BACKGROUND: We provide an overview of Bayesian estimation, hypothesis testing, and model-averaging and illustrate how they benefit parametric survival analysis. We contrast the Bayesian framework to the currently dominant frequentist approach and highlight advantages, such as seamless incorporation of historical data, continuous monitoring of evidence, and incorporating uncertainty about the true data generating process. METHODS: We illustrate the application of the outlined Bayesian approaches on an example data set, retrospective re-analyzing a colon cancer trial. We assess the performance of Bayesian parametric survival analysis and maximum likelihood survival models with AIC/BIC model selection in fixed-n and sequential designs with a simulation study. RESULTS: In the retrospective re-analysis of the example data set, the Bayesian framework provided evidence for the absence of a positive treatment effect of adding Cetuximab to FOLFOX6 regimen on disease-free survival in patients with resected stage III colon cancer. Furthermore, the Bayesian sequential analysis would have terminated the trial 10.3 months earlier than the standard frequentist analysis. In a simulation study with sequential designs, the Bayesian framework on average reached a decision in almost half the time required by the frequentist counterparts, while maintaining the same power, and an appropriate false-positive rate. Under model misspecification, the Bayesian framework resulted in higher false-negative rate compared to the frequentist counterparts, which resulted in a higher proportion of undecided trials. In fixed-n designs, the Bayesian framework showed slightly higher power, slightly elevated error rates, and lower bias and RMSE when estimating treatment effects in small samples. We found no noticeable differences for survival predictions. We have made the analytic approach readily available to other researchers in the RoBSA R package. CONCLUSIONS: The outlined Bayesian framework provides several benefits when applied to parametric survival analyses. It uses data more efficiently, is capable of considerably shortening the length of clinical trials, and provides a richer set of inferences.

• Klíčová slova
• Bayes factor, Bayesian, Historical data, Model-averaging, Survival analysis,
• MeSH
• Bayesova věta MeSH
• lidé MeSH
• nádory tračníku * farmakoterapie   MeSH
• přežití bez známek nemoci MeSH
• retrospektivní studie MeSH
• výzkumný projekt * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: To predict the real-world (RW) cost-effectiveness of carfilzomib in combination with lenalidomide and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in relapsed multiple myeloma (MM) patients after one to three prior therapies. METHODS: A partitioned survival model that included three health states (progression-free, progressed disease and death) was built. Progression-free survival (PFS), overall survival (OS) and time to discontinuation (TTD) data for the Rd arm were derived using the Registry of Monoclonal Gammopathies in the Czech Republic; the relative treatment effects of KRd versus Rd were estimated from the phase 3, randomised, ASPIRE trial, and were used to predict PFS, OS and TTD for KRd. The model was developed from the payer perspective and included drug costs, administration costs, monitoring costs, palliative care costs and adverse-event related costs collected from Czech sources. RESULTS: The base case incremental cost effectiveness ratio for KRd compared with Rd was €73,156 per quality-adjusted life year (QALY) gained. Patients on KRd incurred costs of €117,534 over their lifetime compared with €53,165 for patients on Rd. The QALYs gained were 2.63 and 1.75 for patients on KRd and Rd, respectively. CONCLUSIONS: Combining the strengths of randomised controlled trials and observational databases in cost-effectiveness models can generate policy-relevant results to allow well-informed decision-making. The current model showed that KRd is likely to be cost-effective versus Rd in the RW and, therefore, the reimbursement of KRd represents an efficient allocation of resources within the healthcare system.

• Klíčová slova
• ASPIRE, Carfilzomib, Cost-effectiveness, Multiple myeloma, Real world, Registry of Monoclonal Gammopathies,
• MeSH
• analýza nákladů a výnosů * MeSH
• dexamethason farmakologie   MeSH
• kvalitativně upravené roky života MeSH
• lenalidomid farmakologie   MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   etiologie   MeSH
• mnohočetný myelom farmakoterapie   etiologie   mortalita   MeSH
• náklady na léky MeSH
• oligopeptidy farmakologie   MeSH
• přežití bez známek nemoci MeSH
• protokoly protinádorové kombinované chemoterapie MeSH
• registrace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• carfilzomib MeSH Prohlížeč
• dexamethason MeSH
• lenalidomid MeSH
• oligopeptidy MeSH