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Challenges in conducting fractional polynomial and standard parametric network meta-analyses of immune checkpoint inhibitors for first-line advanced renal cell carcinoma
Aim
Network meta-analyses (NMAs) increasingly feature time-varying hazards to account for non-proportional hazards between different drug classes. This paper outlines an algorithm for selecting clinically plausible fractional polynomial NMA models.
Methods
The NMA of four immune checkpoint inhibitors (ICIs) + tyrosine kinase inhibitors (TKIs) and one TKI therapy for renal cell carcinoma (RCC) served as case study. Overall survival (OS) and progression free survival (PFS) data were reconstructed from the literature, 46 models were fitted. The algorithm entailed a-priori face validity criteria for survival and hazards, based on clinical expert input, and predictive accuracy against trial data. Selected models were compared with statistically best-fitting models.
Results
Three valid PFS and two OS models were identified. All models overestimated PFS, the OS model featured crossing ICI + TKI versus TKI curves as per expert opinion. Conventionally selected models showed implausible survival.
Conclusion
The selection algorithm considering face validity, predictive accuracy, and expert opinion improved the clinical plausibility of first-line RCC survival models.
Authors
S Petersohn, B McGregor, SL Klijn, JR May, F Ejzykowicz, M Kurt, M Dyer, B Malcolm, S Branchoux, K Nickel, S George, S Kroep
Journal
Journal of comparative effectiveness research
Therapeutic Area
Oncology
Center of Excellence
Health Economic Modeling & Meta-analysis
Year
2023
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