Efficient Post-Shrinkage Estimation Strategies in High-Dimensional Cox’s Proportional Hazards Models
Abstract
:1. Introduction
2. Methodology
2.1. Notation and Assumptions
2.2. Signal Strength Regularity Conditions
- (A1)
- There exists a positive constant , such that for ;
- (A2)
- The coefficient vector satisfies for some , where for ;
- (A3)
- , for .
2.3. Cox Proportional Hazards Model
2.4. Variable Selection and Estimation
- Elastic Net (ENet). The Elastic Net estimator implements (4) with the combined penalty
2.4.1. Variable Selection Procedure for and
- Step 1 (detection of ). Obtain a candidate subset of strong signals using a penalized likelihood estimator (PLE). Specifically, consider
- Step 2 (detection of ). To identify , first solve a penalized regression problem with a ridge penalty only on the variables in . Formally,
2.4.2. Post-Selection Shrinkage Estimation
3. Asymptotic Properties
- (B1)
- for some .
- (B2)
- , where for in (A2).
- (B3)
- The existence of a positive definite matrix such that , where the eigenvalues of satisfy .
- (B4)
- Sparse Riesz condition: For the random design matrix , any with , and any vector , there exists such that holds with probability tending to 1.
Asymptotic Distributional Bias and Risk Analysis
- If , then ;
- If and , then for .
4. Simulation Study
Key Observations and Insights
- Superior performance of post-selection estimators: Across all combinations of n and p, the post-selection estimators ( and ) consistently demonstrate lower RMSEs compared to LASSO and ENet. This suggests that these estimators provide better predictive accuracy and stability.
- Impact of censoring percentage:
- When the censoring percentage increases from 15% to 25%, the RMSE values tend to increase across all methods, indicating the expected loss of predictive power due to increased censoring.
- However, the post-selection estimators maintain a more stable RMSE trend, demonstrating their robustness in handling censored data.
- Effect of increasing predictors (p):
- As p increases, the RMSE for LASSO and ENet tends to rise, particularly under higher censoring rates.
- This trend suggests that LASSO and ENet struggle with larger feature spaces, likely due to their tendency to aggressively shrink weaker covariates.
- In contrast, the post-selection estimators show relatively stable RMSE behavior, indicating their ability to retain relevant information even in high-dimensional settings.
- Impact of sample size (n) on RMSE stability:
- Larger sample sizes (n) generally lead to lower RMSE values across all methods.
- However, the gap between LASSO/ENet and the post-selection estimators remains consistent, reinforcing the advantage of the proposed methods even with more data.
- Comparing LASSO and ENet:
- ENet generally has lower RMSE values than LASSO, particularly for small sample sizes, indicating its advantage in balancing feature selection and regularization.
- However, ENet still underperforms compared to post-selection estimators, suggesting that the additional shrinkage adjustments help mitigate underfitting issues.
5. Real Data Example
5.1. Example 1
5.2. Example 2
6. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Nomenclature
Symbol | Description |
General Notation | |
n | Sample size (number of observations) |
p | Number of covariates (predictor variables) |
Set of real numbers | |
Probability measure | |
Expectation operator | |
Indicator function | |
Regression and Estimators | |
Regression coefficient vector | |
Estimated regression coefficients | |
Regularization parameter (for LASSO/ENet) | |
Selected subset of variables | |
-dimensional vector in the selection model | |
Selected regression coefficient estimator | |
Weighted Ridge (WR) estimator | |
Survival Analysis Notation | |
Cox proportional hazards likelihood function | |
Dataset containing observations | |
X | Covariate matrix |
Y | Response variable (time-to-event outcome) |
Hazard function at time t | |
Estimated hazard function | |
Cumulative hazard function | |
Evaluation Metrics | |
RMSE | Root Mean Squared Error |
FPR | False Positive Rate |
AUC | Area Under the Curve (for classification models) |
Methods and Models | |
LASSO | Least Absolute Shrinkage and Selection Operator |
ENet | Elastic Net |
Cox-PH | Cox Proportional Hazards Model |
WR | Weighted Ridge estimator |
PSE | Post-selection Shrinkage Estimator |
RE | Restricted Estimator |
Appendix A. Proofs
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Censoring Percentage | ||||||||
---|---|---|---|---|---|---|---|---|
15% | 25% | |||||||
Method | ||||||||
100 | 300 | LASSO | 1.04 | 1.66 | 1.19 | 1.08 | 1.96 | 1.23 |
ENet | 1.07 | 1.45 | 1.23 | 0.92 | 1.44 | 1.06 | ||
400 | LASSO | 1.03 | 1.10 | 1.60 | 0.96 | 1.03 | 1.98 | |
ENet | 0.90 | 1.00 | 1.45 | 0.89 | 0.98 | 1.36 | ||
500 | LASSO | 1.08 | 1.13 | 1.66 | 0.98 | 1.05 | 1.37 | |
ENet | 0.96 | 1.01 | 1.03 | 0.95 | 1.00 | 1.22 | ||
300 | 300 | LASSO | 0.85 | 1.60 | 0.98 | 0.92 | 1.64 | 1.06 |
ENet | 0.96 | 1.37 | 1.08 | 0.87 | 1.46 | 1.00 | ||
350 | LASSO | 0.83 | 0.99 | 1.01 | 0.90 | 1.07 | 1.17 | |
ENet | 0.85 | 0.99 | 1.52 | 0.87 | 1.02 | 1.56 | ||
400 | LASSO | 0.90 | 1.03 | 1.25 | 0.81 | 0.95 | 1.73 | |
ENet | 0.90 | 1.04 | 1.25 | 0.76 | 0.89 | 1.41 | ||
400 | 400 | LASSO | 0.99 | 1.52 | 1.12 | 0.82 | 1.50 | 0.94 |
ENet | 0.91 | 1.29 | 1.02 | 0.83 | 1.26 | 0.99 | ||
450 | LASSO | 0.83 | 1.00 | 1.13 | 0.84 | 0.94 | 1.61 | |
ENet | 0.92 | 1.05 | 1.46 | 0.85 | 0.99 | 1.79 | ||
500 | LASSO | 0.89 | 0.93 | 1.83 | 0.81 | 0.93 | 1.90 | |
ENet | 0.82 | 0.93 | 1.38 | 0.82 | 0.95 | 1.75 |
Censoring Percentage | ||||||
---|---|---|---|---|---|---|
Method | Average | FPR | Average | FPR | ||
100 | 300 | LASSO | 6.1 | 0.063 | 6.4 | 0.056 |
ENet | 6.2 | 0.063 | 6.6 | 0.052 | ||
400 | LASSO | 4.9 | 0.072 | 5.2 | 0.085 | |
ENet | 5.1 | 0.072 | 4.8 | 0.075 | ||
500 | LASSO | 5.6 | 0.039 | 12.6 | 0.043 | |
ENet | 4.9 | 0.039 | 4.0 | 0.033 | ||
300 | 300 | LASSO | 13.4 | 0.209 | 13.8 | 0.223 |
ENet | 12.9 | 0.209 | 16.3 | 0.282 | ||
350 | LASSO | 15.6 | 0.202 | 15.8 | 0.208 | |
ENet | 15.7 | 0.202 | 22.6 | 0.279 | ||
400 | LASSO | 14.5 | 0.137 | 13.7 | 0.155 | |
ENet | 13.5 | 0.137 | 14.2 | 0.173 | ||
400 | 400 | LASSO | 14.1 | 0.163 | 15.8 | 0.171 |
ENet | 14.2 | 0.163 | 20.4 | 0.212 | ||
450 | LASSO | 18.4 | 0.217 | 23.5 | 0.24 | |
ENet | 19.1 | 0.217 | 30.1 | 0.263 | ||
500 | LASSO | 13.6 | 0.150 | 13.3 | 0.158 | |
ENet | 13.3 | 0.150 | 13.6 | 0.158 |
LASSO | ENet | |||||
---|---|---|---|---|---|---|
Gen ID | ||||||
18 | −0.02 | 0.26 | 0.21 | −0.03 | 0.07 | 0.20 |
97 | 0.01 | 0.27 | 0.00 | 0.01 | 0.26 | 0.01 |
101 | 0.05 | 0.19 | 0.13 | 0.05 | 0.27 | 0.12 |
128 | – | – | – | −0.01 | – | – |
232 | 0.04 | −0.42 | −0.28 | 0.04 | 0.20 | −0.25 |
342 | 0.15 | −0.42 | −0.13 | 0.14 | −0.39 | −0.10 |
369 | −0.09 | −0.05 | 0.04 | −0.08 | −0.40 | −0.12 |
408 | −0.01 | – | – | −0.01 | −0.09 | 0.03 |
410 | 0.03 | −0.26 | −0.15 | 0.03 | −0.06 | −0.14 |
445 | – | – | – | −0.00 | – | – |
468 | 0.14 | 0.08 | 0.02 | 0.13 | −0.26 | −0.01 |
660 | −0.00 | – | – | −0.00 | – | – |
731 | −0.08 | 0.09 | 0.06 | −0.08 | 0.06 | 0.06 |
810 | −0.04 | −0.08 | −0.09 | 0.01 | 0.09 | −0.09 |
907 | – | – | – | 0.01 | – | – |
934 | −0.00 | – | – | −0.00 | – | – |
952 | – | – | – | −0.01 | – | – |
961 | −0.05 | — | – | −0.05 | −0.08 | 0.20 |
1212 | – | – | – | −0.00 | – | – |
AUC | 0.62 | 0.63 | 0.65 | 0.63 | 0.64 | 0.66 |
LASSO | ENet | |||||
---|---|---|---|---|---|---|
Gen ID | ||||||
95 | 0.02 | – | – | −0.34 | – | – |
112 | 0.06 | 0.71 | 0.70 | −0.00 | −0.13 | −0.08 |
173 | −0.63 | – | – | 0.68 | – | – |
205 | – | – | – | – | – | – |
551 | 1.60 | 1.69 | 1.57 | −0.11 | −0.28 | −0.20 |
1377 | −0.22 | −0.84 | −0.80 | −0.09 | −0.16 | −0.12 |
1526 | 0.41 | 0.67 | 0.56 | 0.02 | – | – |
1543 | −0.43 | −0.79 | −0.77 | 0.40 | 0.75 | 0.69 |
2003 | −0.11 | – | – | 1.10 | – | – |
2025 | 0.18 | 0.90 | 0.78 | 1.04 | 1.22 | 1.07 |
2439 | – | – | – | −0.01 | −0.14 | −0.12 |
2705 | −0.85 | – | – | 0.36 | 0.77 | 0.61 |
2973 | 0.59 | 1.23 | 0.99 | −0.63 | −1.12 | −0.81 |
3240 | 1.13 | – | – | 0.03 | – | – |
3598 | −0.22 | −0.59 | −0.54 | 0.29 | 0.55 | 0.49 |
3882 | 0.13 | 0.40 | 0.39 | −0.06 | −0.20 | −0.15 |
4015 | 0.34 | 0.81 | 0.76 | −0.08 | −0.13 | −0.12 |
4186 | −0.50 | −0.72 | −0.53 | – | – | – |
4357 | 0.09 | – | – | −0.59 | −0.70 | −0.65 |
4662 | 0.70 | 0.90 | 0.83 | 0.21 | 0.60 | 0.38 |
5131 | 0.54 | 0.80 | 0.71 | 0.01 | 0.01 | 0.01 |
5222 | −0.15 | −0.38 | −0.26 | 1.24 | 1.67 | 1.34 |
5541 | – | – | – | −0.52 | −0.72 | −0.68 |
5577 | 0.39 | 0.86 | 0.70 | −0.73 | −0.97 | −0.80 |
5778 | −0.62 | – | – | −0.09 | – | – |
5808 | – | – | – | 0.35 | 0.55 | 0.46 |
5951 | – | – | – | 1.29 | 2.12 | 1.70 |
6103 | – | – | – | −0.63 | −0.80 | −0.76 |
6254 | – | – | – | 0.25 | 0.56 | 0.48 |
6493 | – | – | – | 0.65 | – | – |
6510 | – | – | – | 0.86 | 1.09 | 0.99 |
AUC | 0.71 | 0.71 | 0.73 | 0.72 | 0.72 | 0.74 |
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Ahmed, S.E.; Arabi Belaghi, R.; Hussein, A.A. Efficient Post-Shrinkage Estimation Strategies in High-Dimensional Cox’s Proportional Hazards Models. Entropy 2025, 27, 254. https://doi.org/10.3390/e27030254
Ahmed SE, Arabi Belaghi R, Hussein AA. Efficient Post-Shrinkage Estimation Strategies in High-Dimensional Cox’s Proportional Hazards Models. Entropy. 2025; 27(3):254. https://doi.org/10.3390/e27030254
Chicago/Turabian StyleAhmed, Syed Ejaz, Reza Arabi Belaghi, and Abdulkhadir Ahmed Hussein. 2025. "Efficient Post-Shrinkage Estimation Strategies in High-Dimensional Cox’s Proportional Hazards Models" Entropy 27, no. 3: 254. https://doi.org/10.3390/e27030254
APA StyleAhmed, S. E., Arabi Belaghi, R., & Hussein, A. A. (2025). Efficient Post-Shrinkage Estimation Strategies in High-Dimensional Cox’s Proportional Hazards Models. Entropy, 27(3), 254. https://doi.org/10.3390/e27030254