Appraising the evidence

CRITICAL APPRAISAL
 VALIDDITY, IMPORTANCE AND APPLICABILITY

VALIDITY: In Methods section:

 design, sample, sample size, eligibility criteria
(inclusion, exclusion) sampling method,
randomization method, measurements, methods
of analysis, etc
IMPORTANCE: In Results section
 characteristics of subjects, drop out, analysis, p
value, confidence intervals, etc
APPLICABILITY: In Discussion section + our patient’s
characteristics
 CRITICAL APPRAISAL

 1.THERAPY
 2.DIAGNOSIS
 3.PROGNOSIS
 4.HARM
5 SYSTEMATIC REVIEW
 DESCRIPTTION
OF
CRITICAL APPRAISAL
OF
THERAPY
 Validity Questions to ask Key Learning points
(FRISBE)
• Is there outcome data for How do dropouts threaten
all patients show entered validity? Dropouts or those
the trial? • If so, was the lost to follow-up create
F: Patient percentage of patients missing data that might
Follow-Up without outcome data disrupt the balance in
Were all similar between groups? • groups created by
patients who Were reasons why patients randomization, especially
entered the dropped out or were since those who
trial properly missing outcome data well- discontinue a study often
accounted for described? have a different prognosis
and attributed than do those who
at its continue. A large number
conclusion? of dropouts may introduce
Was follow-up systematic differences
complete? between groups in those
lost to follow-up
 Why is randomization
important? Randomization
R: guarantees that each
Randomizati subject has the same
• Were patients selected chance of entering any
on Was the at random from the target
allocation group and aims to
population? • Was the balance groups for known
(assignment) assignment randomized?
of patients to and unknown prognostic
• Was the method to factors so that group
treatment generate randomization differences can be
randomized? appropriate? • Was
Was the attributed to the effect of
evidence of concealment treatment. Allocation
allocation provided?
concealed? concealment assures that
those assessing eligibility
and assigning patients to
groups don’t have
knowledge of the
allocation sequence.
 • Were all patients Why intention-to-treat
analyzed in the groups to analysis is important? ITT
which they were preserves the balance of
I: Intention to randomized? • What prognostic factors in
Treat percentage of patients was groups created by the
Analysis excluded from the original random group
Were patients analyses? • How were allocation. It provides the
analyzed in missing outcomes handled truest estimate of the
the groups to (e.g., were missing data effects of treatment
which they imputed using statistical allocation in real-world
were modeling techniques)? • If practice by including data
randomized? missing data were imputed from crossovers, non-
Were all was a sensitivity analysis adherents, dropouts and
randomized or “worst case scenario” those lost to follow-up
patient data analysis done? If so, what
analyzed? did that analysis show?
 • Was sufficient
information provided Why should the groups
S: Similar about important be similar at baseline? It
Baseline demographic and clinical is important to verify that
Characteristi characteristics known to
those factors known to
cs of affect prognosis? • If influence outcome are
Patients important differences equally distributed. And
Were groups existed between the
to assess the potential
similar at the groups, did the
effect on the study
start of the imbalance favor the outcome of an imbalance
trial? control or treatment that occurs by chance.
group?
 Why is blinding important?
• Potential groups needing Blinding equalizes the
blinding: patients, effect of patient and
providers, raters or therapist expectations on
assessors, data analysts, outcome across groups.
B: Blinding adjudicators. • While For raters, blinding
Were patients, patients and providers are minimizes subjectivity in
health necessarily unblinded in outcome measurement.
workers, and psychotherapy trials, For providers, blinding
study objectivity is enhanced by eliminates the possibility of
personnel the use of blinded raters either
“blind” to and objective outcome conscious/unconscious
treatment? measures. • If appropriate, differential administration
was the integrity of the of effective intervention to
blinding tested and found either group, such as co-
to have been preserved? interventions (unintended
additional care to either
group) or contamination
(provision of the
intervention to the control
group).
E: Equal Why should groups be
Treatment treated equally? Equal
Aside from treatment helps
• Were patients in the
the guarantee that the
different groups treated
experimental differently in any way groups remain
intervention, prognostically balanced
(other than the
were the intervention)? by avoiding systematic
groups differences in the care
treated provided other that the
equally? intervention.
 Notable
strengths:
Weaknesses or
concerns: How
serious are the
Summary of article’s threats to
validity validity and in
what direction
could they bias
the study
outcomes?
 IMPORTANCE
 Calculate
1.CER, (CONTROL EVENT RATE)
2.EER, (EXPERIMENTAL EVENT RATE)
3.ARR, (ABSOLUTE REDUCTION RISK)
4.RRR, (RELATIVE REDUCTION
5.ABI, (ABSOLUTE BENEFIT INCREASE)
6.RBI, (RELATIVE BENEFIT INCREASE)
7.NNT (NUMBER NEEDED TO TREAT)
 CRITICAL APPRAISAL THERAPY WORKSHEET
1a. R- Was the assignment of patients to treatments
Randomised?
What is best? Where do I find the information
Centralised computer The Methods should tell you
randomisation is ideal and how patients were allocated to
often used in multi-centred groups and whether or not
trials. Smaller trials may use randomisation was concealed.
an independent person (e.g,
the hospital pharmacy) to
“police” the randomization.

This paper: Yes  No  Unclear  Comment:

1b. R- Were the groups similar at the start of the trial?
What is best? Where do I find the
information?
If the randomisation process The Results should have a
worked (that is, achieved table of "Baseline
comparable groups) the Characteristics" comparing the
groups should be similar. The randomized groups on a
more similar the groups the number of variables that could
better it is. There should be affect the outcome (ie. age,
some indication of whether risk factors etc). If not, there
differences between groups may be a description of group
are statistically significant (ie. similarity in the first paragraphs
p values). of the Results section.

This paper: Yes  No  Unclear  Comment:

 Were the groups similar
at the start of the trial?
UJI HOMOGENITAS COVARIABLE
(VARIABEL SOSIOGRAFI &
INDEPENDENT LAINNYA YANG DAPAT
DIUJI) SEBELUM TRIAL DIMULAI
BILA HOMOGEN TRIAL BOLEH
DIMULAI BILA TIDAK HOMOGEN
TIDAK BOLEH DILAKUKAN TRIAL
AKAN TETAPI DILAKUKAN RE-
RANDOMISASI DAN DIUJI KEMBALI
2a. A – Aside from the allocated treatment, were groups
treated equally?
What is best? Where do I find the
information?
Apart from the intervention Look in the Methods section
the patients in the different for the follow-up schedule, and
groups should be treated the permitted additional
same, eg., additional treatments, etc and in Results
treatments or tests. for actual use.

This paper: Yes  No  Unclear  Comment:

2b. A – Were all patients who entered the trial accounted for? –
and were they analysed in the groups to which they were

randomised?
What is best? Where do I find the
information?
Losses to follow-up should The Results section should
be minimal – preferably less say how many patients were
than 20%. However, if few Randomised (eg., Baseline
patients have the outcome of Characteristics table) and
interest, then even small how many patients were
losses to follow-up can bias actually included in the
the results. Patients should analysis. You will need to
also be analysed in the read the results section to
groups to which they were clarify the number and reason
randomised – ‘intention-to- for losses to follow-up.
treat analysis’.
This paper: Yes  No  Unclear  Comment:
3. M - Were measures objective or were the patients
and clinicians kept “blind” to which treatment was
being received?
What is best? Where do I find the
information?
It is ideal if the study is First, look in the Methods
‘double-blinded’ – that is, both section to see if there is
patients and investigators are some mention of masking of
unaware of treatment treatments, eg., placebos
allocation. If the outcome is with the same appearance
objective (eg., death) then or sham therapy. Second,
blinding is less critical. If the the Methods section should
outcome is subjective (eg., describe how the outcome
symptoms or function) then was assessed and whether
blinding of the outcome the assessor/s were aware of
assessor is critical. the patients' treatment.
This paper: Yes  No  Unclear  Comment:
 What were the results?
How large was the treatment effect?
Most often results are presented as dichotomous outcomes
(yes or not outcomes that happen or don't happen) and can
include such outcomes as cancer recurrence, myocardial
infarction and death.
Consider a study in which

15% (0.15) of the control group died

10% (0.10) of the treatment group died

after 2 years of treatment.

What is the measure? What does it mean?
Relative Risk (RR) = riskThe relative risk tells us how
of the outcome in the many times more likely it is that
treatment group / risk ofan event will occur in the
the outcome in the control
treatment group relative to the
group. control group. An RR of 1 means
that there is no difference
between the two groups thus, the
treatment had no effect. An RR
< 1 means that the treatment
decreases the risk of the
outcome. An RR > 1 means that
the treatment increased the risk
of the outcome.
In our example, the RR = Since the RR < 1, the treatment
0.10/0.15 = 0.67 decreases the risk of death.
Absolute Risk The absolute risk reduction tells
Reduction (ARR) = risk us the absolute difference in the
of the outcome in the rates of events between the two
control group - risk of the groups and gives an indication
outcome in the treatment of the baseline risk and
group. This is also known treatment effect. An ARR of 0
as the absolute risk means that there is no difference
difference. between the two groups thus,
the treatment had no effect.

In our example, the ARR The absolute benefit of

= 0.15 - 0.10 = 0.05 or 5% treatment is a 5% reduction in
the death rate.
Relative Risk Reduction The relative risk reduction is the
(RRR) = absolute risk complement of the RR and is
reduction / risk of the probably the most commonly
outcome in the control reported measure of treatment
group. An alternative way effects. It tells us the reduction
to calculate the RRR is to in the rate of the outcome in the
subtract the RR from 1 treatment group relative to that
(eg. RRR = 1 - RR) in the control group.

In our example, the RRR The treatment reduced the risk

= 0.05/0.15 = 0.33 or 33% of death by 33% relative to that
Or RRR = 1 - occurring in the control group.
0.67 = 0.33 or 33%
Number Needed to Treat The number needed to treat
(NNT) = inverse of the represents the number of patients
ARR and is calculated as 1 we need to treat with the
/ ARR. experimental therapy in order to
prevent 1 bad outcome and
incorporates the duration of
treatment. Clinical significance
can be determined to some extent
by looking at the NNTs, but also
by weighing the NNTs against
any harms or adverse effects
(NNHs) of therapy.
In our example, the NNT = We would need to treat 20 people
1/ 0.05 = 20 for 2 years in order to prevent 1
death.
 FOR TREATMENT EFFECTIVITY
AS
THE OUTCOMES

Absolute Benefit Increase (ABI) = is the

arithmetic difference between the rates of events in
the experimental and control group.
An Absolute Benefit Increase (ABI) refers to the
increase of a good event as a result of the
intervention.
An Absolute Risk Reduction (ARR) refers to
the decrease of a bed event as the result of
the intervention. [ARR = EER-CER]
 Relative Benefit Increase
(RBI)

Is the proportional increase in

benefit between the rates of
events in the control group and
the experimental group.

[RBI = EER - CER / CER]

How precise was the estimate of the treatment effect?

1.The true risk in the population is estimate the true risk

from sample of patients in the trial.
2.This estimate is called the point estimate and interpret
by the confidence intervals (CI) for each estimate.
3.If the confidence interval is fairly narrow then we can be
confident that our point estimate is a precise reflection of
the population value.
4.The significancy test
Numbers Needed to Treat (NNT) is the
number of patients who need to be
treated to prevent one bad outcome
or produce one good outcome.
In other words, it is the number of
patients that a clinician would have to
treat with the experimental treatment
compared to the control treatment to
achieve one additional patient with a
favorable outcome.
[NNT = 1/ARR]
Will the results help me in caring for my patient
(ExternalValidity/Applicability)

The questions that you should ask before you decide

to apply the results of the study to your patient are:

1.Is my patient so different to those in the study that

the results cannot apply?
2.Is the treatment feasible in my setting?
3.Will the potential benefits of treatment outweigh the
potential harms of treatment for my patient?
 Applying the Evidence Worksheet

Similar Patients
1. Are your patients similar to those in the
study?
2. Are they so different that the results can’t
help you?
3. How much of the study effect can you
expect for your patients?
 Realistic Interventions
4. Is the intervention
realistic in your setting?

5. Does the comparison

intervention reflect your
current practice?
6. What alternatives are
available?
 Right Outcomes
7. Have all the right
outcomes been
considered?
8. Are the outcomes
appropriate to your
patient?
9. Does the intervention
meet their values and
preferences?
Critical appraisal for therapy

 Were the subjects randomized?

 Were all subjects received similar treatment?
 Were all relevant outcomes considered?
 Were all subjects randomized included in the analysis?
 Calculate CER, EER, RRR, ARR, AAI,RAI and NNT
 Were study subjects similar to our patients in terms of
prognostic factors?
 Critical appraisal for
Diagnosis
 Step 1: Are the results of the study valid?
Was the diagnostic test evaluated in a Representative spectrum of
patients (like those in whom it would be used in practice)?
What is best? Where do I find the information?
It is ideal if the diagnostic test is The Methods section should tell you
applied to the full spectrum of how patients were enrolled and
patients - those with mild, severe, whether they were randomly selected
early and late cases of the target or consecutive admissions. It should
disorder. It is also best if the patients also tell you where patients came from
are randomly selected or consecutive and whether they are likely to be
admissions so that selection bias is representative of the patients in whom
minimized. the test is to be used.

This paper: Yes  No  Unclear  Comment:

Was the reference standard applied regardless of the index test
result?
What is best? Where do I find the information?
Ideally both the index test and the The Methods section should
reference standard should be indicate whether or not the
carried out on all patients in the reference standard was applied to
study. In some situations where the all patients or if an alternative
reference standard is invasive or reference standard (e.g., follow-up)
expensive there may be was applied to those who tested
reservations about subjecting negative on the index test.
patients with a negative index test
result (and thus a low probability of
disease) to the reference standard.
An alternative reference standard is
to follow-up people for an
appropriate period of time
(dependent on disease in question)
to see if they are truly negative.
This paper: Yes  No  Unclear  Comment:
Was there an independent, blind comparison between the index
test and an appropriate reference ('gold') standard of diagnosis?
What is best? Where do I find the information?
There are two issues here. First The Methods section should have
the reference standard should bea description of the reference
appropriate - as close to the 'truth' standard used and if you are
as possible. Sometimes there may unsure of whether or not this is an
not be a single reference test that appropriate reference standard you
is suitable and a combination of may need to do some background
tests may be used to indicate the searching in the area. The
presence of disease.Second, the Methods section should also
reference standard and the index describe who conducted the two
test being assessed should be tests and whether each was
applied to each patient conducted independently and
independently and blindly. blinded to the results of the other.
Those who interpreted the results
of one test should not be aware of
the results of the other test.

This paper: Yes  No  Unclear  Comment:

Step 2: What were the results?

There are two types of results commonly reported

in diagnostic test studies.

1. The accuracy of the test and is reflected in

the sensitivity and specificity.

2. How the test performs in the population

being tested and is reflected in predictive
values (also called post-test probabilities).
To explore the meaning of these terms, consider a
study in which 1000 elderly people with suspected
dementia undergo an index test and a reference
standard. The prevalence of dementia in this group is
25%. 240 people tested positive on both the index test
and the reference standard and 600 people tested
negative on both tests. The first step is to draw a 2 x 2
table as shown below. We are told that the prevalence
of dementia is 25% therefore we can fill in the last row
of totals - 25% of 1000 people is 250 - so 250 people
will have dementia and 750 will be free of dementia.
We also know the number of people testing positive
and negative on both tests and so we can fill in two
more cells of the table.
 Gold Standard

+ve -ve
Index test +ve 240

-ve 600

250 750 1000

 Gold Standard

+ve -ve

Index test +ve

240 150 390

-ve
10 600 610
250 750 1000
What is the measure? What does it mean?
Sensitivity (Sn) = the The sensitivity tells us how well the
proportion of people with the test identifies people with the
condition who have a positive condition. A highly sensitive test will
test result. not miss many people.
In our example, the Sn = 10 people (4%) with dementia were
240/250 = 0.96 falsely identified as not having it. This
means the test is fairly good at
identifying people with the condition.
Specificity (Sp) = the The specificity tells us how well the
proportion of people without the test identifies people without the
condition who have a negative condition. A highly specific test will not
test result. falsely identify many people as having
the condition.
In our example, the Sp = 150 people (20%) without dementia
600/750 = 0.80 were falsely identified as having it.
This means the test is only moderately
good at identifying people without the
condition.
Positive Predictive Value (PPV) This measure tells us how well the test
= the proportion of people with a performs in this population. It is
positive test who have the dependent on the accuracy of the test
condition. (primarily specificity) and the
prevalence of the condition.

In our example, the PPV = Of the 390 people who had a positive
240/390 = 0.62 test result, 62% will actually have
dementia.
Negative Predictive Value This measure tells us how well the test
(NPV) = the proportion of people performs in this population. It is
with a negative test who do not dependent on the accuracy of the test
have the condition. and the prevalence of the condition.

In our example, the NPV = Of the 610 people with a -ve test , 98%
600/610 = 0.98 will not have dementia.
 Step 3: Applicability of the results
Were the methods for performing the test described in sufficient
detail to permit replication?
What is best? Where do I find the information?

The article should have sufficient The Methods section should

description of the test to allow its describe the test in detail.
replication and also
interpretation of the results.

This paper: Yes  No  Unclear  Comment:

Hierarchy/Level of evidence

 I a. Meta-analysis of RCT
b. Large RCT
 II a. Controlled trial without randomization
b. Cohort, case control studies
 III a. Cross-sectional
b. Case series, case reports

 IV Expert opinion
 Impelentation
Impelentation of
of EBM
EBM
practice
practice How
How to
to get
get started
started
1. Teaching EBM in medical schools
 Easier than to change the already existing attitude
 Most important
 May be included in formal curricula or integrated in
existing activities: ward rounds, on calls, case
presentations, group discussions, journal clubs, etc
2. Workshop for teaching staff
3. Workshop for practitioners, incl. nurses
Resistance
Resistance to
to EBM
EBM teaching
teaching &
&
learning
learning

 Rudimentary skill in critical appraisal /

methodological skill
 Limited resources, esp. time factor
 Lack of high quality evidence
 Scepticism toward evidence-based
practice
 ‘Happy’ with current practice
Development of EBM practice

 Passive diffusion model

 Active dissemination model
 Coordinated implementation
model:
 Patients & community
 Health administrators
 Public policy makers
 Clinical policy makers
 Strategies for developing EBM
practice

 Clinical guidelines
 Practice development leaders (! Environment)
 Development units
 Dissemination of good practice
 Networking
 Research summaries
 Action research