EVIDENCE BASED MEDICINE:

FORMULATING A FOCUSED CLINICAL QUESTIONS

CLS 603
Lecture 2
 Outline
• Types of clinical questions

• Background and foreground questions

• Components of a focused clinical questions represented
by PICO
• Variations of PICO
• Domains/categories of a searchable questions
• Specifying a proper study design for the type of question
• Examples for each type of questions
 Outline
• Steps for asking a focused clinical question
• Study Design and Levels of Evidence
• Definitions of study types
• Which research designs for which questions
• Usefulness of Formulating a well-structured question
• Why clinical questions must be clear
 Outline
• Types of clinical questions
• Background and foreground questions
• Components of a focused clinical questions represented
by PICO
• Variations of PICO
• Domains/categories of a searchable questions
• Specifying a proper study design for the type of question
• Examples for each type of questions
 Types of clinical questions
• Clinical questions may be categorized, in general, as either background or foreground. Why is this
important?
Determining the type of question will help you to select the best resource to consult for your answer.

A - Background questions:
Questions can be asked about any disorder or health state, a test, a treatment or intervention, or other
aspect of health care and can encompass biological, psychological, or sociologic phenomena. When well
formulated, such background questions usually have two components:
1 – A question root (who, what, where, when, how, why) with a verb.
2 – An aspect of the condition or thing of interest

For example
• How overweight is a woman to be considered slightly obese?
• What are the clinical manifestations of menopause?
• What causes migraines?
 Types of clinical questions
B - Foreground questions:
ask for specific knowledge to inform clinical decisions. These questions typically concern a
specific patient or particular population. Foreground questions tend to be more specific
and complex compared to background questions. Quite often, foreground questions
investigate comparisons, such as two drugs, two treatments, two diagnostic tests, etc.
Foreground questions may be further categorized into one of 4 major types:
1 – The patient situation, population, or problem of interest
2 – The main intervention, defined very broadly, including an exposure, a diagnostic test, a
prognostic factor, a treatment, a patient perception, and so forth.
3 – A comparison intervention or exposure ( also defined very broadly), if relevant.
4 – The clinical outcome(s) of interest, including a time horizon, if relevant.
 Types of clinical questions
For example
• Is Crixivan* effective when compared with placebo in slowing the rate of functional
impairment in a 45 year old male patient with Lou Gehrig's Disease**?
• In paediatric patients with Allergic Rhinitis, are Intranasal steroids more effective than
antihistamines in the management of Allergic Rhinitis symptoms?
 Types of clinical questions
In the following figure, clinicians need both background and foreground
knowledge, in proportion that vary overtime and that depend primarily on
our experience with the particular disorder at hand. When our experience
with a condition is limited, as at point ”A” ( like a beginning student), the
majority of our questions (shown by the vertical dimension) might be about
background knowledge. As we grow in clinical experience and responsibility,
such as at point “B” ( like a house officer), we’ll have increasing proportions
of questions about the foreground of managing patients. Further experience
with the condition puts us at point “C” (like a consultant), where most of our
gestions will be a foreground questions. Note that the diagonal line (circled)
is placed to show that we’re never too green to learn from foreground
knowledge, nor too experienced to outlive the need for background
knowledge.
 Differences in Types of Questions
Background questions Foreground questions
• Composed of question modifier and • Composed of patient and/or problem,
condition intervention (therapy, diagnostic test,
• Cover the full range of biologic, etc.), comparison and outcome.
psychologic, or sociologic aspect of • Often requires more comprehensive
human illness and intensive search strategies
• Can be answered by reference (not necessarily more time
works consuming).
• Can be used as a trampoline for • Suitable to answering using EBM
generating specific questions to be techniques.
answered by EBM
 Outline
• Types of clinical questions
• Background and foreground questions
• Components of a focused clinical questions represented
by PICO
• Variations of PICO
• Domains/categories of a searchable questions
• Specifying a proper study design for the type of question
• Examples for each type of questions
 Components of a Focused Clinical Question
• According to the Centre for Evidence Based Medicine (CEBM)*, "one of the
fundamental skills required for practising EBM is the asking of well-built
clinical questions. To benefit patients and clinicians, such questions need to
be both directly relevant to patients' problems and phrased in ways that
direct your search to relevant and precise answers."
• A well-built clinical foreground question should have all four components.
The PICO model is a helpful tool that assists researchers in organizing and
focusing their foreground question into a searchable query. Dividing into
the PICO elements helps identify search terms/concepts to use in
researchers search of the literature.
 Components of a Focused Clinical Question
• P = Patient, Problem, Population (How would you describe a group of
patients similar to you? What are the most important characteristics of the
patient?)
• I = Intervention, Prognostic Factor, Exposure (What main intervention are
you considering? What do you want to do with this patient?)
• C = Comparison (What are you hoping to compare with the intervention:
another treatment, drug, placebo, a different diagnostic test, etc.? It's
important to include this element and to be as specific as possible.)
• O = Outcome (What are you trying to accomplish, measure, improve or
affect? Outcomes may be disease-oriented or patient-oriented.)
 Components of a Focused Clinical Question
• P = ‘P’ may refer to type of patients. You may specify age, sex, race, disease
severity and co-morbidity, which should be similar to the patients under
consideration or to the type of patients of interest to you. Sometimes, a
question arises: Does P stand for patients, population or problem? The
answer is all of them. A complete description is ‘population of patients with
a problem’. Problem refers to the disease condition. The word ‘population’
comes here because EBM is based on evidence from research. Research
typically studies a sample of patients but always attempts to infer about the
population of patients represented in the sample. Sometimes, you may only
refer to the problem. For example, in the question, ‘In rheumatoid arthritis,
is methotrexate more effective in inducing long-term remission than
chloroquine?’, only problem (condition or disease) is mentioned.
 Components of a Focused Clinical Question

• I = ‘I’ stands for ‘intervention’ of interest, Usually the new intervention. This
applies to a treatment question. In case of diagnostic test question, ‘I’
stands for ‘index test’?. This means the test which is of interest to you. The
most versatile expanded term for ‘I’ is ‘independent’ or ‘input’ variable. In
treatment question, the input variable is the ‘intervention’. In diagnostic
test question, it is the ‘index test’; in prognosis question, it is the prognostic
variable; and in harm question, it is the exposure to potentially harmful
agent. Thus, ‘independent’ or ‘input’ variable covers all of these. Some
experts expand ‘I’ to ‘indicator’. An indicator variable may indicate the likely
prognosis or diagnosis and thus covers a prognostic variable or index test.
 Components of a Focused Clinical Question
• C = ‘C’ stands for ‘comparator’ or ‘comparison’ or ‘control’. Preferably the
term ‘comparator’ because ‘comparison’ to some readers means both the
interventions and tests – one versus another. Only one intervention to
which the new intervention is compared comes under this letter.
• In case of diagnostic test, the comparator is always a ‘gold standard’, which
correctly labels (classifies) ‘disease present’ or ‘disease absent’ with perfect
accuracy.
 Components of a Focused Clinical Question
• O = ‘O’ stands for ‘outcome’. The word ‘outcome’ here refers to health
consequences of exposure or intervention. In case of intervention, it refers
to ‘patient relevant outcomes’ like what happens to the patients as a result
of treatment. Clinicians usually mean ‘mortality and morbidity’, but
outcome also includes adverse effects related to the intervention.
Researcher should also consider both beneficial as well as adverse effects of
the intervention. Outcome in case of diagnostic test is accurate diagnosis of
the patient’s problem or condition.
 Components of a Focused Clinical Question: Variations of PICO

1 - PECO: Here ‘E’ stands for ‘exposure’. In questions about harm, the
potentially harmful agent to which the patients or people are exposed will
come under ‘exposure’. In prognosis question, the prognostic factor may be
taken as the ‘exposure, even though it may be a demographic characteristic
of the patients like age. Questions like ‘whether mobile phone use causes
brain tumour’ is better formulated with ‘E’ in PECO than ‘I’ in PICO.
 Components of a Focused Clinical Question: Variations of PICO

2 - PIO or PEO: Sometimes, there is no separate ‘comparator’. For example, if all patients
are exposed, there is no comparison with unexposed, though comparison may occur
across different levels of exposure. If our question is whether age is a prognostic factor for
outcome after head injury, we are comparing those with older age to those with younger
age, or vice versa, but all patients have some ‘age’. If you do not know which age to
compare to which one, it is not possible to separately identify E and C. Often there is a
linear relationship with perceptible change in outcome for every 5-year change in age.
• If you are interested in the question of whether blood pressure (BP) is related to
vascular events, you may not be able to state which blood pressure to compare to which
one? In fact, you may think (and rightly so) that both lower as well as higher BP may be
related to increase in vascular events. In such a situation, it is much easier to use the
version ‘PEO’ than ‘PECO’.
 Components of a Focused Clinical Question: Variations of PICO

3 - ‘PO’: Sometimes, the clinical question is very simple. For example,

consider a patient who is diagnosed to have amyotrophic lateral sclerosis
(ALS). Patient asks: How long will I survive? You don’t know and decide to
find this from literature. As there is no treatment for this condition, the
question may be formulated as follows: What is the length of survival for
patients with amyotrophic lateral sclerosis? The question only has ‘patients
with ALS’ and the ‘outcome’. Hence, PO is all that is relevant for this question.
Another situation where only ‘PO’ is relevant is when our interest is to
describe phenomena, perception or behaviour. For example, ‘How do
mothers feel about their children in ICU?’ This question asks about
perception and has only P (children in ICU), and O = mothers’ feelings.
 Components of a Focused Clinical Question: Variations of PICO

4 - PICOT or PECOT: Here the added ‘T’ stands for ‘time’. Proponents of PICOT
argue that time period of interest over which the outcome of interest occurs
needs specification. In the end, all patients and all of us are dead, and hence,
any question (of intervention, harm and prognosis) inherently refers to
outcome over a period of time. Therefore, this time period (T) needs
specification. However, sometimes this is not relevant. For example, in the
above question regarding length of survival in patients with ALS, there is no
need to specify the time period. The question seeks to know the length of
survival in such patients. However, other questions like mortality after
thrombolysis in patients with acute myocardial infarction may rightly require
specification like 30-day mortality.
 Components of a Focused Clinical Question: Variations of PICO

5 - PICOS: Some experts add ‘S’ to PICO, where ‘S’ stands for ‘study design’. It
prompts the clinicians to specify the most appropriate study design to
answer the question. It does help in limiting your search to one publication
type. However, for some questions, multiple study designs can be suitable
and for all types of questions, systematic reviews/meta-analyses of primary
studies based on suitable study design are possible. Thus, it is not useful to
specify one type of study design. Thus, PICOS in my opinion is not a very
useful approach.
 Outline
• Types of clinical questions
• Background and foreground questions
• Components of a focused clinical questions represented
by PICO
• Variations of PICO
• Domains/categories of a searchable questions
• Specifying a proper study design for the type of question
• Examples for each type of questions
 Domains/categories of a searchable questions
• Two additional important elements of the well-built clinical question to
consider are the type of foreground question and the type of study
(methodology). This information can be helpful in focusing the question
and determining the most appropriate type of evidence
• Determining the domain or category of a searchable questions is important
to deciding what types of information sources may provide the best
answer to the question
• Knowing the type of foreground question can help selecting the best study
design to answer the question and to yield the highest level of evidence.
 Domains/categories of a searchable questions
Foreground questions can be further divided into questions that relate to
therapy, diagnosis, prognosis, etiology/harm
1 - Therapy: Questions of treatment in order to achieve some outcome. May
include drugs, surgical intervention, change in diet, counselling, etc.
2 - Diagnosis: Questions of identification of a disorder in a patient presenting
with specific symptoms.
3 - Prognosis: Questions of progression of a disease or likelihood of a disease
occurring.
4 -Etiology/Harm: Questions of negative impact from an intervention or
other exposure.
 Domain Type Description of Domain Type of study

Prospective, blind comparison to a

Diagnosis Tests that accurately detect a disease
gold standard or cross-sectional

Selecting effective interventions to treat or Randomized control trial, cohort,

Therapy/Prevention
prevent a disease case-control, case series

Identifying associations, risk factors and Randomized control trial, cohort, case-
Etiology/Harm
causes of a disease control, cross-sectional

Predicting the probable outcome of a

Prognosis disease or treatment Cohort, case-control, case series

* Most EBM questions fall under Therapy.

 Outline
• Types of clinical questions
• Background and foreground questions
• Components of a focused clinical questions represented
by PICO
• Variations of PICO
• Domains/categories of a searchable questions
• Specifying a proper study design for the type of question
• Examples for each type of questions
 Specifying a Proper Study Design for the Type of Question
There are two kinds of objectives: one to properly label the patients at a time
point when clinician see them (classification) and second to see what
happens to patients subsequent to exposure (consequential). The first
.usually requires one time contact and the study design is cross sectional
Sometimes, to know what the patient had at the time point of interest
requires follow-up, but the aim is to know the condition at the specified time
point. In the second, we need to know whether the patient had exposure at
one time point and what was its consequence (outcome) at second time
point
For each study design, one can find systematic reviews or meta-analyses.
Thus, your first attempt should be to locate systematic review of the studies
.of designs appropriate to the type of question
 Examples – Therapy Questions
• ‘In patients with acute ischaemic stroke within few days after onset,
what are the effects (improvement in functional outcome and
bleeding episodes) of I.V. heparin (standard) compared to oral aspirin
over six months’.

Template for Therapy Question

• In P (patients with a certain disease) what are (O) the effects
(beneficial and adverse) of E (new or experimental intervention) as
compared to C (control intervention)?
 Examples – Diagnostic Test Questions
• A 50-year-old gentleman with chronic obstructive pulmonary disease
(COPD) who is bedridden suddenly develops breath lessness and
hypertension. Clinician suspect pulmonary embolism and order
ventilation perfusion (V/Q) scan; however, They do not know and want
to know how good is V/Q scan in the diagnosis of pulmonary embolism.
Before searching the literature, start to formulate the question:
• Patients: middle-aged men with COPD, bedridden and suspected to
have pulmonary embolism
• Index test: ventilation–perfusion scan
• Comparator: gold standard (pulmonary angiography)
• Outcome: diagnosis of pulmonary embolism
 Examples – Diagnostic Test Questions

Template for Diagnostic Test Question

• In (P) patients (middle aged with COPD*, bedridden) suspected to
have pulmonary embolism (PE), how accurate is I (ventilation–
perfusion scan) in diagnosing PE?
• Note: There is no need to specify gold standard as ‘C’ because
comparison in all diagnostic tests is with gold standard which gives
the correct diagnosis of the condition under consideration; and
outcome is accuracy of diagnosis. You have to specify only P and E.
 Examples – Prognosis

• In prognosis, the simplest form of question is:

In (P) patients with a disease, how big is the risk of (O) certain
outcomes (adverse consequences on health) (i.e. Variations of PICO)?
• This is a descriptive level question. But on analytic level, one may
address the question of relationship between a potential prognostic
variable and outcome. The question may take the following form:
In (P) patients with intracerebral haemorrhage, does intraventricular
extension (E) increase the risk of death (O) in the first week?
 Examples – Harm

• A 55-year-old patient on follow-up for migraine present to the clinic

with a newspaper report indicating that mobile phone use may cause
brain tumour. He is concerned that he may be at risk of developing
brain tumour because he uses mobile phone regularly. Clinician do
not know the answer and promise to get back to him after examining
the literature. So, what is the clinical question?
P: People who regularly use mobile phones E: Usage of mobile phone
O: Brain tumour
 Examples – Harm

The template may be as follows:

• Is there a risk (if yes, how much) of development of brain tumour (O)
in middle- aged person (P) who regularly use mobile phone (E)?
• Note: Here, migraine has not been given any reference as the existing
knowledge does not suggest that it may have any influence on brain
tumour development due to mobile phone use.
 Outline
• Steps for asking a focused clinical question
• Study Design and Levels of Evidence
• Definitions of study types
• Which research designs for which questions
• Usefulness of Formulating a well-structured question
• Why clinical questions must be clear
 Steps for asking a focused clinical question

QUESTION DOMAIN
CONVERT TO SEARCHABLE
ASK
QUESTION
Determining the domain or
category of a searchable
EBM uses PICO process to
if your clinical question questions is important to
aid in turning your
a background or foreground deciding what types of
foreground question into a
question ? information sources may
searchable question
provide the best answer to
the question.
Study Design and Levels of Evidence

https://www.precisionnutrition.com/how-to-read-scientific-research
 Study Design and Levels of Evidence
• Knowing the type of foreground question can help you select the best study design
to answer your question. You always want to look for the study design that will yield
the highest level of evidence. Consult the evidence pyramid and the definitions.

• An evidence pyramid visually depicts the evidential strength of different research

designs.. Studies with the highest internal validity, characterized by a high degree of
quantitative analysis, review, analysis, and stringent scientific methodology, are at
the top of the pyramid. Observational research and expert opinion reside at the
bottom of the pyramid.
 Outline
• Steps for asking a focused clinical question
• Study Design and Levels of Evidence
• Definitions of study types
• Which research designs for which questions
• Usefulness of Formulating a well-structured question
• Why clinical questions must be clear
 Study Types: Definitions
Meta-analysis: A statistical technique that summarizes the results of several studies in a
single weighted estimate, in which more weight is given to results of studies with more
events and sometimes to studies of higher quality.

Systematic Review: a review in which specified and appropriate methods have been used
to identify, appraise, and summarize studies addressing a defined question. (It can, but
need not, involve meta-analysis). In Clinical Evidence, the term systematic review refers
to a systematic review of Randomised controlled trial (RCT) unless specified otherwise.

Randomized Controlled Trial: a trial in which participants are randomly assigned to two
or more groups: at least one (the experimental group) receiving an intervention that is
being tested and another (the comparison or control group) receiving an alternative
treatment or placebo. This design allows assessment of the relative effects of
interventions.
 Study Types: Definitions

• Controlled Clinical Trial: a trial in which participants are assigned to two or more
different treatment groups. In Clinical Evidence, we use the term to refer to
controlled trials in which treatment is assigned by a method other than random
allocation. When the method of allocation is by random selection, the study is
referred to as a randomized controlled trial (RCT). Non-randomized controlled trials
are more likely to suffer from bias than RCTs.

• Cohort Study: a non-experimental study design that follows a group of people

(a cohort), and then looks at how events differ among people within the group.
A study that examines a cohort, which differs in respect to exposure to some
suspected risk factor (e.g. smoking), is useful for trying to ascertain whether exposure
is likely to cause specified events (e.g. lung cancer). Prospective cohort studies (which
track participants forward in time) are more reliable than retrospective cohort
studies.
 Study Types: Definitions
• Case control study: a study design that examines a group of people who have
experienced an event (usually an adverse event) and a group of people who have not
experienced the same event, and looks at how exposure to suspect (usually noxious)
agents differed between the two groups. This type of study design is most useful for
trying to ascertain the cause of rare events, such as rare cancers.

• Case Series: analysis of series of people with the disease (there is no comparison
group in case series).

• Case Study: An investigation of a single subject or a single unit, which could be a small
number of individuals who seem to be representative of a larger group or very
different from it
 Study Types: Definitions
• Editorial: Work consisting of a statement of the opinions, beliefs, and policy of the
editor or publisher of a journal, usually on current matters of medical or scientific
significance to the medical community or society at large. The editorials published by
editors of journals representing the official organ of a society or organization are
generally substantive.
• Opinion: A belief or conclusion held with confidence but not substantiated by positive
knowledge or proof.
• Animal Research: A laboratory experiment using animals to study the development
and progression of diseases. Animal studies also test how safe and effective new
treatments are before they are tested in people.
• In Vitro Research: In the laboratory (outside the body). The opposite of in vivo (in the
body).
Study Design and Levels of Evidence: Which Research Designs for Which Questions?

• Different types of research studies are better suited to answer different categories
of clinical questions. Researcher might not always find the highest level of evidence
(i.e., systematic review or meta-analysis) to answer his/her question. When this
happens, work the way down the Evidence Pyramid to the next highest level of
evidence.

• Therapy: Which treatment does more harm than good?

RCT > Cohort Study > Case Control > Case Series
Study Design and Levels of Evidence: Which Research Designs for Which Questions?

• Diagnosis: Which diagnostic test should I use?

Prospective, blind comparison to a gold standard, i.e.. A controlled trial that looks at
patients with varying degrees of an illness and administers both diagnostic tests - the
test under investigation and the "gold standard" test - to all of the patients in the study
group.

• Prognosis: What is the patient's likely clinical course over time?

Cohort Study > Case Control > Case Series

• Etiology / Harm: What are the causes of this disease or condition?

RCT > Cohort Study > Case Control > Case Series
Study Design and Levels of Evidence: Which Research Designs for Which Questions?

• Prevention: How do we reduce the chance of disease by identifying and modifying

risk factors?

RCT > Cohort Study > Case Control > Case Series

• Cost: Is one intervention more cost-effective than another?

Economic Analysis

• Quality of Life: What will be the patient's quality of life following an intervention?

Qualitative Study
 Outline
• Steps for asking a focused clinical question
• Study Design and Levels of Evidence
• Definitions of study types
• Which research designs for which questions
• Usefulness of Formulating a well-structured question
• Why clinical questions must be clear
 Usefulness of Formulating a Well-Structured Question
- Research wise

• The advantages of formulating a well-built question are:

(I) It helps to focus on the most relevant paper(s).
(II) It increases efficiency of search for the evidence.
(III) It helps you to set the desired outcomes, particularly in cases of
therapy questions. This is important because many papers address only
surrogate outcomes not the clinical (patient important) outcomes.
 Clearness of Clinical Questions
• A well- structured and clear clinical questions can help in:
1 – Focus valuable learning time on evidence that is directly relevant to
patients'’ clinical needs
2 – Focus on evidence that directly addresses our particular knowledge
needs
3 – Can suggest high-yield search strategies
4 – They suggest the forms that useful answers might take
5 – When our question get answered, our knowledge grows, our curiosity
is reinforced, our cognitive resonance is restored, and we can become
better, faster, and happier clinicians
 Lecture 2 References
• Prasad, K. (2013). Fundamentals of evidence based medicine, Springer.
• Evidence-Based Practice: Levels of Evidence and Study Designs, This guide is designed to assist health care professionals to
become effective and efficient users of the medical and nursing literature, Ascension Wisconsin Library Services Blog.
https://ascension-wi.libguides.com/c.php?g=873880&p=6274266
• Asking focused questions, The Oxford Centre for Evidence-Based Medicine (CEBM).
https://www.cebm.ox.ac.uk/resources/ebm-tools/asking-focused-questions
• Further Readings:
• https://guides.dml.georgetown.edu/ebm/ebmjournals
• Burns, P. and Chung, K., Developing Good Clinical Questions And Finding The Best Evidence To Answer Those Questions.
2020