Subgroup analysis of treatment effects for misclassified biomarkers with time-to-event data

Wan, Fang and Titman, Andrew and Jaki, Thomas (2019) Subgroup analysis of treatment effects for misclassified biomarkers with time-to-event data. Journal of the Royal Statistical Society: Series C (Applied Statistics), 68 (5). pp. 1447-1463. ISSN 0035-9254

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Abstract

Analysing subgroups defined by biomarkers is of increasing importance in clinical research. In many situations the biomarker is subject to misclassification error, meaning that the subgroups are identified with imperfect sensitivity and specificity. In these cases, it is improper to assume the Cox proportional hazards model for the subgroup‐specific treatment effects for time‐to‐event data with respect to the true subgroups, since the survival distributions with respect to the diagnosed subgroups will not adhere to the proportional hazards assumption. This precludes the possibility of using simple adjustment procedures. Two approaches to modelling are considered; the corrected score approach and a method based on formally modelling the data as a mixture of Cox models using an expectation–maximization algorithm for estimation. The methods are comparable for moderate‐to‐large sample sizes, but the expectation–maximization algorithm performs better when there are 100 patients per group. An estimate of the overall population treatment effect is obtained through the interpretation of the hazard ratio as a concordance odds. The methods are illustrated on data from a renal cell cancer trial.

Item Type:
Journal Article
Journal or Publication Title:
Journal of the Royal Statistical Society: Series C (Applied Statistics)
Additional Information:
This is the peer reviewed version of the following article: Wan, F. , Titman, A. C. and Jaki, T. F. (2019), Subgroup analysis of treatment effects for misclassified biomarkers with time‐to‐event data. J. R. Stat. Soc. C, 68: 1447-1463. doi:10.1111/rssc.12364 which has been published in final form at https://rss.onlinelibrary.wiley.com/doi/10.1111/rssc.12364 This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1800/1804
Subjects:
ID Code:
133938
Deposited By:
Deposited On:
29 May 2019 13:00
Refereed?:
Yes
Published?:
Published
Last Modified:
01 Dec 2020 07:02