The Research Question

1. The Research Question Alka M. Kanaya, MD Associate Professor of Medicine, Epidemiology & Biostatistics UCSF October 3, 2011

2. Anatomy of research:What it’s made of • Research question • significance • Study design • Study participants: • The target population • The study population (and how they will be sampled) • Variables (and how they will be measured) • Predictor • Outcome • Analysis plan, sample size calculation

3. NIH Roadmap Initiative-translating discoveries into health Westfall JM et al, JAMA 2007

4. Translational Research and Studies for this course • Not the best choice for this course: • Animals, molecules without humans • Data syntheses, e.g. decision analysis, cost-effectiveness analysis, meta-analysis • Qualitative research • Ideal • An observational study involving humans that you could do in limited time as a resident (secondary data analysis of an existing database)

5. Secondary data analysis • Rethink the decisions that were already made and getting thoughts and suggestions for colleagues • Design a new study you aren’t (currently) planning to do

6. Physiology of research: How it works Using measurements in a sample to draw inferences about phenomena in a population

7. DCR Figure 1.3

8. DCR Figure 1.4

9. DCR Figure 1.5

10. My preliminary research question • Is HRT associated with diabetes? • Is postmenopausal HRT use associated with lower incidence of diabetes?

11. Background • Effect of hormone therapy on glucose: • RCT evidence: variable • Observational studies: consistent benefit • Effect of hormone therapy on diabetes incidence: • Observational studies: variable • No RCT has evaluated this outcome

12. Specify the Study Design • Observational study • Cohort • Cross-sectional • Cohort • Case control • Randomized clinical trial • Surrogate endpoints • Endpoints of primary interest • Importance of thorough literature review and scholarship

13. Does the Research Question meet the FINER criteria? Feasible Interesting Novel Ethical Relevant

14. Cohort Design • Subjects: participants of a large cohort (Nurses Health Study) • Predictor: HRT use • Outcome: incidence of diabetes

15. Cross-sectional design • Subjects: large sample of postmeno-pausal women • Predictor: HRT use • Outcome: Diabetes (prevalent)

16. Case-control design • Subjects: • Cases: 100 women with diabetes • Controls: 100 adults selected from same population setting, without diabetes • Predictor: HRT use • Outcome: cases vs. controls

17. Randomized blinded trial design: Surrogate outcomes • Subjects: 1,000 postmenopausal women • Predictor: • randomized to HRT vs. placebo • Outcome: 1 year later • Change in fasting glucose levels

18. Randomized blinded trial design:Disease event outcomes • Subjects: 2,700 postmenopausal women • Predictor: • randomized to HRT vs. placebo • Outcome: 4 years later • Incidence of type 2 diabetes

19. Effect of HRT on Fasting Glucose (HERS post-hoc analysis)

20. * % * * * * p  0.05 Glucose  126 alone Inclusive Defn. 4 year Incidence of Diabetes

21. NNT To prevent one case of incident diabetes: 31

22. Risk of Incident Diabetes * adjusted for age, race, education, alcohol, smoking, physical activity, BMI, waist circumference, TG, HDL, HTN, use of diuretics, B-blockers, ACE inhibitors, and statins Kanaya, Annals Int Med, 2003

23. My next research question • Does yoga improve the metabolic syndrome (waist circumference, blood pressure, glucose, lipids)? • Does yoga prevent/delay type 2 diabetes?

24. Proven Methods to Prevent T2DM • Intensive lifestyle change • Weight loss, exercise, healthier diet • Medications: • Metformin • Rosiglitazone • Acarbose • Orlistat • Other non-pharmacologic methods?

25. Improve Met. Syn ↓ Glucose ↓ BP Improve lipids ↓ Stress ↓ Visceral fat Yoga ↑ Sleep Why Yoga? • Systematic review—small trials with benefit • BP reduction in hypertensive patients • Glucose reduction in diabetes patients • Cholesterol lowering in CHD patients

26. Does the Research Question meet the FINER criteria? Feasible Interesting Novel Ethical Relevant

27. Add “G”: Good for your career Try to identify a research question that will allow you to • Learn more about an area of potential long-term interest • Acquire new skills you could use on other projects • Work with people and/or organizations with whom you want to develop a long term relationship • Build on the project for future work

28. Cohort Design • Subjects: Nurses Health Study- that includes questions about yoga practice, lab measures; (no waist circumference); • Predictor: yoga practice (frequency) • Outcome: incidence of the metabolic syndrome (or individual components); incidence of type 2 diabetes in future visits

29. Cross-sectional design • Subjects: CHIS survey that includes questions about yoga practice, lab measures, at one time-point • Predictor: yoga practice (frequency) • Outcome: metabolic syndrome; diabetes (prevalence)

30. Case-control design • Subjects: • Cases: 100 adults with the metabolic syndrome • Controls: 100 adults without the metabolic syndrome • Predictor: practice yoga? • Outcome: cases vs. controls

31. Randomized blinded trial design: Surrogate outcomes • Subjects: 180 adults with the metabolic syndrome • Predictor: • randomized to yoga vs. stretch intervention • Outcome: 1 year later • Change in metabolic syndrome (each components)

32. Randomized blinded trial design:Disease event outcomes • Subjects: adults with the metabolic syndrome • Predictor: • randomized to yoga vs. stretch intervention • Outcome: 3-5 years later • Incidence of type 2 diabetes

33. Does the Research Question meet the FINER criteria? Feasible Interesting Novel Ethical Relevant

34. Infer conclusions Design study Analyze results Implement study The research cycle Develop research question

35. One sentence describing anatomy of your study • Research question • Design • Subjects • Variables • Predictor • Outcome

36. Do you have a FINER research question? Feasible Interesting Novel Ethical Relevant

37. Alka.Kanaya@ucsf.edu Funded by K23 HL080026 and a UCSF REAC grant