Biostatistics I: Basic for Public Health

Lecture No.: KUI 6111

Starting Date: 01/09/2019

BIOSTATISTIK
LABORATORY ASSIGNMENT MODUL 11
Introduction to Survival Analysis

Tutor : Althaf Setyawan, S.Si, M.PH.

Oleh :
ROESMIYANTI PRATIWI

(19/448529/PKU/18043)

KESELAMATAN DAN KESEHATAN KERJA (K3)

PROGRAM PASCASARJANA ILMU KESEHATAN MASYARAKAT

FAKULTAS KEDOKTERAN KESEHATAN MASYARAKAT KEPERAWATAN
UNIVERSITAS GADJAH MADA
YOGYAKARTA

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 2019

Homework
1. The following figure displays the Kaplan-Meier curves from a randomized trial comparing
botulism toxin A with botulism toxin B for the treatment of cervical dystonia (n=122). Patients
were followed until their pain returned or until they were censored.
a. Which of the following can be concluded directly from the figure?

Figure 1: The Kaplan-Meier curves from a randomized trial comparing botulism toxin
A with botulism toxin B for the treatment of cervical dystonia

(a) Botulism toxin A is a better drug for treating cervical dystonia than toxin B.
(b) Botulism toxin B is a better drug for treating cervical dystonia than toxin A.
(c) The median time to return of pain was longer in the botulism toxin A group than the B
group.
(d) The median time to return of pain was longer in the botulism toxin B group than the A
group.
(e) There is a statistically significant difference between the treatments.

2. The authors also ran a univariate Cox regression to get the hazard ratio comparing treatment A
to treatment B for the outcome return of pain. The hazard ratio from this model will be:
(a) =1.0
(b) > 1.0
(c) < 1.0
(d) ≥ 1.0
(e) ≤ 1.0

3. The median time to return of pain in the botulism toxin A group was approximately:

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 (a) 0 weeks
(b) 5 weeks
(c) 12 weeks
(d) 14 weeks
(e) 25 weeks

4. The estimate of survival from pain for the botulism toxin A group at 19 weeks is about:
(a) 100%
(b) 80%
(c) 70%
(d) 50%
(e) 30%

Reading a Cox Regression Analysis

Read the Hazards Ratios derived from five different Cox regression models in artilce: "Weekend
versus Weekday Admission and Mortality from Myocardial Infarction" by William J. Kostis, Ph.D.,
Kitaw Demissie, M.D., Ph.D., Stephen W. Marcella, M.D., M.P.H., Yu-Hsuan Shao, M.H.S., Alan
C. Wilson, Ph.D., and Abel E. Moreyra, M.D., for the Myocardial Infarction Data Acquisition
System (MIDAS 10) Study Group.
N Engl J Med 2007; 356:1099-1109 March 15, 2007
Use the table 4 from the article in the NEJM available in the web as follow: http:
//content.nejm.org/cgi/reprint/356/11/1099.pdf
Please answer questions 1-4 belows.
1. Which of the following is the result of an unadjusted (univariate) analysis?
(a) Female sex
(b) 1.039 (1.012-1.066)
(c) 1.023 (0.997-1.049)
(d) None of the above. Since this is a Cox-Regression, it is always an adjusted (multivariate)
analysis.

2. Weekend admission is a statistically significant predictor of death in all the following except?
(a) Model 1 (column 1)
(b) Model 2 (column 2)
(c) Model 3 (column 3)
(d) Model 4 (column 4)
(e) Model 5 (column 5)

3. According to the statistical modeling performed by the authors, which of the following variable
groups may be explaining the increased risk of death among patients admitted on the weekends
for treatment of M.I.?
(a) Age of patient and female sex
(b) Mechanical and arrhythmic complications
(c) Longer length of stay when patients are admitted on the weekend
(d) No invasive cardiac procedure within 30 days of admission

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 4. Which of the following pair reflects the 1) PRIMARY INDEPENDENT VARIABLE of
interest AND the 2) DEPENDENT VARIABLE in this table of Cox Regression Models.
(a) Primary Indep: Weekend Admission. Depend Variable: Cardiac Intervention
Procedures (including catheterization, PCI, and CABG).
(b) Primary Indep: Cardiac Intervention Procedures (including catheterization, PCI, and
CABG). Depend Variable: Time to Death.
(c) Primary Indep: Weekend Admission. Depend Variable: Time to Death.
(d) Primary Indep: Age. Depend Variable: Time to Death.

Using Stata for Survival Analysis

Use data glioma.dta from our work presented at the 14th Asian Society for Neuro-Oncology (ASNO)
Meeting Osaka, 29th to Tuesday 31st October 2017. Article title: "Survival rates and risk factors for
high-grade glioma (HGG) treated at the National Cancer Referral Hospital, Jakarta, Indonesia".
Excute the following commands:
(a) * This is excercise on survival analysis *
use "gliomaosaka.dta", replace
describe
stset endate, failure(event==1) \\\
enter(randate) origin(randate) scale(30.15) id(id)
keep if _t<28
*Maximum axis x so that consistent \\\
with the longest survival time observed

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 (b) Run following command :
. sts list
. sts test sex, logrank
. sts graph, by(sex)
. stcox sex
. stcox chemo sex
Interpret the result! Do you conclude sex is confounding factor for chemotherapy?

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Berdasarkan tabel diatas diketahui bahwa median dari survival time nya adalah 13.2 dengan survivor
function sebesar 45.89%.

Secara statistik jenis kelamin tidak efektif mempengaruhi lama hidup pasien HGG karena p-value
sebesar 0.9125 sehingga tidak signifikan secara statistik.

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 Kaplan-Meier survival estimates

1.00
0.75
0.50
0.25
0.00
0 5 10 15 20 25
analysis time

sex = Male sex = Female

Berdasarkan grafik diatas diketahui bahwa ada garis yang saling berpotongan sehingga tidak
memenuhi assumsi proportional Hazard Ratio.

Berdasarkan data diatas bahwa Hazard Ratio utuk sex==1 (laki-laki) adalah 1.058. Sehingga laki-laki
lebih beresiko untuk hidup 1.058 lebih besar dibandingkan wanita.

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Diketahui bahwa Hazard Ratio untuk kemoterapi adalah 0,133. Sehingga pasien kemoterapi dengan
temozolamide lebih beresiko untuk hidup (1- 0,133 = 0,867) lebih besar dibandingkan pasien
dengan kemoterapi lainnya.
(c) Please do similar analysis for variable radiasi and chemo. Report your findings. File glioma.do
shows you how to create a nicer graph using STATA software. You might try it.

Kaplan-Meier survival estimates

1.00
0.75
0.50

Berdasarkan grafik disamping diketahui bahwa

survior rate untuk pasien glioma yang diradiasi
0.25

lebih besar dibandingkan yang tidak diradiasi.

Pasien yang diradiasi dapat bertahan hidup hingga
0.00

0 5 10 15 20 25
waktu ke-25 sedangkan pasien yang tidak diradiasi analysis time

radiasi = Yes radiasi = No

hanya sampai waktu ke-12.

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 Kaplan-Meier survival estimates

1.00
0.75
0.50
0.25
0.00
0 5 10 15 20 25
analysis time

chemo = no chemotheraphy chemo = temozolamide

chemo = bevacizumab

Berdasarkan grafik Kaplan Meier diatas dapat diketahui bahwa pada pasien yang melakukan
kemoterapi awal dengan bevacizumab dapat bertahan hidup sampai waktu ke-14. Pasien yang
menggunakan kemoterapi temozolamide semua dapat bertahan hidup sampai waktu ke-9,
kemudian berkurang, terisisa 75% yang dapat bertahan hidup sampai waktu ke-19. Pada pasien
yang tidak kemoterapi akan lebih banyak yang meninggal pada waktu pertama sampai waktu ke-16,
namun pasien yang tidak kemoterapi dapat bertahan hidup sampai waktu minggu ke-25 meskipun
hanya dibawah 25%.

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