title: Alternative statistical methods for estimating efficacy of interferon beta-1b for multiple sclerosis clinical trials.
abstract: BACKGROUND
  In the randomized study of interferon beta-1b (IFN beta-1b) for multiple sclerosis (MS), it has usually been evaluated the simple annual relapse rate as the study endpoint. This study aimed to investigate the performance of various regression models using information regarding the time to each recurrent event and considering the MS specific data generation process, and to estimate the treatment effect of a MS clinical trial data.
  
  
  METHODS
  We conducted a simulation study with consideration of the pathological characteristics of MS, and applied alternative efficacy estimation methods to real clinical trial data, including 5 extended Cox regression models for time-to-event analysis, a Poisson regression model and a Poisson regression model with Generalized Estimating Equations (GEE). We adjusted for other important covariates that may have affected the outcome.
  
  
  RESULTS
  We compared the simulation results for each model. The hazard ratios of real data were estimated for each model including the effects of other covariates. The results (hazard ratios of high-dose to low-dose) of all models were approximately 0.7 (range, 0.613 - 0.769), whereas the annual relapse rate ratio was 0.714.
  
  
  CONCLUSIONS
  The precision of the treatment estimation was increased by application of the alternative models. This suggests that the use of alternative models that include recurrence event data may provide better analyses.
authors: Department of Medical Informatics, Jichi Medical University, Shimotsuke, Japan. mnaka@jichi.ac.jp
authors: Makiko N
authors: MN
authors: Mieno
authors: Takuhiro
authors: T
authors: Yamaguchi
authors: Yasuo
authors: Y
authors: Ohashi
references: Stat Med. 2006 Jan 15;25(1):165-79
references: 16217859
references: Neurology. 1993 Apr;43(4):655-61
references: 8469318
references: Neurology. 1999 Aug 11;53(3):457-65
references: 10449104
references: Neurology. 2006 Oct 10;67(7):1242-9
references: 16914693
references: Lancet. 1997 Mar 1;349(9052):589-93
references: 9057729
references: N Engl J Med. 2003 Jan 2;348(1):15-23
references: 12510038
references: Curr Opin Neurol. 1999 Jun;12(3):345-9
references: 10499179
references: BMC Med Res Methodol. 2008 May 30;8:35
references: 18513418
references: Mult Scler. 2009 Aug;15(8):951-8
references: 19465446
references: Neurology. 1995 Jul;45(7):1268-76
references: 7617181
references: J Neurol Sci. 2009 Oct 15;285(1-2):206-11
references: 19709676
references: Neurology. 1998 May;50(5):1273-81
references: 9595974
references: Lancet. 1998 Nov 7;352(9139):1498-504
references: 9820297
references: Neurology. 2005 Feb 22;64(4):621-30
references: 15728282