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Causation and association of disease
- 1. Causation and Association of Disease Md. Nur Alam B.Sc. in Public Health Nutrition
- 2. Association Terms – Association and relationship used interchangeably Defined as the co-occurrence of two or more variables at a frequency which is more than that expected by chance Association does not mean causation Correlation indicates the Degree of Association 2
- 4. Factors involved in Causation Cause – an event, condition, characteristic (or a combination) which plays an important role / regular / predicable change in occurrence of the outcome (e.g. smoking & lung cancer) 4 Causation Repeated Exposure Reinforcing Factors Low SEC, Malnutrition Age, Sex, Previous illness Exposure to agent, Imm. Co Enabling Factors Predisposing Factors Precipitating Factors
- 5. Association Types of Association 1. Spurious Association 2. Indirect Association 3. Direct Association a. One-to-One Causal Relationship b. Multi-Factorial Causation 5
- 6. Association 1. Spurious Association Some observed associations b/n a suspected factor and disease may not be real. This Fallacy of presumption arises when two variables are improperly compared (due to Bias) 6
- 7. Association 2. Indirect Association It is a statistical association between a characteristic of interest and a disease due to the presence of another factor i.e. common factor (Confounding variables). 7
- 8. Association Confounding Factors-1 8 Confounder (e.g. smoking) Factor (Coffee drinking) Disease Outcome (e.g. CVD) 1. Smoking is a known cause of CVD 2. Coffee drinking could be common among smokers (not a causal link) 3. If so, drinking coffee will appear to be linked to CVD McMohan study (Pancreatic cancer)
- 9. Association Confounding Factors-2 9 3. Yudkin & Roddy’s wrong hypothesis on Sucrose & CHD association (Smoking is the Confounder). 4. Jacob Yerushalamy identified the association b/n Smoking & Low birth weight babies is due to Confounding.
- 10. Association 3. Direct Association a) One-to-One Causal Relationship 10 This model suggests that two factor (A&B) exhibit one to one relationship, if Change in A is followed by Change in B.
- 11. Association 3. Direct Association a) One-to-One Causal Relationship 11 KOCH’S POSTULATES (Germ Theory of Disease) 1) Necessary, and 2) Sufficient But this model does not fit well for many diseases, like in Tuberculosis, tubercle bacilli is clearly a necessary factor, but its presence may or may not be sufficient to produce the d/s. A Single Factor may produce several Outcomes. Hemolytic Streptococci Erysipelas Scarlett Fever Tonsillitis
- 12. Association 3. Direct Association b) Multifactorial Causation In Several Modern Diseases, more than one factor is implicated in the Web of Causation. E.g., Both Asbestos exposure & Smoking cause Lung Cancer independently As our Knowledge on disease increases, we may discover a common biochemical event, which can be altered by each of these factors 12
- 13. Causal Relationship If a Relationship is Causal, Four Types of causal relationships are possible: 13 1. Necessary and Sufficient A Factor is both necessary & sufficient for producing the disease. Without that factor, the disease never develops (the factor is necessary), and in the presence of that factor, the disease always develops (the factor is sufficient). N S 2. Necessary But not Sufficient Each factor is necessary, but not, in itself, sufficient to cause the disease. Thus, multiple factors are required, often in a specific Temporal sequence.
- 14. Causal Relationship 14 3. Sufficient But not Necessary The factor alone can produce the disease, but so can other factors that are active alone. But the criterion of sufficient is rarely met by a single factor. 4. Neither Necessary nor Sufficient A Factor, by itself, is neither sufficient nor necessary to produce disease. This is a more complex model, which probably most accurately represents the causal relationship that operate in most chronic diseases.
- 15. Guidelines for Judging Causality 15 Without any Experimental aid, the evidence to justify Causation was lacking in our methods. So, certain additional Criteria was added by U.S. Surgeon general (1964), which is further strengthened by Bradford Hill (1965) Criteria. Bradford Hill (1965) Criteria Temporality Plausibility Consistency Strength Dose-response relationship Specificity Reversibility Coherence Analogy Surgeon general (1964) Criteria Temporality Plausibility Strength Consistency Specificity Coherence
- 16. Guidelines for Judging Causality 16 1. Temporal Relationship The causal attribute must precede the disease or unfavorable outcome. (Exposure before Disease) Length of interval between exposure and disease very important. (Asbestos exposure takes 20yrs to cause d/s)
- 17. Guidelines for Judging Causality 17 2. Strength of the association With increasing level of exposure to the risk factor an increase in incidence of the disease is found. This can be calculated either by ODDS ratio or Relative Risk.
- 18. Guidelines for Judging Causality 18 3. Dose Response Relationship As the dose of exposure increase, the risk of disease also increases. Presence of D-R relationship strengthens Causality, whereas its absence doesn’t rule out Causal relationship. In some cases in which a threshold may exist, no disease may develop up to a certain level of exposure (a threshold); above this level, disease may develop. 4. Cessation of exposure If a factor is a cause of a disease, we would expect the risk of the disease to decline when exposure to the factor is reduced or eliminated.
- 19. Guidelines for Judging Causality 19 5. Specificity of the Association Specificity implies a one to one relationship between the cause & effect (Weakest Criteria) Lack of specificity does not negate causation. 6. Consistency of the Association If the relationship is causal, we would expect to find it consistently in different studies & in different populations. Causal Association b/n Smoking & Lung cancer is found consistently in: 50 retrospective studies 9 prospective studies Not everyone who smokes develop Lung Cancer, Not everyone who develops cancer has smoked.
- 20. Guidelines for Judging Causality 20 7. Biological Plausibility The association must be consistent with the current knowledge of disease. (viz mechanism of action, evidence from animal experiments etc). Sometimes the lack of plausibility may simply be due to the lack of sufficient knowledge about the pathogenesis of a disease. 8. Coherence of the Association The association must be coherent with the known facts of relevant origins. Male & Female differences in trends of lung cancer Deaths is coherent with recent adoption of Cigarette smoking by women.
- 21. Guidelines for Judging Causality 21 9. Consideration of alternate explanations In judging whether a reported association is causal, the extent to which the investigators have taken other possible explanations into account and the extent to which they have ruled out such explanations are important considerations. Deriving Causal inferences by eliminating – Bias, Confounding and Chance etc.
- 22. Conclusion 22 The Causal inferences resulted from the Epidemiological Studies are very important to Public health and provide inputs for Political and Judicial decisions. E.g., The Causal association b/n Smoking and Lung Cancer has resulted in labeling of Cigarette packets and Increased campaign ads. Correlation does not Imply Causation. Apart from outbreak investigations, no single study is capable of establishing a causal relation or fully informing either individual or policy decisions. It is thus important for public health and policy makers to understand the fundamentals of causal inference.
- 23. References 23 Park K, Textbook of Preventive and Social medicine, 22nd edition, Chp 3, P 80-84. Gordis, Leon. Textbook of Epidemiology, 3rd Edition, Elsevier, Chp 14, P 203-215. http://en.Wikipedia.org/wiki/Epidemiology#As_causal_inference R.Beaglehole & Bonita, Basic Epidemiology, 4th edition, Chp 5, P 71-81. Fletcher, Robert. Clinical Epidemiology, 3rd edition, Chp 11, P 237-239
- 24. Group -E November 29, 2019 Nutrition Profile