Introduction of Cohort Study

Aug, 17, 2011

Hirohide Yokokawa, M.D., Ph.D.Department of General Medicine,

Juntendo University School of Medicine

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

Overview of study designs Clinical studies

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

Cohort Study Case-Control Study

Measures Incidence Rate, Relative Risk(RR)

Odds Ratio (OR) only

Cost Expensive Inexpensive

Study term Long term Short term

Sample size Need large sample Powerful with small sample cases

Exposure Good for rare exposure Limited to rare exposure

Disease Poor potential for rarePossible for several disease

Good for rare diseaseOnly one disease

Causal Potentially strong Potentially less strong

Generalization Possibly generalizable Probably not generalizable

Advantage and Disadvantage of Cohort Study compared to Case-Control study

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

Procedure of Cohort StudyDefine Study Participants

EXPOSED NOTEXPOSED

DISEASEDEVEPOPS

DISEASEDOSE NOTDEVEPOPS

DISEASEDEVEPOPS

DISEASEDOSE NOTDEVEPOPS

①

②③

④

① Define eligible Study Participants② The investigator selects a group

of EXPOSED individuals and a group of NON EXPOSED individuals

③ Follow up both groups④ Compare incidence of disease

Follow up To obtain data about outcome to be determined

(morbidity or death)

Mailed questionnaire, telephone callsPeriodic medical examinationReviewing recordsSurveillance of death recordsFollow 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.

Types of Cohort studies

ProspectiveRetrospective

Time

NOW

EXPOSE

EXPOSE

OUTCOME

OUTCOME

Collect Informatio

n

MeasureOutcome

Time course of Cohort studies

Study Participants

EXPOSED NOTEXPOSED

DISEASEDEVEPOPS

DISEASEDOSE NOTDEVEPOPS

DISEASEDEVEPOPS

DISEASEDOSE NOTDEVEPOPS

Retrospective Cohort Study(10 years follow-up)

2001(10 years ago)

2011 (Now)

Study Participants

EXPOSED NOTEXPOSED

DISEASEDEVEPOPS

DISEASEDOSE NOTDEVEPOPS

DISEASEDEVEPOPS

DISEASEDOSE NOTDEVEPOPS

Prospective Cohort Study(10 years follow-up) 2011

Now

2021

Prospective Retrospective

Cost Expensive Inexpensive

Needed time for study

Long term Short term(Possible to determine measure factors and outcome at same time)

Validity for exposed information

Good validity Relatively less validity

Adding new measures

Possible Impossible

Advantage and Disadvantage of Prospective and Retrospective Cohort Study

EXPOSED

NOT EXPOSE

D

a b

c d

DISEASEPRESENT

DISEASENOT

PRESENT

Follow-up

Relative Risk (RR)= Risk in EXPOSEDRisk in NOT EXPOSED =

a/(a+d)c/(c+d)

Risk measurement in Cohort Study

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)

An Example of Cohort Study and

A Case of Publishing Data

Hirohide Yokokawa ， Aya Goto ， Hironobu Sanada ，Tsuyoshi Watanabe ， Robin A. Felder, Pedro A. Jose, Seiji Yasumura

Gaps between hypertension Gaps between hypertension treatment guidelines and treatment guidelines and

practice in Japanpractice in Japan

Fukushima Research of Fukushima Research of Hypertension Hypertension

～～ (FRESH)(FRESH) ～～

Fukushima Research of Hypertension Fukushima Research of Hypertension (FRESH)(FRESH)

Introduction of our Cohort studyIntroduction of our Cohort study

Observational Cohort Study(from July 2006 to May 2007)

Research Research DesignDesign

SubjectsSubjects Subjects were 3,358 registered hypertensive patients who received antihypertensive medication by 72 physician members of Fukushima Hypertension Conference.

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

夏

Fulfill Registration form and collect basic information

Fulfill Follow-up form and collect follow-up data

Return these forms by mail

2006-JulyRegistration

Summer

2006-October1st Follow-up

Time Course of the Study

Autumn

Winter

Spring

2007-Janualy2st Follow-up

2007-April3st Follow-up

Analysis of Baseline Data(Cross-sectional analysis)

Gaps between hypertension treatment Gaps between hypertension treatment guidelines and practice in Japanguidelines and practice in Japan

～～ Baseline survey results from Baseline survey results from Fukushima Research of Hypertension Fukushima Research of Hypertension

(FRESH)(FRESH) ～～

J Clin Hypetens 2009; 11:333-341.

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

Variables Odds Ratio 95% Confidence Interval

Waist circumference (cm)c) 1.26 1.01-1.57 *

Number of antihypertensive drug used

1 1.00(Reference)

2 1.15 0.91-1.46

3 1.96 1.42-2.71 *

Table.1 Association of blood pressure achievement failure in elderly patients without DMa) or RDb) (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

Variables Odds Ratio

95% Confidence Interval

Body mass index (BMI) 25 or higher 1.74 1.19-2.56 *

Family history of hypertension (yes) 1.67 1.14-2.45 *

Organ damage/ cardiovascular disease

Brain (yes) 0.33 0.16-0.68 *

Hypertensive retinopathy (yes) 0.33 0.12-0.91 *

Table.2 Association of blood pressure achievement failure in young and middle aged patients without DMa) or RDb) (multivariate logistic regression analyses)

*<0.05, **<0.01 a)Diabetes mellitus, b)Renal disease

Variables Odds Ratio

95% Confidence Interval

Body mass index (BMI) 25 or higher 1.34 1.03-1.75 *

Family history of diabetes mellitus (yes)

1.40 1.04-1.87 *

Dyslipidemia (yes) 1.41 1.08-1.84 *

Organ damage/ cardiovascular disease

Brain (yes) 0.62 0.44-0.87 *

Blood vessel (yes) 0.48 0.33-0.70 *

Table.3 Association of blood pressure achievement failure in patients with DMa) or RDb) (multivariate logistic regression analyses)

*<0.05, **<0.01 a)Diabetes mellitus, b)Renal disease

Caution!

It is limited to interpret causal relationship in cross-sectional data.

Need longitudinal data analysis to access causal relationship.

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.

3358 registered initially

3320 followed through a year

38 excluded due to missing dataor 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 DMa) or RDb)

480 Young or Middle aged Patients

without DMa) or RDb)

937 DMa) and RDb)

a)DM; Diabetes mellitus, b)RD; Renal disease.

Flow of registered patients

Follow-up rate82.6%

N (%)

Groups Year-round failure

Year-round success

Elderly patients without

DMa) or RDb) (n=1319)

124 (9.4) 407 (30.8)

Young or middle aged patients without DMa) or RDb) (n=482)

207 (42.9) 19 (3.9)

Patients with DMa) or RDb)

(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 diseasea)DM; Diabetes mellitus, b)RD; Renal disease

Significant variables N (%) Odds Ratio

95% Confidence

Interval

Number of antihypertensive

drug used

1 632 (47.9) 1.00

2 508 (38.5) 2.08 1.34-3.25 **

3 180 (13.6) 4.45 2.68-7.40 **

Presence of organ damage or cardiovascular disease

475 (36.0) 0.55 0.36-0.84 **

Table 3-1. Risk factors for failure to meet blood pressure goals in elderly patients without DMa) or RDb)

across all seasons. (multivariate logistic regression analysis)

**<0.01a)DM; Diabetes mellitus, b)RD; Renal diseasea)DM; Diabetes mellitus, b)RD; Renal disease

Significant variables N (%) Odds Ratio

95% Confidence

Interval

Gender (male) 274 (56.8) 0.63 0.43-0.92 **

Body mass index (≥25) 204 (42.6) 2.11 1.44-3.07 **

Presence of organ damage or cardiovascular disease

88 (18.3) 0.47 0.28-0.79 **

Table 3-2. Risk factors for failure to achieve blood pressure goals in young or middle aged patients without DMa) or RDb) across all seasons. (multivariate logistic regression analysis)

**<0.01a)DM; Diabetes mellitus, b)RD; Renal diseasea)DM; Diabetes mellitus, b)RD; Renal disease

Significant variables N (%) Odds Ratio

95% Confidence

Interval

Family history

Hypertension (yes)

508 (53.9) 1.40 1.07-1.83 **

Alcohol consumption (daily) 175 (18.7) 1.64 1.15-2.32 **

Current smoking status 128 (13.6) 1.53 1.02-2.30 **

Instruction in home blood pressure

measurement (yes)

560 (59.6) 1.41 1.07-1.86 **

Dyslipidemia (yes) 511 (54.4) 1.35 1.03-1.77 **

Presence of organ damage or

cardiovascular disease

459 (48.8) 0.58 0.44-0.76 **

Table 3-3. Risk factors for failure to achieve blood pressure goals in patients with DMa) or RDb)

across all seasons. (multivariate logistic regression analysis)

a)DM; Diabetes mellitus, b)RD; Renal diseasea)DM; Diabetes mellitus, b)RD; Renal disease

The Odds Ratio in Cohort Study

Year Round Failure

NOT Year Round Failure

Atherosclerotic Complications

a bNot Atherosclerotic Complications

c d

Odds Ratio (OR)=

Odds in Atherosclerosis complicationsOdds in NOT Atherosclerosis Complications

=a/bc/d