DOI QR코드

DOI QR Code

Pattern-Mixture Model of the Cox Proportional Hazards Model with Missing Binary Covariates

결측이 있는 이산형 공변량에 대한 Cox비례위험모형의 패턴-혼합 모델

  • Received : 2011.09.30
  • Accepted : 2012.03.27
  • Published : 2012.04.30

Abstract

When fitting a Cox proportional hazards model with missing covariates, it is inefficient to exclude observations with missing values in the analysis. Furthermore, if the missing-data mechanism is not Missing Completely At Random(MCAR), it may lead to biased parameter estimation. Many approaches have been suggested to handle the Cox proportional hazards model when covariates are sometimes missing, but they are based on the selection model. This paper suggest an approach to handle Cox proportional hazards model with missing covariates by using the pattern-mixture model (Little, 1993). The pattern-mixture model is expressed by the joint distribution of survival time and the missing-data mechanism. In the pattern-mixture model, many models can be considered by setting up various restrictions, and different results under various restrictions indicate the sensitivity of the model due to missing covariates. A simulation study was conducted to show the sensitivity of parameter estimation under different restrictions in a pattern-mixture model. The proposed approach was also applied to mouse leukemia data.

공변량에 결측이 발생한 Cox 비례위험 모형을 적합할 때, 결측이 발생하는 개체를 모두 제거한 후 분석을 실시한다면 정보 손실에 의해 비효율적이고 결측의 발생 메커니즘이 완전 임의 결측(missing completely at random; MCAR)이 아니라면 모수의 추정값에 편향이 발생할 수 있다. Cox 비례위험 회귀모형의 공변량에 결측이 있는 경우 적용할 수 있는 여러 가지 방법들이 제안되어져 왔으나 이 분석들은 선택모델(selection model)에 기반하고 있다. 본 연구에서는 Little (1993)이 제안한 패턴-혼합 모델(pattern-mixture model)을 사용하여 Cox 비례위험 회귀모형에서 생존시간과 결측 메커니즘의 결합분포를 모델화 하고, 여러 가지 제약에 근거한 생존 분석의 결과를 비교하였다. 모의실험을 통해서 패턴-혼합 모델의 제약(restrictions)에 따른 모수 추정의 민감도를 확인하였고 결측을 무시한 채 분석한 결과 및 선택모형에 근거한 분석결과와 비교하였다. 패턴-혼합 모델의 제약에 따라 공변량의 결측으로 인한 모수 추정의 민감성 정도를 쥐백혈병 자료 예제를 통해 설명하였다.

Keywords

References

  1. Chen, H. Y. and Little, R. J. A. (1999). Proportional hazards regression with missing covariates, Journal of the American Statistical Association, 94, 896-908. https://doi.org/10.1080/01621459.1999.10474195
  2. Cox, D. R. (1972). Regression models and life-tables (with discussion), Journal of the Royal Statistical Society, Series B, 34, 187-220.
  3. Cox, D. R. (1975). Partial likelihood, Biometrika, 62, 269-279. https://doi.org/10.1093/biomet/62.2.269
  4. Demirtas, H. (2005). Multiple imputation under Bayesianly smoothed pattern-mixture models for nonignorable drop-out, Statistics in Medicine, 24, 2345-2363. https://doi.org/10.1002/sim.2117
  5. Herring, A. H. and Ibrahim, J. G. (2001). Likelihood-based methods for missing covariates in the Cox proportional hazards model, Journal of the American Statistical Association, 96, 292-302. https://doi.org/10.1198/016214501750332866
  6. Herring, A. H., Ibrahim, J. G. and Lipsitz, S. R. (2004). Non- ignorable missing covariate data in survival analysis: A case-study of an International Breast Cancer Study Group trial, Journal of the Royal Statistical Society, 53, 293-310. https://doi.org/10.1046/j.1467-9876.2003.05168.x
  7. Hogan, J. W. and Laird, N. M. (1997). Model-based approaches to analysing incomplete longitudinal and failure time data, Statistics in Medicine, 16, 259-272. https://doi.org/10.1002/(SICI)1097-0258(19970215)16:3<259::AID-SIM484>3.0.CO;2-S
  8. Kalb eisch, J. D. and Prentice, R. L. (1980). The Statistical Analysis of Failure Time Data, Wiley, New York.
  9. Lin, D. Y. and Ying, Z. (1993). Cox regression with incomplete covariate measurements, Journal of the American Statistical Association, 88, 1341-1349. https://doi.org/10.1080/01621459.1993.10476416
  10. Little, R. J. A. (1993). Pattern-Mixture models for multivariate incomplete data, Journal of the American Statistical Association, 88, 125-134. https://doi.org/10.2307/2290705
  11. Little, R. J. A. and Rubin, D. B. (2002). Statistical Analysis With Missing Data, Wiley, New York.
  12. Molenberghs, G., Michiels, B., Kenward, M. G. and Diggle, P. J. (1998). Monotone missing data and patternmixture models, Statistica Neerlandica, 52, 153-161. https://doi.org/10.1111/1467-9574.00075
  13. Thijs, H., Molenberghs, G., Michiels, B., Verbeke, G. and Curran, D. (2002). Strategies to fit pattern-mixture models, Biostatistics, 3, 245-265. https://doi.org/10.1093/biostatistics/3.2.245
  14. Wang, C. and Daniels, M. J. (2011). A note on MAR, identifying restrictions, model comparison, and sensitivity analysis in Pattern-Mixture models with and without covariates for incomplete data, Biometrics, 67, 810-818. https://doi.org/10.1111/j.1541-0420.2011.01565.x