Association causation

Epidemiology topic

1. ASSOCIATION & CAUSATION Dr. Y. Vishnu Vardhan 1 st year PG Community Medicine

2. Contents INTRODUCTION TYPES OF ASSOCIATION CAUSAL RELATIONSHIP CAUSAL INFERENCE & CONCLUSION REFERENCES GUIDELINES TO ASSESS CASUALITY

3. INTRODUCTION

4. INTRODUCTION Epidemiology aims at Promotion of health by discovering the causes of diseases & the way in which they can be modified. Identification of Causal relationships b/n disease and suspected factor. Disease or Other Outcome Environmental exposure

5. Identify Disease in Community Descriptive Study Relate to Environment & Host Factor Suggests an Aetiological hypothesis Analytical & Experimental Studies Test the Hypothesis Which either confirms or refute the Observed Association. Causal or Not?

6. ASSOCIATION Concurrence of Two Variables more often, than would be expected by Chance. CORRELATION indicates the Degree of Association.

7. Association doesn’t imply Causation CORRELATION CAUSATION

8. 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 and lung cancer) Precipitating Factors Predisposing Factors Enabling Factors Reinforcing Factors Age, Sex, Previous Illness Exposure to agent, Imm . Co Low SEC, malnutrition Repeated Exposure Factors involved in Causation

9. TYPES OF ASSOCIATION 1. SPURIOUS ASSOCIATION 2. INDIRECT ASSOCIATION 3. DIRECT ASSOCIATION A. One-to-One Causal Relationship B. Multi-Factorial Causation

10. 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). PMR Home Deliveries (5174) Perinatal Mortality Rate Hosp Deliveries (11,156) 27.8 / 1000 5.4 / 1000

11. 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 variable).

12. Confounding Factor McMohan Study (Pancreatic Cancer) 1.

13. Iodine Deficiency E- Goitre Altitude Confounding Factor 2. 3. Yudkin & Roddy’s wrong hypothesis on Sucrose and CHD association (Smoking is the Confounder) 4. Jacob Yerushalamy identified the association b/n Smoking and Low birth weight babies is due to Confounding.

14. DIRECT ASSOCIATION A. One-to-One Causal 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)

15. DIRECT ASSOCIATION A. One-to-One Causal 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. DIRECT ASSOCIATION A. One-to-One Causal 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. KOCH’S POSTULATES (Germ Theory of Disease ) Necessary, and 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

18. B. Multifactorial Causation In Several 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. Web of Causation of Diabetes Mellitus

20. CAUSAL RELATIONSHIPS If a Relationship is Causal, Four Types of causal relationships are possible: Necessary and Sufficient Necessary But not Sufficient Sufficient But not Necessary Neither Necessary nor Sufficient

21. Necessary and Sufficient A F actor is both necessary and 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

22. DISEASE Factor A Factor B Factor C + + 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.

23. CANCER Initiator Promoter Trigger + + 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.

24. Factor A Factor B Factor C Or Or DISEASE Sufficient But not Necessary The factor alone can produce the disease, but so can other factors that are acting alone. But the criterion of sufficient is rarely met by a single factor.

25. Radiation Benzene Exp Smoking Or Or Leukemia Sufficient But not Necessary The factor alone can produce the disease, but so can other factors that are acting alone. But the criterion of sufficient is rarely met by a single factor.

26. Factor A Factor C Factor E + Factor B + + Factor D Factor F DISEASE Or Or 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 relationships that operate in most chronic diseases.

27. 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. Guidelines for Judging Causality It first appeared in “Smoking and Health” Report by advisory Committee Austin Bradford Hill

28. Surgeon General’s Criteria

29. 1. Temporal Relationship They are swinging in Temporal Sequence. Its not bullying, its Science. The causal attribute must precede the disease or unfavorable outcome. ( Exposure before Disease ) Length of interval between exposure and disease very important. ( A sbestos exposure takes 20 yrs to cause d/s )

30. Smoking( Cause) Precedes Cancer (Effect)

31. 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.

32. Relative Risk Relative Risk = Incidence among Exposed Incidence among Non Exposed RR = 1 No association RR > 1 Positive association (possibly causal) RR < 1 Negative association (possibly protective) It is direct measure of the strength of association.

33. Odds Ratio Cases(with disease) Controls (without disease) H/O of exposure a b No H/O exposure c d Odds Ratio = OR = ad/ bc Odds of disease in exposed group Odds of disease in Non-exposed group

34. 3. Dose-Response Relationship As the dose of exposure increases, 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.

35. 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.

36. 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. Annual Death Rate per 1000 men 1989 1987 1988 1986 0.5 1.5 1 Years stopped smoking

37. 5. Specificity Of The Association Specificity implies a one to one relationship between the cause and effect (Weakest Criteria). Not everyone who smokes develop Lung Cancer, Not everyone who develops cancer has smoked. Lack of specificity does not negate causation.

38. 6. Consistency Of The Association If the relationship is causal, we would expect to find it consistently in different studies and in different populations. Causal Association b/n Smoking and Lung cancer is found consistently in: - 50 retrospective studies - 9 prospective studies .

39. 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.

40. 8. Coherence of the Association The association must be coherent with the known facts of relevant origins. Male and Female differences in trends of lung cancer Deaths is coherent with recent adoption of Cigarette smoking by women. Cigarette Smoking Lung cancer Mortality Cigarette Smoking

41. Coherence of the Association

42. 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,.

43. CAUSAL INFERENCE It is Process of drawing conclusions about a Causal connection based on the conditions of the Occurrence of an Effect. Deriving Causal inference from an Association should be done Through the decision tree approach.

44. OBSERVED ASSOCIATION Could it be due to BIAS? Could it be CONFOUNDING? Could it be result of CHANCE? Could it be CAUSAL RELATION? Apply Guidelines and Make Judgement . No No No Yes

45. CONCLUSION The Causal inferences resulted from the Epidemiological Studies are very important to Public health and provide inputs for Political and Judicial decisions. Eg : The Causal association b/n Smoking and Lung Cancer has resulted in labeling of Cigarette packets and Increased campaign ads.

46. 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.

47. REFERENCES Park K , Textbook of Preventive and Social medicine, 22 nd edition, Chp 3, P 80-84. Gordis , Leon . Textbook of Epidemiology, 3 rd Edition, Elsevier, Chp 14, P 203-215. R. Beaglehole & Bonita , Basic Epidemiology, 4 th edition, Chp 5, P 71-81. http://en.wikipedia.org/wiki/Epidemiology#As_causal_inference Fletcher, Robert . Clinical Epidemiology, 3 rd edition, Chp 11, P 237-239.

48. THANK YOU

49. REFERENCES Park K , Textbook of Preventive and Social medicine, 22 nd edition, Chp 3, P 80-84. Gordis , Leon . Textbook of Epidemiology, 3 rd Edition, Elsevier, Chp 14, P 203-215. R. Beaglehole & Bonita , Basic Epidemiology, 4 th edition, Chp 5, P 71-81. http://en.wikipedia.org/wiki/Epidemiology#As_causal_inference Fletcher, Robert . Clinical Epidemiology, 3 rd edition, Chp 11, P 237-239.