4.3 Article

Modified score function for monotone likelihood in the semiparametric mixture cure model

Journal

BIOMETRICAL JOURNAL
Volume 64, Issue 3, Pages 635-654

Publisher

WILEY
DOI: 10.1002/bimj.202000254

Keywords

Cox regression; cure rate; em algorithm; firth method; melanoma

Funding

  1. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -CAPES
  2. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico -CNPq
  3. Fundacao deAmparo a Pesquisa doEstado deMinas Gerais FAPEMIG

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The paper focuses on addressing parameter estimation issues in cure fraction models by introducing the Firth correction method to avoid nonfinite estimates resulting from the monotonicity of likelihood functions. Through simulation studies, it is found that the performance of coefficients related to binary covariates is strongly influenced by the degree of imbalance.
The cure fraction models are intended to analyze lifetime data from populations where some individuals are immune to the event under study, and allow a joint estimation of the distribution related to the cured and susceptible subjects, as opposed to the usual approach ignoring the cure rate. In situations involving small sample sizes with many censored times, the detection of nonfinite coefficients may arise via maximum likelihood. This phenomenon is commonly known as monotone likelihood (ML), occurring in the Cox and logistic regression models when many categorical and unbalanced covariates are present. An existing solution to prevent the issue is based on the Firth correction, originally developed to reduce the estimation bias. The method ensures finite estimates by penalizing the likelihood function. In the context of mixture cure models, the ML issue is rarely discussed in the literature; therefore, this topic can be seen as the first contribution of our paper. The second major contribution, not well addressed elsewhere, is the study of the ML issue in cure mixture modeling under the flexibility of a semiparametric framework to handle the baseline hazard. We derive the modified score function based on the Firth approach and explore finite sample size properties of the estimators via a Monte Carlo scheme. The simulation results indicate that the performance of coefficients related to the binary covariates are strongly affected to the imbalance degree. A real illustration, in the melanoma dataset, is discussed using a relatively novel data set collected in a Brazilian university hospital.

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