Advantage of the modified Lunn-Mcneil technique over Kalbfleisch-

Prentice technique in competing risks

Iing Lukman*a, Noor Akma Ibrahim**b, Isa Bin Daud**b, Fauziah Maarof**b, Mohd Nasir Hassan*a
a
Dept.of Environmental Science; bDept.of Mathematics
Faculty of Science and Environmental Studies
Universiti Putra Malaysia

Abstract

Survival analysis algorithm is often applied in the data mining process. Cox regression is one of the survival analysis tools
that has been used in many areas, and it can be used to analyze the failure times of aircraft crashed. Another survival
analysis tool is the competing risks where we have more than one cause of failure acting simultaneously. Lunn-McNeil
analysed the competing risks in the survival model using Cox regression with censored data. The modified Lunn-McNeil
technique is a simplify of the Lunn-McNeil technique. The Kalbfleisch-Prentice technique is involving fitting models
separately from each type of failure, treating other failure types as censored. To compare the two techniques, (the modified
Lunn-McNeil and Kalbfleisch-Prentice) a simulation study was performed. Samples with various sizes and censoring
percentages were generated and fitted using both techniques. The study was conducted by comparing the inference of
models, using Root Mean Square Error (RMSE), the power tests, and the Schoenfeld residual analysis. The power tests in
this study were likelihood ratio test, Rao-score test, and Wald statistics. The Schoenfeld residual analysis was conducted to
check the proportionality of the model through its covariates. The estimated parameters were computed for the cause-
specific hazard situation. Results showed that the modified Lunn-McNeil technique was better than the Kalbfleisch-
Prentice technique based on the RMSE measurement and Schoenfeld residual analysis. However, the Kalbfleisch-Prentice
technique was better than the modified Lunn-McNeil technique based on power tests measurement.
Key words: Survival analysis, data mining, Cox model, the modified Lunn-McNeil, Kalbfleisch-Prentice.

1.Introduction

Competing risks is a survival model dealing with more than one possible cause of death or failure to a subject in the
population (David and Moeschberger, 1978). Cox and Oakes (1984) suggested that in competing risks quite often interest is
focussed on one type of failure on its own. According to Kalbfleisch-Prentice (1980) the failure on an individual may be
caused by one of several distinct types or causes. In general, study subjects may experience a variable number of failures
each with its own type or cause. Each study subject has an underlying failure time T and a covariate vector z . The T may
be subject to censoring. Vector z is more generally a covariate function of Z = {z (u ) : u ≥ 0}, where failure can occur
due to m distinct types or causes denoted by J ∈ {1,2,..., m}. This paper compares the estimation of caused-specific
hazards method of Kalbfleisch-Prentice (1980) with the modified Lunn-McNeil (Lukman, 1999).

In this simulation study, two regression models for competing risks with censored data are compared. The first technique is
the Kalbfleisch-Prentice with Cox model. The second technique is based on the modified Lunn-McNeil. The modified
Lunn-McNeil technique is a simplification of Lunn-McNeil technique due to Lukman (1999). Both techniques can be used
for any number of different failure types assuming the risks are independent. In this study sample of various sizes and
censoring proportion are generated and fitted using both models. The cause specific hazard of joint estimation of
parameters obtained from the data duplication approach of the modified Lunn-McNeil has an advantage over the
Kalbfleisch-Prentice technique thus provide new insight into the analysis of survival data.

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 1.1 Kalbfleisch-Prentice technique

The modelling of the cause-specific hazard as a function of a covariate vector xi pertinent to each individual for the type
failure j with Cox model is
h j (t : xi ) = h0 j (t ) exp( β l xi ), j=1,2,…,m.
T
(1)
This is a straightforward extension of
λ (t , x i ) = λ 0 (t ) exp( β T xi ) , i = 1,..., n.
However both the underlying hazard h0l (t ) ≥ 0 and the vector of regression coefficients are specific to each of the m
failure types. As shown by Kalbfleisch-Prentice (1980.p.170), the parameter estimation is based upon the method of partial
likelihood. Resorting (1) , its conditional log likelihood function can be expressed as
n    

L( β ) = ∑  β lT xi − ln ∑ exp( β lT xi )  .
k =1 
  j∈R  
β l ' s are estimated separately for each failure type by considering failures of the remaining types as censored
T
The
observations on each individual.

1.2 The modified Lunn-McNeil technique

The assumption is the same as in the Lunn-McNeil technique. The data entries are the same. Suppose that we have two
failure type, where failure type I and failure type II are denoted by δ and 1 − δ where δ = 0 or 1. If subject i fails at
time t i and the first failure type δ i (or 1 − δ i ) then the second failure type is 1 − δ i (or δ i ). By providing a column for
the second failure type, two entries are made as follows
Table 1. Data handling of the modified Lunn-McNeil technique
__________________________________________________________________
Failure Type Covariates
__________________________________________________________________
Subj Failure time Status I II I II
__________________________________________________________________
i ti 1 δi 1−δi xi , δ i xi xi , ( 1 − δ i ) xi

i (rep) ti 0 1−δi δi xi , ( 1 − δ i ) xi xi , δ i xi
__________________________________________________________________
If subject i is censored repeat as above but now the status for both failure type is equal to 0. The augmentation of the
second failure type in Table 1 is useful for seeking the joint estimation of parameters as shown in Table 4 of Lunn-McNeil
(1995). Later, we will regress the duplicated data on failure type (either one of two failure types) and its covariates.

The mechanism of modification is as follows; Cox model is run on the duplicated data set, failure type δ (or 1 − δ ) being
included with the covariates x and δ x (or x and 1 − δ ). Within the competing risks framework Kay (1986) says, for a

patient with covariate values x 2 ,..., x p the estimated hazards for cause–specific j is as follows

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 λ j (t ; x) = λ 0 j (t )(exp( β j1 x1 ))(exp( β j 2 x 2 + .......β jp x p ), j = 1,2,......, m (2)

Where x1 is the binary treatment indicator and x 2 ,..., x p are the background covariates. Then run (2) using the approach
shown in Table 1.

The regression model introduced by Cox (1972) specifies the hazard rate λ j (t ; x) for each individual in terms of a vector
of covariates xi = ( xi1 ,...., xip ) specific to that individual and its vector of regression parameters β = ( β 1 ,....., β p ) , (2)
can then be written as follows
p
λ j (t ; xi ) = λ * (t ) exp ∑ β r x jr (3)
r =1

Contribution of (3) to the partial likelihood corresponding to the jth risk set is as follows

p
exp ∑ β r x jr
r =1
p
(4)
∑ exp ∑ β
j∈R r =1
r x jr

By introducing censoring indicator ϕ i (Noor Akma Ibrahim and Isa Daud, 1995) where ϕ i =1 if t i is failure and ϕ i = 0 if
t i is censored, (4) can be written as

p
exp((∑ β r x jr )ϕ i )
r =1
p
(5)
∑ exp(∑ β
j∈R r =1
r x jr ) ϕi

Hence the required conditional log likelihood becomes

n  p   p  
L( β ) = ∑ ϕ i ∑ β r x jr − ln ∑ exp ∑ β r x jr   , (6)
i =1  r =1  j∈R  r =1  
which is not different from conditional log likelihood of Cox model.

2.Simulation study

The first objective of this simulation study is to compare the mean, biasness, and root means square error (rmse) obtained
from fitting the cause-specific proportional hazards model by both techniques namely cause-specific hazards Kalbfleisch-
Prentice technique and cause–specific hazards based on Lunn-McNeil. In this simulation study the covariates chosen are

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 similar to the Stanford heart transplant data. All generated data is obtained using SAS software. The simulated data is based
on the Stanford Heart Transplant Data for two types of failure. The five covariates generated for both types of failures are
the same as in the initial parameter. These covariates are age, mismatch score, age by failure type, and mismatch score by
failure type. The data for the interaction between type of failure ( δ i ) and covariates ( xi ) such as age or mismatch score by
failure type are merely the product of δ i and xi as indicated by Lunn-McNeil (1995) as δ i xi . The second objective of
this simulation study is to compare the power of the tests by fitting the cause-specific proportional hazards model by both
techniques. The power tests are based on three tests, namely Likelihood Ratio Test, Rao-score test and Wald statistic test.
The third is to examine the residual of both techniques through the calculation of the Schoenfeld residual. The two types of
failure are considered here follows the example in the Cox (1972) and complying with competing risks where j ≥ 2 . The
initial parameters of the distribution function to generate covariates of one type of failure are the same as the initial
parameter of which to generate covariates of another type. Exponential distribution is used for generating failure time, age
and mismatch score. Binomial distribution is used for the indicator variable related to type of failure. The events for type of
failure and covariates are regarded as independent. Censoring percentage in every data set is fixed. Therefore if we have
1000 simulated data for certain sample size and certain percentage of censoring then the percentage of censored
observations in each data set out of 1000 is always the same.

In generating the failure times we impose two values for λ (parameter of an exponential variate), in the first type of failure
λ=1.25, the second λ= .75. This is to get the proportionality between the two types of failure. Hence the curves of both
types of failure are parallel (in vertical distance). The data generated is simulated 1000 times for every sample size together
with the designated percentage of censoring. The observations to be censored, were randomly chosen. True (Initial)
Parameter of any failure type β 1 =1, β 2 =. 06605 (for age), β 3 =. 200 (for mismatch score), β 4 =. 0654 (for age by any
failure type), β 5 =. 198 (for mismatch score by any failure type).

2.1 Results from simulation for rmse

Table 2. Analysis of maximum likelihood estimates of cause-specific hazard for rmse

Sample size of 15 and censoring percentage of 25 are as follows

Kalbfleisch-Prentice technique Modified Lunn-McNeil technique
Par β1 β2 β3 β4 β5 β1 β2 β3 β4 β5
Mean 37.398 .318 .801 -.286 1.405 .134 -.008 -.038 .003 .019
Bias 36.408 -.252 .601 -.351 1.207 -.856 -.074 -.238 -.062 -.179
RMSE 612.95 15.49 19.46 32.75 40.31 1.97 .104 .333 .117 .375
Sample size of 15 and censoring percentage of 50 are as follows
Kalbfleisch-Prentice technique Modified Lunn-McNeil technique
Par β1 β2 β3 β4 β5 β1 β2 β3 β4 β5
Mean 15.586 -.831 .124 .000 .049 .622 -.058 -.161 .036 -.195
Bias 14.596 -.149 .059 -.065 -.149 -.368 -.124 -.361 -.102 -.393
RMSE 222.48 3.034 10.16 .078 106.3 13.13 .859 3.077 1.627 11.27
Sample size of 45 and censoring percentage of 25 are as follows
Kalbfleisch-Prentice technique Modified Lunn-McNeil technique
Par β1 β2 β3 β4 β5 β1 β2 β3 β4 β5
Mean 23.252 .005 -2.94 -.005 2.942 .063 -.002 -.004 .001 0

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 Bias 22.262 -.061 -3.14 -.070 2.744 -.927 -.068 -.204 -.065 -.198
RMSE 201.45 6.71 47.32 6.71 47.23 1.105 .071 .213 .072 .22
Sample size of 45 and censoring percentage of 50 are as follows
Kalbfleisch-Prentice technique Modified Lunn-McNeil technique
Par β1 β2 β3 β4 β5 β1 β2 β3 β4 β5
Mean 19.58 -.075 -1.883 .073 1.881 .087 -.004 -.013 0 .004
Bias 18.59 -.141 -2.083 .008 1.683 -.903 -.070 -.213 -.065 -.194
RMSE 138.06 5.163 38.207 5.16 38.19 1.197 .071 .23 .078 .231
Sample size of 80 and censoring percentage of 25 are as follows
Kalbfleisch-Prentice technique Modified Lunn-McNeil technique
Par β1 β2 β3 β4 β5 β1 β2 β3 β4 β5
Mean 29.964 -.475 3.527 .476 -3.527 -.234 .001 -.036 0 .102
Bias 28.974 -.541 3.327 .410 -3.725 -1.22 -.065 -.236 -.07 -.095
RMSE 257.53 4.77 87.79 -3.72 87.82 1.272 .067 .313 .066 .168
Sample size of 80 and censoring percentage of 50 are as follows
Kalbfleisch-Prentice technique Modified Lunn-McNeil technique
Par β1 β2 β3 β4 β5 β1 β2 β3 β4 β5
Mean 28.30 -.343 3.36 .342 -3.35 -.236 0 -.032 0 .103
Bias 27.31 -.409 3.16 .277 -3.55 -1.23 -.066 -.232 -.066 -.095
RMSE 269.62 4.22 91.34 4.21 91.37 1.383 .069 .34 .068 .268
Sample size of 80 and censoring percentage of 75 are as follows
Kalbfleisch-Prentice technique Modified Lunn-McNeil technique
Par β1 β2 β3 β4 β5 β1 β2 β3 β4 β5
Mean 17.634 -.105 -1.70 .101 2.183 -.313 -.004 -.015 .001 .123
Bias 16.644 -.171 -1.90 .035 1.985 -1.30 -.072 -.215 -.065 -.075
RMSE 48.563 .326 66.81 1.32 67.33 1.764 .076 .419 .072 .462

In the rmse computation above we find that in general for every sample size and censoring percentage the modified Lunn-
McNeil technique gives values of estimated parameter for mean, biasness, and root mean square error (rmse) smaller than
those of Kalbfleisch-Prentice technique.

2.2 Power of test measuremnet

Bruning and Kintz (1997) wrote that the power of a statistical test is defined as the probability of rejecting the null
hypothesis when it is false.
On the simulation study regarding the power of the tests of the Likelihood ratio test, Rao-score test, and Wald statistic we
set α = .05, the power is set at .80 for the entire performances of those three tests.
The statistical inference on β = ( β 1 , . . ., β Κ ) are tested using the three tests which are based on the properties
of the likelihood function (Marubini and Valsecchi,1995). Suppose the hypothesis to be tested is
H0 : β = β 0
(a) The likelihood ratio (LR) test.
The test statistics for H 0 is based on the difference of the log-likelihood values. Miller (1981) wrote the
likelihood ratio test as follows

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 L( β 0 )
− 2 log 
Lβ ()  
(7)

is asymptotically distributed under ( ) ()

H 0 , where L β 0 is evaluated at β =0 and L β evaluated at β ≠ 0 .
(b) The Wald test

It is based on the maximum likelihood estimator β . Miller (1981) Wald statistics is

(β − β ) I ( β ) (β − β )
0 T 0 0
(8)
Which is asymptotically distributed as χ under H 0 with p degrees of freedom, where I (β ) is the Fisher information of
2

 
the entire sample or the expected value of the sample information matrix, Ε(i (β )) = Ι(β ) , and i β = −
∂2
∂β 2
()
log L β ()

is called the sample information matrix at β .
(c) Rao’s Score test
According to Miller (1981) the Rao’s score test is as follows
∂ ∂
log L( β 0 ) T Ι −1 ( β 0 ) log L( β 0 ) (9)
∂β ∂β
It is asymptotically distributed as χ with p degrees of freedom under H 0 , where Ι β
2 0
( )
is the Fisher information,

when under censoring we may need to replace Ι β ( )

with sample information matrix i (β ) . The three tests often lead to
0

identical conclusions on the regression parameters (parameter estimate) (Marubini and Valsecchi, 1995). Powers of the
Wald, Rao-score, and the Likelihood Ratio statistics were used to test H 0 : β = β 0 , where β = (β 1 ,......., β Κ ) is the
vector of parameters with Κ = 1,2,3,........, n

Table 3 gives the results of power tests of the cause-specific hazards in the competing risks with censored data per 1000
Simulated Data. The value of the power is written using 3 digits, for example for Wald statistics of Kalbfleisch-Prentice
technique, for sample size 45 and censoring percentage 25% the power is written as 022. The 022 means that the χ value of
2

Wald statistics where the p-value < .05, occured only 22 out of 1000 chances. The interpretation is the same for Likelihood
ratio statistics and for Rao-score test. For the overall of 1000 data sets, the size of test is set at α = .05 and
β = 4 × α = .200 , and the power becomes 1- β = .800. This complies with the desired level of its power, that is in 1000
simulated data sets, any test of power can be powerful if only if it power occurs in at least 800 simulated data sets.

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 2.3 Results from simulation of the power tests
Table 3: Results of power of tests of the cause-specific hazards in the competing risks with censored data for both
techniques per 1000 simulated data Set. K-P is Kalbfleisch-Prentice, mLM is modified Lunn-McNeil. C.p is
censoring percentage.

No. Sample C.p. Technique Wald- Rao- Likelihood

size Statistic Score Ratio
1. 45 50 mLM 044 059 046
2. 45 25 K-P 022 974 977
3. 15 25 K-P 000 202 200
4. 15 25 mLM 007 079 071
5. 15 50 K-P 000 160 114
6. 45 50 K-P 001 938 977
7. 15 50 mLM 000 081 084
8. 80 25 mLM 054 063 057
9. 45 25 mLM 040 045 034
10. 80 50 K-P 048 974 974
11. 80 50 mLM 048 057 056
12. 80 75 K-P 009 966 975
13. 80 25 K-P 128 951 951
14. 80 75 mLM 040 053 051

From Table 3 above it is clear that in the sample size of 45 (c.p of 25, and 50), and sample size of 80 (c.p of 25,50, and 75)
the Kalbfleisch-Prentice technique is powerful than the modified Lunn-McNeil technique with respect to the likelihood ratio
test and Rao-score test. The Wald statistic is weak in both techniques.

2.4 Schoenfeld Residual

In accordance with the Schoenfeld residual, if the model holds, the hazards proportionality’s assumption is met, the
residuals will randomly be fluctuating around zero, and gradually converge to zero with regards to the time.

Suppose n individuals are indexed by i = 1,..., n and that each has a p − vector of covariates z i = ( z i1 ,..., z ip ) T . The
proportional hazards regression model specifies that the hazard function of the i th individual is
λi (t ) = λ0 (t ) exp( β T z i ),
where β is a vector of p parameters and λ 0 (t ) is an arbitrary function.

Let D be the indices of the individuals who failed and let Ri be the indices of those under observation when the i th
individual fails. Using partial (Cox, 1975) or marginal (Kalbfleisch and Prentice, 1980, p. 71) likelihood arguments, one

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 can estimate β by maximizing the likelihood function of the following model: for i ∈ D, an index l ∈ Ri is selected
with probability
exp( β T z l ) / ∑ exp( β T z k ).
k∈Ri

In this model z i is a random variable with

E ( z ij | Ri ) = ∑z
k∈Ri
kj exp( β T z k ) / ∑ exp( β T z k ),
k∈Ri

the maximum likelihood estimate of β is a solution to

∑ {z ij − E ( z ij | Ri }= 0.
i∈D

Denote this solution by β̂ and let Eˆ ( z ij | Ri ) be E ( z ij | Ri ) with β̂ substituted for β .

We can obtain Schoenfeld residuals (Schoenfeld, 1982) for the Cox proportional hazards regression analysis by
calculating
 
rik = z ik − E ( z ik | Ri ) (10)
    T
Where rik is Schoenfeld partial residual at t i as the vector ri = ( ri1 , . . . , rip ) . Thus the Schoenfeld residual is the
difference between the observed value of Z ik and its conditional expectation given Ri .
 
Since ri is a vector, each rik may be examined graphically. There is one covariate coded 0 or 1. Thus the residuals are
equals to 1 − E ( z | Ri ) if z i is coded as 1 or equals to − E ( z | Ri ) if z i is coded as 0. If the proportional hazard holds
the expected value of Schoenfeld residual or Ε( rik ) = 0 , the plot of Schoenfeld residual of a covariate versus time will be
centered about zero with random scatter. The following are the results of plotting Schoenfeld residual for particular
covariate from the simulation.

Table 4. Results of Schoenfeld Residual on the Simulated Data

n =15 n=45 n=80
Covariate C.p 25 C.p50 C.p 25 C.p 50 C.p 25 C.p 50 C.p 75
.
z L.D. L.D. L.D. L.D. L.D. L.D. L.D.
2K −P

z 2 mLM L.D. L.D. L.D. L.D. L.D. L.D. L.D.

z3K −P L.D. L.D. L.D. L.D. L.D. L.D. L.D.

z 3mLM L.D. L.D. L.D. L.D. L.D. L.D. L.D.

z4K −P L.D. L.D. L.D. L.D L.D. L.D. L.D.

z 4 mLM V.o.p V.o.p V.o.p V.o.p L.D. V.o.p V.o.p

z5 K −P L.D. L.D. L.D. L.D L.D. L.D. L.D.

z 5mLM V.o.p V.o.p V.o.p V.o.p L.D. V.o.p V.o.p

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 z 2 K − P is covariate
Notes V.o.p is validity of proportional hazards model. L.D is little departure from proportional hazards.
of age from Kalbfeisch-Prentice technique (K-P), z 2 mLM is covariate of age from modified Lunn-McNeil (mLM). z 3 K − P is
covariate of mismatch score from K-P. z 4 K − P is covariate of interaction between type of failure and age fromn K-P.
z 5mLM is covariate of interaction between type of failure and mismatch score from mLM. From Table 4 it can be seen that
the result of Schoenfeld residual analysis for covariate of z 4 mLM and z 5 mLM from mLM demonstrated the validity of the
proportional hazards assumtion (except for n=80 and c.p=25), when there is none from K-P.

3. Conclusion

Using cause-specific hazards for parameter estimation in competing risks, the modified Lunn-McNeil technique is better
than the Kalbfleisch-Prentice technique with respect to the values of the rmse and results from Schoenfeld residual analysis.
However, the Kalbfleisch-Prentice is better than the modified Lunn-McNeil with respect to its powerfulness in power test
measurement.

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Iingl@yahoo.com; phone 603-89466742; Fax 603-89438109; Department of Environmental Science, Universiti Putra Malaysia, Serdang-
UPM,Selangor D.E. Malaysia 43400; nakma@fsas.upm.edu.my; phone 603-89466847; Fax 603-89437958; http://www.upm.edu.my;
Department of Mathematics, Serdang UPM, Selangor, D.E. Malaysia 43400;

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