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Confounding
Introduction

LEARNING OBJECTIVES
The student will be able to:

1. Define confounding.
2. Discuss the implications of confounding for epidemiological
research.
3. Describe the nature and uses of a directed acyclic graph.
4. Create a directed acyclic graph based on a real research
question, and use it to identify potential confounders.
5. Compare and contrast different methods to deal with
confounding.
Introduction

MOTIVATION

Confounding is the most
important topic in
epidemiology.
Epidemiology is...
X

Y
What do we mean when we say
one thing causes another?
Why are causes so important in
epidemiology?
What is the gold standard study
design for testing causal
hypotheses?
Why?
When is it not possible to use a
RCT?
X

Cause

Y
X

Statistical Association

Y
Statistical Association
When variables vary similarly.
Correlated; Covary; Dependent
Draw Inferences
Statistical inferences
Causal inferences
“Correlation does not
imply causation.”
BREAK
QUESTIONS?
Confounding

DEFINITIONS
Synonym:
Spurious association
Confounding is...
“...the problem of confusing or mixing
of exposure effects with other
"extraneous" effects...”

Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding revisited.
Epidemiol Perspect Innov. 2009; 6: 4. doi: 10.1186/1742-5573-6-4
Early definitions were based on notions
of...
Comparability
or
Collapsibility
Comparability
Inherent difference in risk between
exposed and unexposed groups.

Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding. Int J
Epidemiol. 1986;15:413–419. doi: 10.1093/ije/15.3.413.
Collapsibility
Apparent differences between the crude
estimate of a statistical association and
strata-specific estimates.

Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding. Int J
Epidemiol. 1986;15:413–419. doi: 10.1093/ije/15.3.413.
Problems with collapsibility:
1.

Parameter estimates can change upon controlling for mediators,
by controlling for variables that introduce new biases, or because
of measurement error.

2.

There are situations where controlling for a “true” confounder
leads to no change in the estimate.

Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding revisited.
Epidemiol Perspect Innov. 2009; 6: 4. doi: 10.1186/1742-5573-6-4
Comparability
Inherent difference in risk between
exposed and unexposed groups.

Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding. Int J
Epidemiol. 1986;15:413–419. doi: 10.1093/ije/15.3.413.
Imagine that individuals can be classified
based on their inherent risk of the
outcome, prior to any exposure.
These classifications incorporate the
entirety of causal mechanisms
operating, known or unknown.
Rothman K. Causes. AJE. (1995) 141 (2):90-95.
Is exposure a cause of
disease?
Is there an assumption we can make
that allows us to infer that the
exposure causes the disease?
Counterfactuals, or Potential Outcomes

Yix = 1

Yix = 0
Exchangeability

The strong assumption that they are of
the same type.
Comparability assumption (or partial exchangeability):
The proportion who would fall ill in the absence of exposure is the same in both
groups.
(p1 + p3) = (q1 +q3)
Alternately, the baseline risk (prior to any possibility of exposure) is the same
in both groups.
Thus an observed difference in risk between exposure and unexposed is due to
the relative proportion of types 2 and 3 in the exposed.
If IPD > 0

Then P2 >P3

If IPD < 0

Then P3 > P2

If IPD = o

Then P3 = P2
We can, if we wish, further assume that
P3 (or P2) is equal to zero.

For example, we might assume
smoking is never good for anyone.
If P3 = 0 and IPD = 0

Then P2 = 0
Causal inferences, which we must make, rely on a strong
assumption – the comparability (or exchangeability) of
exposed and unexposed groups.
Comparability is synonymous with “no confounding”.
(p1 + p3) = (q1 + q3)

Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding. Int J
Epidemiol. 1986;15:413–419. doi: 10.1093/ije/15.3.413.
How seriously do
“epidemiologists” take
this?
“We adjusted for appropriate
confounders.”

...
Corollary 4:

“The greater the flexibility in designs, definitions,
outcomes, and analytical modes in a scientific field, the
less likely the research findings are to be true.”
“Implicit in these pressures* is a growing

dissatisfaction outside the field of epidemiology
with epidemiologic description and
correlation...”

Galea S. An Argument for a Consequentialist Epidemiology. AJE. 2013; doi: 10.1093/aje/kwt172
Good for science
Vs
Good for a scientist
BREAK
QUESTIONS?
Direct Acyclic Graphs

OVERVIEW
1. DAGs are a tool.

2. They help clarify causal thinking.
3. They guide the modelling process by helping to identify
potential confounding.
4. They have been used to identify many of the problems with
earlier approaches to confounding.

5. They are a great compliment to comparability based definitions
of confounding.
Traditional rules of thumb for identifying
confounders:
1.

It must be predictive of risk among the unexposed.

2.

It must be associated with the exposure in the population under
study.

3.

It must not fall on the causal path from exposure to outcome, or

be a consequence of the outcome.

Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding. Int
J Epidemiol. 1986;15:413–419. doi: 10.1093/ije/15.3.413.
These don’t always work. Is there
something better?
Directed
Acyclic
Graphs
This is a graph.
It is directed.
It is acyclic.
This is a graph.
It is directed.
It is acyclic.
In a DAG, any unblocked path between two
nodes implies a marginal (unadjusted)
association.
Algorithm for identifying confounders.
1. Erase all directed edges emanating from the exposure.

2. Identify all unblocked, backdoor paths between the exposure and
outcome.
Each of these paths implies confounding.
Confounding is removed by controlling for a
variable along that path.
Adjustment for one variable can address
confounding due to multiple paths.
Erase all directed edges emanating from
the exposure.
Identify unblocked, backdoor paths.
This means we can identify an optimal*
sufficient set for adjustment.

* The optimal sufficient set might be the smallest possible set, or the set that
is easiest to collect, or the least expensive, etc.
At what stage in the research process should
we employ a DAG?
But we aren’t done yet.
Controlling for a collider has the effect of
inserting a new edge between its parents.
Fast and agile

Tough and strong

Rugby Ability

Glymour M. USING CAUSAL DIAGRAMS TO UNDERSTAND COMMON PROBLEMS IN SOCIAL EPIDEMIOLOGY. Methods in Social
Epidemiology
Fast and agile

Tough and strong

Rugby Ability
Algorithm for identifying confounders.
1. Erase all directed edges emanating from the exposure.
2. Identify all unblocked, backdoor paths from between the exposure

and outcome.
3. Define S, your sufficient set of variables needed to adjust for
confounding.
4. Draw an edge to connect all pairs of variables with a child in S, or a
child with a descendent in S.

5. Identify any new unblocked, backdoor paths, and update S.
Direct Acyclic Graphs

MAKING A DAG
1. Identify an important health outcome, and a modifiable

exposure. Draw an arrow from the later to the former.
2. Think about what other variables might be related to these.
Brainstorm, use existing literature, etc.
3. Draw in any hypothesized causal paths.
4. Follow the steps previously outlined.
Direct Acyclic Graphs

MAKING A DAG
5. Explore choices, and consider how these affect your optimal

sufficient set for adjustment (S).
6. Draw your DAG so it flows in the same direction you read (as
best as possible).
7. Use colour, notes, etc.
8. There are programs available, but pencil and lots of paper work

best at first.
Learning Task
• Based on the topic of your research thesis, create a DAG.
• It should include a preventable exposure, an important
outcome, and at least 3 other potentially important
covariates.
• Send me an image of your DAG before 17:00, next
Wednesday (ddahly@ucc.ie).
Confounders

SUMMARY
1. Epidemiologists should be preoccupied with causes.
2. Confounding is the single greatest threat to our causal inferences – which we
must make, or risk irrelevance.
3. Definitions and rules of thumb based on collapsibility are not sufficient to
identify many commonly encountered confounders.

4. Comparability based definitions are better, but don’t lend themselves to simple
rules of thumb.
5. Epidemiologists do not consistently use the same level of rigour when trying to

address confounding.
6. As a field, this limits our ability to effect positive change.
Direct Acyclic Graphs

SUMMARY
1. DAGs are a useful tool.

2. They help clarify causal thinking.
3. They guide the modelling process by helping to identify
potential confounding.
Next week

PREVIEW
1. More DAG examples.

2. Critiques of DAGs, and my responses to these.
3. Methods for dealing with confounding, once you suspect it.

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Confounding and Directed Acyclic Graphs

  • 2. Introduction LEARNING OBJECTIVES The student will be able to: 1. Define confounding. 2. Discuss the implications of confounding for epidemiological research. 3. Describe the nature and uses of a directed acyclic graph. 4. Create a directed acyclic graph based on a real research question, and use it to identify potential confounders. 5. Compare and contrast different methods to deal with confounding.
  • 3. Introduction MOTIVATION Confounding is the most important topic in epidemiology.
  • 5. X Y
  • 6. What do we mean when we say one thing causes another?
  • 7. Why are causes so important in epidemiology?
  • 8.
  • 9. What is the gold standard study design for testing causal hypotheses?
  • 10. Why?
  • 11. When is it not possible to use a RCT?
  • 12.
  • 13.
  • 14.
  • 17. Statistical Association When variables vary similarly. Correlated; Covary; Dependent
  • 20.
  • 21.
  • 22. BREAK
  • 25.
  • 27. Confounding is... “...the problem of confusing or mixing of exposure effects with other "extraneous" effects...” Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding revisited. Epidemiol Perspect Innov. 2009; 6: 4. doi: 10.1186/1742-5573-6-4
  • 28.
  • 29.
  • 30. Early definitions were based on notions of... Comparability or Collapsibility
  • 31. Comparability Inherent difference in risk between exposed and unexposed groups. Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding. Int J Epidemiol. 1986;15:413–419. doi: 10.1093/ije/15.3.413.
  • 32. Collapsibility Apparent differences between the crude estimate of a statistical association and strata-specific estimates. Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding. Int J Epidemiol. 1986;15:413–419. doi: 10.1093/ije/15.3.413.
  • 33.
  • 34.
  • 35.
  • 36.
  • 37. Problems with collapsibility: 1. Parameter estimates can change upon controlling for mediators, by controlling for variables that introduce new biases, or because of measurement error. 2. There are situations where controlling for a “true” confounder leads to no change in the estimate. Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding revisited. Epidemiol Perspect Innov. 2009; 6: 4. doi: 10.1186/1742-5573-6-4
  • 38. Comparability Inherent difference in risk between exposed and unexposed groups. Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding. Int J Epidemiol. 1986;15:413–419. doi: 10.1093/ije/15.3.413.
  • 39.
  • 40. Imagine that individuals can be classified based on their inherent risk of the outcome, prior to any exposure. These classifications incorporate the entirety of causal mechanisms operating, known or unknown.
  • 41. Rothman K. Causes. AJE. (1995) 141 (2):90-95.
  • 42.
  • 43.
  • 44.
  • 45. Is exposure a cause of disease?
  • 46.
  • 47.
  • 48.
  • 49.
  • 50.
  • 51.
  • 52. Is there an assumption we can make that allows us to infer that the exposure causes the disease?
  • 53.
  • 54. Counterfactuals, or Potential Outcomes Yix = 1 Yix = 0
  • 55. Exchangeability The strong assumption that they are of the same type.
  • 56.
  • 57.
  • 58.
  • 59.
  • 60. Comparability assumption (or partial exchangeability): The proportion who would fall ill in the absence of exposure is the same in both groups. (p1 + p3) = (q1 +q3) Alternately, the baseline risk (prior to any possibility of exposure) is the same in both groups.
  • 61. Thus an observed difference in risk between exposure and unexposed is due to the relative proportion of types 2 and 3 in the exposed.
  • 62. If IPD > 0 Then P2 >P3 If IPD < 0 Then P3 > P2 If IPD = o Then P3 = P2
  • 63. We can, if we wish, further assume that P3 (or P2) is equal to zero. For example, we might assume smoking is never good for anyone. If P3 = 0 and IPD = 0 Then P2 = 0
  • 64.
  • 65.
  • 66.
  • 67.
  • 68. Causal inferences, which we must make, rely on a strong assumption – the comparability (or exchangeability) of exposed and unexposed groups. Comparability is synonymous with “no confounding”. (p1 + p3) = (q1 + q3) Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding. Int J Epidemiol. 1986;15:413–419. doi: 10.1093/ije/15.3.413.
  • 70. “We adjusted for appropriate confounders.” ...
  • 71.
  • 72. Corollary 4: “The greater the flexibility in designs, definitions, outcomes, and analytical modes in a scientific field, the less likely the research findings are to be true.”
  • 73. “Implicit in these pressures* is a growing dissatisfaction outside the field of epidemiology with epidemiologic description and correlation...” Galea S. An Argument for a Consequentialist Epidemiology. AJE. 2013; doi: 10.1093/aje/kwt172
  • 74.
  • 75.
  • 76.
  • 77. Good for science Vs Good for a scientist
  • 78. BREAK
  • 80. Direct Acyclic Graphs OVERVIEW 1. DAGs are a tool. 2. They help clarify causal thinking. 3. They guide the modelling process by helping to identify potential confounding. 4. They have been used to identify many of the problems with earlier approaches to confounding. 5. They are a great compliment to comparability based definitions of confounding.
  • 81. Traditional rules of thumb for identifying confounders: 1. It must be predictive of risk among the unexposed. 2. It must be associated with the exposure in the population under study. 3. It must not fall on the causal path from exposure to outcome, or be a consequence of the outcome. Greenland S, Robins JM. Identifiability, exchangeability, and epidemiological confounding. Int J Epidemiol. 1986;15:413–419. doi: 10.1093/ije/15.3.413.
  • 82. These don’t always work. Is there something better?
  • 84.
  • 85.
  • 86.
  • 87. This is a graph. It is directed. It is acyclic.
  • 88. This is a graph. It is directed. It is acyclic.
  • 89.
  • 90. In a DAG, any unblocked path between two nodes implies a marginal (unadjusted) association.
  • 91.
  • 92.
  • 93.
  • 94. Algorithm for identifying confounders. 1. Erase all directed edges emanating from the exposure. 2. Identify all unblocked, backdoor paths between the exposure and outcome.
  • 95.
  • 96. Each of these paths implies confounding. Confounding is removed by controlling for a variable along that path. Adjustment for one variable can address confounding due to multiple paths.
  • 97.
  • 98. Erase all directed edges emanating from the exposure.
  • 99.
  • 101.
  • 102.
  • 103. This means we can identify an optimal* sufficient set for adjustment. * The optimal sufficient set might be the smallest possible set, or the set that is easiest to collect, or the least expensive, etc.
  • 104. At what stage in the research process should we employ a DAG?
  • 105. But we aren’t done yet.
  • 106.
  • 107. Controlling for a collider has the effect of inserting a new edge between its parents.
  • 108. Fast and agile Tough and strong Rugby Ability Glymour M. USING CAUSAL DIAGRAMS TO UNDERSTAND COMMON PROBLEMS IN SOCIAL EPIDEMIOLOGY. Methods in Social Epidemiology
  • 109. Fast and agile Tough and strong Rugby Ability
  • 110.
  • 111.
  • 112. Algorithm for identifying confounders. 1. Erase all directed edges emanating from the exposure. 2. Identify all unblocked, backdoor paths from between the exposure and outcome. 3. Define S, your sufficient set of variables needed to adjust for confounding. 4. Draw an edge to connect all pairs of variables with a child in S, or a child with a descendent in S. 5. Identify any new unblocked, backdoor paths, and update S.
  • 113. Direct Acyclic Graphs MAKING A DAG 1. Identify an important health outcome, and a modifiable exposure. Draw an arrow from the later to the former. 2. Think about what other variables might be related to these. Brainstorm, use existing literature, etc. 3. Draw in any hypothesized causal paths. 4. Follow the steps previously outlined.
  • 114. Direct Acyclic Graphs MAKING A DAG 5. Explore choices, and consider how these affect your optimal sufficient set for adjustment (S). 6. Draw your DAG so it flows in the same direction you read (as best as possible). 7. Use colour, notes, etc. 8. There are programs available, but pencil and lots of paper work best at first.
  • 115. Learning Task • Based on the topic of your research thesis, create a DAG. • It should include a preventable exposure, an important outcome, and at least 3 other potentially important covariates. • Send me an image of your DAG before 17:00, next Wednesday (ddahly@ucc.ie).
  • 116. Confounders SUMMARY 1. Epidemiologists should be preoccupied with causes. 2. Confounding is the single greatest threat to our causal inferences – which we must make, or risk irrelevance. 3. Definitions and rules of thumb based on collapsibility are not sufficient to identify many commonly encountered confounders. 4. Comparability based definitions are better, but don’t lend themselves to simple rules of thumb. 5. Epidemiologists do not consistently use the same level of rigour when trying to address confounding. 6. As a field, this limits our ability to effect positive change.
  • 117. Direct Acyclic Graphs SUMMARY 1. DAGs are a useful tool. 2. They help clarify causal thinking. 3. They guide the modelling process by helping to identify potential confounding.
  • 118. Next week PREVIEW 1. More DAG examples. 2. Critiques of DAGs, and my responses to these. 3. Methods for dealing with confounding, once you suspect it.

Editor's Notes

  1. We’ll handle the first 3 today.
  2. Impact on career.
  3. Discuss
  4. To me, epidemiology is simplified to this...
  5. Discuss
  6. Discuss
  7. Discuss
  8. Discuss...It really comes down to confounding, our topic.
  9. Long time follow up; ethics
  10. The most abused phrase to sound smart.
  11. Obvious to most
  12. Bias and error
  13. Why does randomization work?
  14. That’s a pretty monumental assumption....
  15. This is a path
  16. Colliders block paths