A process for assessing the feasibility of a network meta-analysis: a case study of everolimus in combination with hormonal therapy versus chemotherapy for advanced breast cancer

Abstract

BackgroundThe aim of this study is to outline a general process for assessing the feasibility of performing a valid network meta-analysis (NMA) of randomized controlled trials (RCTs) to synthesize direct and indirect evidence for alternative treatments for a specific disease population.MethodsSeveral steps to assess the feasibility of an NMA are proposed based on existing recommendations. Next, a case study is used to illustrate this NMA feasibility assessment process in order to compare everolimus in combination with hormonal therapy to alternative chemotherapies in terms of progression-free survival for women with advanced breast cancer.ResultsA general process for assessing the feasibility of an NMA is outlined that incorporates explicit steps to visualize the heterogeneity in terms of treatment and outcome characteristics (Part A) as well as the study and patient characteristics (Part B). Additionally, steps are performed to illustrate differences within and across different types of direct comparisons in terms of baseline risk (Part C) and observed treatment effects (Part D) since there is a risk that the treatment effect modifiers identified may not explain the observed heterogeneity or inconsistency in the results due to unexpected, unreported or unmeasured differences. Depending on the data available, alternative approaches are suggested: list assumptions, perform a meta-regression analysis, subgroup analysis, sensitivity analyses, or summarize why an NMA is not feasible.ConclusionsThe process outlined to assess the feasibility of an NMA provides a stepwise framework that will help to ensure that the underlying assumptions are systematically explored and that the risks (and benefits) of pooling and indirectly comparing treatment effects from RCTs for a particular research question are transparent.

A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer

“…Based on the report recently published by Cope et al [23] about the feasibility of performing NMA of RCTs to synthesize direct and indirect Assuming that PFS is a clinically important measure of drug efficacy [24]; in our analysis, the EXE/EVE combination was at least as efficacious as any chemotherapy given alone or in combination. This observation is reproduced in the NMA of HR for PFS/TTP and in the NMA for RR.…”

Thirty Years of Evidence on the Efficacy of Drug Treatments for Chronic Heart Failure With Reduced Ejection Fraction

“…The feasibility of conducting a valid NMA was assessed using the process described by Cope et al, 14 which involves an assessment of clinical heterogeneity in terms of the characteristics of the treatments, outcomes, study design, and patients and a comparison of differences within and across treatments in terms of baseline risk and the observed treatment effects. The following factors were identified a priori as potential treatment effect modifiers: use of concomitant treatments (eg, digoxin), duration of follow-up, year of publication, severity of included patients (eg, New York Heart Association class and left ventricular ejection fraction), heart failure etiology (eg, ischemic versus nonischemic), and history of myocardial infarction.…”

Comparing antibiotic treatment for leptospirosis using network meta-analysis: a tutorial

“…This exception might be due to the ethical issues associated with withholding treatment for a fatal illness or possibly due to the lack of sponsorship by industry. In the absence of trials involving a direct comparison of interventions, an indirect comparison can provide valuable evidence for the relative treatment effects between competing interventions [17, 18]. If we want to make best use of the evidence, it is necessary to analyse all the evidence jointly [19].…”