Treatment sequences for advanced renal cell carcinoma: A health economic assessment.

ObjectiveAdvanced renal cell carcinoma (RCC) is commonly treated with vascular endothelial growth factor or mammalian target of rapamycin inhibitors. As new therapies emerge, interest grows in gaining a deeper understanding of treatment sequences. Recently, we developed a patient-level, discretely integrated condition event (DICE) simulation to estimate survival and lifetime costs for various cancer therapies, using a US payer perspective. Using this model, we explored the impact of treatments such as nivolumab and cabozantinib, and compared the clinical outcomes and cost consequences of commonly used treatment algorithms for patients with advanced RCC.MethodsIncluded treatment sequences were pazopanib or sunitinib as first-line treatment, followed by nivolumab, cabozantinib, axitinib, pazopanib or everolimus. Efficacy inputs were derived from the CheckMate 025 trial and a network meta-analysis based on available literature. Safety and cost data were obtained from publicly available sources or literature.ResultsBased on our analysis, the average cost per life-year (LY) was lowest for sequences including nivolumab (sunitinib → nivolumab, $75,268/LY; pazopanib → nivolumab,$84,459/LY) versus axitinib, pazopanib, everolimus and cabozantinib as second-line treatments. Incremental costs per LY gained were $49,592,$73,927 and $30,534 for nivolumab versus axitinib, pazopanib and everolimus-containing sequences, respectively. The model suggests that nivolumab offers marginally higher life expectancy at a lower cost versus cabozantinib-including sequences.ConclusionTreatment sequences using nivolumab in the second-line setting are less costly compared with sequential use of targeted agents. In addition to efficacy and safety data, cost considerations may be taken into account when considering treatment algorithms for patients with advanced RCC

Application of dynamic modeling for survival estimation in advanced renal cell carcinoma.

OBJECTIVE:In oncology, extrapolation of clinical outcomes beyond trial duration is traditionally achieved by parametric survival analysis using population-level outcomes. This approach may not fully capture the benefit/risk profile of immunotherapies due to their unique mechanisms of action. We evaluated an alternative approach-dynamic modeling-to predict outcomes in patients with advanced renal cell carcinoma. We compared standard parametric fitting and dynamic modeling for survival estimation of nivolumab and everolimus using data from the phase III CheckMate 025 study. METHODS:We developed two statistical approaches to predict longer-term outcomes (progression, treatment discontinuation, and survival) for nivolumab and everolimus, then compared these predictions against follow-up clinical trial data to assess their proximity to observed outcomes. For the parametric survival analyses, we selected a probability distribution based on its fit to observed population-level outcomes at 14-month minimum follow-up and used it to predict longer-term outcomes. For dynamic modeling, we used a multivariate Cox regression based on patient-level data, which included risk scores, and probability and duration of response as predictors of longer-term outcomes. Both sets of predictions were compared against trial data with 26- and 38-month minimum follow-up. RESULTS:Both statistical approaches led to comparable fits to observed trial data for median progression, discontinuation, and survival. However, beyond the trial duration, mean survival predictions differed substantially between methods for nivolumab (30.8 and 51.5 months), but not everolimus (27.2 and 29.8 months). Longer-term follow-up data from CheckMate 025 and phase I/II studies resembled dynamic model predictions for nivolumab. CONCLUSIONS:Dynamic modeling can be a good alternative to parametric survival fitting for immunotherapies because it may help better capture the longer-term benefit/risk profile and support health-economic evaluations of immunotherapies

Correction:Economic evaluation of the one-hour rule-out and rule-in algorithm for acute myocardial infarction using the high-sensitivity cardiac troponin T assay in the emergency department

[This corrects the article DOI: 10.1371/journal.pone.0187662.]

Economic evaluation of the one-hour rule-out and rule-in algorithm for acute myocardial infarction using the high-sensitivity cardiac troponin T assay in the emergency department

BACKGROUND: The 1-hour (h) algorithm triages patients presenting with suspected acute myocardial infarction (AMI) to the emergency department (ED) towards "rule-out," "rule-in," or "observation," depending on baseline and 1-h levels of high-sensitivity cardiac troponin (hs-cTn). The economic consequences of applying the accelerated 1-h algorithm are unknown. METHODS AND FINDINGS: We performed a post-hoc economic analysis in a large, diagnostic, multicenter study of hs-cTnT using central adjudication of the final diagnosis by two independent cardiologists. Length of stay (LoS), resource utilization (RU), and predicted diagnostic accuracy of the 1-h algorithm compared to standard of care (SoC) in the ED were estimated. The ED LoS, RU, and accuracy of the 1-h algorithm was compared to that achieved by the SoC at ED discharge. Expert opinion was sought to characterize clinical implementation of the 1-h algorithm, which required blood draws at ED presentation and 1h, after which "rule-in" patients were transferred for coronary angiography, "rule-out" patients underwent outpatient stress testing, and "observation" patients received SoC. Unit costs were for the United Kingdom, Switzerland, and Germany. The sensitivity and specificity for the 1-h algorithm were 87% and 96%, respectively, compared to 69% and 98% for SoC. The mean ED LoS for the 1-h algorithm was 4.3h-it was 6.5h for SoC, which is a reduction of 33%. The 1-h algorithm was associated with reductions in RU, driven largely by the shorter LoS in the ED for patients with a diagnosis other than AMI. The estimated total costs per patient were £2,480 for the 1-h algorithm compared to £4,561 for SoC, a reduction of up to 46%. CONCLUSIONS: The analysis shows that the use of 1-h algorithm is associated with reduction in overall AMI diagnostic costs, provided it is carefully implemented in clinical practice. These results need to be prospectively validated in the future.Correction in: PLoS ONE, vol. 13, issue 1, e0191348.DOI: 10.1371/journal.pone.0191348</p

Clinical implementation of one-hour rule-out and rule-in algorithm.

<p>Abbreviations: AMI, acute myocardial infarction; ECG, electrocardiogram; ED, emergency department; hs-cTn, high-sensitivity cardiac troponin assays.</p

Multivariate regression model for LoS of patients with AMI and non-AMI diagnosis: SoC.

<p>Multivariate regression model for LoS of patients with AMI and non-AMI diagnosis: SoC.</p