumab 40 mg QW (0.32 [0.17, 0.48]) and oral upadacitinib 30 mg once daily (0.30 [0.08, 0.53]) (Figure A). Endoscopic response data were available from LIBERTY-CD, FORTIFY and U-ENDURE: among 5 treatment arms, SC infliximab 120 mg Q2W showed the highest RD (95% CI) versus PBO for achieving endoscopic response (0.39 [0.29, 0.49]), followed by SC risankizumab 180 mg Q8W (0.37 [0.17, 0.56]) and SC risankizumab 360 mg Q8W (0.27 [0.06, 0.48]) (Figure B). Conclusion In this updated NMA, SC infliximab 120 mg Q2W demonstrated a favourable efficacy profile in terms of achieving clinical remission and endoscopic response, when administered as a first-line advanced therapy for maintenance treatment of patients with moderate-to-severe CD. 1Remsima summary of product characteristics (https://www.ema.europa.eu/en/documents/product-information/remsima-epar-product-information_en.pdf). Accessed 1 November 2023. 2Barberio B et al. Gut 2023;72:264–74.

Efficacy and effectiveness of antipsychotics in schizophrenia: network meta-analyses combining evidence from randomised controlled trials and real-world data

There is debate about the generalisability of results from randomised clinical trials (RCTs) to real-world settings. Studying outcomes of treatments for schizophrenia can shed light on this issue and inform treatment guidelines. We therefore compared the efficacy and effectiveness of antipsychotics for relapse prevention in schizophrenia and estimated overall treatment effects using all available RCT and real-world evidence. We conducted network meta-analyses using individual participant data from Swedish and Finnish national registries and aggregate data from RCTs. The target population was adults (age >18 and <65 years) with schizophrenia and schizoaffective disorder with stabilised symptoms. We analysed each registry separately to obtain hazard ratios (HRs) and 95% CIs for relapse within 6 months post-antipsychotic initiation as our main outcome. Interventions studied were antipsychotics, no antipsychotic use, and placebo. We compared HRs versus a reference drug (oral haloperidol) between registries, and between registry individuals who would be eligible and ineligible for RCTs, using the ratio of HRs. We synthesised evidence using network meta-analysis and compared results from our network meta-analysis of real-world data with our network meta-analysis of RCT data, including oral versus long-acting injectable (LAI) formulations. Finally, we conducted a joint real-world and RCT network meta-analysis. We included 90 469 individuals from the Swedish and Finnish registries (mean age 45·9 [SD 14·6] years; 43 025 [47·5%] women and 47 467 [52·5%] men, ethnicity data unavailable) and 10 091 individuals from 30 RCTs (mean age 39·6 years [SD 11·7]; 3724 [36·9%] women and 6367 [63·1%] men, 6022 White [59·7%]). We found good agreement in effectiveness of antipsychotics between Swedish and Finnish registries (HR ratio 0·97, 95% CI 0·88-1·08). Drug effectiveness versus no antipsychotic was larger in RCT-eligible than RCT-ineligible individuals (HR ratio 1·40 [1·24-1·59]). Efficacy versus placebo in RCTs was larger than effectiveness versus no antipsychotic in real-world (HR ratio 2·58 [2·02-3·30]). We found no evidence of differences between effectiveness and efficacy for between-drug comparisons (HR ratio vs oral haloperidol 1·17 [0·83-1·65], where HR ratio >1 means superior effectiveness in real-world to RCTs), except for LAI versus oral comparisons (HR ratio 0·73 [0·53-0·99], indicating superior effectiveness in real-world data relative to RCTs). The real-world network meta-analysis showed clozapine was most effective, followed by olanzapine LAI. The RCT network meta-analysis exhibited heterogeneity and inconsistency. The joint real-world and RCT network meta-analysis identified olanzapine as the most efficacious antipsychotic amongst those present in both RCTs and the real world registries. LAI antipsychotics perform slightly better in the real world than according to RCTs. Otherwise, RCT evidence was in line with real-world evidence for most between-drug comparisons, but RCTs might overestimate effectiveness of antipsychotics observed in routine care settings. Our results further the understanding of the generalisability of RCT findings to clinical practice and can inform preferential prescribing guidelines. None.

Best step-up treatments for children with uncontrolled asthma: a systematic review and network meta-analysis of individual participant data.

There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids (ICS) and international guidelines make different recommendations. We evaluated the pharmacological treatments to reduce asthma exacerbations and symptoms in uncontrolled patients age <18 years on ICS. We searched MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, Web of Science, National Institute for Health and Care Excellence Technology Appraisals, National Institute for Health and Care Research Health Technology Assessment series, World Health Organization International Clinical Trials Registry, conference abstracts and internal clinical trial registers (1 July 2014 to 5 May 2023) for randomised controlled trials of participants age <18 years with uncontrolled asthma on any ICS dose alone at screening. Studies before July 2014 were retrieved from previous systematic reviews/contact with authors. Patients had to be randomised to any dose of ICS alone or combined with long-acting β2-agonists (LABA) or combined with leukotriene receptor antagonists (LTRA), LTRA alone, theophylline or placebo. Primary outcomes were exacerbation and asthma control. The interventions evaluated were ICS (low/medium/high dose), ICS+LABA, ICS+LTRA, LTRA alone, theophylline and placebo. Of the 4708 publications identified, 144 trials were eligible. Individual participant data were obtained from 29 trials and aggregate data were obtained from 19 trials. Compared with ICS Low, ICS Medium+LABA was associated with the lowest odds of exacerbation (OR 0.44, 95% credibility interval (95% CrI) 0.19-0.90) and with an increased forced expiratory volume in 1 s (mean difference 0.71, 95% CrI 0.35-1.06). Treatment with LTRA was the least preferred. No apparent differences were found for asthma control. Uncontrolled children/adolescents on low-dose ICS should be recommended a change to medium-dose ICS+LABA to reduce the risk for exacerbation and improve lung function.

Immunogenicity and seroefficacy of 10-valent and 13-valent pneumococcal conjugate vaccines: a systematic review and network meta-analysis of individual participant data.

Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. In this systematic-review and network meta-analysis, we searched the Cochrane Library, Embase, Global Health, Medline, clinicaltrials.gov and trialsearch.who.int up to February 17, 2023 with no language restrictions. Studies were eligible if they presented data comparing the immunogenicity of either PCV7, PCV10 or PCV13 in head-to-head randomised trials of young children under 2 years of age, and provided immunogenicity data for at least one time point after the primary vaccination series or the booster dose. Publication bias was assessed via Cochrane's Risk Of Bias due to Missing Evidence tool and comparison-adjusted funnel plots with Egger's test. Individual participant level data were requested from publication authors and/or relevant vaccine manufacturers. Outcomes included the geometric mean ratio (GMR) of serotype-specific IgG and the relative risk (RR) of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Seroefficacy was defined as the RR of seroinfection. We also estimated the relationship between the GMR of IgG one month after priming and the RR of seroinfection by the time of the booster dose. The protocol is registered with PROSPERO, ID CRD42019124580. 47 studies were eligible from 38 countries across six continents. 28 and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. GMRs comparing PCV13 vs PCV10 favoured PCV13 for serotypes 4, 9V, and 23F at 1 month after primary vaccination series, with 1.14- to 1.54- fold significantly higher IgG responses with PCV13. Risk of seroinfection prior to the time of booster dose was lower for PCV13 for serotype 4, 6B, 9V, 18C and 23F than for PCV10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Two-fold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (RR 0.46, 95% CI 0.23-0.96). Serotype-specific differences were found in immunogenicity and seroefficacy between PCV13 and PCV10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These findings could be used to compare PCVs and optimise vaccination strategies. The NIHR Health Technology Assessment Programme.

Multi-state network meta-analysis of progression and survival data.

Multiple randomized controlled trials, each comparing a subset of competing interventions, can be synthesized by means of a network meta-analysis to estimate relative treatment effects between all interventions in the evidence base. Here we focus on estimating relative treatment effects for time-to-event outcomes. Cancer treatment effectiveness is frequently quantified by analyzing overall survival (OS) and progression-free survival (PFS). We introduce a method for the joint network meta-analysis of PFS and OS that is based on a time-inhomogeneous tri-state (stable, progression, and death) Markov model where time-varying transition rates and relative treatment effects are modeled with parametric survival functions or fractional polynomials. The data needed to run these analyses can be extracted directly from published survival curves. We demonstrate use by applying the methodology to a network of trials for the treatment of non-small-cell lung cancer. The proposed approach allows the joint synthesis of OS and PFS, relaxes the proportional hazards assumption, extends to a network of more than two treatments, and simplifies the parameterization of decision and cost-effectiveness analyses.

Comparison and validation of metadta for meta-analysis of diagnostic test accuracy studies.

We developed metadta, a flexible, robust and user-friendly statistical procedure that fuses established and innovative statistical methods for meta-analysis, meta-regression, and network meta-analysis of diagnostic test accuracy studies in Stata. Using data from published meta-analyses, we validate metadta by comparing and contrasting its features and output to popular procedures dedicated to the meta-analysis of diagnostic test accuracy studies; (midas (Stata), metandi (Stata), metaDTA (web application), mada (R), and MetaDAS (SAS)). We also demonstrate how to perform network meta-analysis with metadta, for which no alternative procedure is dedicated to network meta-analysis of diagnostic test accuracy data in the frequentist framework. metadta generated consistent estimates in simple and complex diagnostic test accuracy data sets. We expect its availability to stimulate better statistical practice in the evidence synthesis of diagnostic test accuracy studies. This article is protected by copyright. All rights reserved.

Completion, safety, and efficacy of tuberculosis preventive treatment regimens containing rifampicin or rifapentine: an individual patient data network meta-analysis

3 months of weekly rifapentine plus isoniazid (3HP) and 4 months of daily rifampicin (4R) are recommended for tuberculosis preventive treatment. As these regimens have not been compared directly, we used individual patient data and network meta-analysis methods to compare completion, safety, and efficacy between 3HP and 4R. We conducted a network meta-analysis of individual patient data by searching PubMed for randomised controlled trials (RCTs) published between Jan 1, 2000, and Mar 1, 2019. Eligible studies compared 3HP or 4R to 6 months or 9 months of isoniazid and reported treatment completion, adverse events, or incidence of tuberculosis disease. Deidentified individual patient data from eligible studies were provided by study investigators and outcomes were harmonised. Methods for network meta-analysis were used to generate indirect adjusted risk ratios (aRRs) and risk differences (aRDs) with their 95% CIs. We included 17 572 participants from 14 countries in six trials. In the network meta-analysis, treatment completion was higher for people on 3HP than for those on 4R (aRR 1·06 [95% CI 1·02-1·10]; aRD 0·05 [95% CI 0·02-0·07]). For treatment-related adverse events leading to drug discontinuation, risks were higher for 3HP than for 4R for adverse events of any severity (aRR 2·86 [2·12-4·21]; aRD 0·03 [0·02-0·05]) and for grade 3-4 adverse events (aRR 3·46 [2·09-6·17]; aRD 0·02 [0·01-0·03]). Similar increased risks with 3HP were observed with other definitions of adverse events and were consistent across age groups. No difference in the incidence of tuberculosis disease between 3HP and 4R was found. In the absence of RCTs, our individual patient data network meta-analysis indicates that 3HP provided an increase in treatment completion over 4R, but was associated with a higher risk of adverse events. Although findings should be confirmed, the trade-off between completion and safety must be considered when selecting a regimen for tuberculosis preventive treatment. None. For the French and Spanish translations of the abstract see Supplementary Materials section.

Efficacy of deep brain stimulation for the treatment of anorexia nervosa: a systematic review and network meta-analysis of patient-level data.

Deep brain stimulation (DBS) has been approved as a therapy for movement disorders and obsessive-compulsive disorder. Recently, DBS has been studied in patients with anorexia nervosa (AN), which is a debilitating and life-threatening psychiatric disorder. Several stimulation locations have been tested without a clear indication of the best region. In this systematic review and network meta-analysis, the authors used patient-level data to identify stimulation targets with the greatest evidence for efficacy in increasing body mass index (BMI). A systematic search was performed on or before August 4, 2022, using PubMed/MEDLINE, Ovid, and Scopus. Articles were included if patient-level data were presented, patients were diagnosed with AN and treated with DBS, and 6 months or more of postoperative follow-up data were reported. Quality and risk of bias were assessed with the NIH assessment tools. Patient data were collected and stratified by stimulation location. A network meta-analysis was performed. This review was written in accordance with PRISMA guidelines for systematic reviews. Eleven studies consisting of 36 patients were included. The mean age and BMI at the time of surgery were 38.07 (SD 11.64) years and 12.58 (SD 1.4) kg/m2, respectively. After 6 months of DBS, a significant difference in percentage change in BMI was found between the nucleus accumbens and subcallosal cingulate cortex (SCC) (SMD 0.78; 95% CI 0.10, 1.45) and between the SCC and ventral anterior limb of the internal capsule (SMD -1.51; 95% CI -2.39, -0.62). Similarly, at 9-12 months, a significant difference in percentage change in BMI was found between the SCC and ventral anterior limb of the internal capsule (SMD -1.18; 95% CI -2.21, -0.15). With hierarchical ranking, this study identified SCC as the most supported stimulation location for BMI change at 6 and 9-12 months (P-scores 0.9449 and 0.9771, respectively). Several DBS targets have been tested for AN, and this study identified the SCC as the most supported region for BMI change. However, further studies with blinded on/off periods are necessary to confirm this finding.

MSR61 Lessons Learned From Network Meta-Analysis of Survival Data With Fractional Polynomials

Fractional polynomials (FP) have been proposed for network meta-analysis (NMA) of survival data without relying on the proportional hazards assumption. However, there is limited guidance on modelling choices such as time intervals for data aggregation and model selection. This research aims to make recommendations for fitting FP models based on lessons learned from fitting a large number of FP models for a NICE guideline.

125P A parametric network meta-analysis of PD-1 inhibitors in second-line treatment for advanced esophageal squamous cell carcinoma

The Network meta-analysis (NMA) of survival data is often based on the reported hazard ratios and relies on the proportional hazard (PH) assumption. To address the violation of the PH assumption, a non-proportional hazard (NPH) NMA was conducted using pseudo-patient-level data to assess the comparative efficacy of PD-1 inhibitors and chemotherapy in second-line treatment for advanced esophageal squamous cell carcinoma.

Oral nutrition interventions in hospitalised older people at nutritional risk: a network meta-analysis of individual participant data

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess in hospitalised older people with (risk of) malnutrition the effects of different nutrition interventions (e.g. supportive interventions, nutritional counselling, food modifications, oral nutritional supplements, comprehensive individualised nutritional interventions or combined approaches) compared to control groups (usual care, placebo or health education materials) on patient‐relevant outcomes, and to rank the effects of the different treatments by using a network meta‐analysis with individual participant data.

Complex speech-language therapy interventions for stroke-related aphasia: the RELEASE study incorporating a systematic review and individual participant data network meta-analysis

Complex speech-language therapy interventions for stroke-related aphasia: the RELEASE study incorporating a systematic review and individual participant data network meta-analysis

Direct oral anticoagulants versus warfarin in nonvalvular atrial fibrillation patients with prior gastrointestinal bleeding: a network meta-analysis of real-world data.

The objective of present study was to compare the safety and efficacy of resuming direct-acting oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and prior gastrointestinal bleeding (GIB). PubMed, Embase, Web of Science, and the Cochrane Library were searched from their inception until 2 June 2021 for observational cohort studies in patients with AF, who resumed VKAs or DOACs after a history of GIB. Studies that reported data on clinical outcomes including risk of recurrent GIB, thromboembolic events, or all-cause mortality were included. A network meta-analysis was performed to calculate the pooled hazard ratio (HR) and associated 95% credible intervals (CIs), using a random effects model in a Bayesian framework. A total of 10 studies were included in the final analysis, including 59,244 AF patients with prior GIB, of whom 27,793 resumed DOACs, 24,635 resumed warfarin, and 6816 did not resume anticoagulation. Compared with no resumption of anticoagulation, resumption of warfarin was associated with an increased risk of recurrent GIB (HR 1.33, 95% CI: 1.06-1.70), but no increased risk of recurrent GIB was found with resumption of DOACs (HR 1.22, 95% CI: 0.88-1.71); among individual DOACs, only rivaroxaban was associated with an increased risk of recurrent GIB (HR 1.67, 95% CI: 1.16-2.65). Compared with no resumption of anticoagulation, resumption of DOACs and warfarin was associated with a significant reduction in all-cause mortality (HR 0.57, 95% CI: 0.40-0.84; HR 0.58, 95% CI: 0.44-0.79), but no statistically significant reduction in thromboembolic events (HR 0.69, 95% CI: 0.4-1.2; HR 0.83, 95% CI: 0.55-1.29). In AF patients with prior GIB, resumption of DOACs may be safer, except for rivaroxaban.

Network Meta-Analysis of Chicken Microarray Data following Avian Influenza Challenge-A Comparison of Highly and Lowly Pathogenic Strains.

The current bioinformatics study was undertaken to analyze the transcriptome of chicken (Gallus gallus) after influenza A virus challenge. A meta-analysis was carried out to explore the host expression response after challenge with lowly pathogenic avian influenza (LPAI) (H1N1, H2N3, H5N2, H5N3 and H9N2) and with highly pathogenic avian influenza (HPAI) H5N1 strains. To do so, ten microarray datasets obtained from the Gene Expression Omnibus (GEO) database were normalized and meta-analyzed for the LPAI and HPAI host response individually. Different undirected networks were constructed and their metrics determined e.g., degree centrality, closeness centrality, harmonic centrality, subgraph centrality and eigenvector centrality. The results showed that, based on criteria of centrality, the CMTR1, EPSTI1, RNF213, HERC4L, IFIT5 and LY96 genes were the most significant during HPAI challenge, with PARD6G, HMG20A, PEX14, RNF151 and TLK1L having the lowest values. However, for LPAI challenge, ZDHHC9, IMMP2L, COX7C, RBM18, DCTN3, and NDUFB1 genes had the largest values for aforementioned criteria, with GTF3C5, DROSHA, ATRX, RFWD2, MED23 and SEC23B genes having the lowest values. The results of this study can be used as a basis for future development of treatments/preventions of the effects of avian influenza in chicken.

Efficacy and safety of electronic cigarettes as a smoking cessation intervention: A systematic review and network meta-analysis.

INTRODUCTIONThis systematic review of randomized controlled trials (RCTs) evaluated the efficacy and safety of electronic cigarettes (e-cigarettes, ENDS) in helping people who smoke to achieve abstinence compared with electronic non-nicotine delivery systems (ENNDS, no nicotine) or any smoking cessation comparator treatment or combination of treatments at 24–26 weeks and at 52 weeks.METHODSSystematic review techniques involved searches of three databases in February 2020 with update searches run on 14 May 2021, two-person independent screening, two-person independent assessment of bias, formal extraction of data with verification by a second person, a feasibility assessment to decide if meta-analysis was appropriate, and network meta-analysis (NMA) of data at 24–26 weeks. Data at 52 weeks were narratively summarized.RESULTSTen RCTs met the inclusion criteria, eight for efficacy and ten for safety. Eight of the nine RCTs were assessed as at high risk of bias. The sample sizes of the RCTs were 30–2012. Using nicotine replacement therapy (NRT) as the reference treatment, the incidences of smoking cessation at 24–26 weeks were comparable between ENDS and NRT groups (RR=1.17; 95% CrI: 0.66–1.86). Three sensitivity analyses were carried out indicating the main findings for 24–26 weeks were robust to assumptions. The findings at 52 weeks were inconclusive.CONCLUSIONSThis systematic review and NMA indicates that there is no clear evidence of a difference in effect between nicotine containing e-cigarettes and NRT on incidences of smoking cessation at 24–26 weeks, and substantial uncertainty remains.

Review Article: The Flagship of Evidence-Based Medicine.

Global literature is ever-growing and physicians rely on it for evidence-based decision making. Review articles summarize available literature and provide the current state of knowledge on a given topic. Various review types exist, the main ones being narrative and systematic reviews. The former are based on studies selected in an undefined manner. They express the authors' opinions of a given topic, lack a systematic search, and are prone to bias. By contrast, the latter represent an unbiased synthesis of knowledge on a particular topic and attempt to offer all relevant evidence. A systematic review may include a meta-analysis, which combines the results of quantitative studies using statistical techniques to provide a more precise summary of the evidence. With a dramatic increase in literature complexity, new "next-generation" types of reviews emerged to improve the quality of evidence synthesis: network meta-analysis, umbrella review, and meta-analysis of individual patient data, among others. Finally, scoping reviews are a special type, conducted as precursors to systematic reviews aiming to reveal specific knowledge gaps in a given subject.

Comparative safety and benefit-risk profile of biologics and oral treatment for moderate-to-severe plaque psoriasis: A network meta-analysis of clinical trial data

The comparative safety and benefit-risk profiles of moderate-to-severe psoriasis treatment have not been well studied. To compare the short-term (12-16weeks) and long-term (48-56weeks) safety and benefit-risk profiles of moderate-to-severe psoriasis treatments. A systematic literature review of phase II-IV randomized controlled trials of moderate-to-severe psoriasis treatments was conducted (cutoff: July 1, 2020). Any adverse events (AEs), any serious AEs, and AEs leading to treatment discontinuation were compared using Bayesian network meta-analyses (NMAs). Fifty-two and 7, respectively, randomized controlled trials were included in the short- and long-term NMAs, respectively. In the short-term NMA, the rates of any AEs were the lowest for tildrakizumab (posterior median: 46.0%), certolizumab (46.2%), and etanercept (49.1%). The rates of any serious AE were the lowest for certolizumab (0.8%), risankizumab (1.2%), and etanercept (1.6%). The rates of AEs leading to treatment discontinuation were the lowest for risankizumab (0.5%), tildrakizumab (1.0%), and guselkumab (1.5%). In the long-term NMA, risankizumab had the lowest rates of all 3 outcomes (67.5%, 4.4%, and 1.0%, respectively) and the most favorable benefit-risk profile. The results may not be generalizable to real-world populations. Anti-interleukin 23 agents were associated with low rates of safety events. Risankizumab had the most favorable benefit-risk profile in the long term.

Pattern-mixture model in network meta-analysis of binary missing outcome data: one-stage or two-stage approach?

BackgroundTrials with binary outcomes can be synthesised using within-trial exact likelihood or approximate normal likelihood in one-stage or two-stage approaches, respectively. The performance of the one-stage and the two-stage approaches has been documented extensively in the literature. However, little is known about how these approaches behave in the presence of missing outcome data (MOD), which are ubiquitous in clinical trials. In this work, we compare the one-stage versus two-stage approach via a pattern-mixture model in the network meta-analysis using Bayesian methods to handle MOD appropriately.MethodsWe used 29 published networks to empirically compare the two approaches concerning the relative treatment effects of several competing interventions and the between-trial variance (τ2), while considering the extent and level of balance of MOD in the included trials. We additionally conducted a simulation study to compare the competing approaches regarding the bias and width of the 95% credible interval of the (summary) log odds ratios (OR) and τ2 in the presence of moderate and large MOD.ResultsThe empirical study did not reveal any systematic bias between the compared approaches regarding the log OR, but showed systematically larger uncertainty around the log OR under the one-stage approach for networks with at least one small trial or low event risk and moderate MOD. For these networks, the simulation study revealed that the bias in log OR for comparisons with the reference intervention in the network was relatively higher in the two-stage approach. Contrariwise, the bias in log OR for the remaining comparisons was relatively higher in the one-stage approach. Overall, bias increased for large MOD. For these networks, the empirical results revealed slightly higher τ2 estimates under the one-stage approach irrespective of the extent of MOD. The one-stage approach also led to less precise log OR and τ2 when compared with the two-stage approach for large MOD.ConclusionsDue to considerable bias in the log ORs overall, especially for large MOD, none of the competing approaches was superior. Until a more competent model is developed, the researchers may prefer the one-stage approach to handle MOD, while acknowledging its limitations.

Comparison of detection rate of 16 sampling methods for respiratory viruses: a Bayesian network meta-analysis of clinical data and systematic review

BackgroundRespiratory viruses (RVs) is a common cause of illness in people of all ages, at present, different types of sampling methods are available for respiratory viral diagnosis. However, the diversity...

Multivariate network meta-analysis of survival function parameters.

Network meta-analysis (NMA) of survival data with a multidimensional treatment effect has been introduced as an alternative to NMA based on the proportional hazards assumption. However, these flexible models have some limitations, such as the use of an approximate likelihood based on discrete hazards, rather than a likelihood for individual event times. The aim of this article is to overcome the limitations and present an alternative implementation of these flexible NMA models for time-to-event outcomes with a two-step approach. First, for each arm of every randomised controlled trial (RCT) connected in the network of evidence, reconstructed patient data are fit to alternative survival distributions, including the exponential, Weibull, Gompertz, log-normal, and log-logistic. Next, for each distribution, its scale and shape parameters are included in a multivariate NMA to obtain time-varying estimates of relative treatment effects between competing interventions. An illustrative analysis is presented for a network of RCTs evaluating multiple interventions for advanced melanoma regarding overall survival. Alternative survival distributions were compared based on model fit criteria. Based on the log-logistic distribution, the difference in shape and scale parameters for each treatment versus dacarbazine (DTIC) was identified and the corresponding log hazard and survival curves were presented. The presented two-step NMA approach provides an evidence synthesis framework for time-to-event outcomes grounded in standard practice of parametric survival analysis. The method allows for a more transparent and efficient model selection process.