2. Contents
Definitions.
Introduction.
Evolution of PE.
Types of epidemiology.
Observational VS Experimental studies.
Purpose of descriptive PE.
PE study designs.
Drug utilization study.
Special application of PE.
Reports.
4. “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
5. “The study of drugs as
determinants of health and
disease in the general
unselected population.”
Spitzer
6. What Is Pharmacoepidemiology?
• All drugs have adverse effects. Pharmacoepidemiology
will never succeed in preventing them. It can only
detect them, hopefully early, and thereby educate
health care providers and public, which will lead to
better medication use.
7. • The net results of increased activity in
Pharmacoepidemiology will be better for industry
and Academia but most importantly, for public’s
health.
• Pharmacoepidemilogy can minimize its adverse
public health impact by detecting it early. At the
same time, it can improve the use of drugs that
have genuine role, protecting against the loss of
useful drugs.
8. Introduction
• In recent decades, modern medicine has been
blessed with a pharmaceutical armamentarium
that is much more powerful than it had before.
Although this has given health care providers the
ability to provide better medical care for their
patients, it has also resulted in the ability to do
much greater harm.
9. • It has also generated an enormous number of
product liability suits against pharmaceutical
manufacturers, some appropriate and others
inappropriate..
• In fact, the history of drug regulation parallels
the history of major adverse drug reaction
“disasters”. Each change in pharmaceutical law
was a political reaction to an epidemic of
adverse drug reactions.
10. Evolution of pharmacoepidemiology.
Recent data indicate that 100000 Americans die each
year from Adverse Drug Reactions, and 1.5 million US
hospitalizations each year result from Adverse Drug
Reactions; yet, 20-70% of Adverse Drug Reactions may
be preventable. The harm that drugs can cause has led
to the development of the field of
pharmacoepidemiology.
12. The joining of the fields of clinical pharmacology and
epidemiology has resulted in the development of a
new field:
pharmacoepidemiology, the study of the use of and
the effects of drugs in large numbers of people.
13. Types:
Epidemiology is defined as the study of the
distribution and resulting determinants of
diseases on populations.
Epidemiological studies can be divided into two
main types:
1. Observational Study
2. Intervention Study
14.
15. Observational VS Experimental studies
•Observational studies , Allow nature to take
its cause; the investigator measures but does
not intervene.
•Descriptive study: focuses on the description
of the occurrence of a disease in a
population.
•Analytical study analyses relationships
between health status and other variables.
16. Observational VS Experimental studies
•Experimental or interventional studies: involve
an active attempt to change a disease
determinant(e.g an exposure or a behaviour) or
the progress of a disaese (through treatment)
•The studies are based on a group which has had
the experience compared with control group
which has not had the experience.
17. Purpose of descriptive epidemiology
•To generate hypothesis
•To permit evaluation of trends in health &
disease and comparisons among countries and
subgroups within countries.
•To provide a basis for planning, provision and
evaluation of health services
•To identify problems to be studied by
analytical methods and to suggest areas that
may be fruitful for investigation.
18. Case studies(Case series)
•Case reports:documents unusual medical occurrence
and can represent the first clues to the formulation of
hypothesis, generally report a new or unique findings
and previous undescribed disease.
Eg; Zappacosta presented a case report of a patient
treated with minoxidil that was discovered to
stimulate the hair growth. Subsequently a topical
formulation of minoxidil was developed to take
advantage of that effect
19. Case series: collection of individual case reports
which may occur within a fairly short time, and
experience of a group of patients with similar
diagnosis.
Eg: Krishnamoorthy and king reported on the adverse
effects associated with the use of olanzapine in 5
children with severe behavioural problems.
Adverse events includes: wt. gain(3/5 children)
sedation(2/5 children) and akathisia( 2/5 children).
20. Case Series
Advantages
Useful for hypothesis generation
Informative for very rare disease with few
established risk factors
Usually of short duration.
Disadvantages
Cannot study cause and effect
relationships
Cannot assess disease frequency
21. Cross-sectional study
• It is also called epidemiologic study or prevalence
study.
• It analyses (describes)data collected on a group of
subjects at one point in time rather than over a
period of time. i.e. they survey exposure and disease
at a single point in time.
• Both exposure and outcome variables are been
evaluated at the same point in time(without any
inbuilt directionality).
• Most sophisticated descriptive study.
• It answers the question “WHAT IS HAPPENING RIGHT
NOW?”
22. Question: “what is happening?”
no direction of inquiry
subjects
With outcome
Without outcome
endonset time
23. Cross-sectional studies
• Eg: cross-sectional studies was
published by Dua and colleagues, who
examined inappropriate sale of
antibiotic use in pharmacies in Nagpur.
Such studies can identify problem areas
and suggest where remedial action
should be directed.
24. Cross-sectional studies
ADV
• Best for
determining the
status
(prevalence)
• Quick
• Relatively
inexpensive
DISADV
• Only a snapshot at
a time leading to
a misinformation
• Response rate
may be low ,with
result not
representative of
the population
25. Correlational study designs
• A study comparing incidence/prevalence of one
event against another on a global scale
• Measures that represent characteristics of entire
populations are used to describe the disease in
relation to some factor of interest (such as age,
calendar time, food consumption, drug use and
utilization of health services)
26. Correlational study designs
ADV
• Compares events
among nations.
DISADV
• Doesn’t compare
individuals, so it
might lead to
overgeneralization.
27. Analytical studies
Two basic designs:
• Case – control or retrospective study
• Cohort or prospective
• NOTE
• There must be a comparison group
• No control No conclusion(NCNC)
29. Advantages of case control
• It is relatively easy to carry out.
• It is also rapid and inexpensive.
• It requires comparatively few subjects.
• It can assist one in studying different
etiological factors.
• One does not need an ethical clearance.
• There is no risk to the subject .
30. Disadvantages of case control
• It introduces bias
• To select an appropriate control could be
difficult
• It may be difficult to distinguish between the
cause of a disease and an associated factor
31. Cohort study
• A cohort is a group of people who have something in
common and remain part of a group over an
extended time
• A group of people exposed to a suspected
etiological agent are compared with a matched
control who have not been similarly exposed.
Subject selected on the basis of exposure [a
etiological factor; cigarette smoking]
• Follow-up over a period to compare the outcome
• Also a longitudinal study or prospective study
32.
33. Advantages Of cohort study
• There is no bias
• The risk can be calculated bcos the incidence
can be calculated
• It is effective for studying rare exposures
• It allows the study of the natural history of the
disease
• It assists in determining the temporal
relationship between the etiological factor &
the disease
34. Disadvantages of cohort study
• It takes a long time
• It is expensive
• Large no of subjects are needed
• There could be changes in the standard methods
or diagnostic criteria
35. Experimental studies
• Studies in which 1 group is deliberately
subjected to an experience compared with a
control group with no similar experience
• The gold standard in medicine because it proves
causality
• Can be controlled or uncontrolled
36. Uncontrolled experimental studies
• Intervention is not compared with a control
• The aim is to confirm that the Intervention
made a difference
37. Controlled experimental studies
• In this study, a drug or procedure is
compared to:
1. Another drug
2. Procedure
3. Placebo
4. Previously accepted tx
• The aim is to prove the difference due
to tx
38. Controlled experimental studies
• Control could be:
• Blind trial-single or double
A. METHODOLOGY
1. Concurrent or parallel: randomized or non-
randomized(quasi)
2. Sequential control: self controlled or cross
over
3. External control
40. Experimental studies
ADV
• Best study type
• Greatest proove of
causality
• Gold standard for other
design
• Least bias
• Proves best tx or
procedure efficacy
DISADV
• Greatest expense
• Long duration
• Unproven facts
adopted by
community can
hinder study
acceptance
41. Drug utilization study:
• Drug utilization studies aim to evaluate factors
related to the prescribing, dispensing,
administering and taking of medication, and
its associated events (either beneficial or
adverse).
• Since the early 1960’s the interest in Drug
Utilization Studies has been increasing, first
with market-only purposes, then for evaluating
the quality of medical prescription and
comparing patterns of use of specific drugs.
42. • The increasing importance of drug utilization studies as
a valuable investigation resource in
pharmacoepidemiology has been bridging it with other
health related areas, such as public health,
pharmacovigilance, pharmacoeconomics, eco-
pharmacovigilance or pharmacogenetics.
• Drug utilization research is thus an essential part of
pharmacoepidemiology as it describes the extent,
nature and determinants of drug exposure. In common
use, the distinction between these two terms has
become less sharp, and they are sometimes used
interchangeably.
43. Drug utilization research and pharmacoepidemiology may
provide insights into the following aspects of drug use
and drug prescribing:
• Pattern of use: extent and profiles of drug use and
trends in drug use and costs over time.
• Quality of use: audits comparing actual use to national
and regional prescription guidelines or local drug
formularies. Quality indices of drug use may include the
choice of drug (compliance to recommended
assortment), drug cost (compliance to budgetary
recommendations), drug dosage (awareness of inter-
individual variations in dose requirements and age
dependence), drug interaction awareness, ADR
awareness, proportion of patients being aware
of/unaware of the cost/benefit of the treatment, etc.
44. • Determinants of use: user characteristics (e.g. socio-
demographic parameters, attitude towards drugs),
prescriber characteristics (e.g. specialty, education and
factors influencing therapeutic decisions), and drug
characteristics (e.g. therapeutic properties,
affordability)
• Outcomes of use: health outcomes (benefits and
adverse effects) and economic consequences.
45.
46. Special applications of Pharmacoepidemiology
• Studies of Drug Utilization
•Evaluating and improving physician prescribing
•Drug Utilization Review
• Special methodologic issues in PE studies of Vaccine
Study
•PE studies of Devices
• Studies of Drug induced birth defects
•PE and Risk management
•Use of PE to study Medication Errors
•Hospital PE.
47. REPORT 1-Novel anticoagulants given to 60% of
newly diagnosed AF patients.
Novel oral anticoagulants introduced since October
2010 have been adopted into clinical practice rapidly,
and within 2.5 years were prescribed for more than 60%
of patients with newly diagnosed atrial fibrillation,
according to a report published online May 20 in the
American Journal of Medicine. the new drugs are being
prescribed for a different patient population from that
indicated by the clinical trials on which Food and Drug
Administration (FDA) approval was based. Specifically,
dabigatran, rivaroxaban, and apixaban are selectively
prescribed for younger, healthier men who have high
48. incomes and reside in wealthier communities,
reported Dr. Nihar R. Desai of the division of
pharmacoepidemiology and pharmacoeconomics,
Brigham and Women’s Hospital and Harvard Medical
School, Boston, and his associates. In what they
described as the first study to evaluate real-world use
of all novel anticoagulants, researchers found that the
rapid uptake of the drugs as first-line therapy for
atrial fibrillation (AF) was accompanied by a marked
decline in the use of warfarin. The difference in total
costs between the generic warfarin and the
proprietary dabigatran, rivaroxaban, or apixaban
totaled $900 per patient during the first 6 months
alone, which "translates into billions of dollars at the
national level."
49. The researchers analyzed nationwide medical and
prescription claims data for 6,893 adults covered by
Aetna who had newly diagnosed nonvalvular AF and
were prescribed an oral anticoagulant between October
2010 and June 2013. The direct thrombin inhibitor
dabigatran was approved in October 2010, and the
factor Xa inhibitors rivaroxaban and apixaban were
approved in November 2011 and December 2012During
the study period, these patients filled 45,472
prescriptions for oral anticoagulants: 57.7% for
warfarin, 32.8% for dabigatran, 9.3% for rivaroxaban,
and 0.1% for apixaban. Within 1 year of appearing on
the market, dabigatran was equally likely to be
prescribed as warfarin was for new AF patients. Its use
as a first-line therapy..
50. REPORT 2- A case-control study design was used. A new
prescription of an antidiabetic medication was used to
identify new cases of diabetes mellitus.
Odds ratios were calculated for exposure to second-generation
antipsychotics (clozapine, risperidone, olanzapine,
quetiapine, and multiple second-generation antipsychotics)
compared with exposure to first-generation antipsychotics.
Cases and controls were identified by using a database that
contained drug prescription information from the inpatient
facilities that were operated by the New York State Office of
Mental Health. Data from January 1, 2000, to December 31,
2002, were examined. Among 13,611 unique patients who
received antipsychotics, 8,461 met entry criteria of being
hospitalized for at least 60 days and not having an
antidiabetic medication prescribed in the past. A total of 181
of these inpatients received prescriptions for an antidiabetic
51. medication at least 30 days after their admission. Eight
controls (N=1,448) for each case (N=181) were matched
by calendar year, length of observation period, race,
age group, and diagnosis, giving a total sample of 1,629
patients.
RESULTS: Statistically significant elevations in risk
were seen among patients who received more than one
second-generation antipsychotic or clozapine or
quetiapine, compared with patients who received first-
generation antipsychotics alone. Although not
statistically significant, odds ratios for olanzapine and
risperidone were also elevated.Conditional logistic
regression adjusting for gender and age did not change
the results.
52. Crude odds ratios (ORs) for receiving a new prescription
of an antidiabetic agent were calculated, and 95
percent confidence intervals (CIs) were determined
53. Conclusion:
Exposure to multiple second-generation
antipsychotics or clozapine or quetiapine
significantly increased the risk of treatment-
emergent diabetes mellitus.
54. References
1-Parthasarthi, “A Textbook Of Clinical Pharmacy
Practice”, Edition-2001, page no-466-482.
2-Edward Ralph, Santoso Budiono, J.Van Boxtel Chris,
“Drugs Benefits And Risks:International Textbook of Clinical
Pharmacology” Edition-2008, publishers-John Wiley & sons,
LTD.
3-Koller E, Schneider B, Bennett K, et al: Clozapine-
associated diabetes. American Journal of
Medicine 111:716—723, 2001
4-http://ps.psychiatryonline.org/article.aspx?articleid=89028
