Survival analysis problems often involve dual timescales, most commonly calendar date and lifetime, the latter being the elapsed time since an initiating event such as a heart transplant. In our main example attention is focused on the hazard rate of ‘death’ as a function of calendar date. Three different estimates are discussed, one each from proportional hazards analyses on the lifetime and the calendar date scales, and one from a symmetric approach called here the ‘two-way proportional hazards model’, a multiplicative hazards model going back to Lexis in the 1870s. The three are connected through a Poisson generalized linear model for the Lexis diagram. The two-way model is shown to combine the information from the two ‘one-way’ proportional hazards analyses efficiently, at the cost of more extensive parametric modelling.
We propose a constrained maximum partial likelihood estimator for dimension reduction in integrative (e.g., pan-cancer) survival analysis with high-dimensional predictors. We assume that for each population in the study, the hazard function follows a distinct Cox proportional hazards model. To borrow information across populations, we assume that each of the hazard functions depend only on a small number of linear combinations of the predictors (i.e., “factors”). We estimate these linear combinations using an algorithm based on “distance-to-set” penalties. This allows us to impose both low-rankness and sparsity on the regression coefficient matrix estimator. We derive asymptotic results that reveal that our estimator is more efficient than fitting a separate proportional hazards model for each population. Numerical experiments suggest that our method outperforms competitors under various data generating models. We use our method to perform a pan-cancer survival analysis relating protein expression to survival across 18 distinct cancer types. Our approach identifies six linear combinations, depending on only 20 proteins, which explain survival across the cancer types. Finally, to validate our fitted model, we show that our estimated factors can lead to better prediction than competitors on four external datasets.
more » « less- Award ID(s):
- 2113589
- NSF-PAR ID:
- 10486005
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Biometrics
- Volume:
- 79
- Issue:
- 3
- ISSN:
- 0006-341X
- Format(s):
- Medium: X Size: p. 1610-1623
- Size(s):
- p. 1610-1623
- Sponsoring Org:
- National Science Foundation
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