In fitting the Cox regression model by maximizing the partial likelihood, the estimate of an explanatory variable X
will be infinite if the value of X
at each uncensored failure time is the largest of all the values of X
in the risk set at that time (Tsiatis, 1981; Bryson and Johnson, 1981). You can exploit this information to artificially create a data set that has the condition of monotone likelihood for the
Cox regression. The following DATA step modifies the Myeloma
data in Example 67.1 to create a new explanatory variable, Contrived
, which has the value 1 if the observed time is less than or equal to 65 and has the value 0 otherwise. The phenomenon of
monotone likelihood will be demonstrated in the new data set Myeloma2
.
data Myeloma2; set Myeloma; Contrived= (Time <= 65); run;
For illustration purposes, consider a Cox model with three explanatory variables, one of which is the variable Contrived
. The following statements invoke PROC PHREG to perform the Cox regression. The IPRINT option is specified in the MODEL statement
to print the iteration history of the optimization.
proc phreg data=Myeloma2; model Time*Vstatus(0)=LOGbun HGB Contrived / itprint; run;
The symptom of monotonity is demonstrated in Output 67.4.1. The log likelihood converges to the value of –136.56 while the coefficient for Contrived
diverges. Although the Newton-Raphson optimization process did not fail, it is obvious that convergence is questionable.
A close examination of the standard errors in the “Analysis of Maximum Likelihood Estimates” table reveals a very large value for the coefficient of Contrived
. This is very typical of a diverged estimate.
Output 67.4.1: Monotone Likelihood Behavior Displayed
Maximum Likelihood Iteration History | |||||
---|---|---|---|---|---|
Iter | Ridge | Log Likelihood | LogBUN | HGB | Contrived |
0 | 0 | -154.8579914384 | 0.0000000000 | 0.000000000 | 0.000000000 |
1 | 0 | -140.6934052686 | 1.9948819671 | -0.084318519 | 1.466331269 |
2 | 0 | -137.7841629416 | 1.6794678962 | -0.109067888 | 2.778361123 |
3 | 0 | -136.9711897754 | 1.7140611684 | -0.111564202 | 3.938095086 |
4 | 0 | -136.7078932606 | 1.7181735043 | -0.112273248 | 5.003053568 |
5 | 0 | -136.6164264879 | 1.7187547532 | -0.112369756 | 6.027435769 |
6 | 0 | -136.5835200895 | 1.7188294108 | -0.112382079 | 7.036444978 |
7 | 0 | -136.5715152788 | 1.7188392687 | -0.112383700 | 8.039763533 |
8 | 0 | -136.5671126045 | 1.7188405904 | -0.112383917 | 9.040984886 |
9 | 0 | -136.5654947987 | 1.7188407687 | -0.112383947 | 10.041434266 |
10 | 0 | -136.5648998913 | 1.7188407928 | -0.112383950 | 11.041599592 |
11 | 0 | -136.5646810709 | 1.7188407960 | -0.112383951 | 12.041660414 |
12 | 0 | -136.5646005760 | 1.7188407965 | -0.112383951 | 13.041682789 |
13 | 0 | -136.5645709642 | 1.7188407965 | -0.112383951 | 14.041691020 |
14 | 0 | -136.5645600707 | 1.7188407965 | -0.112383951 | 15.041694049 |
15 | 0 | -136.5645560632 | 1.7188407965 | -0.112383951 | 16.041695162 |
16 | 0 | -136.5645545889 | 1.7188407965 | -0.112383951 | 17.041695572 |
Analysis of Maximum Likelihood Estimates | ||||||
---|---|---|---|---|---|---|
Parameter | DF | Parameter Estimate |
Standard Error |
Chi-Square | Pr > ChiSq | Hazard Ratio |
LogBUN | 1 | 1.71884 | 0.58376 | 8.6697 | 0.0032 | 5.578 |
HGB | 1 | -0.11238 | 0.06090 | 3.4053 | 0.0650 | 0.894 |
Contrived | 1 | 17.04170 | 1080 | 0.0002 | 0.9874 | 25183399 |
Next, the Firth correction was applied as shown in the following statements. Also, the profile-likelihood confidence limits for the hazard ratios are requested by using the RISKLIMITS=PL option.
proc phreg data=Myeloma2; model Time*Vstatus(0)=LogBUN HGB Contrived / firth risklimits=pl itprint; run;
PROC PHREG uses the penalized likelihood maximum to obtain a finite estimate for the coefficient of Contrived
(Output 67.4.2). The much preferred profile-likelihood confidence limits, as shown in (Heinze and Schemper, 2001), are also displayed.
Output 67.4.2: Convergence Obtained with the Firth Correction
Maximum Likelihood Iteration History | |||||
---|---|---|---|---|---|
Iter | Ridge | Log Likelihood | LogBUN | HGB | Contrived |
0 | 0 | -150.7361197494 | 0.0000000000 | 0.000000000 | 0.0000000000 |
1 | 0 | -136.9933949142 | 2.0262484120 | -0.086519138 | 1.4338859318 |
2 | 0 | -134.5796594364 | 1.6770836974 | -0.109172604 | 2.6221444778 |
3 | 0 | -134.1572923217 | 1.7163408994 | -0.111166227 | 3.4458043289 |
4 | 0 | -134.1229607193 | 1.7209210332 | -0.112007726 | 3.7923555412 |
5 | 0 | -134.1228364805 | 1.7219588214 | -0.112178328 | 3.8174197804 |
6 | 0 | -134.1228355256 | 1.7220081673 | -0.112187764 | 3.8151642206 |
Analysis of Maximum Likelihood Estimates | ||||||||
---|---|---|---|---|---|---|---|---|
Parameter | DF | Parameter Estimate |
Standard Error |
Chi-Square | Pr > ChiSq | Hazard Ratio |
95% Hazard Ratio Profile Likelihood Confidence Limits |
|
LogBUN | 1 | 1.72201 | 0.58379 | 8.7008 | 0.0032 | 5.596 | 1.761 | 17.231 |
HGB | 1 | -0.11219 | 0.06059 | 3.4279 | 0.0641 | 0.894 | 0.794 | 1.007 |
Contrived | 1 | 3.81516 | 1.55812 | 5.9955 | 0.0143 | 45.384 | 5.406 | 6005.404 |