Intervention Studies

1. Intervention Studies Sue Lindsay, Ph.D., MSW, MPH Division of Epidemiology and Biostatistics Institute for Public Health San Diego State University

2. What Causes this Disease? • Risk Factors • Age • Gender • Bacteria or virus • Exposure to toxins • Diet • Exercise/activity • Genetics • Stress • Childhood trauma • Body mass index • Smoking/alcohol Disease

3. How can we prevent, detect, and treat this disease? • Interventions • New screening techniques • New medical technologies • Medication • Surgical interventions • Diet and exercise programs • Educational interventions • Stress reduction programs • Smoking cessation programs • Genetic screenings • Health promotion activities • Case management and support • Others? Disease

4. Intervention Studies Research designs that are utilized to evaluate the impact of a therapy, intervention, or prevention strategy

5. Observational Designs (4) • Comparison Group Designs (4) Types of Designs • Experimental designs (4) • Clinical Trials (4)

6. Comparison Group vs. Control Group

7. 1. Before and after studies 2. Cross-sectional studies with non- uniform programs Observational Designs 3. Panel or Cohort Studies 4. Population-based time series

8. Observational Designs Before and After Studies (pre-test, post-test) Select persons to receive the intervention Measure outcome of interest before intervention Measure outcome of interest after intervention Intervention Pre-test Post-test

9. Observational Designs High users Cross-Sectional Studies for Non-Uniform Programs Select persons to receive the intervention Carefully measure participation in the program Measure outcome of interest after intervention Intervention Low users Measure outcome

10. Observational Designs Panel or Cohort Studies Select persons to receive the intervention Measure participation in the program at multiple points in time Measure outcome at multiple points in time Intervention Measure Initial Measure 6 months Measure 1 year

11. Observational Designs Population-based time series Many cross-sectional measures of a population Track the exposure of the population to an intervention Compare cross-sectional results with exposure Measure Intervention Measure Intervention Measure Intervention Initial Survey 1 year Survey 2 year Survey

12. 1. Historic or Generic Comparison Group 2. Concurrent Comparison Group Comparison Group Designs 3. Matched Comparison Group 4. Comparison Cross-Over Designs

13. Comparison Group Designs Comparison group:Previous year County, State, or National rates Historic or Generic Comparison Group Select persons to receive the intervention Select historic control group or publicly available norms Measure outcome of interest after intervention Intervention Measure outcome

14. Comparison Group Designs Concurrent Comparison group Select persons to receive the intervention Select another group that does not receive the intervention Measure outcome of interest before and after intervention Intervention Comparison Group No Intervention Final Measure Initial Measure

15. Comparison Group Designs Intervention Matched comparison group Select persons to receive the intervention Select comparison group matched to intervention group Measure outcome of interest before and after intervention Matched comparison group No Intervention Final Measure Initial Measure

16. Comparison Group Designs Comparison Cross-Over Designs Select persons to receive the intervention Select comparison group After some time, intervention group becomes comparison group, and comparison group becomes intervention group. Intervention Intervention No Intervention No Intervention Initial Measure Measure At Cross-Over Final Measure

17. 1. Randomized Clinical Trial 2. Stratified Randomization Experimental Designs Clinical Trials 3. Experimental Cross-Over Designs 4. Factorial Designs

18. Clinical Trial Study Designs Defined Population Randomize Treatment #1 Treatment #2 Not Improved Not improved Improved Improved

19. Therapeutic Trials • relieve symptoms or improve survivorship • 2. Intervention Trials • intervention to prevent disease with persons at risk Types of Clinical Trials (David E. Lilienfeld) • 3. Preventive (Prophylactic) Trials • determine efficacy of a preventive agent

20. Criteria for study subject selection must • be very precise and written • Avoid subjective decision-making concerning • who will be in the study and who will not Selection of Study Subjects

21. Assignment to either study or control group will not be • predictable • Elimination of investigator bias in the process of selecting • patients for either the treatment or control group. • Randomization increases the likelihood that groups will be • comparable on known variables • Randomization increases the likelihood that groups will be • comparable on unknown variables Randomization

22. Subjects do not know whether they • are in the study or control group • (single blinding) • Data collectors and analyzers do not • know which patients are in the study • or control group • (double blinding) Masking (Blinding)

23. Clinical Trials Measure outcome Intervention Randomized Clinical Trial Select persons to participate in study Randomize into intervention (“study”) or control group Measure outcome of interest after intervention Randomize participants into intervention or control group Measure outcome Control Frequently uses multiple arms of intervention

24. Clinical Trials Measure outcome Intervention Stratified Randomization Stratify variables of interest into subgroups Randomize each subgroup into intervention and control groups Measure outcome of interest after intervention Measure outcome Control Randomize Into intervention or control group

25. Clinical Trials Experimental Cross-Over Designs Select persons to receive the intervention Randomize them into two different intervention groups After some time, the two groups change interventions Intervention Intervention Randomize No Intervention No Intervention Initial Measure Measure At Cross-Over Final Measure

26. Clinical Trials Measure outcome Treatment A and B Measure outcome Factorial Designs Studying the effects of two independent treatments (A & B) Randomize into one of four intervention groups Measure outcome of interest after interventions Treatment A only Randomize participants into one of four groups Measure outcome Treatment B only Measure outcome Neither A nor B

27. Selection of subjects is not well-defined or well followed • Improper randomization, failure of randomization procedures • Data collection for study subjects and controls not standardized • No masking or unintentional unmasking • Unintentional cross-over • Lack of compliance of study or control subjects • Differential drop-out rates • Errors in analysis: • Intent to treat analysis: everyone randomized is analyzed Challenges to the Validity of Clinical Trials

28. Relative Risk • Efficacy Analysis of Clinical Trials • NNT: Number of patients who would • need to be treated to prevent one • adverse outcome

29. Relative Risk in a Clinical Trial Risk Disease No Disease a a b Intervention (+) (a + b)* c c d Control (-) (c + d)* a/(a+b) Relative Risk = c/(c+d) * Denominator is often person-years in the study

30. An Example In a study to evaluate the efficacy of a new treatment for the common cold, 1,000 children 2-18 years old with newly diagnosed viral colds were recruited from pediatrician offices. 500 were randomly assigned to receive the new antiviral therapy and 500 were assigned to a control group. After five days, 200 of the study group had no cold symptoms, while only 100 of the control group had no cold symptoms. What is the relative risk of curing the common cold for the study group compared to the control group. 200/500 0.40 = = 2.0 0.20 100/500 Children with colds who took the antiviral medication were 2.0 times more likely to by asymptomatic after 5 days than those who did not.

31. Efficacy The reduction in the risk of disease or outcome because of the intervention. Rate in the Control Group Rate in the Study Group __ X 100 Rate in the Control Group

32. An Example In a study to evaluate the efficacy of a new vaccine for the prevention of a viral respiratory disease (VRD), 1,000 health care workers who volunteered to work with VRD patients were recruited by participating hospitals, 500 were given the new vaccine, and 500 received a placebo. After one month’s time, researchers noted that 25 of the treated workers had acquired VRD, while 100 of the control workers contracted VRD. What is the efficacy of the new vaccine? - 100/500 0.20-0.05 25/500 = = 0.75 0.20 100/500 75% of VRD infections can be reduced with the vaccine

33. NNT The number of patients who would need to be treated (NNT) to prevent one adverse outcome. 1 _ Rate in the Untreated Group Rate in the Treated Group

34. An Example In a study to evaluate the effectiveness of a supervised diet and exercise routine to prevent the development of obesity in overweight children, 3,000 overweight children were enrolled by participating pediatricians. 1,500 were randomized to the diet and exercise plan while 1,500 were randomized to normal pediatric care and recommendations. After one year’s time, 375 of the normal care children had developed obesity, while 325 of the diet and exercise children were obese. Calculate the NNT 1 1 = = _ 33 _ 375/1,500 325/1,500 0.25 0.22 We would need to treat 33 overweight children to prevent one from becoming obese

35. A mini quiz

36. What is the study design? A pharmaceutical company has developed a new sunscreen and decides to evaluate it using lifeguards at Mission Beach. Lifeguards are recruited and randomly assigned to both an intervention and control group. Those in the intervention group are given a lotion that looks identical to the lotion given to control group. Both groups are asked to use the sunscreen daily and report to a spot on the beach each Friday afternoon to be measured for evidence of sun damage.

37. What is the study design? In an effort to reduce obesity and the potential for Type II diabetes, many schools are considering removing high sugar content soda machines from their campuses. Ten elementary schools in a school district volunteered to be part of a study to evaluate this approach and removed soda machines from their campus. These ten schools were then matched with schools of similar socioeconomic status and race/ethnicity with soda machines. Incoming first graders were weighed and measured at each school, and followed forward until sixth grade with measurements each year.

38. What is the study design? Between 1990 and 1995 bicycle safety helmet laws were enacted in all 50 states, requiring children to wear helmets at all times while riding bikes. A study was done using San Diego Trauma Center data to compare the rates of bicycle head trauma injuries in the years 1985, 1990, 1995, and 2000.

39. What is the study design? The hypothesis is that diet and exercise can both independently improve the risk of developing certain types of cancer. Women and men are recruited to participate in a long-term study of diet and exercise. Men and women separately are randomized into one of four groups: 1) a group educated only about the benefits of good eating habits, 2) a group educated only about the benefits of exercise, 3) a group educated about the benefits of both good eating habits and exercise, and 4) a group provided no specific intervention.

40. What is the study design? 1,000 men being treated for mild hypertension were recruited to participate in a study of a new medication for the prevention of mild hypertension. 500 of the men were randomized to receive the new medication while 500 were randomized to continue with their current medications. Each month, blood pressure measurements were taken. After six months, those on the new medication were switched back to their old medication, while those on their old medication were switched to the new drug.

41. What is the study design? A study was designed to evaluate the use of home visiting by professional nurses and social workers for the prevention of family violence. Intact families reporting stress were assigned a home visitor who made weekly contacts and referrals for the family. Comprehensive initial assessments were performed, and the families were assessed at six month intervals for family functioning and evidence of violence.