Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer

Clinicoecon Outcomes Res. 2016 Jun 30:8:323-33. doi: 10.2147/CEOR.S107498. eCollection 2016.

Abstract

Background: Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data.

Objectives: This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo.

Methods: Data from 392 patients (lenvatinib: 261, placebo: 131) from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model.

Results: A piecewise model, in which the Kaplan-Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model.

Conclusion: In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and populate future cost-effectiveness analyses.

Keywords: decision criteria; parametric extrapolation; piecewise models; radioiodine-refractory differentiated thyroid cancer; survival analysis.