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Open Access Research article

Time-dependent endpoints as predictors of overall survival in multiple myeloma

Jorge Félix1*, Filipa Aragão1, João M Almeida1, Frederico JM Calado1, Diana Ferreira1, António BS Parreira2, Ricardo Rodrigues3 and João FR Rijo4

Author Affiliations

1 Exigo Consultores, Av. Humberto Delgado 33, Alhos Vedros, 2860-021, Portugal

2 Portuguese Oncology Institute–Lisboa, Lisbon, Portugal

3 Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal

4 Hospital Egas Moniz, Lisbon, Portugal

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BMC Cancer 2013, 13:122  doi:10.1186/1471-2407-13-122

Published: 16 March 2013

Abstract

Background

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.

Methods

Studies (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.

Results

We 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.

Conclusion

TDEs predict OS in MM patients; this relationship may be valuable in clinical trial design, drug comparisons, and economic evaluation.

Keywords:
Multiple myeloma; Overall survival; Survival predictors; Time-dependent endpoint; Time to progression