1. Types of Studies and Study Design

2. Research classifications Observational vs. Experimental Observational – researcher collects info on attributes or measurements of interest, but does not influence results. Experimental – researcher deliberately influences events and investigates the effects of the intervention, e.g. clinical trials and laboratory experiments. We often use these when we are interested in studying the effect of a treatment on individuals or experimental units.

3. Experiments & Observational Studies We conduct an experiment when it is (ethically, physically etc) possible for the experimenter to determine which experimental units receive which treatment.

4. Experiments & Observational Studies Experiment Terminology Experimental Unit Treatment Response patient drug cholesterol patient pre-surgery antibiotic infection mouse radiation mortality

5. Experiments & Observational Studies In an observational study, we compare the units that happen to have received each of the treatments.

6. e.g. You cannot set up a control (non-smoking) group and treatment (smoking) group. Observational Study patientsmokinglung cancer RNunitjob stress walleyewaterwayHg level Experiments & Observational Studies UnitTreatmentResponse

7. Experiments & Observational Studies Note: Only a well-designed and well-executed experiment can reliably establish causation. An observational study is useful for identifying possible causes of effects, but it cannot reliably establish causation.

8. 1. Completely Randomized Design The treatments are allocated entirely by chance to the experimental units.

9. 1. Completely Randomized Design Example: Which of two varieties of tomatoes (A & B) yield a greater quantity of market quality fruit? Factors that may affect yield: different soil fertility levels exposure to wind/sun soil pH levels soil water content etc.

10. Divide the field into plots and randomly allocate the tomato varieties (treatments) to each plot (unit). 8 plots – 4 get variety A (A) (B) 1. Completely Randomized Design What if the field sloped upward from left to right? UPHILL Discuss for ½ Minute (B) (A) Randomly assign A & B varieties in each strip of similar elevation.

11. 1. Completely Randomized Design Note: Randomization is an attempt to make the treatment groups as similar as possible — we can only expect to achieve this when there is a large number of experimental units to choose from.

12. 2. Blocking Group (block) experimental units by some known factor and then randomize within each block in an attempt to balance out the unknown factors. Use: blocking for known factors (e.g. slope of field in previous example) and randomization for unknown factors to try to “balance things out”.

13. 2. Blocking Example 2: Multi-Center Clinical Trial Suppose a Mayo clinical trial comparing two chemotherapy regimens in treatment of patients with colon cancer will be conducted using cancer patients in Scottsdale, AZ and Rochester, MN.

14. Scottsdale Rochester 2. Blocking How should we allocate treatments to the 12 patients? Discuss in groups for 1/2 minute. 7 (B) 2 (A) 3 (A) 5 (A) 6 (A) 1 (A) 2 (B) 3 (A) 4 (B) 8 (B) 4 (B) 1 (B) Randomly assign treatments to 4 the patients from Scottsdale and then to the 8 Rochester patients.

15. 2. Blocking Example 3: Comparing Three Pain Relievers for Headache Sufferers How could blocking be used to increase precision of a designed experiment to control to compare the pain relievers? What are some other design issues?

16. Example 4: Comparing 17 Different Leg Wraps on Used on Race Horses 17 “boots” tested, each boot is tested n = 5 times. Why? Because of the time constraints all boots were not tested on the same day. 8 tested 1 st day, 5 tested 2 nd day, 4 tested 3 rd day. Leg was placed in freezer and thawed before the 2 nd and 3 rd days of testing.

17. Horse Leg Wraps (cont’d) What problems do you foresee with this experimental design? Discuss What actually happened? What are the implications of these results? Discuss Forces readings obtained from cadaver leg when no boot or wrap was used.

18. Horse Leg Wraps (cont’d) FINAL BOOT COMPARISONS

19. Horse Legs Wraps (cont’d) What should have been done? Discuss

20. 3. People as Experimental Units Example: Cholesterol Drug Study – Suppose we wish to determine whether a drug will help lower the cholesterol level of patients who take it. How should we design our study? Discuss for two minutes in groups.

21. Polio Vaccine Example

22. Dr. Jonas Salk, vaccine pioneer 1914-95 Iron Lung

23. The Salk Vaccine Field Trial 1954 Public Health Service organized an experiment to test the effectiveness of Salk’s vaccine. Need for experiment: –Polio, an epidemic disease with cases varying considerably from year to year. A drop in polio after vaccination could mean either: Vaccine effective No epidemic that year

24. The Salk Vaccine Field Trial Subjects: 2 million, Grades 1, 2, and 3 500,000 were vaccinated –(Treatment Group) 1 million deliberately not vaccinated –(Control Group) 500,000 not vaccinated - parental permission denied

25. The Salk Vaccine Field Trial NFIP Design Treatment Group: Grade 2 Control Group: Grades 1 and 3 + No Permission Flaws ? Discuss for 30 seconds. Polio contagious, spreading through contact. i.e. incidence could be greater in Grade 2 (bias against vaccine), or vice-versa. Control group included children without parental permission (usually children from lower income families) whereas Treatment group could not (bias against the vaccine).

26. The Salk Vaccine Field Trial Double-Blinded Randomized Controlled Experimental Design Control group only chosen from those with parental permission for vaccination Random assignment to treatment or control group Use of placebo (control group given injection of salted water) Diagnosticians not told which group the subject came from (polio can be difficult to diagnose) i.e., a double-blind randomized controlled experiment

27. (NFIP rate) (25) Grade 2 (54) Grade 1/3 (44) Grade 2 The Salk Vaccine Field Trial The double-blind randomized controlled experiment (and NFIP) results Size of group Rate per 100,000 Treatment200,00028 Control200,00071 No consent350,00046

28. 3. People as Experimental Units control group: –Receive no treatment or an existing treatment blinding: –Subjects don’t know which treatment they receive double blind: –Subjects and administers / diagnosticians are blinded placebo: –Inert dummy treatment

29. 3. People as Experimental Units placebo effect: –A common response in humans when they believe they have been treated. –Approximately 35% of people respond positively to dummy treatments - the placebo effect

30. Observational Studies There are two major types of observational studies: prospectiveand retrospective studies

31. Observational Studies 1. Prospective Studies –(looking forward) –Choose samples now, measure variables and follow up in the future. –E.g., choose a group of smokers and non-smokers now and observe their health in the future.

32. Observational Studies –Looks back at the past. –E.g., a case-control study Separate samples for cases and controls (non-cases). Look back into the past and compare histories. E.g. choose two groups: lung cancer patients and non-lung cancer patients. Compare their smoking histories. 2. Retrospective Studies –(looking back)

33. Observational Studies Important Note: 1. Observational studies should use some form of random sampling to obtain representative samples. 2.Observational studies cannot reliably establish causation.

34. Controlling for various factors A prospective study was carried out over 11 years on a group of smokers and non- smokers showed that there were 7 lung cancer deaths per 100,000 in the non- smoker sample, but 166 lung cancer deaths per 100,000 in the smoker sample. This still does not show smoking causes lung cancer because it could be that smokers smoke because of stress and that this stress causes lung cancer.

35. Controlling for various factors To control for this factor we might divide our samples into different stress categories. We then compare smokers and non-smokers who are in the same stress category. This is called controlling for a confounding factor.

36. Example 1 “Home births give babies a good chance” NZ Herald, 1990 –An Australian report was stated to have said that babies are twice as likely to die during or soon after a hospital delivery than those from a home birth. –The report was based upon simple random samples of home births and hospital births. Q: Does this mean hospitals are dangerous places to have babies in Australia? Why or why not? Discuss for 1 minute in groups.

37. Example 2 “Lead Exposure Linked to Bad Teeth in Children” ~ USA Today The study involved 24,901 children ages 2 and older. It showed that the greater the child’s exposure to lead, the more decayed or missing teeth. Q: Does this show lead exposure causes tooth decay in children? Why or why not? Discuss for 1 minute.

38. Example 2 ~ cont’d “Lead Exposure Linked to Bad Teeth in Children” ~ USA Today Researcher: “We controlled for income level, the proportion of diet due to carbohydrates, calcium in the diet and the number of days since the last dental visit.”

39. Additional Example 1 – Determine Whether Age at 1 st Pregnancy is a Risk Factor for Cervical Cancer How might we proceed? Discuss

40. Additional Example 2 – Conduct a study to determine if sentencing of convicted felons is racially biased? How might we proceed? Discuss

41. Additional Example 3 – Determine if a fruit juice supplement reduces muscle pain experience following exercise? How might we proceed? Discuss