Tugas Metodologi Penelitian (2) – Ilmu Kedokteran Klinis

Septina ayu samsiati - MS PPDS IK Anak

1. Berdasarkan usulan penelitian saudara, jelaskan populasi penelitian saudara

a Populasi target Pasien anak terdiagnosis ALL di RS Sardjito

b Accessible population pasien anak terdiagnosis ALL yang dirawat di bangsal Onkologi
Anak RSUP Dr. Sardjito Yogyakarta pada 1 Januari 2010 sampai
dengan 30 November 2016.

c Inclusion criteria 1. Pasien berusia 0-18 tahun

2. Terdiagnosis LLA pada periode 1 Januari 2011 sampai dengan
30 November 2016 berdasarkan hasil morfologi sel, sitokimia
dan imunofenotip.

Exclusion criteria - rekam medis tidak lengkap

d. Jelaskan mengapa variable tersebut dimasukkan ke dalam kriteria eksklusi?

Karena penelitian yang rencana saya lakukan merupakan penelitian kohort retrospektif. Sehingga
diperlukan data yang lengkap untuk dapat membuktikan hipotesis.

e. Jelaskan variable apa saja yang harus dipertimbangkan untuk menghindari bias atas kesimpulan saudara
Variabel yang dapat menjadi bias diantaranya:
- usia
- angka leukosit
- adanya keterlibatan CNS

2. Carilah satu buah paper penelitian dengan design case control, jelaskan apa tujuan penelitian tersebut
serta berikan argumentasi saudara terkait kelayakan design case control pada penelitan tersebut.
Lakukan critical appraisal terhadap paper tersebut dan jelaskan secara rinci validitas hasil penelitian
jelaskan variable paa saja yang memungkinkan menjadi factor confounding dan bagaimana cara
mengetahuinya dengan rumus OR-MH ?
 1. Were the groups comparable other than presence of disease in cases or absence of disease in
controls?

Eligible for the IDEFICS case-control study on obesity were all children from the baseline survey for whom a basic
set of anthropometric indicators and pregnancy information was present (N = 16,113). From these children, all
children aged 4 to 8 years that met the IOTF criteria for childhood obesity were identified as cases (N = 1,024).
Controls were selected from the group of IOTF normal weighted children (N= 11,193) and matched 1:1 by study

center, sex and age (sliding window +/-0.5 years) to the cases. For all cases, controls with identical sex and study
center and a minimal distance with respect to age were selected. The decision for a 1:1 matched design was
based on a sample size calculation.

Iya
Pada studi ini, sebelumnya telah dilakukan penelitian baseline dengan populasi anak kelas 1 & 2 sekolah
dasar pada beberapa negara di eropa (belgia, Cyprus, jerman, hungaria, italia, spanyol dan swedia). Dari
penelitiian baseline tersebut didapatkan sampel N= 16.113. Dan diantaranya terdapat data anak dengan
berat badan normal sebanyak N= 11.193.

Dari anak-anak tersebut, diambil sampel anak dengan usia 4-8 tahun yang memenuhi ktiteria obesitas
IOTF sejumlah N = 1.024.

Kemudian diambil sampel untuk grup kontrol dari grup data anak berat badan normal, dengan
melakukan pencocokan 1:1 berdasarkan jenis kelamin, usia dan lokasi study center.

Kedua grup tersebut sama sama telah dilakukan pengukuran antropometri sebelumnya pada penelitian
baseline, dan keduanya juga telah dilakukan pengambilan data dengan kuesioner.

2. Were cases and controls matched appropriately?

IDEFICS is a multi-center population-based intervention study on childhood obesity that is carried out in selected
regions of 8 European countries comprising Belgium, Cyprus, Estonia, Germany, Hungary, Italy, Spain and
Sweden. The study was set up in pre- and primary school settings in a control and an intervention region in
each of these countries. Two major surveys (baseline and follow-up) were conducted in pre-schools and primary
school classes (1st and 2nd grades at baseline). The baseline survey (September 2007–May 2008) reached a
response proportion of 51% and included 16 220 children aged 2 to 9 years.

Eligible for the IDEFICS case-control study on obesity were all children from the baseline survey for whom a basic
set of anthropometric indicators and pregnancy information was present (N = 16,113). From these children, all
children aged 4 to 8 years that met the IOTF criteria for childhood obesity were identified as cases (N = 1,024).
Controls were selected from the group of IOTF normal weighted children (N= 11,193) and matched 1:1 by study

center, sex and age (sliding window +/-0.5 years) to the cases. For all cases, controls with identical sex and study
center and a minimal distance with respect to age were selected. The decision for a 1:1 matched design was
based on a sample size calculation.

Iya
Dari penelitiian baseline tersebut didapatkan sampel N= 16.113. Dan diantaranya terdapat data anak
dengan berat bodan normal sebanyak N= 11.193. Dari anak-anak tersebut, diambil sampel anak dengan
usia 4-8 tahun yang memenuhi ktiteria obesitas IOTF sejumlah N = 1.024.

Kemudian diambil sampel untuk grup kontrol dari grup data anak berat badan normal, dengan
melakukan pencocokan 1:1 berdasarkan jenis kelamin, lokasi, dan usia.

3. Were the same criteria used for identification of cases and controls?
Body mass index (BMI) was calculated as weight (kg) divided by height squared (m). For obtaining the
International Task Force of Obesity (IOTF) category, BMI categories were interpolated for continuous age as
proposed [13,14].

Eligible for the IDEFICS case-control study on obesity were all children from the baseline survey for whom a basic
set of anthropometric indicators and pregnancy information was present (N = 16,113). From these children, all
children aged 4 to 8 years that met the IOTF criteria for childhood obesity were identified as cases (N = 1,024).
Controls were selected from the group of IOTF normal weighted children (N= 11,193) and matched 1:1 by study

center, sex and age (sliding window +/-0.5 years) to the cases. For all cases, controls with identical sex and study
center and a minimal distance with respect to age were selected. The decision for a 1:1 matched design was
based on a sample size calculation.

Iya
Kedua grup dibagi menjadi grup dengan obesitas dan grup kontrol dengan berat badan normal
menggunakan kriteria IOTF (International task force for obesity).
Grup kasus diambil dari sampel data penelitian baseline yang memenuhi kriteria, yaitu pasien yang
memiliki data antropometrik, dan data kehamilan. Kemudian dari sampel tersebut diambil anak anak
dengan usia 4-8 tahun yang memenuhi kriteria obesitas berdasarkan kriteria IOTF.
Grup kontrol diambil dari sampel data penelitian baseline anak berat badan normal. Kemudian
dilakukan pencocokan 1:1 berdasarkan jenis kelamin, lokasi, dan usia dengan grup kasus.

4. Was exposure measured in a standard, valid and reliable way?

Within the baseline survey, a self-administered questionnaire was filled in by the parents to gather information
on the children’s behavior, parental attitudes and on the social microenvironment of the children (IDEFICS
parental questionnaire). A further questionnaire on health-related and medical information was given to the
parents in the course of the physical examination of the child (IDEFICS medical questionnaire). Questionnaires
were developed in English, translated to the respective languages and back translated to English to minimize any
heterogeneity due to translation problems. Different language versions were available in the centers, and help was
offered to those parents who felt they were not able to fill in the questionnaire by themselves. For filling in the
IDEFICS medical questionnaire, the help of medical personnel was offered directly at the survey sites.

Iya
Exposure berupa faktor risiko prepartum, peripartum dan postpartum didapatkan dari kuesioner IDEFICS
(Identification and prevention od Dietary and lifestyle induced health effects in children and infants).

Disediakan bantuan tenaga medis di tempat survey untuk membantu pengisian kuesioner. Karena samel
terdiri dari pasien dari beberapa negara, kuesioner telah diterjemahkan sesuai dengan lokasi tempat
survey.

5. Was exposure measured in the same way for cases and controls?
Within the baseline survey, a self-administered questionnaire was filled in by the parents to gather information
on the children’s behavior, parental attitudes and on the social microenvironment of the children (IDEFICS
parental questionnaire). A further questionnaire on health-related and medical information was given to the
parents in the course of the physical examination of the child (IDEFICS medical questionnaire). Questionnaires
were developed in English, translated to the respective languages and back translated to English to minimize any
heterogeneity due to translation problems. Different language versions were available in the centers, and help was
offered to those parents who felt they were not able to fill in the questionnaire by themselves. For filling in the
IDEFICS medical questionnaire, the help of medical personnel was offered directly at the survey sites.

The investigated risk factors directly related to the child can be grouped into prepartum, peripartum, and
postpartum factors (see Table 1). Further family-related risk factors included in the present analysis are familial
clustering and parental social background. All information was assessed by the IDEFICS parental questionnaire,

except for the occurrence of gestational diabetes that was taken from the IDEFICS medical questionnaire. All
investigated risk factors are based on self-report.

Iya

Exposure berupa faktor risiko prepartum, peripartum dan postpartum didapatkan dari kuesioner IDEFICS
(Identification and prevention od Dietary and lifestyle induced health effects in children and infants).

6. Were confounding factors identified?

Iya
Pada studi ini dalam tabel disebutkan faktor risiko dan faktor yang mungkin menjadi confounder pada
faktor risiko tersebut

7. Were strategies to deal with confounding factors stated?

For each of the investigated factors, we built multivariate models adjusting for known or suspected confounders
from the literature (cf. Table 1). Since many of the investigated risk factors are correlated, we finally built a
multivariate model containing all factors that were shown to be influential in the analyses. Wereported the Wald
statistics to judge the relative importance of the single factors.

Iya

Pada penelitian telah dilakukan langkah langkah untuk mengendalikan faktor cofounding:

- telah dilakukan matching 1:1 pada kelompok kasus dan kelompok kontrol

- dilakukan analisis multivariat pada faktor yang dicurigai sebagai confounding faktor (tabel 1)

8. Were outcomes assessed in a standard, valid and reliable way for cases and controls?
Anthropometric measurements were done during a physical examination. Weight to the nearest 0.1 kg and foot-
to-foot bioelectrical resistance in Ohm was measured using an electronic scale TANITA BC 420 SMA (TANITA
Europe GmbH, Sindelfingen, Germany) with the children being in a fasting status and wearing only underwear.
Standing height was measured with the children’s head in a Frankfort plane using a stadiometer SECA 225 (seca
GmbH & Co. KG., Hamburg, Germany) to the nearest 0.1 cm. As in the weight measurement, the children were
wearing only underwear, all hair ornaments were removed and all braids undone. Body mass index (BMI) was
calculated as weight (kg) divided by height squared (m). For obtaining the International Task Force of Obesity
(IOTF) category, BMI categories were interpolated for continuous age as proposed [13,14]. Cubic splines were
used for this interpolation. The resistance index (RI) was calculated as squared height (cm2) divided by resistance
(Ohm). The RI was shown to be a good predictor for fat free mass in children [15].

Eligible for the IDEFICS case-control study on obesity were all children from the baseline survey for whom a basic
set of anthropometric indicators and pregnancy information was present (N = 16,113). From these children, all
children aged 4 to 8 years that met the IOTF criteria for childhood obesity were identified as cases (N = 1,024).
Controls were selected from the group of IOTF normal weighted children (N= 11,193) and matched 1:1 by study

center, sex and age (sliding window +/-0.5 years) to the cases.

Iya
Kedua grup dibagi menjadi grup dengan obesitas dan grup kontrol dengan berat badan normal
menggunakan kriteria IOTF (International task force for obesity).
Pada jurnal juga dituliskan dengan jelas cara dan metode pengukuran yang dilakukan untuk
mendapatkan data antropometrik

9. Was the exposure period of interest long enough to be meaningful?

Iya
Penelitian dilakukan dengan sampel penellitian anak usia 4-8 tahun dengan faktor risiko exposure yang
diteliti semenjak fase pre-partum.
It is particularly important in a case control study that the exposure time was sufficient enough to show
an association between the exposure and the outcome. It may be that the exposure period may be too
short or too long to influence the outcome.

10. Was appropriate statistical analysis used?

‘To evaluate the impact of a putative risk factor, conditional logistic regression models were fitted to the data.
This allows an unbiased estimation of effects in matched case-control studies with regard to the matching
variables. Within this approach, each matched set forms a stratum.

The estimation of the bs was done using Cox’ proportional hazard model with maximum likelihood estimation
[24]. 95% confidence intervals (95% CI) were computed. For all variables, the influence of the child’s sex and age
group (<= 6 years, .>6 years) on the raw odds ratio (OR) was tested using the Breslow-Day test for homogeneity
of the odds ratios [25]. We found all OR to be homogenous regarding age group. OR that were found to be
heterogeneous over sexes are reported in the text”

“For each of the investigated factors, we built multivariate models adjusting for known or suspected confounders
from the literature (cf. Table 1). Since many of the investigated risk factors are correlated, we finally built a
multivariate model containing all factors that were shown to be influential in the analyses. We reported the Wald
statistics to judge the relative importance of the single factors.”

Iya
Dipergunakan analisis logistik regresi, dan dilakukan analisis multivariate untuk menyesuaikan faktor
confounding

As with any consideration of statistical analysis, consideration should be given to whether there was a
more appropriate alternate statistical method that could have been used. The methods section should
be detailed enough for reviewers to identify which analytical techniques were used (in particular,
regression or stratification) and how specific confounders were measured.

For studies utilizing regression analysis, it is useful to identify if the study identified which variables
were included and how they related to the outcome. If stratification was the analytical approach used,
were the strata of analysis defined by the specified variables? Additionally, it is also important to assess
the appropriateness of the analytical strategy in terms of the assumptions associated with the
approach as differing methods of analysis are based on differing assumptions about the data and how
it will respond.
Pada jurnal telah ditampilkan perhitungan OR dengan memperhitungkan confounding faktors (adjusted
OR)

In the overall group, statistically significant risk factors for obesity were Caesarian section (adjusted OR=1.38;
95%CI 1.10– 1.74), gestational weight gain in kg (adjusted OR= 1.02; 95%CI 1.00–1.04), maternal smoking
during pregnancy (adjusted OR= 1.48; 95%CI 1.08–2.01) and breastfeeding 4 to 11 months (adjusted
OR=0.77; 95%CI 0.62–0.96). After additional adjustment for parental BMI and parental educational level,
statistically

significant factors were maternal BMI in kg/m2 (adjusted OR= 1.16; 95%CI 1.11–1.20), paternal BMI in kg/m2
(adjusted OR= 1.11; 95%CI 1.07–1.16), and gestational weight gain in kg (adjusted OR= 1.04; 95%CI 1.01–
1.07).