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Causation. Learning Objectives To be able to discuss Different Theories of causation Causation in Infectious vs. Chronic Disease Modern view of causation. Jay M. Fleisher MS, Ph.D. Associate Professor, Nova Southeastern University Studied at:
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Causation Learning Objectives To be able to discuss Different Theories of causation Causation in Infectious vs. Chronic Disease Modern view of causation
Jay M. Fleisher MS, Ph.D. • Associate Professor, Nova Southeastern University • Studied at: • Columbia University School of Public Health MS Epidemiology • NYU Ph.D. Environmental Epidemiology/Biostatistics
Causation • Two types of medical research • Bench work • Epidemiology • Bench work usually describes the underlying biology of disease • Epidemiology either tests the results of bench work on human populations or provides input to the biomedical scientist on what we still do not know
Example #1 - HIV and AIDS • Epidemiology identifies new disease caused by defect in immune system • Bench science identifies the infectious agent • Epidemiological studies confirm that agent causes disease in humans • Causation is proven
Example #2 - What Causes an MI • Epidemiological studies combined with laboratory study identify risk factors • Cigarette smoking • Cholesterol • Elevated blood pressure • Stress • Family history • Obesity • Etc • Which of the above contribute the most risk • What are the relationships between risk factors
Therefore: • The issue of causation is not as simple as it first appears • Thus, the need for a unifying concept of causation
The 2 Components: • Sufficient Cause • precedes the disease • if the cause is present, the disease always occurs • Necessary Cause • precedes the disease • if the cause is absent, the disease cannot occur
1. Necessary and Sufficient* Disease Only Factor A Sickle Cell Anemia Genetic factors * RARELY OCCUR
2. Necessary but Not Sufficient Factor A + Factor B Disease + Factor C
2. Necessary but Not Sufficient - Example Initiation + Latent Period Cancer + Promoter
3. Sufficient but Not Necessary Factor A Factor B Disease Factor C
3. Sufficient but Not Necessary - Example Ionizing Radiation or Benzene Leukemia or Electromagnetic Fields?
4. Neither Sufficient Nor Necessary Factor A + Factor B and/or + Disease Factor C Factor D and/or + Factor E Factor F
4. Neither Sufficient Nor Necessary - Example Smoking + Cholesterol and/or + MI HBP Fam. History and/or + Stress Obesity
Therefore: • Concept of Necessary vs. Sufficient Causes provides a theoretical framework for causation of all disease • How do we actually assess whether a Risk Factor is indeed Causal
Criteria for Assessing Causation • Temporal relationship • Exposure precedes the disease • Strength of the Association • Measured by the Relative Risk ( either the Rate Ratio or the Odds Ratio) • Dose-response Relationship • As the dose of exposure increases the risk of disease also increases • Example: Cigarette Smoking and Lung Ca • Replication of the Findings • Results replicated in other studies • Biologic plausibility • Does the association fit with what we know about the underlying biology • Sometimes we know little or nothing about the undelieing biology ( “Black Box” epidemiology • Consistency • Alternative explanation eliminated • Cessation effects • Specificity of the Association • Dose-response
Criteria for Assessing Causation • Biologic plausibility • Does the association fit with what we know about the underlying biology • Sometimes we know little or nothing about the underlying biology ( “Black Box” epidemiology) • Example – Asbestosis and Lung Ca.. Only have theory of mechanism • Consideration of Alternate Explanations • If knowledge exists, rule out or make sure studies took into account • Cessation of Exposure • If exposure is reduced or eliminated Risk will decline • Example Ex-Smokers • Specificity of the Association • A specific agent is associated with only 1 disease • OK for infectious agents but falls apart with many Risk Factors for Chronic Illness • Example: Cigarette Smoking associated with several diseases
Relevant Web Sites • http://www.defendingscience.org/sites/default/files/upload/Rothman-Greenland.pdf • http://www.facmed.unam.mx/deptos/salud/censenanza/spiii/spiii/rothman.pdf