CONFOUNDING

VARIABLE
IZHA FAJAR AL-ISYNAIYNI
SRI WULANDARI
ANNISA WENINGTYAS
DEFINITION

“A simple definition of confounding is the confusion of

effects.”
A confounding variable is a variable that correlates (positively
or negatively) with both the exposure and outcome.
Confounding can be a major problem with any observational
(nonrandomized) study.
Vetter TR, Mascha EJ. Bias, Confounding, and Interaction: Lions and Tigers, and Bears, Oh My! Anesth Analg.
2017 Sep;125(3):1042-1048. doi: 10.1213/ANE.0000000000002332. PMID: 28817531.
DEFINITION

A confounder is a variable that is unevenly distributed

between study groups and is associated with either the
intervention or outcome. If the confounder is not
recognized, it will give the false impression that the
potential predictor is the causal factor, rather than the
confounder.
Yan H, Karmur BS, Kulkarni AV. Comparing Effects of Treatment: Controlling for Confounding. Neurosurgery.
2020 Mar 1;86(3):325-331. doi: 10.1093/neuros/nyz509. PMID: 31807787.
CRITERIA

A confounder is a variable that distorts the association between

two other variables (the exposure and the outcome).
Often the exposure is what is being studied as a potential cause of
the outcome.
Statistical adjustment for the confounder results in a change of
relative risk.

Kamangar F. Confounding variables in epidemiologic studies: basics and beyond. Arch Iran Med. 2012
Aug;15(8):508-16. PMID: 22827790.
CRITERIA

1) it must be associated with the exposure (causally or

not);
2) it must be a cause, or a surrogate of the cause, of the
health outcome;
3) it should not be in the causal pathway between the
potential risk factor and outcome
Kamangar F. Confounding variables in epidemiologic studies: basics and beyond. Arch Iran Med. 2012
Aug;15(8):508-16. PMID: 22827790.
Kamangar F.
Confounding
variables in
epidemiologic
studies: basics and
beyond. Arch Iran
Med. 2012
Aug;15(8):508-16.
PMID: 22827790.
 TYPES

For qualitative confounders, the For quantitative confounders,

association between exposure positive confounders are those
and outcome completely that magnify the association
disappears or even reverses beyond its real size – i.e.,
direction, meaning that the make the association seem to
quality or nature of the be bigger than it is. Negative
association changes. confounders are those that
make the association seem to
be smaller than it is.
Kamangar F. Confounding variables in epidemiologic studies: basics and beyond. Arch Iran Med. 2012
Aug;15(8):508-16. PMID: 22827790.
TYPES

Kamangar F. Confounding variables in epidemiologic studies: basics and beyond. Arch Iran Med. 2012
Aug;15(8):508-16. PMID: 22827790.
 Controlling
Confounding Variable

Study Design Techniques Data Analysis Techniques

1. Randomization 1. Regression
2. Stratified Randomization 2. Propensity Score
3. Minimization Randomization 3. Subgroup Analysis
4. Restriction of Sample
5. Matching
Study Design Techniques

1. Randomization
- is the gold standard for dealing with confounding, and it is the method by which all
others are judged
- to avoid systematic bias of confounding by balancing the distribution of patient
characteristics that may influence the outcome (potential confounders) between
treatment arms
- The principle is simple: if only pure chance determines which intervention a patient
receives, removed from the potential biases of patients and physicians, then, over the
course of enough patients, chance should provide a roughly equal distribution of
patient characteristics between the intervention arms.
- Randomization: simple randomization and blocked randomization
Yan, H., Karmur, B. S., & Kulkarni, A. V. (2020). Comparing Effects of Treatment: Controlling for Confounding. Clinical
Neurosurgery, 86(3), 325–331. https://doi.org/10.1093/neuros/nyz509
Study Design Techniques

2. Statified Randomization
- aimed at trying to balance a potential confounding variable between treatment
arms
- using separate randomization lists for each subgroup of patients within a
potential confounder
- can be extended to stratify based on 2 or more potential confounders;
however, this can result in a dramatic reduction in sample size of each group,
making it impractical for smaller studies

Yan, H., Karmur, B. S., & Kulkarni, A. V. (2020). Comparing Effects of Treatment: Controlling for Confounding. Clinical
Neurosurgery, 86(3), 325–331. https://doi.org/10.1093/neuros/nyz509
Study Design Techniques

3. Minimization Randomization
- more-complicated, but well-accepted, dynamic randomization technique with
the goal of balancing prognostic factors across treatment groups
- similar to stratified randomization, with the difference of using an imbalance
score, instead of separate randomization schemes, to ensure that groups are
balanced with respect to potential confounders
- A minimization randomization trial design was used by the PROTECT III
investigators, who evaluated the administration of early progesterone as a
treatment for traumatic brain injury (TBI)

Yan, H., Karmur, B. S., & Kulkarni, A. V. (2020). Comparing Effects of Treatment: Controlling for Confounding. Clinical
Neurosurgery, 86(3), 325–331. https://doi.org/10.1093/neuros/nyz509
Study Design Techniques

4. Restriction of Sample
- The idea is simple: you restrict the sample under investigation to those within
a narrow range of a particular potential confounder or you exclude those with
the potential confounder entirely
- For example, consider again the Swedish Spinal Stenosis Study, which
eliminated the potential confounder of number of spinal levels of stenosis by
restricting the study sample of only patients with up to 2 levels of stenosis

Yan, H., Karmur, B. S., & Kulkarni, A. V. (2020). Comparing Effects of Treatment: Controlling for Confounding. Clinical
Neurosurgery, 86(3), 325–331. https://doi.org/10.1093/neuros/nyz509
Study Design Techniques

5. Matching
- to provide individual pairs who are closely matched on prespecified confounders,
but with one of the pairs having received treatment A and the other treatment B
- The authors compared American Society of Anesthesiologists (ASA) with
clopidogrel and ASA with ticagrelor by using a matched-cohort study design
- The matching procedure must be specified as part of the initial study design,
making it difficult to further match on additional factors once the matched cohorts
are created. Another difficulty of matching is that once the groups are matched
on the potential confounders, that confounder cannot be evaluated as a risk
factor

Yan, H., Karmur, B. S., & Kulkarni, A. V. (2020). Comparing Effects of Treatment: Controlling for Confounding. Clinical
Neurosurgery, 86(3), 325–331. https://doi.org/10.1093/neuros/nyz509
Data Analysis Techniques

1. Regression
- to provide an equation that will input independent variables and predict the
value of the dependent variable
- By inputting data from a large sample, a regression analysis will determine
the mathematical relationship between any of the independent variables and
the outcome
- Linear regression, logistic regression, proportional hazard regression (cox
regression)

Yan, H., Karmur, B. S., & Kulkarni, A. V. (2020). Comparing Effects of Treatment: Controlling for Confounding. Clinical
Neurosurgery, 86(3), 325–331. https://doi.org/10.1093/neuros/nyz509
Data Analysis Techniques

2. Propensity Score
- A propensity score is simply a way to quantify how likely it is that
- Technically, the estimated propensity score is actually the conditional
probability ranging from 0 to 1, of being assigned to a particular treatment
given certain patient characteristics

Yan, H., Karmur, B. S., & Kulkarni, A. V. (2020). Comparing Effects of Treatment: Controlling for Confounding. Clinical
Neurosurgery, 86(3), 325–331. https://doi.org/10.1093/neuros/nyz509
Data Analysis Techniques

3. Subgroup Analysis
- is similar to restricting the sample, in the sense that the cohort is broken down
into subgroups, each containing a very restricted range of the potential
confounder
- Statistical analysis is then carried out within each subgroup, where the
confounder cannot be unequally distributed between the treatment arms,
because the range of that confounder is so limited
- needs to be used carefully, because of the risk of incurring false-positive
findings after scouring many different subgroups, in search of a significant
finding
Yan, H., Karmur, B. S., & Kulkarni, A. V. (2020). Comparing Effects of Treatment: Controlling for Confounding. Clinical
Neurosurgery, 86(3), 325–331. https://doi.org/10.1093/neuros/nyz509
Putri, B. D., & Ferdinandus, E. D. (2020). The Mantel-Haenszel Analysis to Control Confounding Variable between Birth-Weight Andearly-Onset Neonatal Sepsis at Hajj Hospital, Surabaya,
Indonesia. Indian Journal of Public Health Research & Development, 11(05), 615–619. https://doi.org/10.37506/ijphrd.v11i5.9400
METHODS
Penelitian ini bersifat analitik
Observasional dengan
desain cross sectional.
Sampel : 1.461 neonatus
yang lahir pada bulan
Januari 2018 hingga
Desember 2018
Variabel Perancu : Ketuban
Variabel Perancu
dihubungkan dengan penyakit
dan variabel perancu
dikaitkan dengan paparan.
Dengan menggunakan Uji-Chi
Square
Setelah diketahui bahwa cairan ketuban
terbukti sebagai variabel perancu.
Penelitian ini
menggunakan uji Mantel Haenszel untuk
stratifikasi antara berat badan lahir dan
sepsis neonatal awitan dini.
Analisis data menggunakan SPSS
19
Conclusion
- Risiko Relatif (RR) pada kedua strata cairan ketuban meningkat 4 kali lebih besar dibandingkan
tanpa mempertimbangkan kondisi cairan ketuban
- Hasil regresi logistik biner menunjukkan bahwa sepsis neonatal awitan dini dipengaruhi oleh
berat badan lahir dengan mempertimbangkan kondisi cairan ketuban
- Pada kelompok cairan ketuban yang mengandung mekonium neonatus dengan berat badan lahir
rendah mempunyai risiko mengalami sepsis neonatal awitan dini 24.839 kali lebih besar
dibandingkan kelompok lainnya Dapat disimpulkan bahwa kondisi cairan ketuban dapat
meningkatkan kemungkinan terjadinya sepsis neonatal pada neonatus yang mempunyai berat
badan lahir rendah
THANK
YOU