Prospective Studies (cohort, longitudinal, incidence studies) Sue Lindsay, Ph.D., MSW, MPH Division of Epidemiology and Biostatistics Institute for Public

Prospective Studies(cohort, longitudinal, incidence studies)

Sue Lindsay, Ph.D., MSW, MPH

Division of Epidemiology and Biostatistics

Institute for Public Health

San Diego State University

Prospective Study Design

Develop disease

Do not develop disease

Develop disease

Do not develop disease

Exposed Not Exposed

Population (does not have disease)

select select

Design Considerations

• These investigations are oriented to exposure status

• The objective is to find exposures that lead to disease.

• How well can you identify exposed individuals?

• How long should your follow-up be?

• How frequently do you need to measure exposure?

• Can you ensure that study subjects do not have the disease at the beginning of the study?

Design Considerations

• Baseline characteristics of exposed and not exposed subjects should not differ. Use comparable source populations with equivalent information.

• Both groups should be equally available for follow-up.

• The degree of surveillance for disease should be equal in both groups.

• Those assessing for disease should be blind to risk factor group.

Cohort Study Analysis

• Incidence rate

• Relative Risk with Confidence Intervals

• Risk Difference

• Attributable Risk

• Population Attributable Risk

The 2 X 2 Table for Cohort Studies

a

Disease

Develops No Disease

Exposed (+)

Not

Exposed (-)

b

c d

Totals

a + b

c + d

First Select

Incidence Rate

Incidence

Per 1,000=

No. of New Cases of Disease

In a Population

No. of Persons at Risk of

Developing Disease

During a Specified Period of Time

Relative Risk

Risk of disease among exposed

Risk of disease among the not exposed

OR

Risk (exposed) Incidence (exposed)

Risk (unexposed) Incidence (unexposed)

Relative Risk in a 2 X2 Table

a

Disease No Disease

Exposed (+)

Not

Exposed (-)

b

c d

Risk

a

c

a + b

c + d

Relative Risk = a/(a+b)

c/(c+d)

Relative Risk

• Relative risk measures the strength of an association

• The larger the relative risk, the stronger the association between

the risk factor and the disease

• Relative risk does not tell you about the actual risk of the

disease (this is measured with incidence)

Etiologic Objective

• If exposure is associated with disease, the incidence rate in the exposed group will be greater than in the not exposed group.

a

a + b>>>

c

c + d

Exposed Not exposed

Hypothetical Example:Maternal stress and preterm birth

110

Preterm birth Full term birth

Stressed

Not stressed

2,890

87 4,913

Risk

110

3,000

87

5,000

Relative

Risk=

110/3000

87/5000= 2.18

= 0.037

= 0.017

RR = 1: There is no association between the risk factor and the disease.

RR > 1: There is a positive association between the risk factor and the disease. The risk factor may be a cause of disease. Possible range 1 to infinity.

RR < 1: There is a negative association between the risk factor and the disease. The risk factor may be protective against the disease. Possible range 0-1.

Interpretation of Relative Risk

The Health Risk of Passive Smoking

• Hirayama et al. 1981

• Study Objective: To assess the health effects of passive cigarette smoking

• Japan 1965 - Data collected in 6 prefectures

• Studied the smoking habits of the spouses of:• 91,540 non-smoking wives

• 20,289 non-smoking husbands

IDENTIFY

NEW CASES OF

LUNG CANCER

Not exposed to

second

hand smoke

1965 1979

PASSIVE SMOKING IN JAPAN

14 YEAR FOLLOW-UP

(Death Certificates)

Population:

Non-smoking

spouses

Exposed to

second

hand smoke

Mortality In Non-Smoking Wives

00.2

0.40.6

0.8

11.2

1.41.6

1.8

Non-Smokers

1-14Cigs/Day

15-19Cigs/Day

>20Cigs/Day

Deaths • Shows increasing risk of

mortality with increasing number of cigarettes smoked by spouse

• Dose-response relationship

Rel

ativ

e R

isk

Mortality in Non-Smoking Husbands

0

0.5

1

1.5

2

2.5

Non-Smokers 1-14 Cigs/Day > 15 Cigs/Day

Deaths • Shows increasing risk of

mortality with increasing number of cigarettes smoked by spouse

Rel

ativ

e R

isk

Exposure to Second Hand Smoke Number Cancers Incidence15+ cigarettes/day 1,000 20 20/1,00010-15 cigarettes/day 1,000 10 10/1,000

5-10 cigarettes/day 1,000 8 8/1,000<5/day 1,000 5 5/1,000occasional (not daily) 1,000 4 4/1,000quitter 1,000 4 4/1,000never smoked 1,000 2 2/1,000TOTAL 7,000 53 7.6/1,000

Ever smoked 6,000 51 8.5/1,000

occasional,quitter,never 3,000 10 3.3/1,000

Relative Risk is Relative: Hypothetical Example

Relative Risks:

15+ cigarettes/never smoked: 20/2 = 10.00

Ever smoked/never smoked: 8.5/2 = 4.25

Daily/occasional,quitter,never: 10.8/3.3 = 3.25

The Royal College of General Practitioners (RCGP)

Oral Contraception Study

• England: Is oral contraceptive use a risk factor for cardiovascular disease?

• May 1968 - July 1969 • 23,000 oral contraceptive users identified and

recruited by physicians

• Equal number of non-users identified, matched for marital status and age

The RCGP Oral Contraceptive Study

1968 - 1969

23,000 OC

Users

23,000

Non- Users

1974

1974

1977

1977

1981

1981

Morbidity and Mortality Follow-up

RCGP Oral Contraceptive Study: Relative Risks for Cardiovascular Disease

0

1

2

3

4

5

6

Heart Disease

HypertensionIschemic

Heart Disease

Subarachnoid

Hemorrhage

Stroke

The Hepatitis B Virus Cohort Study

• Taiwan: November 1975 – June 1978

• Is Hepatitis B etiologically associated with primary hepatocellular cancer?

• 21,227 male Taiwanese government civil servants recruited

The Hepatitis B Cohort Study

Recruit 22,707

Taiwanese Men

1975- 1978

3,454

Hepatitis B +

1986

161 new cases

of primary

hepatocellular

cancer19,253

Hepatitis B -

The Hepatitis B Cohort Study

152

Cancer No

Cancer

HBsAg (+)

HBsAg (-)

3302

9 19244

Risk

152

3454

9

19,253

Relative

Risk=

152/3454

9/19,253= 98.1

Potential Bias in Cohort Studies

• Bias in Ascertainment of Outcome

• Staff responsible for the identification of disease are aware of exposure status

or hypotheses

• Diagnostic suspicion bias


• Information Bias

Occurs when the extent or quality of the information obtained is different for exposed and not exposed study subjects.


• Non-response and Loss to Follow-up

Occurs if non-response or loss is different for exposed compared to non-exposed study subjects.

Risk Difference

Risk (exposed)

Incidence (exposed)

Risk (unexposed)

Incidence (unexposed)

__

__

Maternal Stress and Preterm Birth:Risk Difference

110

Preterm birth Full term

Stressed

Not stressed

2,890

87 4,913

Risk

110

3,000

87

5,000

Risk difference = 0.037-0.017 = 0.020

= 0.037

= 0.017

The risk of preterm birth is increased by 0.020 for women who are stressed in their pregnancies

Attributable Risk Percent

Risk (exposed) Risk (not exposed)__

What percent of the risk in the exposed population

is due to the exposure?

Risk (exposed)

X 100

Maternal stress and preterm birth:Attributable risk percent

110

Preterm birth Full term

Stressed

Not stressed

2,890

87 4,913

Risk

110

3,000

87

5,000

Attributable risk = 0.037- 0.017 X 100 54%

= 0.037

= 0.017

54% of the total risk for preterm birth among stressed pregnant women is their stress

0.037=

Population Attributable Risk Percent(PARP, Etiologic Fraction)

Incidence (total population) Incidence (not exposed)__

The reduction in the incidence of the disease that

can be expected if we eliminate the risk factor.

X 100Incidence (total population)


This statistic is influenced by two things:

• Prevalence of the risk factor in the population

• The strength of the association between

risk factor and disease


Prevalence of the risk factor in the population

Incidenceof lungcancer

20%15%10% 5%

Smokers (25%) Non-smokers (75%)

17%

4%

What is the incidence of lung cancer in this population?

(17 * .25) + ( 4 * .75) = 7.25%

Population Attributable Risk Percent


20%15%10% 5%


17%

4%

Incidence in total pop = 7.25%

Among the total population, what is the reduction in incidence that we could expect if we eliminated smoking (exposure) from the population?

7.25 - 4

PAR% = 7.25 X 100 = 44.8%


44.8% of incidence could be reduced if smoking is eliminated


20%15%10% 5%


17%

4%

What if there were far more smokers in the population?Incidence of lung cancer in this population = (17*.75) + (4*.25) = 13.75%

PAR% = 13.75 - 4 13.75

X 100 = 70.9%




The strength of the association between

the risk factor and the disease


20%15%10% 5%


10%

4%

What if there were just as many smokers but they smoked less?(only 2 cigarettes per day each)

Incidence of lung cancer in this population = (10*.75) + (4*.25) = 8.5%

PAR% = 8.5 - 4 8.5

X 100 = 52.9%



Population Attributable Risk Percent: A comparison of three populations

PARP = Incidence in population - incidence in not exposed (incidence of lung cancer in not Incidence in population exposed is 4%)

Pop #1: Total population incidence = (.25*17) + (.75*4) = 7.25%

25% smokers PARP = 7.25 – 4 = 44.8%17% cancer incidence 7.25


75% smokers PARP = 13.75 – 4 = 70.9%

17% cancer incidence 13.75


75% smokers PARP = 8.5 – 4 = 52.9%

Only 2 a day 8.510% cancer incidence

Documents

Prospective Studies (cohort, longitudinal, incidence studies) Sue Lindsay, Ph.D., MSW, MPH Division of Epidemiology and Biostatistics Institute for Public