STAR

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STAR

• Bias and Confounding
• Knut Borch-Johnsen

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Epidemiology Natural History

• Birth Genetically determined (often unknown)
  variability
• of susceptibility
• Exposure Environment
• (family, social environment, macro
  environment
• occupation etc.) (rarely objective)
• Disease Diagnostic threshold
• (not objective)
• Death Heterogeneity with respect to lethality
  (unknown)
• Cause of death Heterogeneity
• Autopsy Heterogeneity

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Where do we get the evidence from?

• Epidemiology/observational studies
• Intervention studies
• Structured
• unstructured experiments

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INTERVENTION STUDIES Clinical trials 

• RANDOMIZED (DOBBELT BLIND)
• CONTROLED CLINICAL TRIAL
•  
• RANDOMIZED SINGLE-BLIND CONTRILED CLINICAL TRIAL
• OPEN TRIAL
•  
•  
• AIM
• To Compare the effect of different treatment
  regiments

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RCCT

• Blinding with respect to exposure
• Allocation by chance
• Control for unknown prognostic factors (versus
  stratification)
• "Simple" interpretation of results

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RCCT vs. Epidemiology
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Some key problems in epidemiology

• Study population
• Methods
• Measurements
• Multifactorial diseases
• Can all risk factors be measured

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Validity of the association

• Due to chance
• Bias
• Confounding

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Did this occur by chance Statistical test
p-value/confidence intervals

• Retinopathy in sample 60 in males 40 in
  females
• How to test this what do you need ?

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Did this occur by chance Statistical test
p-value/Confidence Intervals

• Retinopathy in sample 60 in males 40 in
  females
• The probability of observing en effect at least
  as extreme as the observed effect, provided that
  the nill-hypothesis (no effect) is true

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Sample size
Each collor is one socioeconomic group How many
needed in the sample to obtain a valid estimate?
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2 minutes
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Types of problems

• Bias
• Any systematic error in data collection an
  epidemiological study that results in an
  incorrect estimate of the association between
  exposure and risk of disease
• Confounding
• Mixing of the effect of the exposure under study
  on the disease with that of a third factor
  associated with the exposure and independent of
  that exposure be a risk factor for the disease

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Bias

• Any systematic error in en epidemiological study
  that results in an incorrect estimate of the
  association between exposure and risk of disease

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Bias

• Selection bias
• Observation or information bias

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Selection bias

• Relates to selection of study-population
• Descriptive studies
• Sample representative for the population
• Analytical studies/C-C studies
• Study populations from the same populations

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Descriptive studies
Sampling strategy Representative sample
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Descriptive studies
Sampling strategy Representative sample HOW TO
MAKE A REPRESENTATIVE SAMPLE
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2 minutes
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Descriptive studies

• Prevalence of complications among patients with
  type 2 diabetes
• Screened population
• Population based sample
• Primary care
• Secondary care
• Tertiary care

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Descriptive studies

• Representative ness of sample
• Population based sampling
• Responders
• Non-responders
• Non-responders differs with respect to
• Socioeconomic status
• Morbidity
• Mortality
• Life style

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Selection biasprobability of sampling

• Will all with the disease have the same
  probability of being diagnosed/sampled
• Women and gallstones
• Men and gastric/duodenal ulcers
• Asbestos exposure and COLD/Cancer

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Selection biasprobability of sampling

• Will all with the disease have the same
  probability of being diagnosed/sampled
• Women and gallstones
• Men and gastric/duodenal ulcers
• Difference in diagnostic threshold
• Asbestos exposure and COLD/Cancer
• Economic incentive for diagnosis
• Organic solvents and dementia
• Asbestos and COLD/Cancer

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Selection bias analytical studies

• Case-control studies
• Oral contraceptives and thromboembolism
• Hospital based C-C studies
• Doctors aware of the possible link
• Women with symptoms and using OC more likely to
  be hospitalised
• Leads to selection bias

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Observation/information bias

• Is a consequence of systematic differences in the
  way data on exposure or outcome are obtained from
  the various study groups
• Recall bias
• Interviewer bias

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Recall bias

• The diseased individual remember and report their
  previous exposure experience differently from
  non-diseased
• Or
• The exposed individual reports events differently
  from unexposed

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Recall bias

• Birth defects among laboratory technicians
  working with organic solvents OS
• Case-control study
• Case birth defect, control normal child
• Exposure self reported exposure to OS
• C-C-study OR gt 1.5 (plt0.01)
• Cohort study RR 1.02 (ns)
• WHY

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2 minutes
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Interviewer bias

• Soliciting, recording or interpretation of
  information may differ between cases and controls

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Interviewer bias - solutions

• Blinding of interviewer
• Structured interviews
• Interview guides
• dummy questions (exposures known to be
  unrelated to condition under study)

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Question

• Compare and contrast the likelihood of selection
  and observation/information bias in case-control
  and cohort study

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2 minutes
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Confounding

• Mixing of the effect of the exposure under study
  on the disease with that of a third factor
  associated with the exposure and independent of
  that exposure be a risk factor for the disease

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CONFOUNDING
CONFOUNDER
DISEASE
STUDY FACTOR
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Confounder characteristics

• Associated to exposure
• Risk factor in it self
• If 1 not 2 Intermediate variable
• If 2 not 1 Independent Risk Factor

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Confounders

• Diabetes and macrovascular disease
• Hypertension
• Dyslipidaemia
• Smoking
• Low physical activity

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Bias and Confoundingwhat to do ?

• Bias
• In general terms error in data leading to
  incorrect estimation of association between
  exposure and outcome
• Solution improve data collection

• Confounding
• In general terms incorrect estimation of
  association between exposure and outcome due to a
  third factor associated to exposure and disease
• Solution restriction matching stratification
  multivariate analysis

Bias design problem Confounding analysis
problem
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Other important terms

• Misclassification
• By exposure
• By event
• Systematic
• Random

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Other important terms

• Misclassification
• By exposure often systematic (recall bias)
• By event often systematic (by exposure)
• Systematic any result possible
• Random underestimates the effect

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