KSMU

Department of clinical pharmacology

“Evidence-based medicine”

Lecturer, associate Professor Yulia Luneva

The concept of “evidence-based medicine”
was proposed by Canadian scientists in
Toronto in 1990.

Evidence Based Medicine -

conscientious, accurate and meaningful
use of the best results of clinical trials for
the choice of treatment for a particular
patient.
(D. Sackett et al.)
 Different types of clinical trials
Treatment trials test new medicines, treatments or therapies for a
disease or health condition.
Prevention trials look for new and improved ways to prevent a
disease or a health condition. Prevention trials may involve testing
out medicines, vitamins, vaccines or lifestyle changes.
Diagnostic or screening trials study the best ways to diagnose or
detect a disease or health condition.
Quality of life trials study how the side effects of a treatment (like
dialysis) affect the patient’s well-being and daily functions.
Genetic trials look at how genes (DNA) are related to certain
diseases or health conditions.
Epidemiological (ep′i·de′mi·o·log′i·cal) trials look for patterns of
certain diseases or health conditions across groups of people (for
example: people of certain races/ethnicities may have a disease more
than others).
Study types in health science
1) CLINICAL TRIAL:
Carefully and ethically-designed experiment, in which
participating subjects are assigned to the different modes of
intervention simultaneously (in the same period of time), at
random and are also supervised in a simultaneous way.
Random distribution is the best method for determining that the
groups formed are comparable in all the prognostic
characteristics except in the intervention they receive.
The clinical trial is the most rigorous epidemiological method for
testing hypotheses.
2) OPEN CLINICAL TRIAL:
Confusing term, used to indicate that a clinical trial does not have
any specific methodological characteristic.
An open clinical trial is a clinical trial without a control group, as
opposed to a controlled clinical trial.
It can also be a non-blinded clinical trial, as opposed to a single-blind
or double-blind clinical trial.
3) SINGLE-BLIND CLINICAL TRIAL:
Trial in which the subject, but not the observer, does not know which
of the possible treatments he is receiving.
4) DOUBLE-BLIND CLINICAL TRIAL:
Trial in which neither the subject nor the observer know which
treatment is being administered.
5) TRIPLE-BLIND CLINICAL TRIAL:
Clinical trial in which the participating subject, the observer-
researcher and the researcher who analyzes the data do not know
which treatment is being received.
This is done when the clinical variables examined are soft, that is,
they can be interpreted in different ways.
9) UNICENTER CLINICAL TRIAL:
A trial carried out by a single researcher or research team in one
hospital or another type of centre.
10) MULTICENTER CLINICAL TRIAL:
According to Royal Decree 561/1993, “A trial carried out in two or
more centres with the same protocol and a coordinator who is
responsible for processing all the data and for analysing the results”.
11) PARALLEL CLINICAL TRIAL:
Clinical trial in which each group of patients receives a single
treatment simultaneously.
 CLASSIFICATION OF THE TYPES OF DESIGN:
a) Cross-sectional descriptive studies
• Prevalence studies.
• Series of cross-sectional cases.
• Evaluation of diagnostic tests
• Concordance studies.
• Case-crossover studies.
b) Longitudinal descriptive studies:
• Incidence studies
• Description of the effects of a non-deliberate intervention
• Natural history description.
c) Observational analytical studies:
• Cause-effect sequence: cohort studies.
• Effect-cause sequence: case-control studies.
d) Experimental analytical studies:
• Controlled trials.
• Uncontrolled trials:
15) PILOT STUDY:
Initial application, on a small scale, of a study protocol, with the
aim of checking whether the design is appropriate, establishing its
viability or obtaining information to determine the sample size for
the definitive study.
16) DESCRIPTIVE STUDY:
Part of statistics which summaries the information about the
sample.
The information collected and summarized in statistics is used to
estimate population parameters.
Study designed solely for describing the distribution of certain
variables, but which is not concerned about the associations
between them.
It generally has a cross-sectional design.
17) OBSERVATIONAL STUDY:
Analytical epidemiological study in which the researcher does not determine the
allocation of the subjects to each group, but simply records (observes) what
actually happens.
It can be a cohort, case-control or cross-sectional study.
a) OBSERVATIONAL DESCRIPTIVE STUDY:
This is carried out when little is known about the occurrence, natural history or
determinants of a disease.
Its objectives include estimating the frequency of a disease or attribute, the
temporal trend in a particular population and elaborating or generating more
specific etiological hypotheses.
b) OBSERVATIONAL ANALYTICAL STUDY:
An analytical (etiological) study is carried out when enough information is known
about the disease before the research, which means that a priori hypotheses already
exist and these can be tested in the study.
The objectives usually involve identifying risk factors for the disease, estimating
the effect of exposure on the disease and therefore deducing possible strategic
interventions.
Sub-types: cohort studies, and case-controls studies.
18) EXPERIMENTAL STUDY:
In epidemiology, controlled clinical trial or community trial with
random distribution.
The researcher manipulates the research conditions and randomly
distributes the groups.
The objective of experimental studies is to estimate the efficacy of a
preventive, curative or rehabilitative intervention.
The groups which are compared are similar in those characteristics
which may have an effect on the response, except for the intervention
which is being assessed.
The study groups are formed randomly.
The use of another active treatment or intervention as a comparative
group is to examine the benefit/risk relation of the new treatment in a
specific clinical situation.
The control group may be:
Untreated and its evolution monitored.
Treated by other means and its evolution compared with another
intervention.
19) CROSS-SECTIONAL STUDIES:
These are studies in which the data of each subject represents essentially a moment
of time.
This data may correspond to the presence, absence or different degrees of a
characteristic or disease.
It consists of examining the relationship between different variables in a defined
population at a specific moment in time.
These designs do not permit the study of an alleged cause-effect relationship.
Cross-sectional studies are descriptive by definition.
Epidemiological strategy in which observations of numerous factors at the same
time are recorded and then a comparison is made between them.
The presence or absence of a disease or other variables (or, if they are quantitative,
their level) are determined in each subject.
The analysis of the results can be made in two senses: by comparing all the
variables in the individuals who suffer from the disease being studied, comparing
them with those who do not suffer from it, or by comparing the prevalence of the
disease in different subgroups of the population.
20) LONGITUDINAL STUDIES:
These are studies in which there is a time lapse between the different
variables, so that a time sequence can be established between them.
They can be both descriptive and analytical.
In analytical studies, it should be taken into account whether the time
sequence is from the cause to the outcome (experimental studies and
cohort studies), or from the outcome to the cause (case-control
studies).
Any study not focused on an alleged cause-effect relationship, but
whose data is used for purely descriptive purposes is considered
descriptive.
This type of study is useful for generating etiological hypotheses
which should subsequently be contrasted with analytical studies.
Any study which evaluates an alleged cause-effect relationship is
considered analytical.
The alleged causal agent may be a factor which is suspected of being
able to lead etiologically to a disease or a treatment to prevent or
improve a clinical situation.
23) ANALYTICAL STUDY:
Study designed to examine associations, with the final object
usually of identifying or measuring the effects of risk factors or
specific interventions on health.
Analytical studies can be controlled clinical trials, cohort
studies, case-control studies or cross-sectional studies.
24) PROSPECTIVE STUDY:
Study in which the patients are included from the time the start
of the study is decided.
25) RETROSPECTIVE STUDY:
Study in which the data collected refers to events which have
occurred.
26) CASE-CONTROL STUDY:
This type of study identifies people with a disease (or another variable of interest)
and compares them with an appropriate control group which does not have the
disease.
An examination is made, comparing the frequency of exposure to this or other
factors between the cases and the controls.
It is an analytical observational study which enables the cause-effect relationship to
be followed.
If the frequency of exposure or the cause is greater in the group of cases with the
disease than in the control group, we can say that there is an association between the
cause and effect.
The measurement of the association which quantifies this association is called the
“odds ratio“(OR).
In medicine, a case-control study is a cross-sectional type of study which is used to
research the etiology of a disease or a given result.
Study in which people with a certain disease or symptom (cases) are compared with
others who do not present the disease or symptom under study (controls), with
regard to prior exposure to risk factors.
27) COHORT STUDY:
In the Roman militia, a centuria was made up of 60 soldiers.
Two centurias formed a manipulo. The manipulos could be made up
of hastate (young, less experienced soldiers, spear throwers or those
with swords or light weapons), principes (soldiers with several years
of service and several campaigns) or triarii (veterans).
At camps and during marches, they formed cohorts, made up of one
manipulo of hastatis, one manipulo of principes and one centuria of
triarii, that is, a total of 300 soldiers.
Epidemiology adopted this term to refer to the idea of a simultaneous
advancement, in time, of a group of individuals defined for possessing
a common characteristic or group of characteristics.
The common characteristic is usually exposure to a factor
(environmental, pharmacological, occupational, etc).
The term “cohort” is used to designate a group of subjects with a
common characteristic or group of characteristics who are monitored
over a period of time.
Phases of clinical trials: when clinical research is used to evaluate medications
and devices
Clinical trials are a kind of clinical research designed to evaluate and test new
interventions such as psychotherapy or medications. Clinical trials are often
conducted in four phases. The trials at each phase have a different purpose and help
scientists answer different questions.
Phase I trials
Researchers test an experimental drug or treatment in a small group of people for the
first time. The researchers evaluate the treatment’s safety, determine a safe dosage
range, and identify side effects.
Phase II trials
The experimental drug or treatment is given to a larger group of people to see if it is
effective and to further evaluate its safety.
Phase III trials
The experimental study drug or treatment is given to large groups of people.
Researchers confirm its effectiveness, monitor side effects, compare it to commonly
used treatments, and collect information that will allow the experimental drug or
treatment to be used safely.
Phase IV trials
Post-marketing studies, which are conducted after a treatment is approved for use by
the FDA, provide additional information including the treatment or drug’s risks,
benefits, and best use.
Guideline Recommendation and Evidence Grading (GREG)
In an attempt to improve the way recommendations and evidence
statements are graded, the GREG grading system has been used:
Evidence grade:
I (High): the described effect is plausible, precisely quantified and
not vulnerable to bias.
II (Intermediate): the described effect is plausible but is not
quantified precisely or may be vulnerable to bias.
III (Low): concerns about plausibility or vulnerability to bias
severely limit the value of the effect being described and
quantified.
Recommendation grade:
A (Recommendation): there is robust evidence to recommend a
pattern of care.
B (Provisional recommendation): on balance of evidence, a
pattern of care is recommended with caution.
C (Consensus opinion): evidence being inadequate, a pattern of
care is recommended by consensus.
Inappropriate use of medicines wastes resources and seriously
undermines the quality of patient care. A drug and therapeutics
committee (DTC) can significantly improve drug use and reduce
costs in hospitals and other health care facilities in the following
ways:
•providing advice on all aspects of drug management
•developing drug policies
•evaluating and selecting drugs for the formulary list
•developing (or adapting) and implementing standard treatment
guidelines
•assessing drug use to identify problems
•conducting interventions to improve drug use
•managing adverse drug reactions and medication errors
•informing all staff members about drug use issues, policies and
decisions.
 Functions of the DTC
• Evaluating and selecting medicines for the formulary list.
Perhaps the most important function of a DTC is the evaluation and
selection of medicines for the essential medicines list or formulary list.
Drugs should be selected on the basis of the standard treatment
guidelines or protocols that have been developed or adapted for use
in the hospital or health facilities. The evaluation of medicines requires
significant expertise and time commitment and a rigorous, transparent
approach. Documented evidence for the efficacy, safety, quality and
cost of all drugs under consideration for inclusion in the formulary list
must be examined.
• Developing standard treatment guidelines.
Standard treatment guidelines (STGs) or protocols are a proven way to
promote rational use of medicines provided they are:
•developed in a participatory way involving end-users
•easy to read and up to date
•introduced with an official launch, training, supervision and wide
dissemination
Clinical Guidelines

• Clinical guidelines have become common in the practice of medicine;

many specialty societies have published such guidelines. Most well-
conceived clinical guidelines are developed using a specified method
that incorporates principles of EBM and consensus recommendations
made by a panel of experts. Although clinical guidelines may describe
standard practice, clinical guidelines alone do not establish the
standard of care for an individual patient.