1. DrugEpi 3-2 Experimental Study - Buprenorphine Example 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 3-2 Experimental Study - Buprenorphine Example Module 3 - Analytical Epidemiology Lesson 3-2 Experimental Study - Buprenorphine Example Content Continued study of the concepts of “association” and hypothesis-testing Use of the 2x2 table as a way to numerically express risk and relative risk Example of an experimental study to examine beneficial health-related effects Understanding of population sampling and inference Demonstration of the necessity and impact of a control group Big Ideas An experimental study of a sample of a population can test a hypothesized association between an exposure and a beneficial health-related outcome In order for an experimental study to be meaningful, it has to include controls The 2x2 table, which includes consideration of a control group, is a tool used to express the numbers of people with and without the exposure, and with and without the outcome, and clarifies how rates and relative risks are calculated. 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 3-2 Experimental Study - Buprenorphine Example 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 3-2 Experimental Study - Buprenorphine Example What do we mean when we say that there is an association between two things? Associated TiedRelated Linked Things that are associated are linked in some way that makes them turn up together. Review of the Concept of Association

5. DrugEpi 3-2 Experimental Study - Buprenorphine Example Suicide Higher in Areas with Guns Smoking Linked to Youth Eating Disorders Snacks Key to Kids’ TV- Linked Obesity: China Study Family Meals Are Good for Mental Health Lack of High School Diploma Tied to US Death Rate Study Links Spanking to Aggression Breakfast Each Day May Keep Colds Away Study Concludes: Movies Influence Youth Smoking Study Links Iron Deficiency to Math Scores Kids Who Watch R-Rated Movies More Likely to Drink, Smoke Pollution Linked with Birth Defects in US Study Depressed Teens More Likely to Smoke Review - Things That Turn Up Together

6. DrugEpi 3-2 Experimental Study - Buprenorphine Example Review - Module 3 is about Analytical Epidemiology Analytical epidemiology can test hypotheses about associations Epidemiologic studies that are concerned with determinants of disease and the reasons for relatively high or low frequencies of disease in specific population subgroups

7. DrugEpi 3-2 Experimental Study - Buprenorphine Example Hypothesis about associations Generate Descriptive Epidemiology Test Analytical Epidemiology An unproven idea, based on observation or reasoning, that can be supported or refuted through investigation An educated guess Hypotheses in epidemiology are statements that suggest associations between an exposure and an outcome Review - Epidemiology and Associations

8. DrugEpi 3-2 Experimental Study - Buprenorphine Example Hypothesis: Buprenorphine will stop heroin addicts from using heroin. Testing Hypotheses

9. DrugEpi 3-2 Experimental Study - Buprenorphine Example Sample 100 Heroin Addicts 10 Weeks 79 Heroin Addicts Tested Positive for Heroin Trial 1 Buprenorphine will stop heroin addicts from using heroin.

10. DrugEpi 3-2 Experimental Study - Buprenorphine Example Handout

11. DrugEpi 3-2 Experimental Study - Buprenorphine Example Bupe Tested Positive for Heroin Total 1007921 Tested Negative for Heroin Trial 1 Buprenorphine will stop heroin addicts from using heroin.

12. DrugEpi 3-2 Experimental Study - Buprenorphine Example When you can measure what you are speaking about, and express it in numbers, you know something about it. Lord Kelvin But when you cannot measure it, when you cannot express it in numbers, your knowledge is of a meager and unsatisfactory kind.

13. DrugEpi 3-2 Experimental Study - Buprenorphine Example A measure of how often an outcome occurs in a defined population in a defined period of time. It consists of a numerator and a denominator. RATE The numerator is the number of people in the population or sample who experienced the outcome and the denominator is the total number of people in the population or sample. Population / Sample Outcome Denominator Numerator Review - Express It In Numbers

14. DrugEpi 3-2 Experimental Study - Buprenorphine Example Rate: A measure of how often an outcome occurs in a defined group of people in a defined period of time. Risk: The likelihood of an outcome occurring in a defined group of people in a defined time period. Concepts of Rate and Risk

15. DrugEpi 3-2 Experimental Study - Buprenorphine Example Express It In Numbers … the rate of positive heroin tests is 79/100 positives per 10-week period 79 tested positive for heroin 100 study subjects Numerator Denominator

16. DrugEpi 3-2 Experimental Study - Buprenorphine Example Trial 1 Bupe Tested Positive for Heroin Total 1007921 Tested Negative for Heroin 79 100 or 79 % Tested Rate of Using Heroin Calculating a Rate / Risk in Trial 1

17. DrugEpi 3-2 Experimental Study - Buprenorphine Example Process of predicting from what is observed in a sample to what is true for the entire population. Inference

18. DrugEpi 3-2 Experimental Study - Buprenorphine Example Trial 1 Bupe Tested Positive for Heroin Total 1007921 Tested Negative for Heroin 79 100 or 79 % Tested Rate of Using Heroin What Can Trial 1 Tell Us About the Hypothesis? What does this tell you about the hypothesis?

19. DrugEpi 3-2 Experimental Study - Buprenorphine Example People who participate in a trial, but do not get the treatment. People whose results are compared to the group that was treated. Control Group

20. DrugEpi 3-2 Experimental Study - Buprenorphine Example Bupe Tested Positive for Heroin Total 1007921 Tested Negative for Heroin 79 100 or 79 % Tested Rate of Using Heroin Including a Control Group Extend and label the table to include a control group.

21. DrugEpi 3-2 Experimental Study - Buprenorphine Example Bupe Tested Positive for Heroin Total 1007921 Tested Negative for Heroin 79 100 or 79 % Tested Rate of Using Heroin 100 ? or ? % No Bupe Including a Control Group

22. DrugEpi 3-2 Experimental Study - Buprenorphine Example 79 100 or 79 % Tested Rate of Using Heroin ? 100 or ? % Total 1002179 100 Tested Positive for Heroin Tested Negative for Heroin Bupe No Bupe ExposureExposure Outcome / Disease ab cd 2x2 Table

23. DrugEpi 3-2 Experimental Study - Buprenorphine Example A cross-classification of data where categories of one variable are presented in rows and categories of another variable are presented in columns. The simplest contingency table is the 2x2 table Review - Contingency Table

24. DrugEpi 3-2 Experimental Study - Buprenorphine Example Sample 100 Heroin Addicts 10 Weeks 79 Heroin Addicts Tested Positive for Heroin Trial 1 Testing Hypotheses - Buprenorphine Trial 1

25. DrugEpi 3-2 Experimental Study - Buprenorphine Example Total ? 100 ? % a b c d Bupe Tested Positive for Heroin Tested Negative for Heroin Tested Rate of Using Heroin No Bupe Trial 2 2x2 Table for Trial 2 100 ? ? %

26. DrugEpi 3-2 Experimental Study - Buprenorphine Example E Assigned E O O O O Heroin Addicts Volunteer Heroin Addicts Study Diagram Time

27. DrugEpi 3-2 Experimental Study - Buprenorphine Example Trial 2 Study Sample Assign Volunteers to 2 Groups Trial 2

28. DrugEpi 3-2 Experimental Study - Buprenorphine Example Trial 2 Results Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin Trial 2 or 7921100 79 100 79% No Bupe

29. DrugEpi 3-2 Experimental Study - Buprenorphine Example The value obtained by dividing one quantity by another. Ratio

30. DrugEpi 3-2 Experimental Study - Buprenorphine Example Comparing Rates - A Risk Ratio for Trial 2 Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin Trial 2 or 7921100 79 100 79% Ratio: The value obtained by dividing one quantity by another Risk Ratio: The ratio of two risks 1 Risk Ratio No Bupe

31. DrugEpi 3-2 Experimental Study - Buprenorphine Example A Formula for Comparing Rates Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin or 7921100 79 100 79% Risk Ratio: The ratio of two risks. 1 Risk Ratio Create a formula a a + b c c + d No Bupe

32. DrugEpi 3-2 Experimental Study - Buprenorphine Example Risk Ratio Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin or 7921100 79 100 79% 1 Risk Ratio Trial 2 Relative Risk: The ratio of the risk of an outcome among the exposed to the risk of the outcome among the unexposed. Relative Risk No Bupe

33. DrugEpi 3-2 Experimental Study - Buprenorphine Example Trial 2 Inference Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin or 7921100 79 100 79% Inference: Process of predicting from what is observed in a sample to what is occurring in the entire population The inference here is that there is no effect of Buprenorphine 1 Risk Ratio Trial 2 Relative Risk No Bupe

34. DrugEpi 3-2 Experimental Study - Buprenorphine Example Total ? 100 ? % a b c d Bupe Tested Positive for Heroin Tested Negative for Heroin Tested Rate of Using Heroin Trial 3 2x2 Table for Trial 3 100 ? ? % No Bupe

35. DrugEpi 3-2 Experimental Study - Buprenorphine Example Trial 3 Study Sample Buprenorphine Trial 3 No Buprenorphine

36. DrugEpi 3-2 Experimental Study - Buprenorphine Example Trial 3 Results Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin Trial 3 or 3862100 38 100 38% No Bupe

37. DrugEpi 3-2 Experimental Study - Buprenorphine Example Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin Trial 3 or 3862100 38 100 38% Trial 3 Relative Risk Relative Risk 2.08 Relative Risk: The ratio of the risk of an outcome among the exposed to the risk of the outcome among the unexposed. No Bupe

38. DrugEpi 3-2 Experimental Study - Buprenorphine Example Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin Trial 3 or 3862100 38 100 38% Trial 3 Relative Risk Relative Risk 2.08 The heroin addicts who received Buprenorphine were ____ times as likely to use heroin as those who did not receive Buprenorphine. 2.08 No Bupe

39. DrugEpi 3-2 Experimental Study - Buprenorphine Example Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin Trial 3 or 3862100 38 100 38% Trial 3 Inference Relative Risk 2.08 Inference: Process of predicting from what is observed in a sample to what is occurring in the entire population. No Bupe

40. DrugEpi 3-2 Experimental Study - Buprenorphine Example Total ? 100 ? % a b c d Bupe Tested Positive for Heroin Tested Negative for Heroin Tested Rate of Using Heroin Trial 4 2x2 Table for Trial 4 100 ? ? % No Bupe

41. DrugEpi 3-2 Experimental Study - Buprenorphine Example Trial 4 Study Sample Buprenorphine Trial 4 No Buprenorphine

42. DrugEpi 3-2 Experimental Study - Buprenorphine Example Trial 4 Results Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin Trial 4 or 946100 94 100 94% No Bupe

43. DrugEpi 3-2 Experimental Study - Buprenorphine Example Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin Trial 4 or 946100 94 100 94% Trial 4 Relative Risk Relative Risk.84 Relative Risk: The ratio of the risk of an outcome among the exposed to the risk of the outcome among the unexposed. No Bupe

44. DrugEpi 3-2 Experimental Study - Buprenorphine Example The heroin addicts who received Buprenorphine were ____ times as likely to use heroin as those who did not receive Buprenorphine. Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin Trial 4 or 946100 94 100 94% Trial 4 Relative Risk Relative Risk 0.84 No Bupe

45. DrugEpi 3-2 Experimental Study - Buprenorphine Example Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin Trial 4 or 946100 94 100 94% Relative Risk 0.84 Trial 4 Inference Inference: Process of predicting from what is observed in a sample to what is not observed in a population. No Bupe

46. DrugEpi 3-2 Experimental Study - Buprenorphine Example Total 79 100 or 79% a b c d 7921 Bupe Tested Positive for Heroin Tested Negative for Heroin 100 Tested Rate of Using Heroin Trial 1 Review of the Four Hypothetical Trials What do the results of tell us about the hypothesis that Buprenorphine will stop heroin addicts from using heroin? Nothing

47. DrugEpi 3-2 Experimental Study - Buprenorphine Example 1007921 90 79 100 or 79% Nothing Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Trial 1 Trial 2 Trial 3 Trial 4 Review of the Four Hypothetical Trials Bupe No Bupe Bupe No Bupe Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk No Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% 1007921 90 79 100 or 79%

48. DrugEpi 3-2 Experimental Study - Buprenorphine Example 1007921 90 79 100 or 79% Nothing Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Trial 1 Trial 2 Trial 3 Trial 4 Review of the Four Hypothetical Trials Bupe No Bupe Bupe No Bupe Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk No Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% There is no association between Bupe and heroin use. 1

49. DrugEpi 3-2 Experimental Study - Buprenorphine Example 1007921 90 79 100 or 79% Nothing Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Trial 1 Trial 2 Trial 3 Trial 4 Review of the Four Hypothetical Trials Bupe No Bupe Bupe No Bupe Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk No Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% 1003862 90 38 100 or 38% There is no association between Bupe and heroin use. Bupe is associated with an increase in heroin use. 1 2.08

50. DrugEpi 3-2 Experimental Study - Buprenorphine Example 1007921 90 79 100 or 79% Nothing Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Trial 1 Trial 2 Trial 3 Trial 4 Review of the Four Hypothetical Trials Bupe No Bupe Bupe No Bupe Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk No Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% 1003862 90 38 100 or 38% 100946 90 94 100 or 94% There is no association between Bupe and heroin use. Bupe is associated with a decrease in heroin use. 1.84 2.08

51. DrugEpi 3-2 Experimental Study - Buprenorphine Example 1007921 90 79 100 or 79% Nothing Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Trial 1 Trial 2 Trial 3 Trial 4 Review of the Four Hypothetical Trials Bupe No Bupe Bupe No Bupe Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk No Bupe Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk Total Tested Positive for Heroin Rate of Using Heroin Tested Negative for Heroin Relative Risk 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% 1007921 90 79 100 or 79% 1003862 90 38 100 or 38% 100946 90 94 100 or 94% There is no association between Bupe and heroin use. Bupe is associated with a decrease in heroin use. Bupe is associated with an increase in heroin use. 1.84 2.08 Nothing Compared to what?

52. DrugEpi 3-2 Experimental Study - Buprenorphine Example Big Ideas in this Lesson (3-2) An experimental study of a sample of a population can test a hypothesized association between an exposure and a beneficial health-related outcome In order for an experimental study to be meaningful, it has to include controls The 2x2 table, which includes consideration of a control group, is a tool used to express the numbers of people with and without the exposure, and with and without the outcome, and clarifies how rates and relative risks are calculated.. 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

53. DrugEpi 3-2 Experimental Study - Buprenorphine Example 6. Where are we?Next Lesson Buprenorphine Buprenorphine & Naloxone Placebo An Actual Randomized Controlled Study