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Updated: Dec 23, 2025
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Critical Appraisal of Published Indirect Comparisons and Network Meta-Analyses of Competing Interventions for
Shannon Cope1, Kabirraaj Toor1, Evan Popoff1
1Precision Health Economics and Outcomes Research, Vancouver, BC, Canada.
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.
Insights
Network meta-analyses (NMA) and unanchored matching-adjusted indirect comparisons (MAIC) in relapsed or refractory multiple myeloma (RRMM) often lack relevance and credibility. Studies frequently fail to account for crucial differences in prior therapies and treatment duration, compromising comparative efficacy estimates.
Area of Science:
- Hematology
- Clinical Epidemiology
- Pharmacoeconomics
Background:
- Relapsed or refractory multiple myeloma (RRMM) necessitates indirect treatment comparisons due to limited head-to-head trials.
- Network meta-analysis (NMA) and unanchored matching-adjusted indirect comparison (MAIC) are common methods for estimating relative treatment effects in RRMM.
Purpose of the Study:
- To critically evaluate the relevance and credibility of published NMA and unanchored MAIC studies in RRMM.
- To assess the comparative efficacy of different treatment options for RRMM using indirect comparison methodologies.
Main Methods:
- A systematic literature search identified 12 relevant studies (7 NMAs, 4 unanchored MAICs, 1 combined).
- Data extraction focused on identifying potential between-trial biases.
- Credibility and relevance were appraised using the ISPOR checklist and clinical expert consultations.
Main Results:
- Most identified NMAs (n=7) did not adequately consider variations in prior therapies or treatment durations across included randomized controlled trials (RCTs).
- This lack of consideration compromised the relevance of the comparative efficacy estimates.
- Unanchored MAICs (n=4) require strong justification due to their reliance on non-randomized comparisons.
Conclusions:
- The majority of NMAs in RRMM are not relevant for estimating comparative efficacy due to failure to account for prior treatment history and duration.
- Differences in effect modifiers between trials can compromise the credibility of NMA estimates.
- Unanchored MAICs present challenges regarding credibility and require careful justification.
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