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Association & Causation
- 1. Association & Causation 1 Dr.Ravi Prakash JR-III Dept. of Community Medicine Katihar Medical College 1
- 2. Why is Association& Causation important? To decide if a factor A causes disease B or not! Is the link true or only facile? Is it true or by chance? If we know the cause(s) we can cure/treat /prevent/minimize the illness. (in a patient or the society) 2
- 3. Association & Causation Association Relation between two or more variables Generally found in snapshot (cross-sectional) studies Relationships can be positive or negative Correlation! (factors moving together– like poverty and under nutrition) Causation A variable (s) lead to another variable that is dependent/ outcome/ event/disease So it suggests Etiology of disease We need analytical studies to find out/prove cause(s) 3
- 4. Associatio n Defined as occurrenceof two variables more often than would be expected by chance. An association is present if probability of occurrence of a variable depends upon one or more variable. 4
- 5. CAUSATION Precipitating Factors Predisposing Factors Enabling Factors Reinforcing Factors Age, Sex, PreviousIllness Exposure to agent Low SEC, malnutrition Repeated Exposure Factors involved in Causation 5 CAUSE - an event, condition, characteristic (or a combination) which plays an important role / regular / predicable change in occurrence of the outcome (e.g. smoking and lung cancer)
- 6. TYPES OF ASSOCIATION 1.SPURIOUS ASSOCIATION 2. INDIRECT ASSOCIATION 3. DIRECT (Causal) ASSOCIATION A. One-to-One Causal association B. Multi-Factorial Causation 6
- 7. Pyramid Of Associations Causal Non-causal Confounded Spurious Positive/negative Raj Bhopal : Cause and effect: the epidemiological approach 7
- 8. Positive:Occurrence ofhigher value of a predictor variable is associated with occurrence of higher value of another dependent variable. Negative: Occurrence of higher value of a predictor variable is associated with lower value of another dependent variable. Ex - Female literacy and IMR 8
- 9. Causal: Independentvariable mustcause change in dependent variable. Ex – salt intake and hypertension Non-causal: Non-directional association between two variables. Ex – alcohol use and smoking 9
- 10. Spurious Association Spurious (nottrue) association •Not real, only apparent Example1: A study in UK of 5174 births at home and 11156 births at hospitals showed perinatal mortality rates of 5.4/1000 in home birth and 27.8/1000 in hospital births. (but this is spurious) Exapmle2: Fire and Fire Brigade may be found together in a snapshot--but Fire brigade is not the cause of FIRE. 10
- 11. SPURIOUS ASSOCIATION Someobserved 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). PMR Home Deliveries (5174) Perinatal Mortality Rate Hosp Deliveries (11,156) 27.8 / 1000 5.4 / 1000 11
- 12. INDIRECT ASSOCIATION Itis a statistical association between a characteristic of interest and a disease due to the presence of another factor i.e. common factor (confounding variable) 12
- 13. E- Goitre Altitude Iodine Deficiency (ConfoundingFactor) Yudkin & Roddy’s wrong hypothesis on Sucrose and CHD association (Smoking is the Confounder). Jacob Yerushalamy identified the association b/n Smoking and Low birth weight babies is due to Confounding. 13
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- 16. DIRECT ASSOCIATION A. One-to-OneCausal Relationship This model suggests that two factors (A & B) exhibit one to one relationship, if – Change in A is followed by Change in B. Cause (A) Effect (B) 16
- 17. DIRECT ASSOCIATION A. One-to-OneCausal Relationship This model suggests that two factors (A & B) exhibit one to one relationship, if – Change in A is followed by Change in B. Cause (A) Effect (B) Paramyxo Virus Measles 17
- 18. KOCH’S POSTULATES (GermTheory of Disease) Hemolytic Streptococci 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. Erysipelas Scarlett Fever Tonsillitis 18
- 19. B. Multifactorial Causation InSeveral Modern Diseases, more than one factor is implicated in the Web of Causation. Eg: Both Asbestos exposure and 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 19
- 20. Multiple factorleads to the disease. Common in non-communicable diseases Alternative causal factors each acting independently. Ex: In lung cancer more than one factor (e.g. air pollution, smoking, heredity) can produce the disease independently. Either the causes are acting Independently OR Cumulatively 20
- 21. Smoking Air pollution Reactionat cellular level Lung cancer Air pollution Reaction at cellular level Lung cancer + Exposure to asbestos Independently Exposure to asbestos Cumulatively Smoking + 21
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- 23. General Models ofCausation The most widely applied models are: – The epidemiological triad (triangle), – The web – The wheel and – The sufficient cause and component causes models (Rothman’s component causes model) 23
- 24. Epidemiological triad Agent Factors PhysicalAgents Chemical Agents Biological Agents Nutritional agents Host Factors Socio-demographic Factors Psycho-social Factors Intrinsic Characteristics Environmental Factors Physical Environment Biological Environment Social Environment 24
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- 26. Web of Causation- CHD CHD 26
- 27. Rothman’s Component Causesand Causal Pies Model • Rothman's model has emphasised that the causes of disease comprise a collection of factors. • These factors represent pieces of a pie, the whole pie (combinations of factors) are the sufficient causes for a disease. • It shows that a disease may have more than one sufficient cause, with each sufficient cause being composed of several factors 27
- 28. • The factorsrepresented by the pieces of the pie in this model are called component causes. • Each single component cause is rarely a sufficient cause by itself, But may be necessary cause. • Control of the disease could be achieved by removing one of the components in each "pie" and if there were a factor common to all "pies“ (necessary cause) the disease would be eliminated by removing that alone. A U B C N 28
- 29. A U B C N Known components(causes) – A, B, C Unknown component (cause) - U N – Necessary cause Known components causes + Unknown component cause = Sufficient cause + Necessary cause 29
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- 31. If a relationshipis causal, four types of causal relationships are possible: (1) Necessary And Sufficient (2) Necessary, But Not Sufficient (3) Sufficient, But Not Necessary (4) Neither Sufficient Nor Necessary 31
- 32. A factoris both necessary and sufficient for producing the disease. Without that factor, the disease never develops and in the presence of that factor, the disease always develops Types of causal relationships I: Each factor is both necessary and sufficient FACTORA DISEASE 32 Necessary and Sufficient
- 33. Necessary, But NotSufficient Each factor is necessary, but not, in itself, sufficient to cause the disease . Thus, multiple factors are required, often in a specific sequence. Ex: Carcinogenesis is considered to be a multistage process involving both initiation and promotion. A promoter must act after an initiator has acted. Action of an initiator or a promoter alone will not produce a cancer. 33
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- 36. Sufficient But NotNecessary The factor alone can produce the disease, but so can other factors that are acting alone Either radiation or benzene exposure can each produce leukemia without the presence of the other. Even in this situation, however, cancer does not develop in everyone who has experienced radiation or benzene exposure, so although both factors are not needed, other cofactors probably are. Thus, the criterion of sufficient is rarely met by a single factor. 36
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- 38. A factorby itself, is neither sufficient nor necessary to produce disease This is a more complex model, which probably most accurately represents the causal relationships that operate in most chronic diseases. Types of causal relationships: IV. Each factor is neither sufficient nor necessary 38 Neither Sufficient Nor Necessary
- 39. – Temporal association –Strength of association – Specificity of association – Consistency of association – Biological plausibility – Coherence of association 39 Additional criteria for judging causality
- 40. Temporal association Thecausal attribute must precede the disease or unfavorable outcome. Exposureto the factor must have occurred before the disease developed. Length of interval between exposure and disease very important. Its more obvious in acute disease than in chronic disease. 40
- 41. Temporal relationship (Relationshipwith time) • Cause must precede the effect. o Drinking contaminated water -occurrence of diarrhea. o However in many chronic cases, because of insidious onset and ignorance of precise induction period, it become hard to establish a temporal sequence as which comes first -the suspected agent or disease. 41
- 42. Strength Of The Association Relationship between cause and outcome could be strong or weak. With increasing level of exposure to the risk factor an increase in incidence of the disease is found. • Strength of association can be estimated by relative risk. • Relative risks/Odds ratio greater than 2 can be considered strong • Larger the relative risk, greater the likelihood of a causal association. 42
- 43. Dose-Response Relationship ( The Biologicalgradient ) As the dose of exposure increases, the risk of disease also increases If a dose-response relationship is present, it is strong evidence for a causal relationship. However, the absence of a dose-response relationship does not necessarily rule out a 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 43
- 44. The causalrelationship of cigarette smoking and lung cancer has been based on three points. Relative risk Dose-response relationship Decrease in risk on cessation of smoking 44
- 45. Biologic Plausibility OfThe Association The association must be consistent with the other knowledge (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, so the criterion of biological plausibility should not be applied rigidly. It is difficult to demonstrate where the confounder itself exhibits a biological gradient in relation to the outcome. 45
- 46. e.g. – cigarettesmoking and lung cancer hypothesis is biologically plausible. Food intake and cancer are interrelated is an old one. Positive association of intestine, rectum, and breast cancer is biologically logical. 46
- 47. Consistency Of The Association Consistency is the occurrence of the association at some other time and place repeatedly. Repeated observation of an association in different populations under different circumstances. Example: consistent association between lung cancer and cigarette smoking – 50 retrospective study and almost 9 prospective studies. 47
- 48. Specificity Of The Association Specific exposure is associated with only one disease. Specificity implies a one to one relationship between the cause and effect. It’s the most difficult to occur for 2 reasons: Single cause or factor can give rise to more than 1 disease Most diseases are due to multiple factors. Ex: Smoking is associated with many diseases. • Not everyone who smokes develops cancer • Not every one who develop cancer has smoke 48
- 49. Coherence of theassociation Based on available evidence or should be coherence with known facts that are thought to be relevant. i.e. historic evidence of rising consumption of tobacco in form of cigarette and rising incidence of lung cancer are coherent. 49
- 50. Deriving causal inferences:example Assessment of the Evidence Suggesting Helicobacter pylori Ulcers as a Causative Agent of Duodenal 1. Temporal relationship. • Helicobacter pylori is clearly linked to chronic gastritis. About 11% of chronic gastritis patients will go on to have duodenal ulcers over a 10- year period. 2. Strength of the relationship. • Helicobacter pylori is found in at least 90% of patients with duodenal ulcer. 50
- 51. 3. Dose-response relationship. •Density of Helicobacter pylori per square millimeter of gastric mucosa is higher in patients with duodenal ulcer than in patients without duodenal ulcer 4. Replication of the findings.(consistency) • Many of the observations regarding Helicobacter pylori have been replicated repeatedly 5. Consideration of alternate explanations. • Data suggest that smoking can increase the risk of duodenal ulcer in Helicobacter pylori-infected patients but is not a risk factor in patients in whom Helicobacter pylori has been eradicated 51
- 52. 6. Biologic plausibility. •Helicobacter pylori also induces mediators of inflammation. • Helicobacter pylori-infected mucosa is weakened and is susceptible to the damaging effects of acid. 7. Cessation of exposure. • Eradication of Helicobacter pylori heals duodenal ulcers at the same rate as histamine receptor antagonists. 52 8. Specificity of the association. Prevalence of Helicobacter pylori in patients with duodenal ulcers is 90% to 100%.
- 53. References Park’s Text bookof Preventive & Social Medicine. 25th ed. Community medicine with Recent advances by A.H.Suryakantha Textbook of Community Medicine by Sunder Lal, Adarsh, Pankaj. 6th ed
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