The PHREG Procedure

Example 86.1 Stepwise Regression

(View the complete code for this example.)

Krall, Uthoff, and Harley (1975) analyzed data from a study on multiple myeloma in which researchers treated 65 patients with alkylating agents. Of those patients, 48 died during the study and 17 survived. The following DATA step creates the data set Myeloma. The variable Time represents the survival time in months from diagnosis. The variable VStatus consists of two values, 0 and 1, indicating whether the patient was alive or dead, respectively, at the end of the study. If the value of VStatus is 0, the corresponding value of Time is censored. The variables thought to be related to survival are LogBUN (log(BUN) at diagnosis), HGB (hemoglobin at diagnosis), Platelet (platelets at diagnosis: 0=abnormal, 1=normal), Age (age at diagnosis, in years), LogWBC (log(WBC) at diagnosis), Frac (fractures at diagnosis: 0=none, 1=present), LogPBM (log percentage of plasma cells in bone marrow), Protein (proteinuria at diagnosis), and SCalc (serum calcium at diagnosis). Interest lies in identifying important prognostic factors from these nine explanatory variables.

data Myeloma;
   input Time VStatus LogBUN HGB Platelet Age LogWBC Frac
         LogPBM Protein SCalc;
   label Time='Survival Time'
         VStatus='0=Alive 1=Dead';
   datalines;
 1.25  1  2.2175   9.4  1  67  3.6628  1  1.9542  12  10
 1.25  1  1.9395  12.0  1  38  3.9868  1  1.9542  20  18
 2.00  1  1.5185   9.8  1  81  3.8751  1  2.0000   2  15
 2.00  1  1.7482  11.3  0  75  3.8062  1  1.2553   0  12
 2.00  1  1.3010   5.1  0  57  3.7243  1  2.0000   3   9
 3.00  1  1.5441   6.7  1  46  4.4757  0  1.9345  12  10
 5.00  1  2.2355  10.1  1  50  4.9542  1  1.6628   4   9
 5.00  1  1.6812   6.5  1  74  3.7324  0  1.7324   5   9
 6.00  1  1.3617   9.0  1  77  3.5441  0  1.4624   1   8
 6.00  1  2.1139  10.2  0  70  3.5441  1  1.3617   1   8
 6.00  1  1.1139   9.7  1  60  3.5185  1  1.3979   0  10
 6.00  1  1.4150  10.4  1  67  3.9294  1  1.6902   0   8
 7.00  1  1.9777   9.5  1  48  3.3617  1  1.5682   5  10
 7.00  1  1.0414   5.1  0  61  3.7324  1  2.0000   1  10
 7.00  1  1.1761  11.4  1  53  3.7243  1  1.5185   1  13
 9.00  1  1.7243   8.2  1  55  3.7993  1  1.7404   0  12
11.00  1  1.1139  14.0  1  61  3.8808  1  1.2788   0  10
11.00  1  1.2304  12.0  1  43  3.7709  1  1.1761   1   9
11.00  1  1.3010  13.2  1  65  3.7993  1  1.8195   1  10
11.00  1  1.5682   7.5  1  70  3.8865  0  1.6721   0  12
11.00  1  1.0792   9.6  1  51  3.5051  1  1.9031   0   9
13.00  1  0.7782   5.5  0  60  3.5798  1  1.3979   2  10
14.00  1  1.3979  14.6  1  66  3.7243  1  1.2553   2  10
15.00  1  1.6021  10.6  1  70  3.6902  1  1.4314   0  11
16.00  1  1.3424   9.0  1  48  3.9345  1  2.0000   0  10
16.00  1  1.3222   8.8  1  62  3.6990  1  0.6990  17  10
17.00  1  1.2304  10.0  1  53  3.8808  1  1.4472   4   9
17.00  1  1.5911  11.2  1  68  3.4314  0  1.6128   1  10
18.00  1  1.4472   7.5  1  65  3.5682  0  0.9031   7   8
19.00  1  1.0792  14.4  1  51  3.9191  1  2.0000   6  15
19.00  1  1.2553   7.5  0  60  3.7924  1  1.9294   5   9
24.00  1  1.3010  14.6  1  56  4.0899  1  0.4771   0   9
25.00  1  1.0000  12.4  1  67  3.8195  1  1.6435   0  10
26.00  1  1.2304  11.2  1  49  3.6021  1  2.0000  27  11
32.00  1  1.3222  10.6  1  46  3.6990  1  1.6335   1   9
35.00  1  1.1139   7.0  0  48  3.6532  1  1.1761   4  10
37.00  1  1.6021  11.0  1  63  3.9542  0  1.2041   7   9
41.00  1  1.0000  10.2  1  69  3.4771  1  1.4771   6  10
41.00  1  1.1461   5.0  1  70  3.5185  1  1.3424   0   9
51.00  1  1.5682   7.7  0  74  3.4150  1  1.0414   4  13
52.00  1  1.0000  10.1  1  60  3.8573  1  1.6532   4  10
54.00  1  1.2553   9.0  1  49  3.7243  1  1.6990   2  10
58.00  1  1.2041  12.1  1  42  3.6990  1  1.5798  22  10
66.00  1  1.4472   6.6  1  59  3.7853  1  1.8195   0   9
67.00  1  1.3222  12.8  1  52  3.6435  1  1.0414   1  10
88.00  1  1.1761  10.6  1  47  3.5563  0  1.7559  21   9
89.00  1  1.3222  14.0  1  63  3.6532  1  1.6232   1   9
92.00  1  1.4314  11.0  1  58  4.0755  1  1.4150   4  11
 4.00  0  1.9542  10.2  1  59  4.0453  0  0.7782  12  10
 4.00  0  1.9243  10.0  1  49  3.9590  0  1.6232   0  13
 7.00  0  1.1139  12.4  1  48  3.7993  1  1.8573   0  10
 7.00  0  1.5315  10.2  1  81  3.5911  0  1.8808   0  11
 8.00  0  1.0792   9.9  1  57  3.8325  1  1.6532   0   8
12.00  0  1.1461  11.6  1  46  3.6435  0  1.1461   0   7
11.00  0  1.6128  14.0  1  60  3.7324  1  1.8451   3   9
12.00  0  1.3979   8.8  1  66  3.8388  1  1.3617   0   9
13.00  0  1.6628   4.9  0  71  3.6435  0  1.7924   0   9
16.00  0  1.1461  13.0  1  55  3.8573  0  0.9031   0   9
19.00  0  1.3222  13.0  1  59  3.7709  1  2.0000   1  10
19.00  0  1.3222  10.8  1  69  3.8808  1  1.5185   0  10
28.00  0  1.2304   7.3  1  82  3.7482  1  1.6721   0   9
41.00  0  1.7559  12.8  1  72  3.7243  1  1.4472   1   9
53.00  0  1.1139  12.0  1  66  3.6128  1  2.0000   1  11
57.00  0  1.2553  12.5  1  66  3.9685  0  1.9542   0  11
77.00  0  1.0792  14.0  1  60  3.6812  0  0.9542   0  12
;

The stepwise selection process consists of a series of alternating forward selection and backward elimination steps. The former adds variables to the model, while the latter removes variables from the model.

The following statements use PROC PHREG to produce a stepwise regression analysis. Stepwise selection is requested by specifying the SELECTION=STEPWISE option in the MODEL statement. The option SLENTRY=0.25 specifies that a variable has to be significant at the 0.25 level before it can be entered into the model, while the option SLSTAY=0.15 specifies that a variable in the model has to be significant at the 0.15 level for it to remain in the model. The DETAILS option requests detailed results for the variable selection process.

proc phreg data=Myeloma;
   model Time*VStatus(0)=LogBUN HGB Platelet Age LogWBC
                         Frac LogPBM Protein SCalc
                         / selection=stepwise slentry=0.25
                           slstay=0.15 details;
run;

Results of the stepwise regression analysis are displayed in Output 86.1.1 through Output 86.1.7.

Individual score tests are used to determine which of the nine explanatory variables is first selected into the model. In this case, the score test for each variable is the global score test for the model containing that variable as the only explanatory variable. Output 86.1.1 displays the chi-square statistics and the corresponding p-values. The variable LogBUN has the largest chi-square value (8.5164), and it is significant (p = 0.0035) at the SLENTRY=0.25 level. The variable LogBUN is thus entered into the model.

Output 86.1.1: Individual Score Test Results for All Variables

The PHREG Procedure

Model Information
Data SetWORK.MYELOMA 
Dependent VariableTimeSurvival Time
Censoring VariableVStatus0=Alive 1=Dead
Censoring Value(s)0 
Ties HandlingBRESLOW 

Summary of the Number of Event and Censored
Values
TotalEventCensoredPercent
Censored
65481726.15

Analysis of Effects Eligible for
Entry
EffectDFScore
Chi-Square
Pr > ChiSq
LogBUN18.51640.0035
HGB15.06640.0244
Platelet13.18160.0745
Age10.01830.8924
LogWBC10.56580.4519
Frac10.91510.3388
LogPBM10.58460.4445
Protein10.14660.7018
SCalc11.11090.2919

Residual Chi-Square Test
Chi-SquareDFPr > ChiSq
18.455090.0302


Output 86.1.2 displays the results of the first model. Since the Wald chi-square statistic is significant (p = 0.0039) at the SLSTAY=0.15 level, LogBUN stays in the model.

Output 86.1.2: First Model in the Stepwise Selection Process


Step 1. Effect LogBUN is entered. The model contains the following effects:


LogBUN

Convergence Status
Convergence criterion (GCONV=1E-8) satisfied.

Model Fit Statistics
CriterionWithout
Covariates
With
Covariates
-2 LOG L309.716301.959
AIC309.716303.959
SBC309.716305.830

Testing Global Null Hypothesis: BETA=0
TestChi-SquareDFPr > ChiSq
Likelihood Ratio7.757210.0053
Score8.516410.0035
Wald8.339210.0039

Analysis of Maximum Likelihood Estimates
ParameterDFParameter
Estimate
Standard
Error
Chi-SquarePr > ChiSqHazard
Ratio
LogBUN11.745950.604608.33920.00395.731


The next step consists of selecting another variable to add to the model. Output 86.1.3 displays the chi-square statistics and p-values of individual score tests (adjusted for LogBUN) for the remaining eight variables. The score chi-square for a given variable is the value of the likelihood score test for testing the significance of the variable in the presence of LogBUN. The variable HGB is selected because it has the highest chi-square value (4.3468), and it is significant (p = 0.0371) at the SLENTRY=0.25 level.

Output 86.1.3: Score Tests Adjusted for the Variable LogBUN

Analysis of Effects Eligible for
Entry
EffectDFScore
Chi-Square
Pr > ChiSq
HGB14.34680.0371
Platelet12.01830.1554
Age10.71590.3975
LogWBC10.07040.7908
Frac11.03540.3089
LogPBM11.03340.3094
Protein10.52140.4703
SCalc11.41500.2342

Residual Chi-Square Test
Chi-SquareDFPr > ChiSq
9.316480.3163


Output 86.1.4 displays the fitted model containing both LogBUN and HGB. Based on the Wald statistics, neither LogBUN nor HGB is removed from the model.

Output 86.1.4: Second Model in the Stepwise Selection Process


Step 2. Effect HGB is entered. The model contains the following effects:


LogBUN HGB

Convergence Status
Convergence criterion (GCONV=1E-8) satisfied.

Model Fit Statistics
CriterionWithout
Covariates
With
Covariates
-2 LOG L309.716297.767
AIC309.716301.767
SBC309.716305.509

Testing Global Null Hypothesis: BETA=0
TestChi-SquareDFPr > ChiSq
Likelihood Ratio11.949320.0025
Score12.725220.0017
Wald12.190020.0023

Analysis of Maximum Likelihood Estimates
ParameterDFParameter
Estimate
Standard
Error
Chi-SquarePr > ChiSqHazard
Ratio
LogBUN11.674400.612097.48330.00625.336
HGB1-0.118990.057514.28110.03850.888


Output 86.1.5 shows Step 3 of the selection process, in which the variable SCalc is added, resulting in the model with LogBUN, HGB, and SCalc as the explanatory variables. Note that SCalc has the smallest Wald chi-square statistic, and it is not significant (p = 0.1782) at the SLSTAY=0.15 level.

Output 86.1.5: Third Model in the Stepwise Regression


Step 3. Effect SCalc is entered. The model contains the following effects:


LogBUN HGB SCalc

Convergence Status
Convergence criterion (GCONV=1E-8) satisfied.

Model Fit Statistics
CriterionWithout
Covariates
With
Covariates
-2 LOG L309.716296.078
AIC309.716302.078
SBC309.716307.692

Testing Global Null Hypothesis: BETA=0
TestChi-SquareDFPr > ChiSq
Likelihood Ratio13.637730.0034
Score15.305330.0016
Wald14.454230.0023

Analysis of Maximum Likelihood Estimates
ParameterDFParameter
Estimate
Standard
Error
Chi-SquarePr > ChiSqHazard
Ratio
LogBUN11.635930.623596.88220.00875.134
HGB1-0.126430.058684.64190.03120.881
SCalc10.132860.098681.81270.17821.142


The variable SCalc is then removed from the model in a step-down phase in Step 4 (Output 86.1.6). The removal of SCalc brings the stepwise selection process to a stop in order to avoid repeatedly entering and removing the same variable.

Output 86.1.6: Final Model in the Stepwise Regression


Step 4. Effect SCalc is removed. The model contains the following effects:


LogBUN HGB

Convergence Status
Convergence criterion (GCONV=1E-8) satisfied.

Model Fit Statistics
CriterionWithout
Covariates
With
Covariates
-2 LOG L309.716297.767
AIC309.716301.767
SBC309.716305.509

Testing Global Null Hypothesis: BETA=0
TestChi-SquareDFPr > ChiSq
Likelihood Ratio11.949320.0025
Score12.725220.0017
Wald12.190020.0023

Analysis of Maximum Likelihood Estimates
ParameterDFParameter
Estimate
Standard
Error
Chi-SquarePr > ChiSqHazard
Ratio
LogBUN11.674400.612097.48330.00625.336
HGB1-0.118990.057514.28110.03850.888


Note:Model building terminates because the effect to be entered is the effect that was removed in the last step.


The procedure also displays a summary table of the steps in the stepwise selection process, as shown in Output 86.1.7.

Output 86.1.7: Model Selection Summary

Summary of Stepwise Selection
StepEffectDFNumber
In
Score
Chi-Square
Wald
Chi-Square
Pr > ChiSq
EnteredRemoved
1LogBUN 118.5164 0.0035
2HGB 124.3468 0.0371
3SCalc 131.8225 0.1770
4 SCalc12 1.81270.1782


The stepwise selection process results in a model with two explanatory variables, LogBUN and HGB.