to Causation What is a Cause MerriamWebster Dictionary Something that brings about a result especially a person or thing that is the agent of bringing something about KJ Rothman An event condition or characteristic without which the disease would not have occurred ID: 1037527
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1. The Epidemiologic Approach to Causation
2. What is a Cause?Merriam-Webster Dictionary: Something that brings about a result especially a person or thing that is the agent of bringing something about.KJ Rothman: An event, condition, or characteristic without which the disease would not have occurred.M Susser: Something that makes a difference.
3. What is a Cause?
4. ProblemHow do we know when something makes a difference?Association is not equal to causation. Consider the following statement: If the rooster crows at the break of dawn, then the rooster caused the sun to rise.
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6. Characteristics of a causeMust precede the effect (proximate vs. distant)Can be either host or environmental factorsCharacteristics, conditionsactions of individualsevents, natural, social or economic phenomenaPositive (presence of a causative exposure) or negative (lack of a preventive exposure)
7. Terminology: Causes vs. Risk Factors Which are the following?CharacteristicsHigh Risk Group for Breast CancerLow Risk Group for Breast CancerCountry of BirthNorth America, Northern EuropeAsia, AfricaSocioeconomic StatusHighLowMarital StatusNever marriedEver Married
8. What are some of the causes of the following diseases and events?Influenza:Lung Cancer:Breast Cancer:Automobile Fatality:
9. Historical Development of Theories of Causation Divine retribution; imbalance in body humors caused by air, water, land, stars; spontaneous generationMiasma: Disease transmitted by miasmas or clouds clinging to earth’s surfaceGerm Theory of Disease and Henle-Koch Postulates: Most important postulate is that the microorganism must always be found with the disease. This postulate embodies the idea of specificity of a cause. That is, a one to one relationship between an exposure and a disease.
10. Historical Development of Theories of Causation Web of Causation: A paradigm for the causes of chronic diseases. Most important shift from Henle-Koch Postulates is the idea of multiple causes. Postulates were also revised for establishing causation in chronic diseases. Recent ControversiesCausation cannot be established. Causal criteria should be abandoned. Has anyone seen the spider that produced the web?
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14. General Model of Causation (Causal Pies) by KJ RothmanSufficient cause: A set of conditions without any one of which the disease would not have occurred. (This is one whole pie.) Component cause: Any one of the set of conditions which are necessary for the completion of a sufficient cause. (This is a piece of the pie.)Necessary cause: A component cause that is a member of every sufficient cause.
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16. Attributes of the Causal PieCompletion of a sufficient cause is synonymous with occurrence (although not necessarily diagnosis) of disease.Component causes can act far apart in time. A component cause can involve the presence of a causative exposure or the lack of a preventive exposure.Blocking the action of any component cause prevents the completion of the sufficient cause and therefore prevents the disease by that pathway.
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22. Causal “Guidelines" Suggested by Sir AB Hill (1965)Strength of the association; Consistency; Specificity; Temporality; Biological gradient; Plausibility; Coherence; Experiment; AnalogyPurpose: Guidelines to help determine if associations are causal.Should not be used as rigid criteria. Hill even stated that he did not intend for these "viewpoints" to be used as “hard and fast rules.”
23. 1. Strength of the associationThe larger the association, the more likely the exposure is causing the disease.Example: Smoking Lung Cancer RR = 9Heavy Smoking Lung Cancer RR = 20Strong associations are more likely to be causal because they are unlikely to be due entirely to bias and confounding.Weak associations may be causal but it is harder to rule out bias and confounding.
24. 2. ConsistencyThe association is observed repeatedly in different persons, places, times, and circumstances.Replicating the association:different samplesdifferent study designsdifferent investigatorsSmoking Lung cancer 29 retrospective and 7 prospective studiesThere are good reasons why study results may differ.low versus high level exposures
25. 3. SpecificityA single exposure should cause a single disease.Stems from infectious diseases Not really true for non-infectious diseasesWhen present, specificity does provide evidence of causality, but its absence does not preclude causation.
26. 4. TemporalityCausal factor must precede the disease in time.This is the only one of Hill's criteria that everyone agrees with. Prospective studies do a good job establishing the correct temporal relationship between an exposure and a disease. Smoking at baseline incident cancer
27. 5. Biological GradientA “dose-response” relationship between exposure and disease. Persons who have increasingly higher exposure levels have increasingly higher risks of disease.Pack Years Smoked Death from Lung Cancer Biology Dose-responseThreshold effect
28. 6/7. Plausibility/CoherenceBiological or social model exists to explain the association. Association does not conflict with current knowledge of natural history and biology of disease. Cigarettes contain many carcinogenic substances. Many epidemiologic studies have identified cause-effect relationships before biological mechanisms were identified. carcinogenic substances in cigarette smoke were discovered after the initial epidemiologic studies
29. 8. ExperimentInvestigator-initiated intervention that modifies the exposure through prevention, treatment, or removal should result in less disease. Smoking cessation programs ↓Lung CancerProvides strong evidence for causation, but most epidemiologic studies are observational.
30. 9. AnalogyHas a similar relationship been observed with another exposure and/ or disease?Example: Effects of Thalidomide and Rubella on the fetus provide analogy for effects of similar substances on the fetus.
31. In summary, Sir Bradford Hill's “guidelines" are useful guides for:Remembering distinctions between association and causation in epidemiologic researchCritically reading epidemiologic studiesDesigning epidemiologic studiesInterpreting the results of your own study
32. TemporalityWas temporal relationship established in the article examining the association between artificial sweeteners and obesity.
33. Strength and Dose Response
34. Consistency
35. Biologic PlausibilityThere may be no causal relationship between AS use and weight gain. Individuals seeking to lose weight often switch to ASs in order to reduce their caloric intake. AS use might therefore simply be a marker for individuals already on weight-gain trajectories, which continued despite their switching to ASs. This is the most obvious possible explanation of our findings. Increased fast food consumption among soda users might further confound apparent associations (24).Do consumers of “lite” products overestimate caloric savings achieved through AS use, and unintentionally overcompensate elsewhere in their diets?Because sucrose partially counteracts decreased resting metabolic rate in low-calorie dieters(39), sugar avoiders might face metabolic-rate disadvantages. This might explain the apparently paradoxical findings of increased ΔBMI among AS users, despite lower baseline caloric intake, as in our own study, and/or apparently healthier food choices, as reported in the American Cancer Society study (16).Finally, aspartame, acesulfame potassium, saccharin, sucralose, and neotame are 180, 200, 300, 600, and 7,000–13,000 times sweeter than sugar, respectively. Has their adoption led to taste distortion, and increased appetite for intensely sweet, highly caloric foods?ASs might directly increase risk of weight gain in some individuals. Some studies have reported that AS use—or sweet taste itself—may increase hunger, cravings, or food intake (10,40–42), though most studies have reported no such increases (43,44). A few studies have reported elevated insulin and/or falling glucose levels (45–47).Of particular concern are results from rodent studies. Elevated levels of aspartate—which constitutes 40% of aspartame—are toxic to neurons in the arcuate nucleus of the hypothalamus( 48,49), a key forebrain site for leptin signaling to reduce food intake (50,51). The earlier the exposure, the more profound the damage (52). Could aspartame exposure at high-normal levels cause neurotoxicity, with increased leptin resistance and obesity, in humans?
36. True or FalseHill’s guidelines of temporality is more easily established in a prospective than a retrospective study.Strong associations are more likely to be causal.All of Hill’s criteria are required to meet causality.Exposure to HIV is a necessary cause of AIDS.Exposure to HIV is a sufficient cause of AIDS.Exposure to cigarette smoke is a necessary cause of lung cancer?Exposure to cigarette smoke is a sufficient cause of lung cancer?The presence of an association is indicative of a causal relationship.Time order is an essential attribute of a cause.If we have ruled out chance, bias, and confounding, as explanations for an association, we may conclude that the association is causal.According to the sufficient-component causal model, blocking the action of a necessary cause will prevent all cases of a disease by all of its causal mechanisms.