The fenoterol story Pharmacoepidemiology Jean-François Boivin 5 November

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Lancet – 29 April 1989 – Pages

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 A B MILD ASTHMA ALL PATIENTS Death SEVERE ASTHMA Death Death RR = 0.5 RR =

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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

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NEJM 1992; 326:

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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 x 10 prescriptionsalive 20

x 10 prescriptions of asthma drugs x death x x 10 prescriptionsalive 20 1 year10 years 1 year10 years

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

x 10 prescriptions of asthma drugs x death x x 10 prescriptionsalive 22 1 year10 years 1 year10 years

x 10 prescriptions of asthma drugs x death x x 10 prescriptions 22 1 year10 years 1 year10 years deathallergy treatment x 2 years

x 10 prescriptions of asthma drugs x death x x 10 prescriptions 22 1 year10 years 1 year8 years deathallergy treatment x 2 years

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, JAMA. 2001;285:

Polio vaccine: Cutter incident Wyeth 26

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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:

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N Engl J Med 2004; 351:

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