Pharmacoepidemiology: Goals and Methods Sean Hennessy, PharmD, PhD Assistant Professor of...
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Transcript of Pharmacoepidemiology: Goals and Methods Sean Hennessy, PharmD, PhD Assistant Professor of...
Pharmacoepidemiology: Goals and Methods
Sean Hennessy, PharmD, PhDAssistant Professor of Epidemiology & Pharmacology
Center for Clinical Epidemiology and BiostatisticsUniversity of Pennsylvania School of Medicine
CCEB
“The study of the use and effects of medications in large numbers of people”
Strom
“The application of epidemiologic knowledge, methods, and reasoning to the study of the effects (beneficial and adverse) and use of drugs in human populations.”
Porta and Hartzema
“The study of drugs as determinants of health and disease in the general unselected population.”
Spitzer
Pharmacoepidemiology
Clinical pharmacology
Epidemiology
Strom
Pharmacoepidemiology
Pharmacology
Epidemiology
Therapeutics
Statistics
Spitzer
Health servicesresearch
Clin
ical
ep
idem
iolo
gy
Health economicsOutcomes
research
Pharmaco-Epidemiology
EpidemiologyEconomics
Conceptualization by Harry Guess
Animal studies
Phase 1
Phase 2
Phase 3
Drug approval
Phase 4
Human subjects
•Human subjects
•Not always required
Pre-marketing
Post-marketing
Pre-de-marketing
Limitations of Pre-marketing Trials-1
• Carefully selected subjects may not reflect real-life patients in whom drug will be used
• Study subjects may receive better care than real-life patients
• Short duration of treatment
• Study size–Studies with 3000 patients cannot
reliably detect adverse events with an incidence of < 1 per 1000, even if severe
–Studies with 500 patients cannot reliably detect adverse events with an incidence of < 1 per 166, even if severe
Limitations of pre-marketing trials-2
• About 20% of drugs get new “black box” warnings after marketing
• About 4% of drugs are ultimately withdrawn for safety reasons
Consequences of Limitations of Pre-marketing Trials
Case report
Case series
Ecologic
Descriptive
Cohort
Case-control
Non-experimental
RCT
Experim ental
Analytic
Epidemiologic study designs
Hypothesis generating
Hypothesis strengthening
Hypothesis testing
Case Reports & Case SeriesCerivastatin (Baycol), an effective and inexpensive lipid lowering drug, was introduced in 1997. It was removed from the market in 2001 because of reports of fatal cases muscle breakdown (rhabdomyolysis).
Ecologic studies
Obtain group-level exposure information and disease prevalence at the same point in time.
Ecologic Studies: Breast Cancer Incidence
by National Fat Intake
0
50
100
150
200
250
500 700 900 1100 1300 1500 1700
Fat intake (kcal/d)
Inc
ide
nc
e p
er
10
0,0
00
p-y
Japan
RomaniaYugoslavia
Hong Kong
IsraelItaly
HungaryPoland
Spain
SwedenUK
N ZealandFrance
SwitzerlandUSA
Case report
Case series
Ecologic
Descriptive
Cohort
Case-control
Non-experimental
RCT
Experim ental
Analytic
Epidemiologic study designs
Randomized Trial
Random process
Treated
Untreated
Observation Period
= Study outcome
Study population
Rate Ratio = Events / person-time in exposed Events / person-time in unexposed
Cohort study
Non-Random process
Treated
Untreated
Observation Period
= Study outcome
Study population
Rate Ratio = Events / person-time in exposed Events / person-time in unexposed
A RCT is just a special case of a cohort study
Case-control study*
Non-Random process
Treated
Untreated
Observation Period
= Study outcome
Study population
Controls sampled
(*using “risk-set sampling”)
Cohort vs. Case-Control• Advantages of cohort studies
-Can calculate incidence
-Can directly calculate relative risk
-Less measurement error?
-Can study multiple outcomes of single exposure
• Advantages of case-control studies
-Need exposure and confounder info on fewer subjects
-Often quicker, less expensive
-Can study multiple causes of a single disease
Data sources• Spontaneous reporting systems
• Ad-hoc studies
• Health Care data– Medicaid
– General Practice Research Database
– Tayside Medicines Monitoring Unit
– Group Health Cooperative of Puget Sound
– United Health
– Etc.