Critical Appraisal of Published Indirect Comparisons and Network Meta-Analyses of Competing Interventions for Multiple Myeloma

Abstract

Objectives: In the field of relapsed or refractory multiple myeloma (RRMM), between-trial or indirect comparisons are required to estimate relative treatment effects between competing interventions based on the available evidence. Two approaches are frequently used in RRMM: network meta-analysis (NMA) and unanchored matching-adjusted indirect comparison (MAIC). The objective of the current study was to evaluate the relevance and credibility of published NMA and unanchored MAIC studies aiming to estimate the comparative efficacy of treatment options for RRMM.Methods: Twelve relevant studies were identified in the published literature (n = 7) and from health technology assessment agencies (n = 5). Data from trials were extracted to identify between-trial differences that may have biased results. Credibility of the performed analyses and relevance of the research questions were critically appraised using the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) checklist and feedback based on consultations with clinical experts. Results:The identified studies concerned NMAs of randomized controlled trials (RCTs; n = 7), unanchored MAICs (n = 4), or both types of analyses (n = 1). According to clinical expert consultation, the majority of the identified NMAs did not consider differences in prior therapies or treatment duration across the RCTs included in the analyses, thereby compromising the relevance. Conclusion:Based on the results and feedback from clinicians, the majority of NMAs did not consider prior treatment history or treatment duration, which resulted in nonrelevant comparisons. Furthermore, it may have compromised the credibility of the estimates owing to differences in effect-modifiers between the different trials. Pairwise comparisons by means of unanchored MAICs require clear justification given the reliance on non-randomized comparisons.

Network meta‐analyses in psoriasis: overview and critical discussion

“…A rising number of NMAs has also been used in current Cochrane reviews 9 . However, a surprisingly low number of meta‐studies investigating the quality and outcomes of different NMAs for one indication and type of intervention has been published 10,11 …”

“…9 However, a surprisingly low number of meta-studies investigating the quality and outcomes of different NMAs for one indication and type of intervention has been published. 10,11 Also for the drug treatment of psoriasis, a large number of NMA have been conducted, which differ in the spectrum of drugs used, the studies included and the results gained. No reviews on these NMAs were, however, found in the literature.…”

Matching adjusted indirect comparisons of efficacy outcomes for idecabtagene vicleucel (ide-cel, bb2121) versus selinexor + dexamethasone and belantamab mafodotin in relapsed and refractory multiple myeloma

“…Prognostic factors for inclusion in the MAIC were driven by a literature review of previous ITC studies in RRMM [19,20] and recommendations from clinical experts. The most relevant prognostic factors that differed between the studies were included as covariates in the propensity model: proportion of patients with high-risk cytogenetics; and (6) the proportion of patients with extramedullary disease (DREAMM-2 only).…”

Effect modification in network meta-analyses for relapsed/refractory multiple myeloma: systematic review and meta-analysis

“…The use of NMA in RRMM has been criticised13 on the basis that variables such as refractory status and LOT are effect modifiers, with the implication that NMAs that do not account for effect modification may be untrustworthy. This article was motivated by a health technology assessment (HTA) we conducted on treatments for RRMM that was commissioned via Norway’s National System for Managed Introduction of New Health Technologies within the Specialist Health Service (‘Nye Metoder’) 14.…”