A review of methods for comparing treatments evaluated in studies that form disconnected networks of evidence

Stevens, John; Fletcher, Christine; Downey, Gerald; Sutton, Anthea

doi:10.1002/jrsm.1278

Cited by 24 publications

(24 citation statements)

References 67 publications

(140 reference statements)

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“…Since the different procedures for EMD application did not form connected networks for EMD or EMD + graft, the standard contrast-based network meta-analysis (Lu and Ades 2006) could not be undertaken. Instead, the baseline model was used: an alternative approach to multiple-treatment comparisons that can be used to compare treatments of a disconnected network (Stevens et al 2018). Given treatment A as the global reference treatment in the network comparing treatments A to K , the baseline model can be written as follows:…”

Section: Methodsmentioning

confidence: 99%

Effect of Flap Design for Enamel Matrix Derivative Application in Intraosseous Defects

Trombelli

Simonelli

Quaranta

et al. 2020

JDR Clinical & Translational Research

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Objective: To systematically review the literature addressing the focused question: What is the effectiveness of different surgical and nonsurgical procedures combined with enamel matrix derivative (EMD) on clinical, radiographic, and patient-centered outcomes in intraosseous defects? Methods: Electronic (Medline, Scopus, and Cochrane databases) and hand literature searches were performed for studies including at least 1 treatment arm where EMD had been applied according to 1 of the following procedures: modified Widman flap; papilla preservation variants (PPVs), including papilla preservation technique, modified papilla preservation technique, and simplified papilla preservation technique; minimally invasive variants, including minimally invasive surgical approach and minimally invasive surgical technique; single-flap variants (SFVs), including single-flap approach and modified minimally invasive surgical technique; or nonsurgical application (flapless approach). Data from 42 selected articles were used to perform a network meta-analysis, and a hierarchy of surgical and nonsurgical applications of EMD was built separately for EMD and EMD + graft based on 6- to 12-mo clinical and radiographic outcomes. Results: Among surgical approaches, EMD was associated with best regenerative outcomes when applied through SFVs, with a mean clinical attachment level gain of 3.93 mm and a reduction in the intrabony component of the defect of 3.35 mm. For EMD + graft, limited differences in regenerative outcomes were observed among surgical procedures. PPVs were associated with the highest residual probing depth for EMD (4.08 mm) and EMD + graft (4.32 mm). Conclusions: In the treatment of periodontal intraosseous defects, 1) SFVs appear to optimize the regenerative outcomes of EMD; 2) substantial regenerative outcomes can be obtained with SFVs and conservative double flaps (i.e., PPVs and minimally invasive variants) when EMD is combined with a graft; and 3) residual probing depth was higher following PPVs for EMD and EMD + graft. Knowledge Transfer Statement: The results of the present systematic review and meta-analysis can be used by clinicians to identify the most effective surgical or nonsurgical procedure to treat an intraosseous defect with EMD or EMD + graft. The main findings indicate that when EMD application is indicated, surgical access based on a single flap seems the most appropriate to optimize clinical outcomes. The application of EMD + graft can be effectively combined with single flaps and conservative double flaps.

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Section: Methodsmentioning

confidence: 99%

Effect of Flap Design for Enamel Matrix Derivative Application in Intraosseous Defects

Trombelli

Simonelli

Quaranta

et al. 2020

JDR Clinical & Translational Research

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“…The NICE Decision Support Unit has published formal submission guidelines for population adjustment with limited access to IPD 6,15 . Various reviews 6,15,16,17 define the relevant terminology and assess the theoretical validity of these methodologies but do not express a preference. Questions remain about the correct application of the methods and their validity in HTA 6,15,18 .…”

Section: Introductionmentioning

confidence: 99%

Methods for population adjustment with limited access to individual patient data: A review and simulation study

Remiro‐Azócar

Heath

Baio

2021

Research Synthesis Methods

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Population‐adjusted indirect comparisons estimate treatment effects when access to individual patient data is limited and there are cross‐trial differences in effect modifiers. Popular methods include matching‐adjusted indirect comparison (MAIC) and simulated treatment comparison (STC). There is limited formal evaluation of these methods and whether they can be used to accurately compare treatments. Thus, we undertake a comprehensive simulation study to compare standard unadjusted indirect comparisons, MAIC and STC across 162 scenarios. This simulation study assumes that the trials are investigating survival outcomes and measure continuous covariates, with the log hazard ratio as the measure of effect. MAIC yields unbiased treatment effect estimates under no failures of assumptions. The typical usage of STC produces bias because it targets a conditional treatment effect where the target estimand should be a marginal treatment effect. The incompatibility of estimates in the indirect comparison leads to bias as the measure of effect is non‐collapsible. Standard indirect comparisons are systematically biased, particularly under stronger covariate imbalance and interaction effects. Standard errors and coverage rates are often valid in MAIC but the robust sandwich variance estimator underestimates variability where effective sample sizes are small. Interval estimates for the standard indirect comparison are too narrow and STC suffers from bias‐induced undercoverage. MAIC provides the most accurate estimates and, with lower degrees of covariate overlap, its bias reduction outweighs the loss in precision under no failures of assumptions. An important future objective is the development of an alternative formulation to STC that targets a marginal treatment effect.

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“…Reweighting of RCT results to reflect real life 31,32 Using RWD (e.g., from disease registries), to "reweight" RCT results may improve external validity and generalizability of RCT results.…”

Section: Methodology Development By Designmentioning

confidence: 99%

Are Novel, Nonrandomized Analytic Methods Fit for Decision Making? The Need for Prospective, Controlled, and Transparent Validation

Eichler

König

Arlett

et al. 2019

Clin Pharma and Therapeutics

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Real‐world data and patient‐level data from completed randomized controlled trials are becoming available for secondary analysis on an unprecedented scale. A range of novel methodologies and study designs have been proposed for their analysis or combination. However, to make novel analytical methods acceptable for regulators and other decision makers will require their testing and validation in broadly the same way one would evaluate a new drug: prospectively, well‐controlled, and according to a pre‐agreed plan. From a European regulators' perspective, the established methods qualification advice procedure with active participation of patient groups and other decision makers is an efficient and transparent platform for the development and validation of novel study designs.

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A review of methods for comparing treatments evaluated in studies that form disconnected networks of evidence

Cited by 24 publications

References 67 publications

Effect of Flap Design for Enamel Matrix Derivative Application in Intraosseous Defects

Effect of Flap Design for Enamel Matrix Derivative Application in Intraosseous Defects

Methods for population adjustment with limited access to individual patient data: A review and simulation study

Are Novel, Nonrandomized Analytic Methods Fit for Decision Making? The Need for Prospective, Controlled, and Transparent Validation

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