Abstract
BackgroundSupporting health care sector decisions using time-dependent endpoints (TDEs) such as time to progression (TTP), progression-free survival (PFS), and event-free survival (EFS) remains controversial. This study estimated the quantitative relationship between median TDE and median overall survival (OS) in multiple myeloma (MM) patients.MethodsStudies (excluding allogeneic transplantation) published from 1970 to 2011 were systematically searched (PubMed). The nonparametric Spearman’s rank correlation coefficient measured the association between median TDE and OS. The quantitative relationship between TDEs and OS was estimated with a two-step approach to a simultaneous Tobit model.ResultsWe identified 153 studies: 230 treatment arms, 22,696 patients and mean study duration of 3.8 years. Mean of median TDEs was 22.5 months and median OS was 39.1 months. Correlation coefficients of median TTP, PFS, and EFS with median OS were 0.51 (P = 0.003), 0.75 (P < 0.0001), and 0.84 (P < 0.0001), respectively. We estimate a 2.5 month (95% confidence interval, 1.7–3.2) increase in median OS for each additional month reported for median TDEs. There was no evidence that this relationship differed by type of surrogate.ConclusionTDEs predict OS in MM patients; this relationship may be valuable in clinical trial design, drug comparisons, and economic evaluation.
Highlights
Supporting health care sector decisions using time-dependent endpoints (TDEs) such as time to progression (TTP), progression-free survival (PFS), and event-free survival (EFS) remains controversial
We found an increase of 2.45 months in the reported median overall survival (OS) for each additional month in the observed median TDE (Table 2)
The maximum variation in the effect of median TDE on median OS is 34% (β = 2.45; 95% confidence intervals (CIs), 1.71–3.20) relative to the base model (β = 1.82; 95% CI, 1.56–2.08)
Summary
Supporting health care sector decisions using time-dependent endpoints (TDEs) such as time to progression (TTP), progression-free survival (PFS), and event-free survival (EFS) remains controversial. This study estimated the quantitative relationship between median TDE and median overall survival (OS) in multiple myeloma (MM) patients. In the US, it was estimated that over 20,500 new cases of MM and more than 10,600 deaths occurred in 2011 [3]. Despite improved survival over the past decades, MM remains an incurable disease, with research focused on finding more effective treatments [4]. Improving overall survival (OS) has been the gold standard outcome for new anticancer treatments, large costly trials with long follow-up periods are required to document an impact on OS [5,6]. Surrogate endpoints that can be measured sooner and more
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