1. Introduction of Cohort Study Aug, 17, 2011 Hirohide Yokokawa, M.D., Ph.D. Department of General Medicine, Juntendo University School of Medicine

2.  What is Cohort Study? Overview of study design Purpose of Cohort study  Types of Cohort Studies Prospective and Retrospective  Procedure of Cohort Study.  Follow up and Risk assessment  An Example of Cohort Study. Contents

3. Overview of study designs Clinical studies

5. To determine whether there is an association between a factor and development of a disease. To derive an appropriate interference regarding with a possible causal relationship. Purpose of Cohort Study

6. Cohort StudyCase-Control Study MeasuresIncidence Rate, Relative Risk(RR) Odds Ratio (OR) only CostExpensiveInexpensive Study termLong termShort term Sample sizeNeed large samplePowerful with small sample cases ExposureGood for rare exposureLimited to rare exposure DiseasePoor potential for rare Possible for several disease Good for rare disease Only one disease CausalPotentially strongPotentially less strong GeneralizationPossibly generalizableProbably not generalizable Advantage and Disadvantage of Cohort Study compared to Case-Control study

7. Review feasibility of the planed study considering with study question, target disease, expose, cost, expected study period, etc!

8. Procedure of Cohort Study Define Study Participants EXPOSED NOT EXPOSED DISEASE DEVEPOPS DISEASE DOSE NOT DEVEPOPS DISEASE DEVEPOPS DISEASE DOSE NOT DEVEPOPS ① ② ③ ④

9. ① Define eligible Study Participants ② The investigator selects a group of EXPOSED individuals and a group of NON EXPOSED individuals ③ Follow up both groups ④ Compare incidence of disease

10. Follow up  To obtain data about outcome to be determined (morbidity or death) Mailed questionnaire, telephone calls Periodic medical examination Reviewing records Surveillance of death records Follow up is the most critical part of the study  Some loss to follow up is inevitable due to death change of address, migration, change of occupation.  Loss to follow-up is one of the draw-back of the cohort study.

11. Types of Cohort studies Prospective Retrospective

12. Time NOW EXPOSE OUTCOME Collect Information Measure Outcome Time course of Cohort studies

13. Study Participants EXPOSED NOT EXPOSED DISEASE DEVEPOPS DISEASE DOSE NOT DEVEPOPS DISEASE DEVEPOPS DISEASE DOSE NOT DEVEPOPS Retrospective Cohort Study (10 years follow-up) 2001 (10 years ago) 2011 (Now)

14. Study Participants EXPOSED NOT EXPOSED DISEASE DEVEPOPS DISEASE DOSE NOT DEVEPOPS DISEASE DEVEPOPS DISEASE DOSE NOT DEVEPOPS Prospective Cohort Study (10 years follow-up) 2011 Now 2021

15. ProspectiveRetrospective CostExpensiveInexpensive Needed time for study Long termShort term (Possible to determine measure factors and outcome at same time) Validity for exposed information Good validityRelatively less validity Adding new measures PossibleImpossible Advantage and Disadvantage of Prospective and Retrospective Cohort Study

16. EXPOS ED NOT EXPOS ED ab cd DISEASE PRESENT DISEASE NOT PRESENT Follow-up Relative Risk (RR)= Risk in EXPOSED Risk in NOT EXPOSED = a/(a+d) c/(c+d) Risk measurement in Cohort Study

17. Interpretation of Relative Risk (RR) Relative Risk (RR) Interpretation =1 No association >1 Risk in EXPOSED greater than Risk in NOT EXPOSED (Positive association; Risk Factor) <1 Risk in EXPOSED less than Risk in NOT EXPOSED (Negative association; Protective Factor)

18. An Example of Cohort Study and A Case of Publishing Data

19. Hirohide Yokokawa ， Aya Goto ， Hironobu Sanada ， Tsuyoshi Watanabe ， Robin A. Felder, Pedro A. Jose, Seiji Yasumura Gaps between hypertension treatment guidelines and practice in Japan Fukushima Research of Hypertension ～ (FRESH) ～

20. Fukushima Research of Hypertension (FRESH) Introduction of our Cohort study Observational Cohort Study (from July 2006 to May 2007) Research Design Subjects Subjects were 3,358 registered hypertensive patients who received antihypertensive medication by 72 physician members of Fukushima Hypertension Conference.

21. To determine 1.Hypertensive patients’ characteristics 2.Success rates in achieving goal blood pressures 3.Factors associated with therapeutic failures for target treatment goals among Japanese hypertensive patients. Aim of the study Fukushima prefecture

22. 夏 Fulfill Registration form and collect basic information Fulfill Follow-up form and collect follow-up data Return these forms by mail 2006-July Registration Summe r 2006-October 1 st Follow-up Time Course of the Study Autum n Winte r Sprin g 2007-Janualy 2 st Follow-up 2007-April 3 st Follow-up

23. Analysis of Baseline Data (Cross-sectional analysis) Gaps between hypertension treatment guidelines and practice in Japan ～ Baseline survey results from Fukushima Research of Hypertension (FRESH) ～ J Clin Hypetens 2009; 11:333-341.

24. To assess the possible factors associated with the focused outcomes using baseline data.

25. VariablesOdds Ratio95% Confidence Interval Waist circumference (cm) c) 1.261.01-1.57* Number of antihypertensive drug used 11.00(Reference) 21.150.91-1.46  3 1.961.42-2.71* Table.1 Association of blood pressure achievement failure in elderly patients without DM a) or RD b) (multivariate logistic regression analyses) *<0.05, **<0.01 a)Diabetes mellitus, b)Renal disease c) 85 or higher for Men, 90 or higher for Women

26. VariablesOdds Ratio 95% Confidence Interval Body mass index (BMI) 25 or higher1.741.19-2.56* Family history of hypertension (yes)1.671.14-2.45* Organ damage/ cardiovascular disease Brain (yes)0.330.16-0.68* Hypertensive retinopathy (yes)0.330.12-0.91* Table.2 Association of blood pressure achievement failure in young and middle aged patients without DM a) or RD b) (multivariate logistic regression analyses) *<0.05, **<0.01 a)Diabetes mellitus, b)Renal disease

27. VariablesOdds Ratio 95% Confidence Interval Body mass index (BMI) 25 or higher1.341.03-1.75* Family history of diabetes mellitus (yes) 1.401.04-1.87* Dyslipidemia (yes)1.411.08-1.84* Organ damage/ cardiovascular disease Brain (yes)0.620.44-0.87* Blood vessel (yes)0.480.33-0.70* Table.3 Association of blood pressure achievement failure in patients with DM a) or RD b) (multivariate logistic regression analyses) *<0.05, **<0.01 a)Diabetes mellitus, b)Renal disease

28. Caution! It is limited to interpret causal relationship in cross-sectional data. Need longitudinal data analysis to access causal relationship.

29. Analysis of Follow-up Data (Longitudinal analysis) Longitudinal community-based assessment of blood pressure control among Japanese hypertensive patients: Fukushima Research of Hypertension (FRESH) J Clin Hypetens 2010;12:166–173.

30. 3358 registered initially 3320 followed through a year 38 excluded due to missing data or lack of medication use 2735 continued and confirmed their medical information 585 excluded due to lost follow up or missing data 1318 Elderly Patients without DM a) or RD b) 480 Young or Middle aged Patients without DM a) or RD b) 937 DM a) and RD b) a)DM; Diabetes mellitus, b)RD; Renal disease. Flow of registered patients Follow-up rate 82.6%

31. N (%) GroupsYear-round failure Year-round success Elderly patients without DM a) or RD b) (n=1319) 124 (9.4)407 (30.8) Young or middle aged patients without DM a) or RD b) (n=482) 207 (42.9)19 (3.9) Patients with DM a) or RD b) (n=942) 429 (45.5)39 (4.1) Table 1. Proportions of year-round failure and success in achieving blood pressure goals. a)DM; Diabetes mellitus, b)RD; Renal disease

32. Significant variablesN (%)Odds Ratio 95% Confidence Interval Number of antihypertensive drug used 1632 (47.9)1.00 2508 (38.5)2.081.34-3.25**  3 180 (13.6)4.452.68-7.40** Presence of organ damage or cardiovascular disease 475 (36.0)0.550.36-0.84** Table 3-1. Risk factors for failure to meet blood pressure goals in elderly patients without DM a) or RD b) across all seasons. (multivariate logistic regression analysis) **<0.01 a)DM; Diabetes mellitus, b)RD; Renal disease

33. Significant variablesN (%)Odds Ratio 95% Confidence Interval Gender (male)274 (56.8)0.630.43-0.92** Body mass index (≥25)204 (42.6)2.111.44-3.07** Presence of organ damage or cardiovascular disease 88 (18.3)0.470.28-0.79** Table 3-2. Risk factors for failure to achieve blood pressure goals in young or middle aged patients without DM a) or RD b) across all seasons. (multivariate logistic regression analysis) **<0.01 a)DM; Diabetes mellitus, b)RD; Renal disease

34. Significant variablesN (%)Odds Ratio 95% Confidence Interval Family history Hypertension (yes) 508 (53.9)1.401.07-1.83** Alcohol consumption (daily)175 (18.7)1.641.15-2.32** Current smoking status128 (13.6)1.531.02-2.30** Instruction in home blood pressure measurement (yes) 560 (59.6)1.411.07-1.86** Dyslipidemia (yes)511 (54.4)1.351.03-1.77** Presence of organ damage or cardiovascular disease 459 (48.8)0.580.44-0.76** Table 3-3. Risk factors for failure to achieve blood pressure goals in patients with DM a) or RD b) across all seasons. (multivariate logistic regression analysis) a)DM; Diabetes mellitus, b)RD; Renal disease

35. The Odds Ratio in Cohort Study Year Round Failure NOT Year Round Failure Atherosclerotic Complications ab Not Atherosclerotic Complications cd Odds Ratio (OR)= Odds in Atherosclerosis complications Odds in NOT Atherosclerosis Complications = a/b c/d