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

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

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

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

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

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

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My preliminary research question n Is HRT associated with diabetes? n Is postmenopausal HRT use associated with lower incidence of diabetes?

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

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

Does the Research Question meet the FINER criteria? F easible I nteresting N ovel E thical R elevant

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

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

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

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

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

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

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

NNT To prevent one case of incident diabetes: 31

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

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

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

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

Does the Research Question meet the FINER criteria? F easible I nteresting N ovel E thical R elevant

Add “G”: G ood 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

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

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

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

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

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

Does the Research Question meet the FINER criteria? F easible I nteresting N ovel E thical R elevant

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

One sentence describing anatomy of your study n Research question n Design n Subjects n Variables –Predictor –Outcome

Do you have a FINER research question? F easible I nteresting N ovel E thical R elevant

Funded by K23 HL and a UCSF REAC grant