Causal Reasoning

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Causal Reasoning

• Cord Heuer
• EpiCentre, IVABS, Massey University, Palmerston
  North
• NZVA EpiBranch Workshop 2007

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Reading

• Human Med.
• M. Elwood, Critical Appraisal of Epidemiologic
  Studies and Clinical Trials 2007
• Washington State Uv., website, glossary
• http//www.vetmed.wsu.edu/courses-jmgay/GlossEpiTe
  rminology.htmCausality

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1747 James Lind

• Scurvy
• 12 patients
• 6 treatments
• Sea water, gruel, cider, various elixiers,
  oranges and lemons
• limeys

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Once upon a time there were five animals living
by the sea, a cow, a donkey, a sheep, a pig, and
a mouse.
One day they decided to go rowing on the bay.
First the cow got into the boat, then the donkey,
then the pig, then sheep. Finally the little
mouse jumped aboard
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Disaster! The boat capsized and the animals had
to swim to the shore. Who sank the boat?
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Agenda

• The concept of cause
• Types of cause
• Causal web models
• Establishing the cause of disease
• Kochs postulates
• Evans concept of causations causation
• Hills criteria
• Views on causal criteria

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The concept of cause

• Always tempting to think that cause is a single
  condition or event that inevitably leads to a
  particular outcome
• In reality, single cause outcomes tend to be
  the exception rather than the rule
• presence or absence of disease depends on a
  complex interplay of factors

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The concept of cause

• Aim of epidemiological research is to provide
  information that helps us to understand
• what factors are involved in causal pathways to
  disease
• the relative importance of each factor as a
  determinant of disease

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The concept of cause

• Cause
• an event, condition, or characteristic without
  which the disease would not have occurred
  (Rothman)

• Conditions
• Must precede the effect
• Can involve host or environmental factors
• Can be either
• Positive the presence of an exposure
• Negative the absence of exposure (e.g.
  vaccination)

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Types of cause

• Cause
• pieces of a pie once the pie is full, disease
  occurs
• RARELY exposure to a single agent will cause
  disease
• only one piece to the pie
• USUALLY some exposed persons dont develop the
  disease, yet others do
• more than one pieces to the pie
• e.g. tuberculosis may only develop in poorly
  nourished/housed individuals

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Example

• Component causes
• these are pieces of the pie
• e.g. coronary heart disease in humans
• high cholesterol
• smoking
• lack of exercise
• genetics
• concurrent diseases

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Types of cause

• Sufficient causes
• the whole pie
• a set of conditions without any one of which the
  disease would not have occurred
• not usually a single factor, often several
• e.g. respiratory disease
• Influenza virus, Pasteurella spp., stress are
  all components of a sufficient cause
• respiratory disease tends to occur when several
  of these factors are present
• Usually, not all components are known

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Types of cause

• Necessary cause
• A component that must be present for disease to
  occur
• e.g. foodborne disease outbreak
• chicken salad and cream desert have been
  identified as component causes for Salmonella
  diarrhoea
• Salmonella spp. is a necessary cause of
  Salmonella diarrhoea

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Types of cause
Sufficient cause the whole pie

• 3 sufficient causal complexes, each having 5
  component causes
• e.g. if ABCDE are present, disease occurs
  with 100 certainty
• A is a necessary cause since it appears as a
  member of each sufficient cause.
• B, C, and F are not necessary causes since they
  do not appear in all 3 sufficient causes.

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Types of cause

• Examples
• TB although M.bovis is a necessary cause it is
  not sufficient since many animals harbour small
  foci of M. bovis without clinical disease
• Lung cancer tobacco smoking is not a sufficient
  cause since many smokers do not get diseased, it
  is not necessary either since exposure to other
  chemicals (e.g. radon or asbestos) are also
  component causes
• Coronary heart disease in humans has no
  necessary cause, but rather a range of component
  causes which become sufficient when some or all
  occur together in individuals at levels that
  accumulate and interact to result in disease.

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Causal web models

• Takes the sufficient and necessary causes of
  disease and displays them as a path diagram
• Direct causes
• no known intervening variable between the
  exposure factor and the disease
• Indirect causes
• effect of exposure is mediated through one or
  more intervening variables

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Establishing the cause of disease

• Interpretation
• do shorts and plastic aprons cause leptospirosis
  ?
• are shorts and plastic aprons associated with the
  presence of leptospirosis

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Establishing the cause of disease

• The epidemiological process
• case definition
• definition of factors of interest (exposures)
• choice of study design
• comparison of disease rates among exposed and
  non-exposed
• identify factors associated with the presence of
  disease statistics
• identify factors causally associated with the
  presence of disease judgement

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Establishing the cause of disease

• Criteria for judging causation
• Kochs postulates
• Hills criteria

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Establishing the cause of disease

• Koch (1884) provided a framework for identifying
  causes of infectious disease
• Kochs postulates
• the agent has to be present in every case of the
  disease
• the agent has to be isolated and grown in pure
  culture
• the agent has to cause disease when inoculated
  into a susceptible animal and the agent must then
  be able to be recovered from that animal and
  identified
• Agent necessary (1) sufficient (3)

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Hills criteria

• Purpose guidelines to help determine if
  associations are causal (judgement criteria)
• Hill
• No rigid criteria to be followed slavishly
• viewpoints not to be used as hard and fast
  rules

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Hills criteria

• Criteria for causation
• Strength of association
• Consistency
• (Specificity)
• Temporality
• Dose response relationship
• Plausibility and coherence
• Evidence from experiment and intervention
• Analogy

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1. Strength of association
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2. Consistency
Effect of CIDR treatment with untreated controls
on submission rate
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2. Consistency
. on conception rate
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Study types

• Meta-analysis
• Experiment
• Randomised trial
• Cohort
• Case-control
• Cross-sectional
• Case series
• Case narrative

Strength of causal evidence
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4. Temporality
Frequency of seat belt use and injury occurrence
in the United Kingdom 1982 1983
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5. Dose-Response Relationship
Age adjusted death rates for lung cancer as a
function of approximate number of cigarettes
smoked per day.
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5. Dose-Response Relationship
Correlation between consumption of manufactured
cigarettes in 1950 and mortality rates from lung
cancer in persons aged 35 - 44 in the mid-1970s.
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5. Dose-Response Relationship
Relationship between asbestos exposure
(particle-years) and relative risk of lung cancer.
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6. Plausibility and Coherence

• known facts of natural history and biology of
  disease and exposure
• biological sense
• consistent with current knowledge/belief
• However could miss new mechanisms for disease
  development

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7. Experiment and Intervention

• Experiment more disease occurring in exposed
  individuals than non-exposed under controlled
  conditions
• Intervention Reduction or removal of the risk
  factor must reduce the risk of the outcome

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8. Analogy

• Similar characteristics with other exposure
  and/or disease
• BSE - scrapie - transmissible mink encephalopathy
  
• Neosporosis toxoplasmosis
• Crohns and Johnes disease
• Tuberculosis and Paratuberculosis

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Popular Vet-Example

• Bovine spongiform encephalopathy in Great Britain
• first case identified November 1986
• a case-control study of the first 200 cases
  identified an association between the use of meat
  and bone meal and BSE-positive farms
• Feeding MB meal from case animals to calves
  produced BSE at about 3-5 years of age
• feeding meat and bone to cattle was banned in
  July 1988
• to date, there have been 170,000 confirmed
  cases of BSE
• how many cases would there have been if the feed
  ban was delayed?

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