1 Outcome evaluation of health promotion/life style change Wei-Chu Chie

2 Health promotion Primary prevention –life style change –education and health behavior

3 Three elements for health promotion Experiment unit –Individual or group (cluster), usually healthy Treatments –education Evaluation –efficacy –safety: less serious and sometimes overlooked

4 Basic characteristics Difficult to follow the rule of randomized controlled double- blinded trials –placebo control with blindness: difficult to make and keep –individual randomization not convenient requires a large sample size –low incidence of the disease to prevent –low incidence of adverse effects

5 Major difficulties (1) No blindness: –Hawthorn effect and information bias –Rater blindness loyalty to the original randomization –Compliance or adherence –‘ Contamination ’ of the control group: got the intervention content elsewhere or from the treatment group

6 Major difficulties (2) Randomization unit –individual: ideal but difficult to implement –group (cluster): easy to implement but has statistical problem

7 ethical concerns administered on healthy people –autonomy emphasized: informed consent –safety less serious than immunization and drug, sometimes overlooked

8 Examples –Diabetes Prevention Program Research Group. Reduction in the incidence or type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346: –Brown KS, et al. Outcome evaluation of a high school smoking reduction intervention based on extracurricular activities. Prev Med 2002;35:

9 DM: background/goal/hypothesis Background: –burden of type 2 DM and delayed diagnosis –previous studies of its preventability Goal/hypothesis: –to determine whether... /DM is preventable by metformin and lifestyle intervention

10 DM: study design Randomized controlled trial –four groups … three two drugs (one DC due to serious AE) + lifestyle one placebo + lifestyle one intensive lifestyle –randomized by individual/stratified by centers –blinded only in the drug vs. placebo groups primary endpoint evaluated centrally/blind unaware of the test results in the middle

11 DM: subjects High-risk people at 27 centers four steps: – (the U.S.) , 3234 subjects (1082:1073:1079) –inclusion: 25 years+, BMI 24 or more, fasting glucose mg/dL, 2 hr 75-g GTT me/dL; half from minorities –exclusion: taking medicines, illness reducing life expectancy or ability to participate.

12 DM: exposure/intervention Group 1: standard lifestyle + metformin 850 mg qd to bid (GI symptoms) Group 2: … troglitazone … DC Group 3: intensive lifestyle Group 4: standard lifestyle + placebo (control)

13 DM: standard vs. intensive lifestyle Standard: –written form+individual session Intensive: –goal: weight reduction 7% –16-lesson curriculum, one-to-one for 1st 24 wks healthy low-calorie, low-fat diet physical activity of moderate intensity –subsequent sessions and group sessions

14 DM: endpoints Primary –efficacy: DM/ safety: adverse effects Secondary –weight, physical activity (MET), glucose Follow-up –annual o-GTT, semi-annual fasting plasma glucose/symptoms to planned 5/2001, actually on 3/31/2001 early stop due to advice from the monitoring board

15 DM: endpoints Definition of DM –abnormal o-GTT tests or fasting plasma sugar –confirmation by a second test within 6 weeks inform the patient and physician fasting sugar /6 months, HbA1c /year fasting sugar <140 mg /dL … continue fasting >= 140 mg/dL … DC and referral

16 DM: d ata analysis Basic characteristics and comparison –for confounding and possible selection bias Intention-to-treat analysis primary: time-to-event, survival (life- table) –modified product-limit … cumulative incidence –proportional hazards regression/ subgroup –persons need to treat secondary: fixed-effects models

17 DM: m ajor results/discussion –Comparison: Table 1 –Efficacy primary: Table 2, Figure 2 / subgroup analysis cumulative incidence P>M>L secondary: Figure 1, 3, 4 L has better weight reduction and increase in physical activity, similar or better glucose & HbA1c to M –Safety: Table 3 M has more GI & L has more MS symptoms

18 DM: m ajor results/discussion Discussion –Confounding, selection bias: randomization –Information bias: blindness –Early termination/ ethics –differentiation of diet and physical activity –Sample size and power of test Conclusion: L>=M>P

19 Smoking:background/goal/hypoth esis Background: –youth smoking rate and intervention –in-class vs. extra-curricular activities Goal/hypothesis: –to determine whether... extra- curricular activities can reduce teenage smoking rate

20 Smoking: study design Randomized controlled trial –two groups intervention usual care (control) –randomized by school (cluster) –no blindness

21 Smoking: subjects Waterloo, Canada Phase 1: 7 school boards/100 schools –teachers/ nurses social influence program –self-preparation materials –high-risk schools phase 2: 6 boards agreed/ 35 high- schools –30 schools agreed –matched within school board … pairs

22 Smoking: subjects Matching –by size, number and proportion of cohort students randomized into two groups –pairs: intervention vs. control grade 9 cohort attending the 30 schools –30 schools 15:15 –3028 students … :1465

23 Smoking: exposure/intervention Mobilizing staff and students/commitments A teacher facilitated students, staff, community participants in planning and implementing prevention and cessation activities … tailored to each school Role of research staff Budgets

24 Smoking: endpoints Primary –efficacy: smoking status –safety: no Secondary –No Follow-up –to grade 10

25 Smoking: endpoints Definition of smoking status By questionnaire: –never, –tried once, quit, experimental (< once/week) –regular (weekly) By CO breath samples

26 Smoking: d ata analysis Basic characteristics and comparison –for confounding and possible selection bias Intention-to-treat analysis Primary: –smoking status –subgroup analysis

27 Smoking: m ajor results/discussion Comparison: Table 1 Efficacy –Table 2 –subgroup analysis: –only effective for male non-smoker at grade 8 No other analyses

28 DM: m ajor results/discussion Discussion –Confounding, selection bias: randomization –Information bias: blindness –Sample size and power of test –Limited to one special group –Adverse effects not analyzed –Cost? Conclusion: limited!