Clinical Epidemiology

(Evidence Based Medicine)

Glossary
Prof. Bhisma Murti
Department of Public Health,
Faculty of Medicine, Universitas Sebelas Maret

Absolute risk: The observed or calculated

probability of an event in the population under
study. (Harm, Therapy)

Absolute risk difference (or risk

difference for short): the difference in the
risk for disease or death between an exposed
population and an unexposed population.
(Harm). Absolute risk difference measures the
increasing risk for disease after an exposure, or
the occurrence of harm resulting from a
therapy (i.e. the adverse effects of an
intervention).

Absolute risk reduction (ARR): similar to

absolute risk difference, the difference in the
absolute risk (rates of adverse events) between
experimental
population
and
control
population. (Therapy) To Calculation. In
contrast to absolute risk difference, ARR
measures the reduction in the risk for death or
other complications resulting from a therapy
(i.e. the beneficial effects of an intervention).

Adjustment: A summarizing procedure for a

statistical measure in which the effects of
differences in composition of the populations
being compared have been minimized by
statistical methods. (Harm). For example,
since blood pressure increases with age, unless
treatment has been allocated randomly at the
baseline, the researcher needs to report the
overall estimated effect of an anti-hypertensive
drug adjusted (controlled) for age.

variables. An association may be fortuitous or

may be produced by various other
circumstances; the presence of an association
does not necessarily imply a causal
relationship. ( Harm)

Bias (Syn: systematic error): Deviation of

results or inferences from the truth, or
processes leading to such deviation. See also
Referral Bias, Selection Bias. ( Harm,
Therapy)

Blind(ed) study (Syn: masked study): A

study in which observer(s) and/or subjects are
kept ignorant of the group to which the
subjects are assigned, as in an experimental
study, or of the population from which the
subjects come, as in a non-experimental or
observational study. Where both observer and
subjects are kept ignorant, the study is termed
a double-blind study. If the statistical
analysis is also done in ignorance of the group
to which subjects belong, the study is
sometimes described as triple blind. The
purpose of "blinding" is to eliminate sources of
bias. (Diagnosis, Harm, Therapy)

Case-series: Report of a number of cases of

disease. ( Harm)

Case-control

study:
Retrospective
comparison of exposures of persons with
disease (cases) with those of persons without
the disease (controls) (see Retrospective
study). (Harm)

Association: Statistical dependence between

two or more events, characteristics, or other
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Causality: The relating of causes to the

effects they produce. Most of epidemiology
concerns causality and several types of causes
can be distinguished. It must be emphasized,
however, that epidemiological evidence by
itself is insufficient to establish causality,
although
it
can
provide
powerful
circumstantial evidence. ( Harm) An
association between two variables is likely to
be causal if it is strong, consistent, specific,
plausible, follows a logical time sequence, and
shows a dose-response gradient

Clinical epidemiology: The important acts

that clinicians carry out require the
particularization, to the individual patient, of
the clinicians prior experience with groups of
similar patients. The clinicians need to project
diagnostic findings, prognoses, and therapeutic
responses from previous groups of patients to
the current individual patient. Therefore,
rational evaluation of a symptom, sign, or
laboratory test result in todays patient requires
critical appraisal of how this clinical finding
behaved previously among groups of patients
with the same differential diagnosis. Similarly,
the rational selection of a treatment for todays
patient requires appraisal of how similar
patients have fared with various treatment in
the past.
Clinical epidemiology is the application of
(population) epidemiologic principles and
strategies plus a few more from biostatistics to
the care of individual patients to improve the
accuracy and efficiency of diagnosis and
prognosis, the effectiveness and efficiency of
management, and to keep up to date with
useful advances in medicine.
Clinical practice comprises the art (the beliefs,
judgments, and intuitions) as well as the
science (the knowledge, logic, and prior
experience) of clinical medicine. For example,
the art aspect of medicine is implied in the
second oldest school of medicine in Indonesia,
Airlangga University. Established during the
Dutch administration, the original name of the
school was Nederland Indische Art School

(NIAS). The use of epidemiologic principles

and some biostatistics adds the scientific basis
to the art of clinical practice in order for
clinicians to reach the correct diagnosis, select
the management that does more good than
harm, and keep up to date with useful advances
in medicine, and thus to improve clinical
performance.

Co-interventions: Interventions other than

the treatment under study that are applied
differently to the treatment and control groups.
Co-intervention is a serious problem when
double blinding is absent or when the use of
very effective non-study treatments is
permitted. ( Therapy)

Cohort study: Follow-up of exposed and

non-exposed defined groups, with a
comparison of disease rates during the time
covered. ( Harm, Prognosis). At the start of the
study, one of the groups has a particular
condition or receives a particular treatment,
and the other does not. At the end of a certain
amount of time, researchers compare the two
groups to see how they did.

Comparison group: Any group to which the

index group is compared, usually synonymous
with control group, although some authors
reserve the term control group for the
comparison group in RCT. ( Harm, Therapy)
The control group of a study is a group that
receives a treatment other than the one being
studied (for instance, a placebo pill that looks
identical to the medication being studied but
that has no active ingredients). Control groups
are necessary since we need to be able to
compare the results of the treatment being
studied to available alternatives. For instance,
the fact that 90% of all patients taking
treatment A for condition B recovered within
one year tells us nothing unless we know the
percentage of patients who recover from
condition B within one year with no treatment
at all! Where placebos cannot be used, the
control group is defined as to "standard"
therapy or to the use of another intervention.
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Paired

(or matched) comparison:

Subjects receiving different treatments are
matched to balance potential confounding
variables such as age and sex; results are
analyzed in terms of differences between
subject pairs
Parallel group comparison: Each group
receives a different treatment, with both groups
being entered at the same time; results are
analyzed by comparing groups

Placebo controlled: Control subjects receive

a placebo (inactive pill) which should look and
taste the same as the active pill. Placebo
(sham) operations may also be used in trials of
surgery

Within subject comparison: Subjects are

assessed before and after an intervention and
results analyzed in terms of changes within the
subjects

Co-morbidity: Coexistence of a disease or

diseases in a study participant in addition to
the index condition that is the subject of study.
( Harm)

Confidence interval (CI): The range of

numerical values in which we can be confident
(to a computed probability, such as 90 or 95%)
that the population value being estimated will
be found. Confidence intervals indicate the
strength of evidence; where confidence
intervals are wide, they indicate less precise
estimates of effect.
The larger the trial's sample size, the larger the
number of outcome events and the greater
becomes the confidence that the true relative
risk reduction is close to the value stated. Thus
the confidence intervals narrow and
"precision" is increased. In a "positive finding"
study the lower boundary of the confidence
interval, or lower confidence limit, should still
remain important or clinically significant if the
results are to be accepted. In a "negative
finding" study, the upper boundary of the

confidence interval should not be clinically

significant if you are to confidently accept this
result. ( Harm, Therapy). To Calculation
Confidence interval allows researchers to
combine and summarize estimates of treatment
effects from a number of similar studies in
meta-analysis studies.

Confounding variable, Confounder: A

variable that can cause or prevent the outcome
of interest, is not an intermediate variable, and
is associated with the factor under
investigation. A confounding variable may be
due chance or bias. Unless it is possible to
adjust for confounding variables, their effects
distort those of factor(s) being studied. ( Harm,
Therapy).

Control event rate(CER): The percentage of

the
control/non-exposed
group
who
experienced
outcome
in
question. To
Calculation

Crossover: Each subject received both the

intervention and control treatments (in random
order), often separated by a washout period
with no treatment

Determinant: Any definable factor that

effects a change in a health condition or other
characteristic. ( Harm)

Diagnostic test: Diagnostic tool that must be

evaluated for its validity (can we trust it?) and
reliabity (would we get the same results every
time?). Preferred study design for evaluating a
diagnostic test is cross sectional survey in
which both the new test and the gold standard
are performed

Dose-response relationship: A relationship

in which change in amount, intensity, or
duration of exposure is associated with a
change-either an increase or decrease-in risk of
a specified outcome.( Harm)

Effectiveness: a measure of the benefit

resulting from an intervention for a given
health problem under usual conditions of
clinical care for a particular group; this form of
evaluation considers both the efficacy of an
intervention and its acceptance by those to
whom it is offered, answering the question,
"Does the practice do more good than harm to
people to whom it is offered?" See Intention
to treat. ( Therapy)

management. Four steps in evidence based

medicine:
1. Formulate a clear clinical question
from a patient's problem
2. Search the literature for relevant
clinical articles
3. Evaluate (critically appraise) the
evidence for its validity and usefulness
4. Implement useful findings in clinical
practice

Efficacy: a measure of the benefit resulting

from an intervention for a given health
problem under the ideal conditions of an
investigation; it answers the question, "Does
the practice do more good than harm to people
who fully comply with the recommendations?"
( Therapy)

Exclusion

Criteria: Conditions which

preclude entrance of candidates into an
investigation even if they meet the inclusion
criteria. ( Diagnosis, Harm, Prognosis,
Therapy)
Experimental

Evidence: Findings from empirical studies.

Effective evidence based practice requires
evidence that is:
1.
2.
3.
4.

Accessible and timely (current)

Valid (credible)
Clinically important
Applicable to patient or population

Evidence Based Medicine: the process of

systematically finding, appraising, and using
contemporaneous research findings as the basis
for clinical decisions. Evidence based
medicine uses simple rules of logic and science
to find, appraise and applies evidence from
research to the care of individual patients.
The aim of evidence based practice is to help
clinicians and healthcare planners improve the
quality and efficiency of healthcare services.
The term "evidence based medicine" was
coined at McMaster Medical School in Canada
in the 1980s to label this clinical learning
strategy, which people at the school had been
developing for over a decade.
Evidence based medicine can be practiced in
any situation where there is doubt about an
aspect of clinical diagnosis, prognosis, or

event rate(EER): The

percentage of intervention/exposed group who
experienced
outcome
in
question. To
Calculation
Factorial design: A study which permits
investigation of the effects (both separately
and combined) of more than one independent
variable on a given outcome (for example, a
2x2 factorial design tested the effects of
placebo, aspirin alone, streptokinase alone, or
aspirin plus streptokinase in acute heart attack)

Follow-up: Observation over a period of time

of an individual, group, or initially defined
population whose relevant characteristics have
been assessed in order to observe changes in
health status or health-related variables. (
Harm, Prognosis)

Gold standard: A method, procedure, or

measurement that is widely accepted as being
the best available. ( Diagnosis)

Incidence: The number of new cases of

illness commencing, or of persons falling ill,
during a specified time period in a given
population. See also Prevalence. ( Harm)

Intention to treat analysis: A method for

data analysis in a randomized clinical trial in
which individual outcomes are analyzed
according to the group to which they have
been randomized, even if they never received
the treatment they were assigned. By
simulating practical experience it provides a
better measure of effectiveness (versus
efficacy). ( Therapy)

Interviewer bias: Systematic error due to

interviewer's subconscious or conscious
gathering of selective data. ( Harm)

Kappa: A measure of the degree of nonrandom agreement between or within

observers, K= (Po-Pe)/(1-Pe), where Po is the
proportion of times the measurements agree,
and Pe the proportion of times they can be
expected to agree by chance alone. If
concordance between or within observers is
perfect, kappa=1; if there is no corcordance,
kappa=0.

Lead-time bias: If prognosis study patients

are not all enrolled at similar, well-defined
points in the course of their disease,
differences in outcome over time may merely
reflect differences in duration of illness. (
Harm, Prognosis)

Likelihood ratio: Ratio of the probability

that a given diagnostic test result will be
expected for a patient with the target disorder
rather than for a patient without the disorder. (
Diagnosis) To Calculation. Likelihood ratio
can be used to refine pretest probability to
posttest probability of disease. Its values range
from 0 to . Likelihood ratio of 0 yields
posttest probability of no disease; likelihood
ratio of 1 does not change the pretest
probability; likelihood ratio of yields certain
posttest probability of disease.
There are two methods by which one applies
likelihood ratios to refine probability: (1) using
a nomogram; (2) using simple math via pretest
odds and posttest odds, where pretest odds

times likelihood ratio equals posttest odds.

Odds = probability/(1-probability).

Meta-analysis:

Systematic review that

employs statistical methods to combine and
summarize quantitatively the results of several
studies. Meta-analysis is a statistical analysis
which combines or integrates the results of
several independent clinical trials considered
by the analyst to be combinable. Since its
recent introduction into clinical epidemiology,
meta-analysis has established itself as an
influential branch of biostatistics, but several
issues remain unresolved. Publication bias is a
major threat to the validity of meta-analysis.
The inclusion of unpublished, non-peer
reviewed data can be problematic, particularly
if these data come from interested sources,
such as the pharmaceutical industry.
Computer software entirely devoted to metaanalysis has been developed, and meta-analytic
procedures have been introduced in general
statistical software packages

Number Needed to Treat (NNT): the

number of patients who must be exposed to an
intervention before the clinical outcome of
interest occurred; for example, the number of
patients needed to treat to prevent one adverse
outcome. ( Therapy) To Calculation. Actually
it is the reciprocal of the absolute risk
reduction (ARR), 1/ARR.
The threshold NNT defines the value above
which the disadvantages of treatment outweigh
the benefits (and treatment may therefore be
withheld), and below which the benefits
outweigh the disadvantages (and treatment
may therefore be offered).Because the cost of
treatment and the benefit to the length and
quality of life vary, each intervention needs a
separate threshold; this threshold will also vary
according to the values of the patient, or
population, being offered the intervention

Odds: a proportion in which the numerator

contains the number of times an event occurs
5

and the denominator includes the number of

times the event does not occur. ( Harm)

Odds Ratio (Syn: cross-product ratio,

relative odds): a measure of the degree of
association; for example, the odds of exposure
among the cases compared with the odds of
exposure among the controls. ( Harm) To
Calculation

Posttest probability (or posterior

probability): the probability that a patient
has the disease after use of a diagnostic test

Precision: The range in which the best

estimates of a true value approximate the true
value. See Confidence interval. ( Diagnosis,
Harm, Prognosis, Therapy)

Predictive value: In screening and diagnostic

tests, the probability that a person with a
positive test is a true positive (i.e., does have
the disease), or that a person with a negative
test truly does not have the disease. The
predictive value of a screening test is
determined by the sensitivity and specificity
of the test, and by the prevalence of the
condition for which the test is used.
(Diagnosis) To Calculation

Pretest
probability
(or
prior
probability): the probability that a patient
has the disease, based on history taking and
physical examination, before use of a
diagnostic test.

development of those outcomes. Compare with

risk factors. Neither prognostic or risk factors
necessarily imply a cause and effect
relationship. ( Prognosis)

Prospective study: Study design where one

or more groups (cohorts) of individuals who
have not yet had the outcome event in question
are monitored for the number of such events
which occur over time. ( Prognosis, Harm)

Randomized controlled trial: Study design

where treatments, interventions, or enrollment
into different study groups are assigned by
random allocation rather than by conscious
decisions of clinicians or patients. If the
sample size is large enough, this study design
avoids problems of bias and confounding
variables by assuring that both known and
unknown determinants of outcome are evenly
distributed between treatment and control
groups. ( Therapy)

Recall bias: Systematic error due to the

differences in accuracy or completeness of
recall to memory of past events or experiences.
( Harm)

Referral filter bias: The sequence of

referrals that may lead patients from primary to
tertiary centers raises the proportion of more
severe or unusual cases, thus increasing the
likelihood of adverse or unfavorable outcomes.
( Prognosis)

Relative risk (RR): the ratio of the

Prevalence: the proportion of persons with a
particular disease within a given population at
a given time. ( Diagnosis)

Prognosis: the possible outcomes of a disease

or condition and the likelihood that each one
will occur. ( Prognosis)

Prognostic factor: Demographic, diseasespecific,

or
co-morbid
characteristics
associated strongly enough with a condition's
outcomes to predict accurately the eventual

probability of developing, in a specified period

of time, an outcome among those receiving the
treatment of interest or exposed to a risk factor,
compared with the probability of developing
the outcome if the risk factor or intervention is
not present. (Therapy, Harm) To Calculation

Relative risk reduction (RRR): the extent

to which a treatment reduces a risk, in
comparison with patients not receiving the
treatment of interest. ( Therapy) To
Calculation
6

Reproducibility (Repeatability, Reliability):

the results of a test or measure are identical or
closely similar each time it is conducted. (
Diagnosis)

Retrospective study: study design in which

cases where individuals who had an outcome
event in question are collected and analyzed
after the outcomes have occurred (see also
Case-control study). ( Harm)

groups of individuals who have the same

values for the confounding variable. ( Therapy)

Strength of Inference: the likelihood that an

observed difference between groups within a
study represents a real difference rather than
mere chance or the influence of confounding
factors, based on both p values and confidence
intervals. Strength of inference is weakened by
various forms of bias and by small sample
sizes. ( Harm, Therapy)

Risk factor: patient characteristics or factors

associated with an increased probability of
developing a condition or disease in the first
place. Compare with prognostic factors.
Neither risk nor prognostic factors necessarily
imply a cause and effect relationship. ( Harm)

Survival curve: A graph of the number of

at a presymptomatic stage and which values

can be applied to large populations. Preferred
study design for evaluating a screening test is
cross sectional survey

events occurring over time or the chance of

being free of these events over time. The
events must be discrete and the time at which
they occur must be precisely known. In most
clinical situations, the chance of an outcome
changes with time. In most survival curves the
earlier follow-up periods usually include
results from more patients than the later
periods and are therefore more precise. (
Prognosis)

Selection Bias: a bias in assignment or a

Systematic review: the application of

Screening test: Test which picks up disease

confounding variable that arises from study

design rather than by chance. These can occur
when the study and control groups are chosen
so that they differ from each other by one or
more factors that may affect the outcome of
the study. ( Harm, Therapy)

Sensitivity (of a diagnostic test): the

proportion of truly diseased persons, as
measured by the gold standard, who are
identified as diseased by the test under study. (
Diagnosis) To Calculation

Specificity (of a diagnostic test): the

proportion of truly non-diseased persons, as
measured by the gold standard, who are so
identified by the diagnostic test under study. (
Diagnosis) To Calculation

Stratification:

division
into
groups.
Stratification may also refer to a process to
control for differences in confounding
variables, by making separate estimates for

scientific strategies that limit bias to the

systematic assembly, critical appraisal and
synthesis of all relevant studies on a particular
topic. Systematic reviews of the best available
evidence regarding the benefits and risks of
medical interventions can inform decision
making in clinical practice and public health.
The main potential biases are in the selection
of studies for inclusion in reviews. Studies
with negative results may not be published as
readily as studies with positive results, leading
to publication bias.

Therapy:

Drug
treatments,
surgical
procedures, alternative methods of service
delivery, or other interventions. Preferred
study design for evaluating therapy is
randomised controlled trial

Validity: the extent to which a variable or

intervention measures what it is supposed to
measure or accomplishes what it is supposed to
7

accomplish. (Diagnosis, Harm, Prognosis,

Therapy)
The internal validity of a study refers to the
integrity of the experimental design.
The external validity of a study refers to the
appropriateness by which its results can be
applied to non-study patients or populations,
also known as generalizability.

Reference:
Gay J (2011). Clinical epidemiology &
evidence-based
medicine
glossary.
Washington State University. http://www.
vetmed.wsu.edu/courses-jmgay/
gloss
clinepiebm.htm. Accessed in September
2011.
University of Alberta (2011). Clinical
epidemiology glossary. http://www.ebm.
med.ualberta.ca/ Glossary.html. Accessed
in September 2011.