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Open Access Research article

Alternative statistical methods for estimating efficacy of interferon beta-1b for multiple sclerosis clinical trials

Makiko N Mieno1*, Takuhiro Yamaguchi2 and Yasuo Ohashi3

Author Affiliations

1 Department of Medical Informatics, Center for Information, Jichi Medical University, Shimotsuke, Japan

2 Department of Biostatistics, Tohoku University School of Medicine, Sendai, Japan

3 Department of Biostatistics, School of Public Health, University of Tokyo, Bunkyo, Tokyo, Japan

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BMC Medical Research Methodology 2011, 11:80  doi:10.1186/1471-2288-11-80

Published: 26 May 2011

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.