title: Time-dependent endpoints as predictors of overall survival in multiple myeloma.
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.
  
  
  CONCLUSIONS
  TDEs predict OS in MM patients; this relationship may be valuable in clinical trial design, drug comparisons, and economic evaluation.
authors.affiliation: Exigo Consultores, Av. Humberto Delgado 33, Alhos Vedros 2860-021, Portugal. jorge.felix@exigoconsultores.com
authors.forename: Jorge
authors.initials: J
authors.lastname: Félix
authors.forename: Filipa
authors.initials: F
authors.lastname: Aragão
authors.forename: João M
authors.initials: JM
authors.lastname: Almeida
authors.forename: Frederico J
authors.initials: FJ
authors.lastname: Calado
authors.forename: Diana
authors.initials: D
authors.lastname: Ferreira
authors.forename: António B S
authors.initials: AB
authors.lastname: Parreira
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rodrigues
authors.forename: João F R
authors.initials: JF
authors.lastname: Rijo
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality* / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D014184:Transplantation, Homologous