PHYSICIANS' HEALTH STUDY

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PHYSICIANS' HEALTH STUDY

• A randomized, double-blind, placebo controlled
  trial designed to test the effects of low-dose
  aspirin and beta-carotene in the primary
  prevention of CVD and cancer among 22,071 US male
  physicians, aged 40 to 84 at baseline in 1982.
  Baseline blood specimens were collected and
  frozen for later analyses from 14,916
  participants.
• Using a 2x2 factorial design
• 325 mg of aspirin (Bufferin, supplied by
  Bristol-Myers Products on alternate days)
• 50 mg of beta-carotene (Lurotin, supplied by
  BASF AG on alternate days)

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PHYSICIANS' HEALTH STUDY

• Randomized aspirin component terminated early,on
  1/25/88
• Randomized beta carotene component ended, as
  scheduled, on 12/21/95
• After an average duration of beta carotene
  treatment and follow-up of 12 years
• Fewer than 1 of participants were lost to
  morbidity and mortality follow-up
• Compliance with pill-taking was gt 80

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Rationale for Choosing Physicians

• Ability to give true informed consent
• Knowledge of possible side effects
• Accuracy and completeness of information
• Ease of follow-up
• Opportunity to conduct trial by mail

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Exclusion Criteria
PHYSICIANS' HEALTH STUDY

• Personal history of
• Myocardial infarction
• Stroke or TIA
• Cancer (except nonmelanoma skin cancer)
• Current liver or kidney disease
• Peptic ulcer or gout
• Contraindication to aspirin use
• Current use of aspirin or other drugs affecting
  platelet function
• Current use of vitamin A or beta-carotene
  supplement

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PHYSICIANS' HEALTH STUDY
Primary Endpoints
Total cancer Prostate cancer Cardiovascular
disease Eye disease ä Cataract ä
Macular degeneration
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PHYSICIANS HEALTH STUDY
Population Hierarchy
261,248 U.S. male MDs, aged 40-84 112,528 respond
ents to questionnaires 59,285 willing to
participate
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PHYSICIANS HEALTH STUDY
Run-in Phase
33,223 willing and eligible MDs enrolled in
run-in (18 weeks on active aspirin
and beta-carotene placebo) 22,071 randomized
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PHYSICIANS' HEALTH STUDY
Randomization Scheme
22,071 Randomized
11,037 Aspirin
11,037 Aspirin placebo
5,517 Beta-carotene
5,520 Beta-caroteneplacebo
5,519 Beta-carotene
5,515 Beta-caroteneplacebo
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PHYSICIANS' HEALTH STUDY I
Baseline Characteristics
Assignment ASA BC ASA PL PL BC PL PL (n
5,517) (n 5,520) (n 5,519) (n 5,515)
Demographic Mean age (years) 53.29.5 53.39.6
53.29.5 53.29.5 Geographic region
Northeast 27.8 27.9 27.3 28.8 Midwest
22.4 21.9 22.1 20.3 South or Southwest
26.8 26.1 27.0 27.9 Mountain or Far
West 22.0 23.3 22.8 22.1 Other
1.0 0.9 0.7 0.9
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PHYSICIANS' HEALTH STUDY I
Baseline Characteristics
Assignment ASA BC ASA PL PL BC PL
PL Medical history Reported hypertension
11.8 11.8 12.4 11.5 Mean systolic
BP 126.011.9 126.312.1 126.111.7 126.111.7 Me
an diastolic BP 78.87.6 78.97.5 78.97.5
78.77.5 High cholesterol 7.9 7.5
8.0 8.0 Mean cholesterol
mg/dl) 211.743.9 212.345.0 212.746.5 211.444.8
Diabetes mellitus 2.1 2.5 2.2
2.2 Mean BMI 24.93.1 24.93.0 24.93.0
24.93.0 Overweight 13.5 14.0 13.6
13.6 History of angina pectoris 1.2
1.4 1.1 1.2 Parental history of Ml
12.7 13.3 12.7 13.6
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PHYSICIANS' HEALTH STUDY I
Baseline Characteristics
Assignment ASA BC ASA PL PL BC PL
PL Health habits Cigarette smoking Never
49.8 48.8 49.6 50.1 Past only
39.3 40.1 39.1 39.0 Current
10.9 11.1 11.4 10.9 Mean
cigarettes/day 21.713.0 22.112.9 22.413.7 22.8
13.5 lt15 (of current smokers) 28.8
27.4 27.3 24.6 15-24 (of current
smokers) 32.5 33.7 34.7
35.4 25 (of current smokers) 38.7
38.8 37.9 40.0 Current cigar smoking
4.7 4.2 4.3 4.3 Current
pipe smoking 8.8 7.7 8.2
8.0
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PHYSICIANS' HEALTH STUDY I
Baseline Characteristics
Assignment ASA BC ASA PL PL BC PL
PL Health habits Alcohol use Mean
drinks/week 3.53.2 3.53.2 3.53.2 3.53.3
Daily 24.8 24.9 24.7 25.2 Rarely
or never 14.8 14.6 14.7 15.4 Exercise
frequency Mean times/month 10.28.5 9.88.3 10.
08.6 10.08.6 Rarely or never 12.8
14.2 14.0 13.5