Dawn Lee, Zain Ahmad, Caroline Farmer, Maxwell S Barnish, Alan Lovell, G J Melendez-Torres
{"title":"Slipping Away: Slippage in Hazard Ratios Over Datacuts and Its Impact on Immuno-oncology Combination Economic Evaluations.","authors":"Dawn Lee, Zain Ahmad, Caroline Farmer, Maxwell S Barnish, Alan Lovell, G J Melendez-Torres","doi":"10.1016/j.jval.2024.09.008","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>This study examines the impact of slippage in hazard ratios (tending toward the null over subsequent datacuts) for overall survival for combination treatment with a PD-(L)-1 inhibitor and a tyrosine kinase inhibitor in advanced renal cell carcinoma.</p><p><strong>Methods: </strong>Four trials' Kaplan-Meier curves were digitized over several datacuts and fitted with standard parametric curves. Accuracy and consistency of early data projections were calculated versus observed restricted mean survival time and fitted lifetime survival from the longest follow-up datacut. The change in economically justifiable price (eJP) was calculated fitting the same curve to both arms, using an assumed average utility of 0.7 and willingness-to-pay threshold of £30 000 per quality-adjusted life-year. The eJP represents the lifetime justifiable price increment for the new treatment, including differences in drug-, administration-, and disease-related costs.</p><p><strong>Results: </strong>Slippage in hazard ratios was observed in trials with longer follow-up, potentially influenced by subsequent PD-(L)-1 use after tyrosine kinase inhibitor monotherapy, early stoppage of PD-(L)-1, and development of resistance. Lognormal and log-logistic curves were more likely to overpredict the observed result; Gompertz and gamma underpredicted. Statistical measures of goodness of fit did not select the curves that resulted in the RMST closest to what was observed in the final data cut. Large differences in incremental mean life-years were observed between even the penultimate and final datacuts for most of the fitted curves, meaningfully affecting the eJP.</p><p><strong>Conclusions: </strong>This work demonstrates the challenge in predicting treatment benefits with novel therapies using immature data. Incorporating information on the impact of subsequent treatment is likely to play a key role in improving predictions.</p>","PeriodicalId":23508,"journal":{"name":"Value in Health","volume":" ","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Value in Health","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jval.2024.09.008","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ECONOMICS","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: This study examines the impact of slippage in hazard ratios (tending toward the null over subsequent datacuts) for overall survival for combination treatment with a PD-(L)-1 inhibitor and a tyrosine kinase inhibitor in advanced renal cell carcinoma.
Methods: Four trials' Kaplan-Meier curves were digitized over several datacuts and fitted with standard parametric curves. Accuracy and consistency of early data projections were calculated versus observed restricted mean survival time and fitted lifetime survival from the longest follow-up datacut. The change in economically justifiable price (eJP) was calculated fitting the same curve to both arms, using an assumed average utility of 0.7 and willingness-to-pay threshold of £30 000 per quality-adjusted life-year. The eJP represents the lifetime justifiable price increment for the new treatment, including differences in drug-, administration-, and disease-related costs.
Results: Slippage in hazard ratios was observed in trials with longer follow-up, potentially influenced by subsequent PD-(L)-1 use after tyrosine kinase inhibitor monotherapy, early stoppage of PD-(L)-1, and development of resistance. Lognormal and log-logistic curves were more likely to overpredict the observed result; Gompertz and gamma underpredicted. Statistical measures of goodness of fit did not select the curves that resulted in the RMST closest to what was observed in the final data cut. Large differences in incremental mean life-years were observed between even the penultimate and final datacuts for most of the fitted curves, meaningfully affecting the eJP.
Conclusions: This work demonstrates the challenge in predicting treatment benefits with novel therapies using immature data. Incorporating information on the impact of subsequent treatment is likely to play a key role in improving predictions.
期刊介绍:
Value in Health contains original research articles for pharmacoeconomics, health economics, and outcomes research (clinical, economic, and patient-reported outcomes/preference-based research), as well as conceptual and health policy articles that provide valuable information for health care decision-makers as well as the research community. As the official journal of ISPOR, Value in Health provides a forum for researchers, as well as health care decision-makers to translate outcomes research into health care decisions.