Multiple Treatment Comparison Meta-analysis Research Articles

The future of Cochrane Neonatal

The future of Cochrane Neonatal

Memantine, Donepezil, or Combination Therapy-What is the best therapy for Alzheimer's Disease? A Network Meta-Analysis.

IntroductionAlzheimer's disease (AD) is a degenerative brain disease that progresses over time, heavily burdening patients, families, and aging societies worldwide. Memantine and donepezil are frequently used in its treatment, both as monotherapy and in combination. This multiple treatment comparison meta‐analysis assessed the efficacy of these regimens and placebo in the management of AD.MethodsWe searched PubMed, Embase, the Cochrane Library, and Wanfang Med Online and China National Knowledge Infrastructure for English and Chinese publications from the first records to 17 April 2020. Two investigators scanned articles for placebo‐controlled trials of memantine and donepezil alone and in combination. We extracted data on the following outcomes: cognition, global assessment, daily activities, neuropsychiatric symptoms, adverse events, and the acceptability and cost of these treatment regimens.ResultsOf 936 records screened, we included 54 trials in this analysis. The combination therapy was more effective in improving cognition (mean difference (MD)‐5.01, 95% credible interval (95% Crl) −10.73 to 0.86 in the Alzheimer's Disease Assessment Scale‐Cognitive Subscale; MD 9.61, 95% Crl 2.29 to 16.97 in the Severe Impairment Battery), global assessment (MD −2.88, 95% Crl −6.04 to 0.40), daily activities (MD 13.06, 95% Crl −34.04 to 58.92), and neuropsychiatric symptoms (MD −6.84, 95% Crl −10.62 to –2.82) compared with placebo. Memantine was more acceptable than placebo (MD 0.93, 95% Crl 0.69 to 1.22).ConclusionsMemantine plus donepezil showed superior outcomes for cognition, global assessment, daily activities, and neuropsychiatric symptoms, but lower acceptability than monotherapy and placebo. Combination therapy may be more cost‐effective, because memantine slows the progression of AD.

Comparative effectiveness of dopamine agonists and monoamine oxidase type-B inhibitors for Parkinson\u2019s disease: a multiple treatment comparison meta-analysis

PurposeTo investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson’s disease.MethodsWe performed a systematic literature search identifying randomized controlled trials investigating 4 dopamine agonists (cabergoline, pramipexole, ropinirole, rotigotine) and 3 MAO-B inhibitors (selegiline, rasagiline, safinamide) for Parkinson’s disease. We extracted and pooled data from included clinical trials in a joint model allowing both direct and indirect comparison of the seven drugs. We considered dopamine agonists and MAO-B inhibitors given as monotherapy or in combination with levodopa. Selected endpoints were change in the Unified Parkinson’s Disease Rating Scale (UPDRS) score, serious adverse events and withdrawals. We estimated the relative effectiveness of each dopamine agonist and MAO-B inhibitor versus comparator drug.ResultsAltogether, 79 publications were included in the analysis. We found all the investigated drugs to be effective compared with placebo when given as monotherapy except safinamide. When considering combination treatment, the estimated relative effects of selegiline, pramipexole, ropinirole, rotigotine, cabergoline, rasagiline and safinamide were 2.316 (1.819, 2.951), 2.091 (1.889, 2.317), 2.037 (1.804, 2.294), 1.912 (1.716, 2.129), 1.664 (1.113, 2.418), 1.584 (1.379, 1.820) and 1.179 (1.031, 1.352), respectively, compared with joint placebo and levodopa treatment.ConclusionsDopamine agonists were found to be effective as treatment for Parkinson’s disease, both when given as monotherapy and in combination with levodopa. Selegiline and rasagiline were also found to be effective for treating Parkinson’s disease, and selegiline was the best option in combination with levodopa among all the drugs investigated.

Management of post-traumatic stress disorder: A protocol for a multiple treatment comparison meta-analysis of randomized controlled trials.

Background:Most systematic reviews have explored the efficacy of treatments on symptoms associated with post-traumatic stress disorder (PTSD), which is a chronic and often disabling condition. Previous network meta-analysis (NMA) had limitations such as focusing on pharmacological or psychotherapies. Our review is aims to explore the relative effectiveness of both pharmacological and psychotherapies and we will establish the differential efficacy of interventions for PTSD in consideration of both symptom reduction and functional recovery.Methods:We will conduct a network meta-analysis of randomized controlled trials evaluating treatment interventions for PTSD. We will systematically search Medline, PILOT, Embase, CINHAL, AMED, Psychinfo, Health Star, DARE and CENTRAL to identify trials that: (1) enroll adult patients with PTSD, and (2) randomize them to alternative interventions or an intervention and a placebo/sham arm. Independent reviewers will screen trials for eligibility, assess risk of bias using a modified Cochrane instrument, and extract data. Our outcomes of interest include PTSD symptom reduction, quality of life, functional recovery, social and occupational impairment, return to work and all-cause drop outs.Results:We will conduct frequentist random-effects network meta-analysis to assess relative effects of competing interventions. We will use a priori hypotheses to explore heterogeneity between studies, and assess the certainty of evidence using the GRADE approach.Conclusion:This network meta-analysis will determine the comparative effectiveness of therapeutic options for PTSD on both symptom reduction and functional recovery. Our results will be helpful to clinicians and patients with PTSD, by providing a high-quality evidence synthesis to guide shared-care decision making.

Management of acute musculoskeletal pain (excluding low back pain): protocol for a systematic review and network meta-analysis of randomised trials

IntroductionAcute, non-low back-related musculoskeletal pain is common and associated with significant socioeconomic costs. No review has evaluated all interventional studies for acute musculoskeletal pain, which limits attempts to make inferences...

Medical and endovascular treatments of symptomatic intracranial stenosis. A Bayesian network meta-analysis

Intracranial stenosis is a well-established stroke risk factor with an increase of stroke recurrence or TIA up to 12.6% at 1 year. Treatments are different: medical and endovascular. We performed a multiple treatment comparison analysis to detect the best treatment in reducing the risk of stroke recurrence. We searched in Medline, Embase, Cochrane Central Register of Controlled Trials databases between 1979 and October 2017. Inclusion criteria were prospective randomized trials that evaluated patients with TIA or stroke due to intracranial stenosis and treated with different medical therapies and/or endovascular procedures. Primary endpoint was the recurrence of TIA or stroke in the territory of intracranial stenosis, while secondary endpoint was represented by any stroke or vascular death. Multiple treatment comparison meta-analysis based on a Bayesian fixed and random effects Poisson model was performed. Seven trials were included with a total of 1337 patients. At multiple treatment comparison, no significant differences between treatments were observed for both primary (median fixed effect standard OR: 0.40; 95%CI: 0.02–1.07) and secondary endpoints (median random effect standard OR: 1.17; 95%CI: 0.32–1.92). Treatment with aspirin alone ranked with high values both for primary and secondary endpoints (surface under the cumulative ranking curve of 70% and 82%, respectively).In patients with symptomatic intracranial stenosis, no differences between treatments were observed. However, aspirin alone was more effective than stenting in the reduction of TIA or stroke recurrences, with a better safety profile than oral anticoagulants.

Aproximación a los metanálisis de comparación de múltiples tratamientos: una revisión de la literatura

Multiple treatment comparison meta-analyses are systematic reviews that allow to make direct or indirect comparisons of different interventions from the data collection results of randomized clinical trials, grouping them in a common outcome or conglomerate which is expressed quantitatively. Other names given are network meta-analyses, or mixed treatment comparison meta-analyses or indirect meta-analyses. The use of the comparison of several treatments allows a greater estimation of the intervention effect. This is a guide for the physician to make more accurate decisions and to apply better care criteria to their patients. This literature review should help the reader to perform an organized and adequate critical reading (according to the JAMA recommendations) of the multiple treatment comparison meta-analyses. The article is addressed to authors and editors, and it contains information on how this type of studies should be interpreted and communicated.

444P Overall survival (OS) by EGFR mutation status and subtypes (Deletion 19/L858R) for first-line therapies with maintenance regimens in advanced non-small-cell lung cancer (NSCLC): a Bayesian multiple treatment comparison (MTC) meta-analysis

444P Overall survival (OS) by EGFR mutation status and subtypes (Deletion 19/L858R) for first-line therapies with maintenance regimens in advanced non-small-cell lung cancer (NSCLC): a Bayesian multiple treatment comparison (MTC) meta-analysis

Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis.

Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis which, though usually self-limiting, may persist or progress without treatment. To compare the relative effectiveness of antiviral agents, interferon, and corneal debridement in the treatment of HSV epithelial keratitis. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 12), PubMed (January 1946 to 31 December 2014), EMBASE (January 1980 to 31 December 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to 31 December 2014), System for Information on Grey Literature in Europe (OpenGrey) (January 1995 to 31 December 2014), BIOSIS (January 1926 to 5 May 2014), Scopus (January 1966 to 31 December 2014), Japan Science and Technology Institute (J-Global) (January 1975 to 31 December 2014), China National Knowledge Infrastructure (CNKI) (January 1979 to 31 December 2014), British Library's Electronic Table of Contents (Zetoc) (January 1993 to 7 May 2014). We looked for trials listed on the the metaRegister of Controlled Trials (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en), Chinese Clinical Trial Registry, the U.S. Food and Drug Administration (FDA) (www.fda.gov/), National Institute for Health and Clinical Excellence (NICE) (www. nhs.uk) and the European Medicines Agency (EMA) (www.ema.europa.eu/ema/) as of 31 December 2014. There were no language or date restrictions in the search for trials. We also culled literature digests and conference proceedings as of 15 April 2014. There were no language or date restrictions in the search for trials. Randomised and quasi-randomised trials of HSV dendritic or geographic epithelial keratitis were included that reported the proportion of eyes healed at one week, two weeks, or both after enrolment. We tabulated data on study characteristics, risk of bias, and outcomes and used direct comparisons to estimate a risk ratio (RR) and, when feasible, a hazard ratio (HR) with a 95% confidence interval (CI). Heterogeneity was assessed by an inconsistency index. A multiple treatment comparison meta-analysis consolidated direct and indirect comparisons of relative healing at 14 days. One hundred thirty-seven studies involving 8333 eyes met the inclusion criteria. Placebo-controlled studies were heterogeneous in comparison with idoxuridine (RR 1.74; 95% CI 1.03 to 2.91) and few in number for vidarabine (RR 1.81; 95% CI 1.09 to 3.01), interferon (RR 1.32; 95% CI 1.06 to 1.64), and debridement. Vidarabine (RR 1.13; 95% CI 1.02 to 1.25), trifluridine (RR 1.30; 95% CI 1.18 to 1.43), acyclovir (RR 1.23; 95% CI 1.14 to 1.34), and brivudine (RR 1.34; 95% CI 1.18 to 1.51) were more effective than idoxuridine. Trifluridine (RR 1.17; 95% CI 1.03 to 1.32) and acyclovir (RR 1.11; 95% CI 1.03 to 1.19) were more effective than vidarabine. No significant differences in healing emerged among trifluridine, acyclovir, brivudine, and foscarnet although few studies compared brivudine or foscarnet with other antivirals. Any potential advantage of ganciclovir compared to acyclovir was mitigated by study heterogeneity and possible publication bias. Only one study evaluated the joint use of two topical antivirals. In a limited number of studies, oral acyclovir (RR 0.92; 95% CI 0.79 to 1.07) or the combination of oral acyclovir with a topical antiviral (RR 1.36; 95% CI 0.68 to 2.74) appeared as effective as a single topical antiviral agent. Compared to topical antiviral monotherapy, the combination of an antiviral with either interferon or debridement had inconsistent effects on expediting healing and improving outcome. Placebo-controlled studies of HSV epithelial keratitis are limited to superseded interventions. Trifluridine and acyclovir are more effective than idoxuridine or vidarabine and similar in therapeutic effectiveness. Brivudine and foscarnet do not substantially differ in effectiveness from trifluridine or acyclovir. Ganciclovir is at least as effective as acyclovir. The addition of interferon to a nucleoside antiviral agent and the combination of debridement with antiviral treatment need to be further assessed to substantiate any possible advantage in healing.

Management of chronic neuropathic pain: a protocol for a multiple treatment comparison meta-analysis of randomised controlled trials

IntroductionChronic neuropathic pain is associated with reduced health-related quality of life and substantial socioeconomic costs. Current research addressing management of chronic neuropathic pain is limited. No review has evaluated all...

Comment on Garas et al., “Which Hemostatic Device in Thyroid Surgery? A Network Meta-Analysis of Surgical Technologies”

Dear Editor: We disagree with the conclusions of the recent article by Garas et al. (1) on permanent recurrent laryngeal nerve injury (p-RLN) following thyroidectomy with different energy-based technologies using network meta-analysis. Since network meta-analysis extends the number and type of studies being combined, there is potential for combining studies that are not adequately similar, possibly leading to erroneous conclusions (2). One of the fundamental requirements of network meta-analysis to improve accuracy is that they include only very similar studies, under similar conditions, with similar patient populations, and clearly defined endpoints. Evaluation of the articles included by Garas et al. shows they have included a study using Starion (3), an electrocautery device, in the Harmonic arm and a nonrandomized trial in the Harmonic arm (4). Furthermore, not all devices are similar in a given treatment arm nor are the procedures performed, patients studied, or diseases treated similar. For example, within the Ultrasound group, devices used include CS-14C, Wave, and Focus, and within the LigaSure arm, Precise, Small Jaw, and unstated devices. Many of the studies in the Harmonic and LigaSure treatment arms combine the use of monopolar and/or bipolar electrosurgery. The disease state and procedures performed vary significantly from total thyroidectomy with central neck dissection to partial thyroidectomy to videoscopic thyroidectomy and from cancer to Graves' disease to multinodular goiter. Thus, to conclude that the populations are suitably similar and satisfactory for comparison through network meta-analysis is erroneous and raises serious questions regarding the conclusions reached. The conclusions of network meta-analysis performed by Garas et al. are that ultrasonic devices and advanced bipolar devices provide less blood loss, less drain output, shorter operative time, and shorter hospital stay compared to the conventional methods of clamp-cut-and-tie (CCT) thyroidectomy, but that the rate of p-RLN paralysis is significantly higher for ultrasonic devices and LigaSure devices compared to CCT. How they came to that conclusion is not evident from the studies they reviewed. When the total actual number of individual cases of p-RLN paralysis reported in the randomized control trials used by Garas et al. (excluding the two studies noted above) are totaled, there were 2/992 cases (0.2%) of p-RLN paralysis for CCT versus 1/1006 (0.1%) for Harmonic in RCTs where both are compared (and 1/266 cases [0.4%] of p-RLN paralysis for CCT vs. 1/266 [0.4%] for LigaSure in studies where CCT and LigaSure were compared directly). Consistent with the absence of a difference in p-RLN paralysis is the I2 value of 0.00% for p-RLN paralysis reported by the authors in Table 2. This statistic is a measure of heterogeneity, and values below 25% represent low heterogeneity. A value of 0.00% suggests no heterogeneity or variability across the studies and is consistent with the finding that the vast majority of studies reported no p-RLN paralysis. What is particularly troubling is that the authors state that the results of this network meta-analysis suggest that the superior safety profile of the CCT technique can contribute to future international thyroidectomy guidelines because they believe there is relative risk of permanent RLN. Based on direct comparison methods using the randomized clinical trials identified in the Garas et al. study, one would logically conclude that there is no increase in the risk of recurrent laryngeal nerve injury when Harmonic or LigaSure devices are used and that the use of these energies will provide less blood loss, less drain output, shorter operative time, and shorter hospital stay compared to the conventional methods of CCT thyroidectomy, all these being of significant benefit to patients, hospitals, and societies.

PRM13 - Easing Decision-Making by Expanding Methods of Multiple Treatment Comparison Meta-Analysis – Incorporating Non-Comparative Studies Via Informative Priors

PRM13 - Easing Decision-Making by Expanding Methods of Multiple Treatment Comparison Meta-Analysis – Incorporating Non-Comparative Studies Via Informative Priors

Comparative efficacy of triptans for the abortive treatment of migraine: A multiple treatment comparison meta-analysis

Migraine is the most common neurological condition in developed countries. The abortive treatment of migraine attacks is important both for quality of life and costs associated with illness. Triptans, serotonin 5-HT1B/1D receptor agonists, effectively relieve the pain, disability, and associated symptoms of migraine while improving health-related quality of life. Although a number of direct head-to-head triptan comparisons have been made, data for all possible permutations are not available, and unlikely to ever be so, although in clinical practice such information would be useful. We aimed to determine the relative efficacy of all available triptans to abort migraine headache among patients with previous adequate response to migraine treatments. We included only double-blinded randomized clinical trials comparing triptans to either placebo or another triptan. Our primary outcomes were pain-free response at two hours and 24-hour sustained pain-free response, and our secondary outcomes were headache response at two hours and 24-hour sustained headache response. We used Bayesian multiple treatment comparison meta-analyses of seven triptans used in adult patients to abort migraine attacks. We applied a random-effects analysis with meta-regression adjusting for dose. Results are reported as odds ratios with 95% credible intervals. We included data from 74 randomized clinical trials. All triptans were significantly superior to placebo for all outcomes, with the exception of naratriptan for 24-hour sustained pain-free response. Eletriptan consistently yielded the highest treatment effect estimates. For the two-hour endpoints, eletriptan was statistically significantly superior to sumatriptan, almotriptan, naratriptan, and frovatriptan for at least one of the two outcomes. Rizatriptan yielded the second highest treatment effects followed by zolmitriptan. For the 24-hour endpoints, eletriptan was statistically significantly superior to sumatriptan, rizatriptan, almotriptan, and naratriptan for at least one of the two outcomes. Frovatriptan data were not available at that endpoint. Further, the probability that eletriptan is the most likely of all triptans to produce a favorable outcome was 68% for pain-free response at two hours, and 54% for 24-hour sustained pain-free response. Triptans appear to offer differing treatment effects. In the populations studied eletriptan was most likely to produce pain-free responses that were sustained.

Interpreting discordant indirect and multiple treatment comparison meta-analyses: an evaluation of direct acting antivirals for chronic hepatitis C infection

Indirect treatment comparison (ITC) and multiple treatment comparison (MTC) meta-analyses are increasingly being used to estimate the comparative effectiveness of interventions when head-to-head data do not exist. ITC meta-analyses can be conducted using simple methodology to compare two interventions. MTC meta-analyses can be conducted using more complex methodology, often employing Bayesian approaches, to compare multiple interventions. As the number of ITC and MTC meta-analyses increase, it is common to find multiple analyses evaluating the same interventions in similar therapeutic areas. Depending on the choice of the methodological approach, the conclusions about relative treatment efficacy may differ. Such situations create uncertainty for decision makers. An illustration of this is provided by four ITC and MTC meta-analyses assessing the efficacy of boceprevir and telaprevir for chronic hepatitis C virus infection. This paper examines why these evaluations provide discordant results by examining specific methodological issues that can strengthen or weaken inferences.

FRI0431 Why the findings of published rheumatoid arthritis multiple treatment comparisons are so different – an overview of recurrent methodological shortcomings

BackgroundSeveral multiple treatment comparison meta-analysis (MTCs) have been conducted over the past years to establish comparative effectiveness between biologic disease modifying anti rheumatic drugs (bDMARDs). Unfortunately, major inconsistencies exist in...

PRM75 - Modelling drug class effects in bayesian multiple treatment comparison meta-analysis: Applications in early and advanced parkinson's disease

PRM75 - Modelling drug class effects in bayesian multiple treatment comparison meta-analysis: Applications in early and advanced parkinson's disease

PRM78 - Impact of multiple treatment comparison meta-analysis on value of information evaluations: a case study of pharmacotherapies for chronic obstructive pulmonary diseases

PRM78 - Impact of multiple treatment comparison meta-analysis on value of information evaluations: a case study of pharmacotherapies for chronic obstructive pulmonary diseases

Direct-acting antiviral therapies for hepatitis C genotype 1 infection: a multiple treatment comparison meta-analysis

Background: New direct-acting antiviral agents for hepatitis C genotype 1 infection, boceprevir and telaprevir, offer enhanced sustained virologic response (SVR) among both treatment-naïve and treatment-experienced patients.Aim: To determine the relative efficacy of the new direct-acting antiviral agents by applying a multiple treatment comparison meta-analysis.Design: We included published Phase II and III randomized controlled trials evaluating head-to-head comparisons between boceprevir, telaprevir, peg-interferon alpha-2a with ribavirin and peg-interferon alpha-2b with ribavirin in hepatitis C genotype 1 patients. We applied Bayesian multiple treatment comparison meta-analysis.Results: We included data from four boceprevir, three telaprevir and six peg-interferon alpha-2a plus ribavirin vs. peg-interferon alpha-2b plus ribavirin randomized controlled trials. Both boceprevir and telaprevir offer statistically superior outcomes for SVR, relapse and discontinuation due to adverse events than either peg-interferons among both treatment-naïve and treatment-experienced patients. Among treatment-naïve patients, clinical outcomes were similar for boceprevir and telaprevir, for SVR [odds ratio (OR) 0.90, 95% credible interval (95% CrI) 0.41–1.91] and for relapse (OR 1.09, 95% CrI 0.19–4.84). Similarly, among treatment-experienced patients, clinical outcomes were similar for boceprevir and telaprevir and for SVR (OR 1.45, 95% CrI 0.70–3.08) and for relapse (OR 0.35, 95% CrI 0.13–1.02). For treatment-naïve patients receiving standard-duration therapy, telaprevir yielded lower rates of anemia and neutropenia, but higher rates of rash and pruritus. For treatment-experience patients, all adverse event rates were higher with telaprevir.Discussion: Boceprevir and telaprevir exhibit similar effects among hepatitis C genotype 1 treatment-naïve and treatment-experienced patients.

CL3 Calibrating Bayesian Multiple Treatment Comparison Meta-Analysis With Multiple Cost-Effectiveness Acceptability Curves

CL3 Calibrating Bayesian Multiple Treatment Comparison Meta-Analysis With Multiple Cost-Effectiveness Acceptability Curves

Why the findings of published multiple treatment comparison meta-analyses of biologic treatments for rheumatoid arthritis are different: an overview of recurrent methodological shortcomings

ObjectivesTo evaluate the quality of published multiple treatment comparison (MTC) meta-analyses on biologic disease modifying antirheumatic drugs (bDMARDs) for rheumatoid arthritis (RA), and to identify methodological issues that can explain...