Evidence-Based Medicine:

Diagnosis of Helicobacter
pylori infection

Clinical Scenario
The patient is a middle aged male with
symptoms of dyspepsia. Your first concern in
managing this patient is to determine if the
dyspepsia is related to peptic ulcer disease.
This generally requires endoscopy, which is a
minimally invasive, but a relatively expensive
diagnostic test. To decrease the use of
endoscopy, you have been considering the
strategy of testing for H. pylori, treating those
that are positive, and then doing an
endoscopy on those that remain symptomatic.

Clinical Scenario
The standard laboratory ELISA has been the
favored screening test for H. pylori but this
test can take days to accomplish. Recently you
have read about more convenient in-office or
"near patient" whole-blood tests (such as
FlexSure) that can show results within hours.
Before you consider a change in practice, you
want to find out if the these "near patient"
tests, such as FlexSure, are as sensitive as the
"gold standard" ELISA test for detecting H.
pylori.

Steps in Practicing
EBM
1.
2.
3.
4.
5.

Convert the need for information into

an answerable question.
Track down the best evidence with which to
answer that question.
Critically appraise the evidence for its
validity, impact, and applicability.
Integrate the evidence with our clinical
expertise and our patients characteristics
and values.
Evaluating our effectiveness and efficiency in
executing steps 14 and seeking ways to
improve them both for next time.

The clinical question: PICO

Patient or
Problem

Interventi
on

Comparis Outcome
on

Adults with
suspected
H. pylori

The "near
patient"
wholeblood tests
such as
FlexSure

Gold
standard:
the ELISA
assay

Diagnosis
of
Helicobact
er pylori
infection

The clinical question

In adults with suspected H. pylori,
are the "near patient" whole-blood
tests such as FlexSure, as accurate
as the ELISA assay in aiding
diagnosis?

Steps in Practicing
EBM
1.
2.
3.
4.
5.

Convert the need for information into an

answerable question.
Track down the best evidence with
which to answer that question.
Critically appraise the evidence for its
validity, impact, and applicability.
Integrate the evidence with our clinical
expertise and our patients characteristics
and values.
Evaluating our effectiveness and efficiency in
executing steps 14 and seeking ways to
improve them both for next time.

The search strategy

Pubmed database:
(http://www.ncbi.nlm.nih.gov/sites/entre
z?db=pubmed)
Using the Clinical Queries function of
PubMed:
Key words:
h pylori AND
flexsure

Clinical Study Categories: Diagnosis

Scope: Narrow

The Evidence
Duggan AE, Elliott, C. Logan
RF.Testing for Helicobacter pylori
infection: validation and diagnostic
yield of a near patient test in primary
care. BMJ. 319(7219):1236-9,1999
Nov 6.
Testing for Helicobacter pylori infecti
on - validation and diagnostic yield o
f a near patient test in primary
care.pdf

Steps in Practicing
EBM
1.
2.
3.
4.
5.

Convert the need for information into an

answerable question.
Track down the best evidence with which to
answer that question.
Critically appraise the evidence for its
validity, impact, and applicability.
Integrate the evidence with our clinical
expertise and our patients characteristics
and values.
Evaluating our effectiveness and efficiency in
executing steps 14 and seeking ways to
improve them both for next time.

Appraising the Evidence

1. Is this evidence about the accuracy
of a diagnostic test valid?
2. Does this (valid) evidence
demonstrate an important ability of
this test to accurately distinguish
patients who do and do not have a
specific disorder?
3. Can I apply this valid, important
diagnostic test to a specific patient?

Is this evidence about the

accuracy of a diagnostic test
valid?

Is this evidence about the

accuracy of a diagnostic test
valid?
1. Measurement

Was the reference (gold) standard

measured independently, i.e. blind to our
target test?
Yes. A 7ml blood sample was taken from each
patient. The FlexSure test was administered at
the variou sites. Then the remaining blood test
was sent to University Hospital were all
samples were also tested with the ELISA assay
by a single operator blinded to the FlexSure
results. (under Methods, p. 1237).

Is this evidence about the

accuracy of a diagnostic test
valid?
2. Representative

Was the diagnostic test evaluated in

an appropriate spectrum of patients
(those in whom we would use it in
practice)?
Yes. Patients were from an appropriate
spectrum representing a wide range of
ages, duration and severity of
symptoms. Patients were recruited from
43 general practices in England.

Is this evidence about the

accuracy of a diagnostic test
valid?
3. Ascertainment

Was the reference standard

ascertained regardless of the
diagnostic test result?
Yes, 389 of 394 patients were tested by
the reference standard ELISA assay
regardless of the results of the FlexSure
test. 5 patients did not have serum
available for the ELISA testing. (See
Results p. 1237).

Are the results of this study

valid?
This is a well designed study
according to ACP Journal Club.

Does this (valid) evidence

demonstrate an important
ability of this test to accurately
distinguish patients who do
and do not have a specific
disorder?

2 x 2 Table
Disease
Totals
Presen Absent
t
Diagnosti Positive
a
b
a+b
c
Negativ
c
d
c+d
Test
e
Totals
a+c
b+d a+b+c
Sensitvity = a/(a+c).
+d
Specificity = d/(b+d).
Positive Predictive Value = a/(a+b).
Negative Predictive Value = d/(c+d).

Technical vs. Clinical

Precision
Baby Jeff: The case of screening for
muscular dystrophy at HH
Technical Precision of CPK test:
Sensitivity (ability to rule out disease): 100%
Specificity (ability to identify disease): 99.98%

But,
The prevalence of MD is 1 in 5000 (0.02%)

Does Baby Jeff have M.D.?

Of 100,000 males, 20 will have
M.D.
(1 in 5,000, or 0.02% prevalence)
The test will correctly identify all 20
who have the disease (sensitivity =
100%)

Does Baby Jeff have M.D.?

Of the 99,980 without M.D.
Specificity = 99.98%
99,980 x 0.9998 = 99,960 will be
negative
Therefore, false positives = 20

. . . The Rest of the Story

Therefore,
Out of 100,000 infants, 20 will be truly
positive and 20 will be false positive
Positive predictive value = 50%
The child with a positive screening test
only has a 50/50 chance of actually having
MD!

HARM!

Another Example: Lyme

Disease
Antibody assay
Sensitivity= 95%; specificity= 95%

High Lyme Disease prevalence (20%)

Positive predictive value = 83%

Low Lyme Disease prevalence (2%)

Positive predictive value = 28%
Brown SL. JAMA 1999;282:62-6.

Another Example:
Mammography
Mammography in women between 4050 yrs
If 100,000 women are screened:
6,034 mammograms will be abnormal
5,998 (99.4%) will be false-positive
36 will actually have breast cancer
Why? Prevalence = 0.036%
Hamm RM. J Fam Pract 1998;47:44-52.

What are the results?

Results were available for 375 patients (9 patients
had indeterminate ELISA results, 5 had invalid
FlexSure results, and 8 had no serum available).
36% of patients had H. pylori infection.

FlexSure Positive
FlexSure negative
Totals

H. pylori ELISA
Positiv Negati
e
ve
90
5
44
236
134
241

Totals

95
280
375

Technical precision

FlexSure Positive
FlexSure negative
Totals

H. pylori ELISA
Positiv Negati
e
ve
90
5
44
236
134
241

Totals

95
280
375

Sensitivity: measures the proportion of patients with

the disease who also test positive for the disease in
this study.
Sensitivity = true positive / all disease positives =
90/134 = 67% 67% of the patient who had H. pylori
infection, tested positive for the disease

Technical precision

FlexSure Positive
FlexSure negative
Totals

H. pylori ELISA
Positiv Negati
e
ve
90
5
44
236
134
241

Totals

95
280
375

Specificity: measures the proportion of patients without

the disease who also test negative for the disease in
this study.
Specificity = true negative / all disease negatives =
236/241= 98% 98% of the patients who did not have
H. pylori, tested negative for the disease.

Clinical precision

FlexSure Positive
FlexSure negative
Totals

H. pylori ELISA
Positiv Negati
e
ve
90
5
44
236
134
241

Totals

95
280
375

Positive Predictive Value: measures the proportion of

patients tested positive for the disease who have H.
pylori.
Positive Predictive Value = true positive / all tested
positive = 90/95= 95% 95% of the patients who
tested positive for the disease have H. pylori.

Clinical precision

FlexSure Positive
FlexSure negative
Totals

H. pylori ELISA
Positiv Negati
e
ve
90
5
44
236
134
241

Totals

95
280
375

Negative Predictive Value: measures the proportion of

patients test negative for the disease who do not have the
disease.
Negative Predictive Value = true negative / all tested
negatives = 236/280= 84% 84% of the patients tested
negative for the disease who did not have H. pylori.

Technical Precision
Specificity: Remember SpPin
When a test has a high Specificity, a
Positive test rules IN the disorder.
Sensitivity: Remember SnNout
When a test has a high Sensitivity, a
Negative result rules OUT the disorder.

Can I apply this valid,

important diagnostic test to
a specific patient?

Are the results of this

diagnostic study applicable to
my patient?
1. Is the diagnostic test available,
affordable, accurate, and precise in
our setting?
Yes

Are the results of this

diagnostic study applicable to
my patient?
2. Can we generate a clinically sensible
estimate of our patients pre-test probability?
a. From personal experience, prevalence statistics,
practice databases, or primary studies.

Yes

b. Are the study patients similar to our own?

Yes

c. Is it unlikely that the disease possibilities have

changed since this evidence was gathered?

Yes

Test-Treatment Thresholds

Do not
test

Do not
test

Test, and treat

on the basis of

.10

Get on
with
treatment

the test result

Do not
treat
.20

.30

.40

.50

.60

.70

.80

Prevalence (pre-test probability) of target disorder

.90

Clinical Probability
Clinical features
of presentation
including
characteristics of
patient, history,
Test (can
and exam.
include

Pre-Test
Probability

distinct
features of
presentation
in history or
examination).

High PostTest
Probability

Knowing
likelihood ratio
allows you to
calculate posttest
probability

Low Post-Test
Probability

Likelihood ratio

FlexSure Positive
FlexSure negative
Totals

H. pylori ELISA
Positiv Negati
e
ve
90
5
44
236
134
241

Totals

95
280
375

Likelihood Ratio+ = sens/(1-spec) = 67/(100-98) = 67/2 = 33.5

Likelihood Ratio- = (1-sens)/spec = (100-67)/98 = 33/98 = 0.34
Prevalence = (a+c)/(a+b+c+d) = 134/375 = 35.7%
Study pre-test odds = prevalence/(1-prevalence) = 35.7/64.3 = 0.56
Post-test odds = pre-test odds x likelihood ratio = 0.56 x 33.5 = 18.76
Post-test probability = post-test odds/(post-test odds +1) = 18.76/19.76 = 0.95

Are the results of this

diagnostic study applicable to
my patient?
3. Will the resulting post-test
probabilities affect our
management and help our patient?
1. Could it move us across a testtreatment threshold?
Yes, from pre-test probability of 35.7% to
post-test probability of 94.9%

Are the results of this

diagnostic study applicable to
my patient?
3. Will the resulting post-test probabilities
affect our management and help our
patient? (cont.)
2. Would our patient be a willing partner in
carrying it out?

Probably yes

3. Would the consequences of the test help our

patient reach his or her goals in all this?

Yes, reassurance when negative, labeling and

possibly generating awful diagnostic and prognostic
news if positive, leading to further diagnostic tests
and treatments, etc.

Steps in Practicing
EBM
1.
2.
3.
4.
5.

Convert the need for information into an

answerable question.
Track down the best evidence with which to
answer that question.
Critically appraise the evidence for its
validity, impact, and applicability.
Integrate the evidence with our clinical
expertise and our patients
characteristics and values.
Evaluating our effectiveness and efficiency in
executing steps 14 and seeking ways to
improve them both for next time.

How can I apply the results to

patient care?
The in-office or "near patient" test had
excellent specificity (98%) but a
sensitivity of only 67%, which means that
one third of patients infected with H.
pylori and a proportionate number of
those with peptic ulcer would be missed.
The authors conclude that tests with such
poor sensitivity should not be used for
the test-and-treat strategy (remember
SpPin and SnNout!).

How can I apply the results to

patient care?
An alternate approach exists, however. Given
its high specificity, the in-office test could be
used to rapidly and reliably diagnose two
thirds of infected patients; the more sensitive
laboratory ELISA could be reserved for those
with negative results. However, the costeffectiveness of this strategy would be highly
dependent on the relative costs of the tests
(the in-office test would have to be much less
expensive than the ELISA) and on the
prevalence of H. pylori in the population (the
fewer people infected, the larger the number
who would need a second test).

How can I apply the results to

patient care?
All of these factors should be
considered before an in-office test is
used for the test-and-treat strategy.

Steps in Practicing
EBM
1.
2.
3.
4.
5.

Convert the need for information into an

answerable question.
Track down the best evidence with which to
answer that question.
Critically appraise the evidence for its validity,
impact, and applicability.
Integrate the evidence with our clinical
expertise and our patients characteristics and
values.
Evaluating our effectiveness and efficiency
in executing steps 14 and seeking ways
to improve them both for next time.

Questions?