1. DrugEpi 3-5 Fundamentals of Study Design Module 3 Introduction Content Area: Analytical Epidemiology Essential Question (Generic): Is there an association between the hypothesized cause and the disease? Essential Question (Drug Abuse Specific): Is there an association between the hypothesized cause and drug use? Enduring Epidemiological Understanding: 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. Synopsis In Module 3, students explore how hypotheses are tested epidemiologically. Students begin to uncover and develop the following epidemiological concepts and skills: the meaning of the term “association;” the need for a control group; uses of the 2x2 table in calculating risks and relative risks; experimental study design; the importance of ethics in human research; observational study designs used in epidemiology; and the strengths and limitations of each design. Lesson 3-1: Associations and the 2x2 Table Lesson 3-2: Experimental Study - Buprenorphine Example Lesson 3-3: An Actual Randomized Controlled Trial Lesson 3-4: Observational Studies of Natural Experiments - Sensation-Seeking Example Lesson 3-5: Fundamentals of Study Design Lesson 3-6: Study Design Exercises

2. DrugEpi 3-5 Fundamentals of Study Design Module 3 - Analytical Epidemiology Lesson 3-5 Fundamentals of Study Design Content Introduction to concepts of epidemiology study designs Overview of the four main study designs used in epidemiology: 1) controlled trial; 2) cohort study; 3) case-control study; and 4) cross-sectional study Ways of explaining the flow of each study design, in text and visually The uncovering of the strengths and limitations of each design Examples of how each design can be applied to evaluating the effectiveness of student drug testing programs Practice in identifying each study design Big Ideas Each study design can be expressed in a 2x2 table format Each study design has a different plan for assessing exposure and disease The experimental design is the most scientifically rigorous and the observational study designs vary in rigor from quite good to poor There is a trade-off between scientifically stronger studies that take more effort and money to conduct well, and the less scientific studies that are “quicker and dirtier” 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 3-5 Fundamentals of Study Design 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. Essential QuestionsEnduring Understandings Where are we?

4. DrugEpi 3-5 Fundamentals of Study Design The Journey

5. DrugEpi 3-5 Fundamentals of Study Design Descriptive Epidemiology Describes those who have the outcome (PPT) Generates hypotheses Surveillance: A way to obtain descriptive information – Example: National Survey on Drug Use and Health Review – What is in your epidemiology Toolbox so far?

6. DrugEpi 3-5 Fundamentals of Study Design Exposed Not Exposed Disease No Disease Total Tests hypotheses Needs an unexposed comparison group Uses the 2x2 table to calculate rates and compare risks in exposed/unexposed However... The 2x2 table does not show how the study was done (study design does this) Analytic Epidemiology... Review – What is in your epidemiology Toolbox so far?

7. DrugEpi 3-5 Fundamentals of Study Design Procedures and methods, established beforehand, that are followed by the investigators conducting the study This Lesson

8. DrugEpi 3-5 Fundamentals of Study Design CDC This will all make sense to you! There are four basic study designs for testing hypotheses. Each design has a different plan for assessing exposure and disease. The plan for each design can be understood by constructing a flow diagram. Whatever the study design and its flow diagram, it can be “fit” into a 2x2 table so that risks can be calculated and compared (RR). Preview

9. DrugEpi 3-5 Fundamentals of Study Design Four Basic Study Designs Controlled Trial Cohort Case-Control Cross-Sectional Observational Experimental

10. DrugEpi 3-5 Fundamentals of Study Design Controlled Trial (a planned experiment) An epidemiologic experiment in which subjects are assigned into groups to receive or not receive a hypothesized beneficial intervention. Examples in Lessons 3-2 and 3-3: Buprenorphine in the treatment of heroin addiction Review of Important Concepts

11. DrugEpi 3-5 Fundamentals of Study Design Epidemiologist Board of Education Hypothesis: Smoking marijuana causes memory loss. Research suggests a relationship between poor grades and drug use Scenario

12. DrugEpi 3-5 Fundamentals of Study Design 200 High School Students No Marijuana 100 Students Control Group Marijuana 100 Students Experimental Group 4 Months Measure Memory Loss 2 x 2 Table, Calculate Risks, and Relative Risk What’s wrong with this picture? Measure Memory Scenario

13. DrugEpi 3-5 Fundamentals of Study Design Natural Experiment (unplanned) Naturally occurring circumstances in which groups of people within a population have been exposed to different levels of the hypothesized cause of an outcome. Review of Important Concepts

14. DrugEpi 3-5 Fundamentals of Study Design Observational Studies of Natural Experiments A study in which the investigator does not decide who will and will not be exposed and to how much, but rather, observes what exposures occur in free-living people. Important Concepts Examples in Lesson 3-4: Sensation-seeking and high risk behaviors

15. DrugEpi 3-5 Fundamentals of Study Design The Journey

16. DrugEpi 3-5 Fundamentals of Study Design Analogy

17. DrugEpi 3-5 Fundamentals of Study Design Reminder Procedures and methods, established beforehand, that are followed by the investigators conducting the study

18. DrugEpi 3-5 Fundamentals of Study Design CD C - Epidemiologists = Medical Detectives

19. DrugEpi 3-5 Fundamentals of Study Design When are the passengers identified as exposed or unexposed? E When are the passengers identified as sick or not sick? DZ Timing When does the epidemiologist start to observe the journey? Study Design – Timing Is Everything

20. DrugEpi 3-5 Fundamentals of Study Design Time E DZ It helps to “see” what is happening Studying the Journey

21. DrugEpi 3-5 Fundamentals of Study Design As the train journey begins, the epidemiologist gives the exposure to randomly selected passengers and does not give it to the other passengers. The epidemiologist stays on the train during the entire journey and continues to give the exposure to the randomly selected passengers. Throughout the train ride, the epidemiologist keeps track of all passengers (exposed and unexposed) to record which ones develop the disease during the journey. Design # 1 Controlled Trial (Experimental)

22. DrugEpi 3-5 Fundamentals of Study Design What’s Happening? When are the passengers identified as exposed or unexposed? E When are the passengers identified as sick or not sick? DZ When does the epidemiologist start to observe the journey? Study Design:Controlled Trial E DZ +++++++++++++++++++++++++++++++++++++++++++++++++++++ +++++++++++++++++++++++++++++++++++++++++++++++++++++ ++ Time

23. DrugEpi 3-5 Fundamentals of Study Design Healthy People Controlled Trial Flow Diagram E Random Assignment E DZ Controlled Trial Flow Diagram Time

24. DrugEpi 3-5 Fundamentals of Study Design Healthy People Controlled Trial Flow Diagram E Random Assignment E DZ Evaluating a Student Drug Testing Program Time

25. DrugEpi 3-5 Fundamentals of Study Design Healthy People Randomized Controlled Trial Evaluating a Student Drug Testing Program Time

26. DrugEpi 3-5 Fundamentals of Study Design Observational Studies of Natural Experiments A study in which the investigator does not decide who will and will not be exposed and to how much, but rather, observes what exposures occur in free-living people. Reminder

27. DrugEpi 3-5 Fundamentals of Study Design Just as in the controlled trial, the epidemiologist is on the train during the entire journey. But there is an important difference. The epidemiologist is not telling passengers what to do. Rather, the epidemiologist is just observing them and counting. Passengers are not being told to have or not have an exposure, they are just living their normal lives. The epidemiologist, on the ride for the whole journey, just keeps observing everyone’s exposures and whether or not they develop the disease during the journey. Design # 2 - Cohort Study

28. DrugEpi 3-5 Fundamentals of Study Design Study Design:Cohort Study What’s Happening? When are the passengers identified as exposed or unexposed? E When are the passengers identified as sick or not sick? DZ When does the epidemiologist start to observe the journey? DZ +++++++++++++++++++++++++++++++++++++++++++++++++++++ +++++++++++++++++++++++++++++++++++++++++++++++++++++ + E Time

29. DrugEpi 3-5 Fundamentals of Study Design Cohort Study Flow Diagram E E DZ Cohort Study Flow Diagram Healthy People Time

30. DrugEpi 3-5 Fundamentals of Study Design Healthy People Cohort Study Flow Diagram Healthy People E E DZ Controlled Trial Similarities Time

31. DrugEpi 3-5 Fundamentals of Study Design Healthy People Cohort Study Flow Diagram Healthy People E E DZ Controlled Trial Random Assignment Difference Time

32. DrugEpi 3-5 Fundamentals of Study Design Cohort Study Flow Diagram E E DZ Evaluating a Student Drug Testing Program Healthy People Time

33. DrugEpi 3-5 Fundamentals of Study Design Cohort Study Flow Diagram Evaluating a Student Drug Testing Program Healthy People Time

34. DrugEpi 3-5 Fundamentals of Study Design The epidemiologist is not on the journey. Rather, the epidemiologist is waiting at the train station at the end of the journey. As passengers get off the train, the epidemiologist selects sick passengers for the case group and selects passengers who are similar but not sick for the control group. The epidemiologist then asks each person in the case group and control group questions about their exposures during the train ride. The epidemiologist relies on passengers’ memories of their exposures that occurred during the train ride. Design # 3 - Case-Control Study

35. DrugEpi 3-5 Fundamentals of Study Design What’s Happening? When are the passengers identified as exposed or unexposed? E When are the passengers identified as sick or not sick? DZ When does the epidemiologist start to observe the journey? Study Design: Case-Control Study E DZ ++++++++++++++++++++++++++++++++++++++++++++++++++++ Time

36. DrugEpi 3-5 Fundamentals of Study Design Case-Control Study Observational Study Flow Diagram Time DZ E E E E Case-Control Study Flow Diagram

37. DrugEpi 3-5 Fundamentals of Study Design Case-Control Study Observational Study Flow Diagram Time DZ E E E E Evaluating a Student Drug Testing Program

38. DrugEpi 3-5 Fundamentals of Study Design Case-Control Study Observational Study Flow Diagram Time Evaluating a Student Drug Testing Program

39. DrugEpi 3-5 Fundamentals of Study Design The epidemiologist, who has not been on the journey, stops the train somewhere during the trip (kind of like a train robbery) and takes a “snapshot” of all the passengers by asking them whether or not they had the exposure and whether or not they have the disease. Then the epidemiologist leaves the train and goes home to analyze the data from that particular day. The journey continues without the epidemiologist. Design # 4 - Cross-Sectional Study

40. DrugEpi 3-5 Fundamentals of Study Design What’s Happening? When are the passengers identified as exposed or unexposed? E When are the passengers identified as sick or not sick? When does the epidemiologist start to observe the journey? Study Design:Cross-Sectional Study Time DZ E +++++++++++++++++++++++++++ ++++++++++++++++++++++++ +++++++++++++++++++++++++ +++++++++++++++++++++++

41. DrugEpi 3-5 Fundamentals of Study Design Cross-Sectional Study Observational Study Flow Diagram E E DZ Cross-Sectional Study Flow Diagram Time

42. DrugEpi 3-5 Fundamentals of Study Design Cross-Sectional Study Observational Study Flow Diagram E E DZ Evaluating a Student Drug Testing Program Time

43. DrugEpi 3-5 Fundamentals of Study Design Cross-Sectional Study Observational Study Flow Diagram Evaluating a Student Drug Testing Program Time

44. DrugEpi 3-5 Fundamentals of Study Design Controlled Trial Cohort Study Case-Control Cross-Sectional Observational Experimental Summary

45. DrugEpi 3-5 Fundamentals of Study Design Time Four Ways to Study the Journey E DZ Trial +++++++++++++++++++++++++++++++++++++++++++++++++++++ +++++++++++++++++++++++++++++++++++++++++++++++++++++ ++ E DZ Case-Control Study ++++++++++++++++++++++++++++++++++++++++++++++++++++ E DZ +++++++++++++++++++++++++++ ++++++++++++++++++++++++ +++++++++++++++++++++++++ +++++++++++++++++++++++ Cross-Sectional Study DZ +++++++++++++++++++++++++++++++++++++++++++++++++++++ +++++++++++++++++++++++++++++++++++++++++++++++++++++ + E Cohort Study

46. DrugEpi 3-5 Fundamentals of Study Design Controlled Trial Cohort Study Case-Control Study Cross-Sectional Study Healthy People E Random Assignment E DZ Healthy People E E DZ E E E E E E The Four Study Designs

47. DrugEpi 3-5 Fundamentals of Study Design CDC Does this all make sense to you? There are four basic study designs for testing hypotheses. Each design has a different plan for assessing exposure and disease. The plan for each design can be understood by constructing a flow diagram. Whatever the study design and its flow diagram, it can be “fit” into a 2x2 table so that risks can be calculated and compared (RR). Making Sense

48. DrugEpi 3-5 Fundamentals of Study Design Big Ideas in this Lesson (3-5) Each study design can be expressed in a 2x2 table format Each study design has a different plan for assessing exposure and disease The experimental design is the most scientifically rigorous and the observational study designs vary in rigor from quite good to poor There is a trade-off between scientifically stronger studies that take more effort and money to conduct well, and the less scientific studies that are “quicker and dirtier” 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. Re-Cap

49. DrugEpi 3-5 Fundamentals of Study Design 6. Where are we?Next Lesson Learn more about epidemiology study designs in Epi Team Challenges