title: Innovative estimation of survival using log-normal survival modelling on ACCENT database.
abstract: BACKGROUND
  The ACCENT database, with individual patient data for 20 898 patients from 18 colon cancer clinical trials, was used to support Food and Drug Administration (FDA) approval of 3-year disease-free survival as a surrogate for 5-year overall survival. We hypothesised substantive differences in survival estimation with log-normal modelling rather than standard Kaplan-Meier or Cox approaches.
  
  
  METHODS
  Time to relapse, disease-free survival, and overall survival were estimated using Kaplan-Meier, Cox, and log-normal approaches for male subjects aged 60-65 years, with stage III colon cancer, treated with 5-fluorouracil-based chemotherapy regimens (with 5FU), or with surgery alone (without 5FU).
  
  
  RESULTS
  Absolute differences between Cox and log-normal estimates with (without) 5FU varied by end point. The log-normal model had 5.8 (6.3)% higher estimated 3-year time to relapse than the Cox model; 4.8 (5.1)% higher 3-year disease-free survival; and 3.2 (2.2)% higher 5-year overall survival. Model checking indicated greater data support for the log-normal than the Cox model, with Cox and Kaplan-Meier estimates being more similar. All three model types indicate consistent evidence of treatment benefit on both 3-year disease-free survival and 5-year overall survival; patients allocated to 5FU had 5.0-6.7% higher 3-year disease-free survival and 5.3-6.8% higher 5-year overall survival.
  
  
  CONCLUSIONS
  Substantive absolute differences between estimates of 3-year disease-free survival and 5-year overall survival with log-normal and Cox models were large enough to be clinically relevant, and warrant further consideration.
authors: NCIC Clinical Trials Group, Queen's University, 10 Stuart Street, Kingston, Ontario, Canada. jchapman@ctg.queensu.ca
authors: J W
authors: JW
authors: Chapman
authors: C J
authors: CJ
authors: O'Callaghan
authors: N
authors: N
authors: Hu
authors: K
authors: K
authors: Ding
authors: G A
authors: GA
authors: Yothers
authors: P J
authors: PJ
authors: Catalano
authors: Q
authors: Q
authors: Shi
authors: R G
authors: RG
authors: Gray
authors: M J
authors: MJ
authors: O'Connell
authors: D J
authors: DJ
authors: Sargent
mesh_terms: D000368:Aged; D017326:Clinical Trials, Phase III as Topic; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery; D003131:Combined Modality Therapy; D019992:Databases as Topic; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic
chemical_list: D005472:Fluorouracil
references: J Clin Oncol. 2010 Jul 10;28(20):3219-26
references: 20498393
references: N Engl J Med. 2008 Oct 23;359(17):1757-65
references: 18946061
references: Stat Med. 1982 Apr-Jun;1(2):93-104
references: 7187092
references: N Engl J Med. 2007 Nov 15;357(20):2040-8
references: 18003960
references: J Clin Oncol. 2009 Feb 20;27(6):872-7
references: 19124803
references: J Clin Oncol. 2007 Oct 10;25(29):4569-74
references: 17876008
references: JAMA. 2010 Oct 27;304(16):1812-20
references: 20978259
references: J Natl Cancer Inst. 2008 Feb 20;100(4):252-60
references: 18270335
references: J Clin Oncol. 2005 Dec 1;23(34):8664-70
references: 16260700
references: J Clin Oncol. 1996 Oct;14(10):2738-46
references: 8874335
references: Comput Methods Programs Biomed. 1989 May;29(1):51-7
references: 2714079
references: Stat Med. 2002 Aug 15;21(15):2175-97
references: 12210632