Improved curve fits to summary survival data: application to economic evaluation of health technologies

Abstract

Background

Mean costs and quality-adjusted-life-years are central to the cost-effectiveness of health technologies. They are often calculated from time to event curves such as for overall survival and progression-free survival. Ideally, estimates should be obtained from fitting an appropriate parametric model to individual patient data. However, such data are usually not available to independent researchers. Instead, it is common to fit curves to summary Kaplan-Meier graphs, either by regression or by least squares. Here, a more accurate method of fitting survival curves to summary survival data is described.

Methods

First, the underlying individual patient data are estimated from the numbers of patients at risk (or other published information) and from the Kaplan-Meier graph. The survival curve can then be fit by maximum likelihood estimation or other suitable approach applied to the estimated individual patient data. The accuracy of the proposed method was compared against that of the regression and least squares methods and the use of the actual individual patient data by simulating the survival of patients in many thousands of trials. The cost-effectiveness of sunitinib versus interferon-alpha for metastatic renal cell carcinoma, as recently calculated for NICE in the UK, is reassessed under several methods, including the proposed method.

Results

Simulation shows that the proposed method gives more accurate curve fits than the traditional methods under realistic scenarios. Furthermore, the proposed method achieves similar bias and mean square error when estimating the mean survival time to that achieved by analysis of the complete underlying individual patient data. The proposed method also naturally yields estimates of the uncertainty in curve fits, which are not available using the traditional methods. The cost-effectiveness of sunitinib versus interferon-alpha is substantially altered when the proposed method is used.

Conclusions

The method is recommended for cost-effectiveness analysis when only summary survival data are available. An easy-to-use Excel spreadsheet to implement the method is provided.