1. DrugEpi 6 - Reverse Time Order Module 4 Overview Context Content Area: Interpretation of Epidemiological Evidence Essential Question (Generic): Is the association causal? Essential Question (Drug Abuse Specific): Is an association with drug abuse causal? Enduring Epidemiological Understanding: Causation is only one explanation for finding an association between an exposure and a disease. Because observational studies are complicated by factors not controlled by the observer, other explanations must also be considered. Synopsis: In Module 4, students explore the rationale and methods of interpreting epidemiological studies. Students develop skills to assess possible explanations for an association found in a study, with consideration of explanations of causality, chance, confounding, reversed time order, and bias. Module 4 concludes with consideration of methods for weighing the overall evidence for an association. Lessons: Lesson 4-1: Introduction to Interpreting Associations Lesson 4-2: Causality Lesson 4-3: Chance Lesson 4-4: Bias Lesson 4-5: Confounding Lesson 4-6: Reverse Time Order Lesson 4-7: Weighing the Evidence

2. DrugEpi 6 - Reverse Time Order Module 4 - Interpretation of Epidemiological Evidence Lesson 4-6 - Reverse Time Order Content Definition and explanation of reverse time order Examples of exposure/outcome scenario that illustrate how reverse time order can be considered Example of an improved epidemiologic study design to determine whether or not there could be reverse time order Big Ideas Association does not necessarily mean causation When an association is found, several possible explanations must be considered, including the possibility that the association is due to reverse time order This project is supported by a Science Education Drug Abuse Partnership Award, Grant Number 1R24DA016357-01, from the National Institute on Drug Abuse, National Institutes of Health.

3. DrugEpi 6 - Reverse Time Order Where Are We? Essential QuestionsEnduring Understandings 1.How is this disease distributed? Health-related conditions and behaviors are not distributed uniformly in a population. They have unique distributions that can be described by how they are distributed in terms of person, place, and time. 2.What hypotheses might explain the distribution of disease? Clues for formulating hypotheses can be found by observing the way a health-related condition or behavior is distributed in a population. 3.Is there an association between the hypothesized cause and the disease? Causal hypotheses can be tested by observing exposures and diseases of people as they go about their daily lives. Information from these observational studies can be used to make and compare rates and identify associations. 4.Is the association causal? Causation is only one explanation for an association between an exposure and a disease. Because observational studies are complicated by factors not controlled by the observer, other explanations also must be considered. 5.What should be done when preventable causes of disease are found? Policy decisions are based on more than the scientific evidence. Because of competing values - social, economic, ethical, environmental, cultural, and political factors may also be considered.

4. DrugEpi 6 - Reverse Time Order Reverse Time Order Is the association due to reverse time order? 1.Cause 2. Chance 3. Chance Confounding Reverse Time Order 4. 5.

5. DrugEpi 6 - Reverse Time Order Which came first? EggChicken “The Riddle” by Charles Bragg

6. DrugEpi 6 - Reverse Time Order Scenario 1

7. DrugEpi 6 - Reverse Time Order Scenario 2

8. DrugEpi 6 - Reverse Time Order Which came first? EggChicken “The Riddle” by Charles Bragg

9. DrugEpi 6 - Reverse Time Order Definition When the hypothesized time order of an exposure and an outcome is actually reversed and the outcome really comes before the exposure. Reverse Time Order

10. DrugEpi 6 - Reverse Time Order Time Random Assignment E E DZ Healthy People Flow Diagram - Trial

11. DrugEpi 6 - Reverse Time Order E E DZ Healthy People - Time Cohort Study Flow Diagram

12. DrugEpi 6 - Reverse Time Order DZ E E E E - Time Case-Control Study Flow Diagram

13. DrugEpi 6 - Reverse Time Order DZ E E - Time Cross- Sectional Study Flow Diagram

14. DrugEpi 6 - Reverse Time Order Which came first? Exposure or Outcome? Time ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ Random Assignment - E E DZ Study Design: Trial Healthy People Time ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ - E E DZ Study Design: Cohort Study Healthy People Time ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ - DZ E E E E Study Design: Case-Control Study Time ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ - DZ E E Study Design: Cross-Sectional Study

15. DrugEpi 6 - Reverse Time Order Which came first? Exposure or Outcome? Time ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ Random Assignment - E E DZ Study Design: Trial Healthy People Time ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ - E E DZ Study Design: Cohort Study Healthy People Time ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ - DZ E E E E Study Design: Case-Control Study Time ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ - DZ E E Study Design: Cross-Sectional Study 1st2nd 3rd4th

16. DrugEpi 6 - Reverse Time Order Which came first? ExposureOutcome “The Riddle” by Charles Bragg

17. DrugEpi 6 - Reverse Time Order Scenario 3 Watching TV No Watching TV Overweight No Overweight Watching TVOverweight

18. DrugEpi 6 - Reverse Time Order b d a c Risks Count Compare Divide Over- weight No Over- weight TV No TV 23 9 or 71.8% 32 23 7 15 32 22 or 31.8% 22 7 Relative Risk = 2.3 Total Count, Divide, and Compare (CDC) Is there an association? Did watching TV and being overweight turn up together?

19. DrugEpi 6 - Reverse Time Order Watching TV Time Order Watching TV No Watching TV Overweight No Overweight Overweight Watching TV causes people to be overweight.

20. DrugEpi 6 - Reverse Time Order Watching TV No Watching TV Overweight No Overweight Watching TVOverweight X Time Order Watching TV causes people to be overweight.

21. DrugEpi 6 - Reverse Time Order Watching TV No Watching TV Overweight No Overweight Watching TVOverweight X Watching TV causes people to be overweight. Time Order

22. DrugEpi 6 - Reverse Time Order It is possible that people who __________ are more likely to ____________. But it is also possible that people who are __________ are more likely to __________. Reversed Time Order watch TV be overweight watch TV overweight

23. DrugEpi 6 - Reverse Time Order Which came first? Watching TVOverweight “The Riddle” by Charles Bragg

24. DrugEpi 6 - Reverse Time Order Watching TV causes weight gain. Watching TV No Watching TV Overweight No Overweight Watching TVOverweight Cigarette Smoking No Cigarette Smoking Depression No Depression Scenario 4 Cigarette Smoking Depression

25. DrugEpi 6 - Reverse Time Order b d a c Count Compare Divide 38 83 59 196 121 255 121 Risks or 31.4% 38 or 23.1% 255 59 Relative Risk = 1.4 Depress- ion No Depress- ion Cigarette Smoking No Cigarette Smoking Total Is there an association? Did cigarette smoking and depression turn up together? Count, Divide, and Compare (CDC)

26. DrugEpi 6 - Reverse Time Order Watching TV causes weight gain. Watching TV No Watching TV Overweight No Overweight Watching TVOverweight Cigarette Smoking No Cigarette Smoking Depression No Depression Time Order Cigarette Smoking Depression Cigarette smoking causes depression.

27. DrugEpi 6 - Reverse Time Order Watching TV No Watching TV Overweight No Overweight Watching TVOverweight Cigarette Smoking No Cigarette Smoking Depression No Depression Cigarette Smoking Depression X Cigarette smoking causes depression. Time Order

28. DrugEpi 6 - Reverse Time Order Watching TV No Watching TV Overweight No Overweight Watching TVOverweight Cigarette Smoking No Cigarette Smoking Depression No Depression Cigarette Smoking Depression X Cigarette smoking causes depression. Time Order

29. DrugEpi 6 - Reverse Time Order It is possible that people who _____________ are more likely to ____________. But it is also possible that people who are __________ are more likely to ______________. Review - Reversed Time Order smoke cigarettes be depressed smoke cigarettes depressed

30. DrugEpi 6 - Reverse Time Order Which came first? Cigarette Smoking Depression “The Riddle” by Charles Bragg

31. DrugEpi 6 - Reverse Time Order Family Meals No Family Meals No Substance Use Substance Use Frequent Family Meals and Lack of Substance Use Family Meals No Substance Use

32. DrugEpi 6 - Reverse Time Order “Having family meals often may well decrease substance use” Family Meals No Substance Use x Family Meals No Family Meals No Substance Use Substance Use Frequent Family Meals and Lack of Substance Use

33. DrugEpi 6 - Reverse Time Order It could be that … using substances may lead to avoidance of family meals... Family Meals No Substance Use x Family Meals No Family Meals No Substance Use Substance Use Frequent Family Meals and Lack of Substance Use

34. DrugEpi 6 - Reverse Time Order Which came first? Family MealsSubstance Use “The Riddle” by Charles Bragg

35. DrugEpi 6 - Reverse Time Order It is possible that people who ________________ are more likely to __________________. But it is also possible that people who _______________ are more likely to _______________. Review - Reversed Time Order attend family meals not abuse substances avoid family meals use substances

36. DrugEpi 6 - Reverse Time Order Reverse Time Order How can I figure out if the association is due to reverse time order?

37. DrugEpi 6 - Reverse Time Order Which came first? Exposure or Outcome? Time ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ Random Assignment - E E DZ Study Design: Trial Healthy People Time ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ - E E DZ Study Design: Cohort Study Healthy People Time ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ - DZ E E E E Study Design: Case-Control Study Time ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ - DZ E E Study Design: Cross-Sectional Study

38. DrugEpi 6 - Reverse Time Order ME Eisenberg, D Neumark-Sztainer, JA Fulkerson, M Story. Family meals and substance use: Is there a long-term protective association? Journal of Adolescent Health 43 (2008) 151-156 A Study to Test Time Order

39. DrugEpi 6 - Reverse Time Order ME Eisenberg, D Neumark-Sztainer, JA Fulkerson, M Story. Family meals and substance use: Is there a long-term protective association? Journal of Adolescent Health 43 (2008) 151-156 A Study to Test Time Order “Most studies regarding health benefits of family meals have used a cross- sectional design...” “Cross-sectional studies... lay important groundwork but raise the question of reverse causality...” “The present study therefore builds upon or earlier cross-sectional research...” “We examine family meal patterns over 5 years and their association with initiation of substance use as young people transition from middle school to high school age.” “We hypothesize that regular family meals during early adolescence will be protective against substance use in middle adolescence, 5 years later.”

40. DrugEpi 6 - Reverse Time Order E E DZ Healthy People - Time Cohort Study Flow Diagram Yes/No 5 or more family meals per week Yes/No Development of substance use Teenagers substance use at start of study

41. DrugEpi 6 - Reverse Time Order Abstract of Journal Report on Study Purpose: To examine 5-year longitudinal associations between family meal patterns and subsequent substance use in adolescents. Methods: A total of 806 Minnesota adolescents were surveyed in public schools in 1998–1999 (mean age, 12.8 years) and again by mail in 2003–2004 (mean age, 17.2 years)... [We] estimated] the odds of tobacco, alcohol, and marijuana use at follow-up for adolescents reporting regular family meals at baseline compared with those without regular family meals, adjusting for family connectedness and prior substance use. Results: Family meal frequency at baseline was associated with significantly lower odds of cigarette smoking, alcohol use, and marijuana use at follow-up among female adolescents, even after adjusting for baseline substance use and additional covariates. Family meals were not associated with use of any substance at follow-up for male adolescents after adjusting for baseline use. Conclusions: Results from this study suggest that regular family meals in adolescence may have a long-term protective association with the development of substance use over 5 years among females. Parents should be encouraged to establish a pattern of regular family meals, as this activity may have long lasting benefits

42. DrugEpi 6 - Reverse Time Order Detail about Study Findings Gender / Exposure Relative Odds (95% Confidence Interval - CI) * ** Say it in English Girls Cigarettes Alcohol Marijuana 0.47 (0.29-0.81) 0.49 (0.29 - 0.83) 0.49 (0.26 - 0.93) The odds of using _____________ are ______ times as likely for those who have 5 or more family meals per week as for those who do not Boys Cigarettes Alcohol Marijuana 0.67 (0.39 - 1.21) 0.91 (0.53 - 1.55) 0.98 (0.54 - 1.76) * Analyses account for “family connectedness,” race, socioeconomic status and baseline substance use ** 95% CI means that 95 of 100 studies, this CI contains the true odds ratio

43. DrugEpi 6 - Reverse Time Order Interpretation Why is the protective effect seen only in girls? Eisenberg in article: “ This study's findings also are in line with our previous findings suggesting that family meals may be associated with more benefits for females than for males. Although measures were not available to explore reasons behind this difference in the current study, existing theory and research point to differences in the way that males and females interact with family members in a variety of domains. Females may, for example, be more attuned to subtle emotional support offered during family meals, resulting in a more profound protective effect for females than for males.”

44. DrugEpi 6 - Reverse Time Order ExposureOutcome If an association was found due to reversed time-order, …. found due to reverse time order, …. Public Health Significance of Reverse Time Order X … and you avoided or eliminated the hypothesized cause, what would happen to the outcome? ?

45. DrugEpi 6 - Reverse Time Order Big Ideas in this Lesson (4-6) Association does not necessarily mean causation When an association is found, several possible explanations must be considered, including the possibility that the association is due to reverse time order Re-Cap

46. DrugEpi 6 - Reverse Time Order Next Lesson Amicus Curiae Friend of the Court