Kaplan Meier Survival Curve and

The Log-Rank test

Kelompok B
BERLIANA SITUMEANG 1506704371
MAULIA AFIDAH CAHYANI 1506704453
WITRI ZUAMA QOMARANIA1506704535
SILVA SANI DARUSMAN 1506785122
Kaplan Meier
Kaplan Meier (KM) or product limit approach to estimating the survival
function provides a response to the limitations of the standard life table
identified in section 5.3.4.
In the KM approach, the observed event times for the cohort studied
define the values t at which st, is evaluated ; in the life table approach
these values are round numbers, usually set in advance of data collection
The KM approach leads to a life table with the smallest possible intervals
Use maximum amount of information in the data, ensuring that the steps
in st are as small as possible
The disadvantages are that the KM approach requires more
computation and produces a less useful tabular display
Kaplan Meier
Essentially in KM estimation is life table estimation with
the life table times (cut points used to define the
intervals) taken to be equal to the time of events in
the cohort
With no censoring, (5.1) through (5.6) are still valid
If any censoring, (5.1) and (5.4) are used rather than
(5.7) and (5.9), or any other adjusted formula
Contoh 5.6 :
Berdasarkan contoh 5.4 (data SHHS), kita coba
menghitung survival time dari follow up tahun
pertama.
Berikut data selama tahun pertama dari follow up
dalam SHHS, yang telah ditentukan dalam section
5.3.2, yakni :
1, 46, 91*, 101, 101, 103, 119, 133*, 137, 145*,
156, 186*, 208, 215, 235, 242, 251, 294, 299, 300,
309*, 312, 336*, 357*
*Menunjukkan pengamatan di sensor
Gambaran skema dari yang mengalami loss to FU
dalam tahun pertama (Gambar 5.7)
0 100 200 300 365
Survival Time (days)
 Selama satu tahun awal, terdapat 17 event penyakit jantung
dan 7 censoring ( namun untuk censoring tidak dicantumkan
didalam tabel, tetapi tetap dihitung untuk menentukan jumlah
orang yang survive pada tahun berikutnya)

Contoh : Pada hari 1, terdapat 1 event, sehingga untuk hari

selanjutnya jumlah partisipan yang dihitung adalah 4401.
selanjutnya pada hari 46 terdapat 1 event dan pada tanggal 91
terdapat 1 censoring. Oleh karena itu pada hari 101, jumlah
subjek yang survive menjadi 4401 1 1 = 4399.
Table 5.5. Data and Kaplan Meier estimation of the survival function;
year 1 of follow-up for the selected subset of SHHS men

Time Number Survival probability

(days) at risk Events Estimate Standard error
0 4402 1
1 4402 1 0,999773 0,0002271
46 4401 1 0,999546 0,0003212
101 4399 2 0,999091 0,0004542
103 5397 1 0,998864 0,0005077
119 4396 1 0,998637 0,0005561
137 4394 1 0,998410 0,0006007
156 4392 1 0,998182 0,0006421
208 4390 1 0,997954 0,0006810
215 4389 1 0,997727 0,0007178
235 4388 1 0,997500 0,0007528
242 4387 1 0,997273 0,0007862
251 4386 1 0,997045 0,0008183
294 4385 1 0,996818 0,0008491
299 4384 1 0,996591 0,0008788
300 4383 1 0,996363 0,0009075
312 4381 1 0,996136 0,0009354
365 4378
Kaplan Meier Curve
First column survival times from smallest to
largest
Second column frequency counts to failures
Third column frequency counts of does
persons censored in the time interval starting
with failure time up to but not including the next
failure time
Fourth column risk set

To estimate survival probability use risk set to

include the information we have on censored
person up to the time of censorship
Kaplan Meier Curve

Group 1 treatment : 9 failed, 12

sensor
Group 2 placebo : 21 failed, 0
sensor
Kaplan Meier Curve (No censor)
Conditional Probability
Term
Komputasi
Komputasi dilakukan 19/21 give the probability
untuk mendapatkan of surviving past the first
ordered failure time, one
nilai survival
week. And than 2 failed at
probability one week

16/17 give the probability

of surviving past the third
ordered failure time at 3
week, given survival up to
week 3 and one of these
then failed. Note that the
17 persons in the
denominator represents
the number in the risk set
at week 3

Notice that the product

terms in the KM formula for
surviving past four
Kaplan Meier Curve (Censor)

Notice that the KM

curve for group 1 is
consistently higher than
the KM curve group 2

These figure indicate

that group 1, which is
the treatment group
has better survival
prognosis than group 2,
the placebo

The beneficial effects

of the treatment over
placebo are greater the
longer on stays in
remission
General KM formula
This formula gives the probability of
t(j-1)
surviving past the previous failure time
, multiplied by the conditional t(j)
probability of surviving past t(j) time ,
given survival to at least time
The above KM formula can also be expressed as
a product limit if we substitute for the survival
probability , the product of all fractions
that estimate the conditionalt(j-1) probabilities for
failure time and earlier
General KM formula
Comparison of two sets
of survival probabilities
Mantel-Haenszel methods

* Suppose that the follow up times for both the cohorts to be compared are
divided into the same concecutive (berurutan) interval (table 5.4)
* consider the number surviving to the start of each interval and the number of
events in each interval
 Consider the first interval (0 to 1 years of follow-up)
The survival experience of two groups during this
interval as 2 x 2table.
We could then use the methods of chapter 4 to
compare the survival experience within this first year
 The fact that table akin (mirip) to Table 5.8 may be
constructed for each interval in table 5.7 ; nine tables in
all.
We seek a summary measure of the chance of an event
or, conversely (sebaliknya), of survival, across the nine
intervals : a situation analogous to that of section 4.6
(hal 143), in which Mantel-Haenszel methodology was
used to produce summaries over strata defined by
confounding variable.
Now the strata are the intervals of time, but otherwise
the methodology transfer.
 E (ai) : expected value (mean)

V(ai) : variance
 The continuity-corrected Cochran-Mantel-Haenszel test
statistic for the null hypothesis of no difference in survival
experience between the housing tenure groups is :

From Table B.3 for 1 d.f., this is significant at the 0,1%

(the exact p value is 0,006). Hence, there is evidence of a
difference in the overall chance of survival. As the sum of
observed values expected is greater than the
sum of expected for those who experience an
event amongst renters, we can conclude that renters are
the more likely to have coronary attack.
 We can use (4.10) or (4.15) to estimate the common
odds ratio or relative risk across the intervals.
the difference is explained by reference to table 5.4: a
disproportionate (tidak proporsional) number of renters
were censored (mainly due to death from other causes)
in the earlier years of follow-up.
The log-rank test
In section 5.5.1 the treatment of censored individuals wa rather crude. One
of the two cohorts (subgroups) loses several subjects during an interval
whilst (sementara) the other does not. The analysis would then be biased
against the cohort with no censoring.
As in section 5.4, we can minimize the chance of such a problem by taking
the intervals to be as small as possible.
In the current situation, we choose the intervals between successive
(berturut-turut) events for the two subgroups combined.
Evaluate whether or not KM curves for two or more groups are statistically
equivalent.
statistically equivalent means based on a testing procedure that
compares the two curves in some overall sense, we do not have evidence
to indicate that the true (population) survival curves are different.
Ex 5.8 during the first year of follow up in the SHHS, the
completed survival times (in days) for the men in owner-
occupied accommodation were :
46, 101, 103, 119, 208, 215, 235, 299, 309*, 336*
For those in rented accommodation, they were :
1, 91*, 101, 133*, 137, 145*, 156, 186*, 242, 251, 294,
300, 312, 357*
 As an example of the calculation required to obtain the final
two columns, consider the first row of the table 5.10. by
reference to the table 4.12 and analogy with example 5.7
gives
 The expected number of events in the renters group, under the null
hypothesis of no difference (in survival) between the groups, is equal to the
risk of an event in the combined cohort times the number at risk in the
renters group. This seems intuitively reasonable.

From (4.21) the continuity-corrected log-rank test statistic is

 This is to be compared with Xi2 but is clearly not
significant at any reasonable significance level.
We conclude that there is no evidence of a difference
between coronary survival probabilities in the first year
of follow-up.
Just as the choice of which group to place in the first
row of table 5.8 and table 5.9 is arbitrary, we could
choose to swap the owner-occupiers and renters data,
keeping the labels for , etc, fixed, in table 5.10. we
would then find find that has the same
magnitude but the opposite sign to that found
previously. Would remain the same. As a
consequence, the value of the log-rank test statistic
would stay the same.
 Weighted Log-Rank Tests
Alternatif dari tes log rank adalah weighted log-rank tests. Merupakan Turunan dari Log
Rank Test tanpa koreksi/ tanpa continuity correction.
Rumus yang digunakan pada Weighted log-rank test adalah
WeightedLog-RankTest Log-Rank Test

Pada Log Rank test nilai resiko pada setiap interval adalah 1 (unity), tidak ada beda
nilai resiko pada beda interval.
Pada Weighted Log Rank Test nilai resiko pada setiap interval adalah berbeda.
Weighted Log Rank Test disebut juga dengan Breslow, Gehan (Generalised) Wilcoxon Test.
Example 5.9
Pada Gambar 5.9 menunjukkan estimasi KM berdasarkan status
kepemilikan rumah selama 9 tahun berdasarkan data SHHS.
Example 5.9
Aplikasi log rank-test pada pada example 5.8 mendapatkan
E = 20,435 dan V= 53,7180
Diperoleh nilai Log-Rank test (corrected) adalah
(20,435 -0,5)2/ 53,7180 = 7,40
Diperoleh nilai Log-Rank test (uncorrected) adalah
20,4352/53,7180 = 0,38
Aplikasi weighted log-rank test
wi menggunakan generalized Wilcoxon, diperoleh
Ew = 78493 dan Vw= 8866 x 108
Diperoleh nilai weighted log-rank test (Lw) yaitu:
784932/(8866 x 108) = 6,95
 Berdasarkan hasil statistik diatas, jika disandingkan
dengan chi-square, mempunyai nilai p < 0,01.
Sehingga dapat disimpulkan terdapat perbedaan yang
signifikan dalam ketahanan (survival) antara 2 grup
(owner-occupier)
Lanjutan..,
Pada tes Cochran-Mantel-Haenzel diasumsikan bahwa
kemungkinan perbandingan dari kejadian tidak bervariasi
berdasarkan level faktor confounding
Sedangkan pada Log-Rank test diasumsikan bahwa
kemungkinan perbandingan dari kejadian tidak terdapat
variasi survival berdasarkan interval waktu asumsi
proportional hazard
Jika memenuhi asumsi proporsional hazard, log-Rank test
merupakan tes yang lebih baik digunakan, namun weighted
juga dapat digunakan.
Allowing for Confounding Variables
Log-Rank
test dapat mengatasi confounding karena data
dibagi menjadi beberapa strata berdasarkan level konfounder.
Kemudian dihitung nilai E dan V untuk setiap strata (Ej dan Vj
untuk strata j).
Test statistik untuk stratified log-rank test adalah

Tes stratified yang mirip juga dapat dilakukan pada weighted log-
rank test
Perbandingan 3 atau Lebih Grup
Log-rank test dan tes lainnya juga dapat digunakan
untuk menyelesaikan permasalahan perbandingan dari
tiga atau lebih kelompok untuk fungsi survival.
Untuk pembahasan lebih lanjut terdapat pada Chapter
11.
Competing Risk
Competing Risk
Competing risks yaitu resiko kematian akibat penyakit
lain selain yang diteliti
Example : Heart disease, follow up may be terminated
due to death from some other disease, such as cancer.
In a sense, heart disease and death from cancer
When having the second event does effect the chance
of a future event of the type that we wish to study, we
should consider taking this into account
Competing Risk
Treating the competing risk as a form of censoring gives
us estimated probabilities of an event on the
assumption that the competing cause does not occur
Example 5.6 : Some of the man who were censored
had non coronary deaths, so that we should consider the
results in the estimate column of table 5.5 as the time
specific probabilities of survival from CHD when death
(other than coronary death) is assumed not to intervene
CR analysis talk about the chance of failure than the
chance of survival
Competing risk
competing risk.xlsx
Terimakasih