Pharmacoepidemiology

Pharmacoepidemiology
Terminology
Endemic
disease that is usually present in a community (Bilharziasis).

Epidemic
An increase — often sudden — in the number of cases of a disease above what is
normally expected in that population in a specific area e.g Malaria.

Pandemic
An epidemic that has spread over several countries or continents and affects many
people e.g COVID -19 Pandemic.

Epidemiology
Science that studies the pattern, causes & effects of health and disease in defined
population and studies the distribution, determinants of disease in population.

Pharmacoepidemiology
• Study of the use and effects of drugs in well-defined large number of
populations.
• Pharmacoepidemiology is the bridge between Pharmacology and
Epidemiology

Correlation
Also known as Association: there is a relationship, or pattern, between two
different variables, but it does not imply relationship between them, or one causes
the other. The correlation between unrelated variables can occur by chance

Causation
implies that there being a relationship between two events, one event causes
another event to occur.

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Reverse causality means that there is a causative relationship between events A

and B, but not in the order that you would expect – the cause and effect are
reversed.
For example, if we observe that the faster the windmill rotates, the more wind there
is, we might falsely conclude that the windmills rotating causes the wind. However,
we know that it is the wind that causes the windmills to rotate.
Reverse causality means that there is a causative relationship between events A and
B, but not in the order that you would expect – the cause and effect are reversed.
High body mass index (BMI) are more likely to be depressed when, in actuality, they
find that depression leads to a high BMI.

Confounding
Variable that can influence the outcome independently of the intervention under
investigation. In a study, confounding occurs when the effect of an intervention on
an outcome is distorted because of an association between the population or
intervention or outcome and another factor.
Example
• A study of heart disease may look at a group of people who exercise regularly
and a group who do not exercise. If the ages of the people in the 2 groups are
different, then any difference in heart disease rates between the 2 groups could
be because of age rather than exercise. Therefore, age is a confounding factor.

Heterogeneity
Combining the results of several studies is not appropriate if the studies differ in
clinically important ways, such as the intervention, outcome, controls, blinding, and
so on. It is also inappropriate to combine the findings if the results of the individual
studies differ widely. Even if the methods used in the studies appear to be similar,
the fact that the results vary markedly suggests that something important was
different in the individual studies. This variability in the findings of the individual
studies is called heterogeneity (and the study findings are said to be heterogeneous);
if there is little variability, the study findings are said to be homogeneous

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Pharmacoepidemiology Scope:
Pharmacoepidemiology is the application of epidemiological principles and methods
to the study of drug effects in human populations. Its goals are to characterize,
control and predict the effects and uses of pharmacological treatment regimens in a
defined population. Pharmacoepidemiology is also concerned with the economic
impact and health benefits of unintended drug effects.

Major area of Epidemiological study include:

Disease etiology
Transmission
Diseases screening
Comparison of treatment effects (Clinical Trials)

Epidemiologists rely on other scientific disciplines :

• Biology: to understand disease processes
• Statistics: to make efficient use of data and draw appropriate conclusion
• Social Science: to understand causes of disease better

Epidemiological study is CORNER STONE of public health, inform policy decision

by identifying risk factors for disease and targets preventive health care. And the
principal role of epidemiology is to describe and explain differences in the
distribution of disease or other health outcomes between populations.
Health outcomes measured in Pharmacoepidemiologic studies include:
Morbidity, Mortality, Infectious disease incidence, Birth defects, Disability,
Injuries, Vaccine efficacy and Utilization of hospital services.

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History of Pharmacoepidemiology
John Snow : father of epidemiology
In the mid-1800s, an anaesthesiologist named John Snow was conducting a series of
investigations in London that warrant his being considered the “father of field
epidemiology.” Twenty years before the development of the microscope, Snow
conducted studies of cholera outbreaks both to discover the cause of disease and to
prevent its recurrence. Because his work illustrates the classic sequence from
descriptive epidemiology to hypothesis generation to hypothesis testing (analytic
epidemiology) to application, two of his investigations will be described in detail.
Snow’s meticulous mapping of the disease in London and creative use of figures to
show how cholera is transmitted.
Snow generate hypothesis: that cholera is a specific disease spread by water
contaminated by faeces. At the time it was generally thought to be a nonspecific
fever transmitted through air.
To confirm that the Broad Street pump was the source of the epidemic, Snow
gathered information on where persons with cholera had obtained their water.
Consumption of water from the Broad Street pump was the one common factor
among the cholera patients. After Snow presented his findings to public officials, the
handle of the pump was removed, and the outbreak ended. The site of the pump is
now marked by a plaque mounted on the wall outside of the appropriately named
John Snow Pub.
Snow used government death-registration data (600) and house-to-house enquiries
to map the victims' residences, showing their proximity to the pump. The second
study involved 300,000 people, from all occupations, social standing, ages and
genders. Getting the relative death rates from cholera for each company was not
easy. Snow found that householders drawing water from the Southwark and
Vauxhall company were many times more likely to die from cholera.

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Studies of Pharmacoepidemiology
• The descriptive Epidemiology (describe disease, exposure, incidence,
prevalence) observes phenomena retrospectively, prospectively.
• The analytic Epidemiology (comparative ) approach investigates associations
between occurrence of effects/outcome and exposure to one (or more) drug.
May be observational or experimental.

Systematic reviews
Systematic reviews identify completed studies that address a research question, and
evaluate the results of these studies to arrive at conclusions about a research.
Systematic reviews use a well-defined and uniform approach to identify all relevant
studies, display the results of appropriate studies, and, calculate a summary estimate
of the overall results. The statistical aspects of a systematic review (calculating
summary effect estimates, statistical tests of heterogeneity, and statistical estimates
of publication bias) are called meta-analysis. A systematic review can be a good
opportunity for a new investigator. Although it takes a surprising amount of time
and effort, a systematic review generally does not require substantial financial or
other resources.
Systematic review findings can be particularly useful for developing practice
guidelines. The Research Question As with any research, a good systematic review
has a well-formulated, clear research question that meets the usual FINER criteria.
Feasibility depends largely on the existence of a set of studies of the question. The
research question should describe the disease or condition of interest, the population
and setting, the intervention and comparison treatment (for trials), and the outcomes
of interest.
Systematic reviews generally include three types of information. First, important
characteristics of each study included in the systematic review are presented in
tables. These often include the study sample size, number of outcomes, length of
follow-up, characteristics of the population studied, and methods used in the study.
Second, the review displays the results of the individual studies (risk estimates,
confidence intervals or P values) in a table or figure.

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Finally, in the absence of significant heterogeneity. The characteristics and findings

of individual studies included in the systematic review should be displayed clearly
in tables and figures so that the reader can form opinions that do not depend solely
on the statistical summary estimates.

Meta-Analysis: Statistics for Systematic Reviews

The term meta-analysis to describe “the statistical analysis of a large collection of
results from individual literature for the purpose of integrating their respective
findings
Meta-analysis has evolved as a technique useful for summarizing a large number of
clinical trials and for resolving discrepancies raised by these trials. There are many
similarities between randomized controlled trials and meta-analyses. Both
randomized trials and meta-analyses are designed to answer a scientifically valid
question. Likewise, both techniques require that the patients or studies included, the
data collected, and the analysis performed be prospectively planned, and that the
results obtained be analyzed for factors that may potentially interact with treatment
effect. Finally, both techniques deal with populations, not with single individuals.
Thus, clinicians must use discretion when applying the conclusions derived from
both these techniques to the individual patient.

Techniques Of Meta-Analysis The steps involved in performing a meta-

analysis are formulating the question; identifying pertinent studies; assessing the
characteristics and quality of these studies for inclusion or exclusion; and extracting,
analyzing, and reporting the data.
1. Formulating the Question As with clinical research in general, the first step in a
meta-analysis is to formulate the question for study and determine that it can be
approached by this technique. The validity and importance of the meta-analysis are
contingent on this first step. A poorly conceived research hypothesis will usually
lead to a meta-analysis of dubious value.

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2. Identifying Studies for Meta-Analysis Analogous to subject selection in patient-

oriented research, the protocols for study inclusion in systematic, and explicit.
Identification of published studies usually begins with a search of personal reference
files and electronic and online databases such as MEDLINE, Current Contents,
Best Evidence, Cochrane, and Health STAR.
3. Defining Eligibility Criteria and Data Abstraction Meta-analyses of experimental
studies ideally include randomized controlled trials that are similar in nature and in
which the diagnosis, outcome, patient characteristics, and treatment groups are
defined.
4.Data Analysis To compare studies.
5. Complete Enrolment of Studies In designing a clinical study, the number of
patients who must be enrolled to address the question of interest with the desired
degree of statistical certainty and power is established a priori. That is, after
enrollment is completed and the study is analyzed, it is not acceptable to simply
enroll additional patients and re-analyze the data. Likewise, once a set of studies is
identified, the data are abstracted, and a meta-analysis is performed, it is not
appropriate to alter a priori established inclusion criteria. However, if a sufficient
number of studies addressing the same question are subsequently published
following the completion of a meta-analysis, an argument can be made to include
these studies in a separate analysis to determine if the previous conclusions are
supported

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Evidence Based Medicine

Evidence-based medicine is the system of practicing medicine in such a way that it

results in improving outcomes and reduces the overall healthcare cost. Evidence-
based medicine also takes care of the individual preference of the patients, along
with the clinical expertise of the clinicians.
Evidence-based medicine is the multidisciplinary approach to provide the best care
to the patient at the right time, involves the use of the experience of the clinician and
the updated evidence available to make the best decision related to the treatment
regimen.
Before evidence-based medicine, medical decisions were made based on individual
clinician’s experience or the marketing strategies of pharmaceutical companies.
Many clinicians disagreed with this approach and advocate for the practice, which
is backed up by the latest medical knowledge.
Evidence-based medicine is the Integration of Best Research Evidence with
clinical expertise and patient value.
5 main steps for applying EBM to clinical practice: (5 As)
• Ask: Defining a clinically relevant question
• Acquire: Searching for the best evidence
• Appraising the evidence, is there a clinical significance
• Applying the evidence
• Analyze: Evaluating the performance of EBM

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EBM starts with a clinical question. The clinical question is an issue which the
health-care provider addresses with the patient. After the clinical question is
formulated, relevant scientific evidence is sought, which relates to the clinical
question. Scientific evidence includes study outcomes and opinions. Not all data has
the same strength. Recommendations from an expert are not as robust as the results
of a well-conducted study, which is not as good as the results of a set of well-
conducted studies. Thus in evidence-based medicine, the levels of evidence or data
should be graded according to their relative strength. Stronger evidence should be
given more weight when making clinical decisions.
The evidence is commonly stratified into six different levels:
• Level I: evidence obtained from a meta-analysis of multiple, well-conducted,
and well-designed randomized trials. Randomized trials provide some of the
strongest clinical evidence, and if these are repeated and the results combined
in a meta-analysis, then the overall results are assumed to be even stronger.

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• Level II: evidence obtained from a single well-conducted and well-designed

randomized controlled trial. The randomized controlled study, when well-
designed and well-conducted, is a gold standard for clinical medicine.
• Level III: evidence from at least one well-designed and executed non-
randomized controlled study. When randomization does not occur, there may
be more bias introduced into the study.
• Level IV: evidence from at least one well-designed case-control
or cohort study. Not all clinical questions can be effectively or ethically
studied with a randomized controlled study.
• Level V: evidence from at least one non-experimental study. Typically level
III evidence would include case series as well as not well-designed case-
control or cohort studies.
• Level VI: expert opinions from respected authorities on the subject based on
their clinical experience.

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Importance in Research and Practice

Evidence-based medicine is positively affecting all the important aspects of
healthcare, which include patient care, patient’s health, and the related cost. This
system of medicine has its importance in research and practice in the following
manner:
Updated information to the clinicians: Evidence-based medicine requires the
clinicians to read the information and latest research articles related to their
therapeutic area. This helps the clinicians to remain updated with the latest evidences
for treating patients.
Data for making treatment decisions: Because of the advancements in technology,
and the availability of user-friendly databases, the clinicians now have access to the
research data and knowledge. This helps clinicians to make informed decisions for
better patient care.

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Enhance the quality of overall care: Through the best-quality articles, the
clinicians have the data and procedures for caring for the patients. The data is
reviewed by experts in the healthcare domain. This improves the overall quality of
patient care.
Make the healthcare system more accountable and transparent: Patients and
their relatives, many times, have concerns about the treatment strategy of the doctor.
Evidence-based medicine makes clinicians more accountable and helps in improving
transparency in the healthcare system.
Improves outcomes: It is one of the best effects of evidence-based medicine. A lot
of data is available that indicates that if evidence-based medicine is applied logically,
it will help in improving the overall healthcare outcomes.

Advantages of EBM
• EBM allows clinicians and patients access to the most recent clinical
knowledge
• EBM can be learnt by people from different backgrounds and at any stage in
their careers.
• It can help providers make better use of limited resources by enabling them to
evaluate clinical- and cost-effectiveness of treatments and services

Disadvantages of EBM
• EMB takes time to both learn and practice
• Some electronic databases are not comprehensive and are not always well
indexed
• EBM can be adversely affected by publication bias, or by a lack of evidence
• EBM is not a drive towards formulaic medicine. A clinician should listen to
the patient, use their own clinical judgement, and be mindful of the best
available evidence, so that the optimum management plan is identified for that
patient.

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