Variability & BiasVariability & Bias

Yulia Sofiatin

Department of Epidemiology and Biostatistics

CRP I

Clinical scenario :Clinical scenario :

An investigator wanted to study the effect of treatment A and B on BP reduction in patients with Hypertension

The investigator asked 4 GPs to collect the data

Treatment A

Treatment B

Normal BP

High BP

Normal BP

High BP

Normal BP High BP

Treatment A

a b

Treatment B

c d

1515 2525 4040

55 7575 8080

2020 100100 120120

The resultThe result

Cohort Relative risk RR = (a/a+b) : (c/c+d) = 6

Case control Odds ratioOR = ad/bc = 9

OR/RR < 1 : PROTECTIVE EXPOSURE

OR/RR = 1 : NO RELATIONSHIP = NULL HYPOTHESIS

OR/RR > 1 : HAZARDOUS EXPOSURE

By definition:By definition:

The measurement of blood pressure depends on :

- The patients

Variability

What kind of mistakes could occur during the study ?

- The GPs

- Manometer

Variability in Medical Research

Variability within the

individual

Variability within

population

Variability related to

measurement

Diurnal variationAge, diet, exercise

Poor calibrationlack of precisionMisreading, misrecording

Genetic variabilityEnvironment variability

What are the consequences of What are the consequences of variability?variability?

BIAS = systematic error

PRECISION X random error

Effect of variationEffect of variation

807060 90 100

Within individual:1 observer2 observersbetween

visitsAmong patients

““To error is human”To error is human”

Any epidemiologic study presents Any epidemiologic study presents many, many opportunities for error many, many opportunities for error in relation to:in relation to:

Selection of study participantsSelection of study participants

Classification and measurementClassification and measurement

Comparison and interpretationComparison and interpretation

Epidemiologic researchEpidemiologic research

measurement

Study participa

nt

ConclusionDecision

BIASCONFOUNDING

CHANCE

1. HOSPITAL SETTING

CaseCase

(CP)(CP)ControlControl

ExposedExposed

(Asphyxia(Asphyxia))7070 5050 120120

Not exposedNot exposed 3030 5050 8080

100100 100100 200200

OR = ad/bc = 3500/1500 = 2.3

2. COMMUNITY SETTING

CaseCase

(CP)(CP)ControlControl

ExposedExposed

(asphyxia)(asphyxia)7070 3535 105105

Not exposedNot exposed 3030 6565 9595

100100 100100 200200

OR = ad/bc = 4550/1050 = 4.3

WHICH ONE IS THE WHICH ONE IS THE TRUTH?TRUTH?

What should we consider????What should we consider????

BiasBias

Is a systematic error that leads to Is a systematic error that leads to distortion of the resultsdistortion of the results

1. Selection bias

2. Information bias

3. confounding

Most common biasMost common bias

SELECTION BIASSELECTION BIAS

COHORT CASE CONTROL

Develop CAD

Did not develop CAD

Total CAD (+) CAD (-) Total

Highest quartile of serum cholesterol

85 462 547 38 34 72

Lowest three quartile of serum cholesterol

116 1511 1627 113 117 230

Total 201 1973 2174 151 151 302Odds ratio 2.40 1.16

Selective survival among the prevalent casesSelective survival among the prevalent cases

Prevalence-Incidence bias Prevalence-Incidence bias

Prevalence- incidencePrevalence- incidence

Self-selection bias Self-selection bias

Healthy (or diseased) people/ volunteers may seek Healthy (or diseased) people/ volunteers may seek out participation in the studyout participation in the study

The prevalence among volunteers in this case will The prevalence among volunteers in this case will be higherbe higher

PILOT STUDY GENERAL POPULATION

Hypertensive

Normal Total Hypertensive

Normal Total

History (+) 23 34 57 745 2775 3520

History (-) 36 65 101 478 3455 3933

Total 59 99 158 1223 6230 7453

Prevalence

58 16

Referral biasReferral bias

Sicker patients are referred to major health Sicker patients are referred to major health centerscenters

Community setting Hospital setting

CP Normal Total CP Normal Total

Birth asphyxia (+) 70 35 105 70 50 120Birth asphyxia (-) 30 65 95 30 50 80Total 100 100 200 100 100 200

OR 4.3 2.3

Response BiasResponse Bias

Response Non response

Total

High school students

Teenage workers

Total

Characteristics of those who response are Characteristics of those who response are different to those who do not response different to those who do not response association will be biased ~ self-selectionassociation will be biased ~ self-selection

Healthy worker biasHealthy worker bias

Exposed worker

General population

workers Non workers

Total

Death 50 4500 2500 7000

Person time

1000 90000 10000 100000

Mortality rate

0.05 0.05 0.25 0.07

The mortality rate of an exposed group of workers compared with that of The mortality rate of an exposed group of workers compared with that of the general population.the general population.

Non workers is also consist of those who Non workers is also consist of those who are are unable to work because of the unable to work because of the disease.disease.

Berkson’s biasBerkson’s bias

the combination of the exposure and the the combination of the exposure and the outcome underoutcome under study increases the rate of study increases the rate of admission to hospital. admission to hospital.

Community setting Hospital setting

Movement disease

(+)

Movement disease (-)

Total Movement disease

(+)

Movement disease (-)

Total

Respiratory disease (+)

17 207 224 5 15 20

Respiratory disease (-)

184 2376 2560 18 219 237

Total 201 2583 2784 23 234 257OR 1.06 4.06

INFORMATION BIASINFORMATION BIAS

Recall biasRecall bias

COHORT CASE CONTROL

Develop Breast Ca

Did not develop Breast Ca

Total Breast Ca (+)

Breast Ca (-)

Total

With family history of Breast Ca

85 462 547 113 34 72

Without family history of Beast Ca

116 1511 1627 38 117 230

Total 201 1973 2174 151 151 302Odds ratio 2.40 3.33

Recall biasRecall bias

caused by differences in accuracy of caused by differences in accuracy of recalling past events by cases and recalling past events by cases and controlscontrols

There is a tendency for diseased There is a tendency for diseased people (or their relatives) to recall people (or their relatives) to recall past exposures more efficiently than past exposures more efficiently than healthy people (selective recall). healthy people (selective recall).

Non-respondent bias; Loss Non-respondent bias; Loss to follow upto follow up

There are a possibility of different There are a possibility of different condition among:condition among: Non-respondents to a survey from Non-respondents to a survey from

respondentsrespondents Volunteers from non-volunteersVolunteers from non-volunteers Late respondents from early Late respondents from early

respondents, respondents, study dropouts from those who study dropouts from those who

complete the studycomplete the study

Hawthorne BiasHawthorne Bias

How will you act if you know that you How will you act if you know that you are being watched?are being watched? NormalNormal BetterBetter WorseWorse

End-aversion bias End-aversion bias (Measurement bias)(Measurement bias)

Corruption is the most critical Corruption is the most critical problem in Indonesiaproblem in Indonesia

How will you response to:How will you response to:(end-of-scale or (end-of-scale or central tendency central tendency bias): respondents bias): respondents usually avoid ends of usually avoid ends of scales in their answersscales in their answers

[ [ [ [ [ [1 2 3 4 5 6Agree not agree

Research QuestionResearch Question

What is the odds of suffering What is the odds of suffering influenza among people with and influenza among people with and without influenza immunizationwithout influenza immunization

What is the effect of different ‘case What is the effect of different ‘case definition’definition’ Definition ADefinition A Definition BDefinition B

Definition A Definition B

Disease (+)

Disease (-)

Total Disease (+)

Disease (-)

Total

Immunization (+)

85 61 146 125 92 151

Immunization (-)

66 90 156 26 69 151

Total 151 151 302 151 151 302Prevalence 0.56 0.4 0.83 0.61

Misclassification biasMisclassification bias

Caused by inaccuracy in measurement Caused by inaccuracy in measurement of classification of study variables. of classification of study variables.

The probability of misclassification The probability of misclassification may be the same in all study groups may be the same in all study groups (nondifferential misclassification) (nondifferential misclassification)

It may vary between groups It may vary between groups (differential misclassification) (differential misclassification) different ‘case definition’ between different ‘case definition’ between case and control groups.case and control groups.