09-Synthesis_Causal_inference_2011

Document Sample
09-Synthesis_Causal_inference_2011 Powered By Docstoc
					Synthesis: Causal Inference

   Kassiani Mellou, based on EPIET material


         EPIET Introductory Course,
          Lazareto, Menorca 2011
How do we understand causality?
Intuitively?




                                  2
3
4
               How is cause defined?


           “Antecedent event, condition, or
  characteristic that was necessary for the
    occurrence of the disease event and
 without, the disease event either would not
   have occurred at all or until some time
                    later.”

Rothman KJ, Greenland: Causation and Causal Inference in Epidemiology,
      (Am J PH, 2005)
                                                                         5
 Cause in the context of epidemiology

Count and compare AND
Search for cause and effect
• Source of the outbreak?
• Risk factor for disease?

Why?
• Implement control
  measures
• Give recommendations
                                        6
   RR = 89.7
95%CI = 82.5 – 91.4

   p<0.001
 Does a statistical association
 automatically mean that there
   is a causal relationship?
                                  7
     Statistical association
• Causal ?
• Result of
    • chance
    • selection bias
    • information bias
    • confounding
                               8
Henle-Koch-Postulates (1890)

            1. Pathogen must identified in
               ill person/animal
            2. Pathogen must be
               culturable
            3. Cultured pathogen should
               cause illness in test animal
            4. Pathogen must be
               reisolated and found
               identical to original



                                          9
    Bradford Hill’s criteria (1965)
                                    1. Strength of Association
                                    2. Consistency
                                    3. Specificity
                                    4. Temporality
                                    5. Biological gradient (dose
                                       response)
                                    6. Plausibility
                                    7. Coherence
                                    8. Experimental Evidence
                                    9. Analogy
AB Hill: The Environment and Disease: Association or Causation?    10
Proc Royal Soc Med 1965;58:295-300
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Extent to which alternate explanations have
   been considered
8. Specificity of the association
9. Consistency with other knowledge


L Gordis: Epidemiology 4th revised edition, W. Saunders publishers July 2008   11
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Extent to which alternate explanations have
   been considered
8. Specificity of the association
9. Consistency with other knowledge

L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008   12
    Temporal Relationship
Exposure must precede disease

Essential criterion for causality

Knowledge of:
• Latency period
• Incubation period
                                    13
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Extent to which alternate explanations have
   been considered
8. Specificity of the association
9. Consistency with other knowledge

L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008   14
      Strength of Association
Strong associations are more likely being
  causal than weak ones.

Smoking > 20 cigarettes/day  laryngeal carcinoma (RR 20)


BUT not all strong associations are causal…


                                                     15
       Cases of Down syndrome by birth order
       Cases of Down Syndrome by Birth Order

           180
           160
           140
Cases per 120
   100 000
live births 100
             80
            60
            40
            20
             0
                  1   2        3        4   5

                          Birth order           16
       Cases of Down Syndrome by Maternal Age
           Cases of Down Syndrome by age groups
                          Groups
              1000
Cases per
               900
100000 live    800
  births       700
               600
               500
               400
               300
               200
               100
                 0
                     < 20   20-24     25-29     30-34     35-39   40+

                                    Maternal Age Groups

                                                                  17
      Strength of Association
Strong associations are more likely being
  causal than weak ones.
Smoking > 20 cigarettes/day  laryngeal carcinoma (RR 20)


BUT:
Not all strong associations are causal…
And weak associations do not rule out
 causality…
                                                     18
   Smoking and Lung cancer?
Breast cancer? Passive smoking
Cigarette smoking and lung cancer
RR= ~ 10

Cigarette smoking and breast cancer
RR = ~ 1 -1.5

Passive smoking and lung cancer
RR = ~ 1.4
                                      19
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Extent to which alternate explanations have
   been considered
8. Specificity of the association
9. Consistency with other knowledge

L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008   20
      Biologic Plausibility
Is consistent with current biological and
  medical common knowledge.

Smoking
Ingesting of chemicals and known
  carcinogens
DNA mutations
lung cancer
                                            21
      Biologic Plausibility
Is consistent with current
  biological and medical common
  knowledge.

• Percivall Pott - scrotum cancer observed in
  chimney sweeps (1775)
• Peptic ulcers and Helicobacter pylori
  (1980s)
                                            22
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Extent to which alternate explanations have
   been considered
8. Specificity of the association
9. Consistency with other knowledge

L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008   23
Dose-response Relationship
Risk increases with more intense/more
 frequent exposure

But:
• High dose at which any further increase has
  no effect
• Low dose may be that no response occurs or
  can be measured
                                            24
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Extent to which alternate explanations have
   been considered
8. Specificity of the association
9. Consistency with other knowledge

L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008   25
    Replication of findings
Findings found in:
•    different populations
•    by using different study designs

Jan Hendrik Schön – organic electronics
Hwang Woo-suk – stem cell research

                                          26
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Extent to which alternate explanations have
   been considered
8. Specificity of the association
9. Consistency with other knowledge

L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008   27
Effect of removing the exposure

A decrease in the outcome of interest is
  seen when the exposure is removed.




                                           28
29
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Extent to which alternate explanations
   have been considered
8. Specificity of the association
9. Consistency with other knowledge

L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008   30
     Extent to which alternate
explanations have been considered


  Has adjustment been made for possible
   confounding?




                                          31
 ”The Norwegian comedian Marve Fleksnes once
 stated: I am probably allergic to leather because
every time I go to bed with my shoes on, I wake up
        with a headache the next morning.”




                                                     32
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Extent to which alternate explanations have
   been considered
8. Specificity of the association
9. Consistency with other knowledge

L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008   33
  Specificity of the association
One cause has one effect.




                              abestosis
Asbestos exposure           mesothelioma

                             lung cancer
                                      34
   Rothman and Greenland
One cause – one effect – simplistic and
 not true

Most outcomes are as the result of many
  contributing causes
• Necessary
• Sufficient
• Probabilistic
                                          35
                                Condition of
 Earlier head                   the sidewalk
    trauma                                                  Use of cane
  leading to                                                to support
 equilibrium                                                 walking
  problems

                                                                  Type of
                                                                 footwear

  Weather
 conditions

                                           brittle bones

Source: Rothman KJ, Greenland: Causation and Causal Inference in Epidemiology, 36
        (Am J PH, 2005)
Criteria for a Causal Relationship
1. Temporal relationship
2. Strength of the association
3. Biologic plausibility
4. Dose–response relationship
5. Replication of the findings
6. Effect of removing the exposure
7. Extent to which alternate explanations have
   been considered
8. Specificity of the association
9. Consistency with other knowledge

L Gordis: Epidemiology 4th revised edition, W. Saunder publishers July 2008   37
Consistency with other knowledge

If an association is supported by the
   results of different disciplines




                                        38
              Summary
• Not a checklist! (don’t stop thinking)
• Beware of biologic plausibility
• Always aim for better evidence
• Association is not causality!!!
• Keep an open mind
• Remain critical
(… especially of your own studies)
                                           39
Thank you for your attention!

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:5
posted:6/30/2012
language:
pages:40