The fenoterol story Pharmacoepidemiology JeanFranois Boivin 5 November

The fenoterol story Pharmacoepidemiology Jean-François Boivin 5 November 2010 1

2

3

4

5

6

7

8

9 Lancet – 29 April 1989 – Pages 917 - 922

Source of cases New Zealand National Asthma Mortality Survey 5 – 45 years old Source of controls Hospitalized asthma patients 10

Sources of data, asthma treatment Cases: General practioner questionnaires completed for the National Asthma Mortality Survey Controls: Hospital record notes 11

TABLE 4 A cohort study Drug SEVERE ASTHMA B + 200 4 - 800 6 1000 10 + Death A 2 4 - 98 96 100 RR = 0. 5 MILD ASTHMA Death RR = 0. 5 ALL PATIENTS + Death 202 8 - 898 102 1100 110 RR = 2. 5 12

13

Source of cases Death from asthma – National Health Statistics Centre Hospitalized in 12 months before death Source of controls Hospitalized for asthma 14

Source of data, asthma treatment Medical record notes 15

16

17 NEJM 1992; 326: 501 -506

18

Saskatchewan data bases Saskatchewan Drug Plan Deaths Hospital discharge diagnoses Procedure codes ( e. g. : intubation) Doctor billing codes Use of health services • • Hospitalizations Doctor visits 19

x 10 prescriptions of asthma drugs x death • death certificates • coroner’s reports • autopsy reports • hospital discharge summaries x 10 prescriptions x alive 20

1 year 10 years x x 10 prescriptions of asthma drugs 1 year x 10 prescriptions death 10 years x alive 20

Death rate in study cohort? 1 death 22 person – years ? 1 death 20 person –years ? 21

1 year 10 years x x 10 prescriptions of asthma drugs 1 year x 10 prescriptions death 10 years x alive 22

1 year 10 years x 10 prescriptions of asthma drugs 2 years 10 years x x 10 prescriptions allergy treatment x death 1 year x death 22

1 year 10 years x 10 prescriptions of asthma drugs 2 years 8 years x x 10 prescriptions allergy treatment x death 1 year x death 22

Death rate, allergy treatment 1 death 8 person – years ? 1 death 10 person – years ? 1 death 11 person – years ? 23

Pharmaco-surveillance: Vaccines 24

Example: Time-trend studies Time Trends in Autism and in MMR Immunization Coverage in California Percentage of Children Receiving Measles-Mumps-Rubella (MMR) Immunization in Second Year of Life and Caseload of Children With Autism, by Year of Birth, California, 1980 -1994 JAMA. 2001; 285: 1183 -1185 25

Polio vaccine: Cutter incident Wyeth 26

27

28

29

30

31

32

33

34

35

36

38

39

Questions that can be studied with a case crossover design (Rothman 2002, page 89) Exposure varies from time to time • coffee • exercise One cannot study • blood group • low weight at birth 40

Case cross-over studies Exposure triggers a short-term effect • asthma • sudden death One cannot study • lung cancer • osteoporosis 41

Case cross-over studies Disease must have abrupt onset • allergic reaction • myocardial infarction • car accident One cannot study • multiple sclerosis • hypercholesterolemia 42

Case cross-over studies Effect of exposure must be brief • • • anxiety in traffic distraction on cell phone panic during earthquake One cannot study • • sedentarity personality disorder 43

N Engl J Med 2000; 343: 1355 -61 44

45

N Engl J Med 2004; 351: 1721 -30 46

N Engl J Med 1997; 336: 453 -8 47