Bias, Confounding and the Role of Chance

Principles of Epidemiology Lecture 5

Dona Schneider, PhD, MPH, FACE

To Show Cause We Use

Kochs Postulates for Infectious Disease Hills Postulates for Chronic Disease and Complex Questions

Strength of Association Tonights entire lecture Biologic Credibility

Specificity
Consistency with Other Associations Time Sequence Dose-Response Relationship Analogy Experiment Coherence

Epidemiology (Schneider)

To Show a Valid Statistical Association

We need to assess:

Bias: whether systematic error has been

built into the study design

Confounding: whether an extraneous

factor is related to both the disease and the exposure

Role of chance: how likely is it that

what we found is a true finding

Epidemiology (Schneider)

BIAS
Systematic error built into the study design Selection Bias

Information Bias

Types of Selection Bias

Berksonian bias

There may be a

spurious association between diseases or between a characteristic and a disease because of the different probabilities of admission to a hospital for those with the disease, without the disease and with the characteristic of interest
Berkson J. Limitations of the application of fourfold table analysis to hospital data. Biometrics 1946;2:47-53

Epidemiology (Schneider)

Types of Selection Bias (cont.)

Response Bias those who agree to be in

a study may be in some way different from those who refuse to participate

Volunteers may be different from those who are enlisted

Epidemiology (Schneider)

Types of Information Bias

Interviewer Bias an interviewers

knowledge may influence the structure of questions and the manner of presentation, which may influence responses

Recall Bias those with a particular

outcome or exposure may remember events more clearly or amplify their recollections

Epidemiology (Schneider)

Types of Information Bias (cont.)

Observer Bias observers may have

preconceived expectations of what they should find in an examination

Loss to follow-up those that are lost to

follow-up or who withdraw from the study may be different from those who are followed for the entire study

Epidemiology (Schneider)

Information Bias (cont.)

Hawthorne effect an effect first

documented at a Hawthorne manufacturing plant; people act differently if they know they are being watched

Surveillance bias the group with the

known exposure or outcome may be followed more closely or longer than the comparison group

Epidemiology (Schneider)

Information Bias (cont.)

Misclassification bias errors are made

in classifying either disease or exposure status

Epidemiology (Schneider)

Types of Misclassification Bias

Differential misclassification Errors in

measurement are one way only

Example: Measurement bias instrumentation may be inaccurate, such as using only one size blood pressure cuff to take measurements on both adults and children

Epidemiology (Schneider)

Misclassification Bias (cont.)

True Classification Cases Exposed Nonexposed
100 50 150

Controls
50 50 100

Total
150 100 250

OR = ad/bc = 2.0; RR = a/(a+b)/c/(c+d) = 1.3

Differential misclassification - Overestimate exposure for 10 cases, inflate rates

Cases Controls
50 50 100

Total
160 90 250

Exposed Nonexposed

110 40 150

OR = ad/bc = 2.8; RR = a/(a+b)/c/(c+d) = 1.6

Misclassification Bias (cont.)

True Classification
Cases
Exposed Nonexposed 100 50 150

Controls
50 50 100

Total
150 100 250

OR = ad/bc = 2.0; RR = a/(a+b)/c/(c+d) = 1.3

Differential misclassification - Underestimate exposure for 10 cases, deflate rates

Cases
Exposed
Nonexposed

Controls
50
50 100

Total
140
110 250

90
60 150

OR = ad/bc = 1.5; RR = a/(a+b)/c/(c+d) = 1.2

Misclassification Bias (cont.)

True Classification
Cases Exposed Nonexposed 100 50 150 Controls 50 50
100

Total 150 100 250

OR = ad/bc = 2.0; RR = a/(a+b)/c/(c+d) = 1.3 Differential misclassification - Underestimate exposure for 10 controls, inflate rates
Cases Exposed Nonexposed 100 50 150 Controls 40 60 100 Total 140 110 250

OR = ad/bc = 3.0; RR = a/(a+b)/c/(c+d) = 1.6

Misclassification Bias (cont.)

True Classification
Exposed Nonexposed
Cases 100 50 150 Controls 50 50 100 Total 150 100 250

OR = ad/bc = 2.0; RR = a/(a+b)/c/(c+d) = 1.3 Differential misclassification - Overestimate exposure for 10 controls, deflate rates
Cases Controls Total

Exposed
Nonexposed

100
50 150

60
40 100

160
90 250

OR = ad/bc = 1.3; RR = a/(a+b)/c/(c+d) = 1.1

Misclassification Bias (cont.)

Nondifferential (random) misclassification errors in assignment

of group happens in more than one
direction

This will dilute the study findings BIAS TOWARD THE NULL

Epidemiology (Schneider)

Misclassification Bias (cont.)

True Classification
Cases Exposed Nonexposed 100 50 150 Controls 50 50 100 Total 150 100 250

OR = ad/bc = 2.0; RR = a/(a+b)/c/(c+d) = 1.3 Nondifferential misclassification - Overestimate exposure in 10 cases, 10 controls bias towards null
Cases Exposed Nonexposed 110 40 150 Controls 60 40 100 Total 170 80 250

OR = ad/bc = 1.8; RR = a/(a+b)/c/(c+d) = 1.3

Controls for Bias

Be purposeful in the study design to minimize the chance for bias

Example: use more than one control group

Define, a priori, who is a case or what constitutes exposure so that there is no overlap

Define categories within groups clearly (age groups, aggregates of person years)

Set up strict guidelines for data collection

Train observers or interviewers to obtain data in the same fashion It is preferable to use more than one observer or interviewer, but not so many that they cannot be trained in an identical manner

Controls for Bias (cont)

Randomly allocate observers/interviewer data collection assignments

Institute a masking process if appropriate

Single masked study subjects are unaware of whether they are in the experimental or control group Double masked study the subject and the observer are unaware of the subjects group allocation Triple masked study the subject, observer and data analyst are unaware of the subjects group allocation

Build in methods to minimize loss to follow-up