Review of Epidemiological Study Methods

1
Review of Epidemiological Study Methods

• Examples from
• The Womens Health Initiative (WHI)

2
Methods of Study - Step 1

• Define the problem
• What is being studied
• Womens Health Initiative
• Study of Post-Menopausal Women (50-79 yrs)

3
Define the Problem - Step 1

• Need methods to prevent the major causes of
  disease, disability death in women
• Need to identify risk factors for women

4
Determine Need- Step 2

• Review prior information
• Why Is WHI Needed
• Previous studies on men only
• NIH office of Research in Womens Health

5
Methods of Study - Step 3

• Assembling the facts on the disease or condition
• Descriptive Studies
• Occurrence distribution (WHO, WHERE, WHEN)

6
Descriptive Studies - Step 3

• Incidence, prevalence, morbidity, mortality
  rates in large population groups

7
Review

• Incidence new cases
• population at risk
• Specified time period
• Cases per 1,000

8
Review

• Prevalence existing cases
• population
• Specified time period
• Cases per 1,000
• Prevalence Incidence X Duration

9
Review

• Annual Mortality Rate
• of deaths in a year
• total population
• U.S. population 262.8 million
• 1995 8.8 per 1,000

10
Review

• Cause Specific Death Rate
• of deaths from specific cause
• total population (mid interval)
• Specified time interval
• Cases per 100,000

11
Review

• Proportionate Mortality Ratio (PMR)
• deaths from specific disease
• Total of deaths in the period

12
Review

• Case Fatality Rate
• cases died from specific cause
• cases with specific cause

13
Coronary Heart Disease

• Most common cause of death in women over age 50
• 50 all CHD deaths in women
• 250,000 deaths in U.S. women per year

14
Breast Cancer

• A major cause of illness and death in women over
  age 50
• 175,000 new cases 44,500 deaths (1991)
• 1 in 8 women will develop breast cancer

15
Breast Cancer

• Incidence increasing 1 /yr (since 1970s)
• Cause is still unknown
• Women want to know what they can do for prevention

16
Cancer of Colon/Rectum

• 3rd most common cancer
• 78,500 new cases in 1991
• 31,000 deaths 1991

17
Fractures

• At age 50, 15 chance of hip fracture in
  remaining lifetime
• Incidence increases sharply after age 75

18
Fractures

• Results in major disability or death
• Effective prevention measures are needed

19
Analytic Studies - Step 4

• Formulate and test hypotheses of association
  between a disease and suspected factor(s)
• Observational Studies
• Experimental Studies

20
Analytic Studies - Step 4

• Observational Studies
• Investigator does not control the factors to
  which the population is exposed
• Individuals self-select lifestyle/medication
  patterns

21
Observational Studies

• Advantages
• Large number and range of variables can be
  studied
• Some environmental occupational exposures not
  amenable to clinical trials

22
Observational Studies

• Cross-Sectional Studies
• Case-Control Studies
• Cohort Studies

23
Cross-Sectional Studies

• Presence of disease factor in a total
  population or sample
• Common conditions of long duration

24
Case-Control Studies

• Select cases with disease
• Select controls without disease
• Calculation of Odds Ratio
• Estimate of relative risk

25
Case-Control Studies Unmatched Design

• Ratio of odds of exposure in cases to odds of
  exposure in the controls
• Cross product ratio

26
Unmatched Odds Ratio (a/c)/(b/d) OR ad/bc
27
Matched Case Control StudiesOdds Ratio ratio
of discordant pairs OR EN/NE
28
Cohort Studies

• Select cohort without disease
• Identify those with without the factor (exposed
  not exposed)
• Follow-up over time determine disease incidence
  in those exposed not exposed

29
Cohort Studies

• Compare incidence (risk) in exposed and not
  exposed
• Calculate relative risk, attributable risk
  attributable risk percent

30
Cohort Studies

• RR incidence in exposed
• incidence in not exposed
• AR I exposed - I not exposed
• AR Attributable Risk X 100
• Incidence in exposed

31
Study Methods - Step 5 Experimental Studies

• Investigators determine exposures
• Assess differences between groups receiving
  different interventions or treatments

32
Controlled Clinical Trial

• Treatments given under controlled conditions -
  double blind to reduce bias
• Selection of study population
• Random assignment to treatment and control groups

33
Controlled Clinical Trial

• Follow compare disease incidence between
  treatment and control groups
• I in controls - I in treated x 100
• I in controls

34
Womens Health Initiative

• Observational study
• Three clinical trials
• Hormone Replacement
• Diet Modification
• Calcium/Vitamin D

35
Sample Size
36
Questionnaire Information

• Demographic
• Medical History
• Family Medical History
• Reproductive History
• Personal Habits
• Diet/Food Intake
• Behavioral/Psychosocial

37
Clinical Measures

• Lipids and lipoproteins
• Coagulation factors
• Blood pressure
• Body weight height
• Body fat distribution
• Cognitive Status (gt 65 HRT)

38
Observational Study Goals

• Support and generalize the findings of the
  clinical trial
• Identify new risk factors patterns of risk for
  specific diseases in women

39
Observational Study Goals

• Create a resource for identification of
  biomarkers for disease
• Examine the impact of changes in individual
  characteristics on disease and total mortality

40
WHI HRT Trial

• Can HRT reduce the risk CHD?
• Can HRT reduce the risk of Fx?
• Can HRT reduce the risk of dementia?
• Does HRT increase the risk of breast Ca?

41
Why HRT Trial

• Long-term HRT?
• Effects of adding progestin?
• Observational study results may be affected by
  confounding, bias
• Need benefit/risk assessment

42
WHI DM Trial

• Does a low fat diet reduce risk of breast cancer?
• Does a low fat diet reduce the risk of heart
  disease?
• Does a high vegetable, fruit and grain diet
  reduce risk of colon cancer?
• Benefit vs. risk assessment

43
WHI Calcium/Vit D Trial

• Does supplementation of calcium vitamin D reduce
  risk of fractures?
• Does CaD reduce risk of colon cancer?
• Benefit vs. risk assessment

44
Study Timeline

• Recruitment 9/93 - 2/98
• Follow-up ends 4/05
• Data analysis 10/07