Taibah University

College of Applied Medical Sciences

(Quality Assurance in Medical Labs)

Lecture 5: Reference Intervals
(v1.7)

Dr. Bandar Suliman, BMSc. MClinSc. DipQA PhD

Medical Scientist, RSci MIBMS, MT(ASCP)
Asst. Prof. Molecular Immunology & Oncology, Taibah University
Adjunct Research Fellow, Center for Cancer Research, Monash University
30 Mar 2014
Objectives:

By the end of this lecture, you should:

• Understand what is reference interval

(range)
• Appreciate how reference ranges are
established and reviewed

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Reference Range:

What is Reference Range (Interval)?

- When a test is used for diagnosis, screening,

or prognosis, the test result is usually
compared with a reference interval (normal
range) that is defined as the usual value for a
healthy population.

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Reference Range:

• When looking at patient’s current results,

you need to also look at the same patient’s
previous results for comparison.

• For every laboratory test, there is an

internationally established reference range
that represent the test value in physiological
conditions.

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Patient’s Result:

• The T4 value for Patient-A is:

25.7 pmol/L

• The reference range for T4:

9.6 pmol/L 23.4 pmol/L

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Patient’s Result:

• The CEA value for Patient-B (who has

undertaken colon cancer surgical removal ):

11.4 ng/ml

• Previous results for CEA from Patient-B:

Pre-Op 43.1 - 41.7 - 42.9 - 44.6 ng/ml

Post-Op 3.4 - 5.6 - 7.2 - 8.9 - 9.7 ng/ml

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Establish a Reference Range:

How to establish reference ranges?

• The International Federation of Clinical
Chemistry (IFCC) has recommended use of
the term reference interval to denote the
usual limits of laboratory data.

• IFCC also recommended that the following

factors be specified when reference intervals
are established:

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Establish a Reference Range:

1. Makeup of the reference population with

respect to age, sex, and genetic &
socioeconomic factors.

2. The criteria used for including or

excluding individuals from the reference
sample group.

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Establish a Reference Range:

3. The physiologic and environmental

conditions under which the reference
population was studied and sampled,
including time, and date of collection,
intake of food and drugs, posture,
smoking, degree of obesity, and stage of
menstrual cycle.

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Establish a Reference Range:

4. The specimen collection procedure,

including preparation of the individual.

5. The analytical method used, including

details of its precision and accuracy.

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The Normal Value:

The IFCC considers the terms normal values

and normal range to be specific reference
interval that correspond to the health-
associated (central 95%) reference intervals.

Can reference ranges established in Mexico

be used in Saudi Arabia?

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Establish a Reference Range:

• In 2000, more than 31% of all US adult

population had LDL > 170 mg/dl.

• A National Cholesterol Education Program

was started, and its results were published
in the Journal of the American Medical
Association. This % dropped to 26 in 2002.

• The established reference range for LDL is

<100 mg/dl.

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Establish a Reference Range:

• Imagine that they established a reference

range for LDL using data from those
healthy people with high LDL values.

• Can the reference range established in

2000 be used in 2002 in the US?

• Can the 2000 reference range established

in the US be used in Africa?

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Selection of Subjects:

Because of the Diversity in:

• Instrumentation
• Methodologies
• Reagents
• Population
It is important that moderate-to large sized
hospital laboratories determine their own
reference intervals.
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Selection of Subjects:

• Plasma testosterone level is low in both

pre-pubertal boys and girls and increases
during puberty, attaining higher levels in
boys.

• Alkaline phosphatase (ALP) levels are

increased during growth as well as in men
and women older than 60 years.

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Selection of Subjects:

In Children:

• Reference-interval studies on healthy

children are limited because of the
psychological and physical pain of
phlebotomy.

• Many such studies are done on pediatric

patients for whom serum and plasma
samples are already available.

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Selection of Subjects:

For every laboratory test, the following

points must be taken into consideration:

• Is it normal?
• Is it significantly different from previous
results?
• Is it consistent with the clinical diagnosis?

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Diagnostic Efficacy:

What is Diagnostic Efficacy?

• The ability of a laboratory test to indicate

the presence/absence of a pathological
state from a specimen of a patient.

• It depends on 3 major factors: sensitivity,

specificity and predictive value.

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Diagnostic Efficacy:

1) What is Diagnostic Sensitivity?

• The probability that a diseased person will
have a positive test result (the frequency
of positive results among diseased person)
• Sensitivity is expressed as percentage.
Sensitivity = TP / (TP + FN) X 100
- TP = True positive
- TN = True negative

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Diagnostic Efficacy:

1) What is Diagnostic Sensitivity?

• The probability of a positive test result

given the presence of disease.
• How good is the test at detecting infection
in those who have the disease?
• A sensitive test will rarely miss people who
have the disease (few false negatives).

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Diagnostic Efficacy:

2) What is Diagnostic Specificity?

• Specificity relates to the test's ability to

exclude a condition correctly.
• Specificity of a test is the proportion of
healthy patients known NOT to have the
disease, who will test negative for it.
• Specificity = TN / (TN+FP) X 100

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Diagnostic Efficacy:

2) What is Diagnostic Specificity?

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Diagnostic Efficacy:

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Diagnostic Efficacy:

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Diagnostic Efficacy:

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Predictive Value:

• How predictive is this test result for this

particular patient?

• Determined by the sensitivity and

specificity of the test, and the prevalence
rate of disease in the population being
tested.

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Predictive Value:

What is the Prevalence Rate?

• Number of cases of illness existing at a

given time divided by the population at
risk..

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Predictive Value:

Predictive value for a positive result (PV+):

PV+ asks " If the test result is positive, what is

the probability that the patient actually has
the disease?"

PV+= TP / ( TP + FP )

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Predictive Value:

Predictive value for a negative result (PV-):

PV- asks: "If the test result is negative, what is

the probability that the patient does not
have the disease?"

PV- = TN / ( TN + FN )

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IF-AT (Individual Work):

Self-Test #5

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What you should remember:

u What is a reference range

u What is the usefulness of reference ranges
u How to establish reference ranges
u What is Diagnostic Efficacy
u What is Diagnostic Sensitivity, Specificity, and
Predictive Value?
u How to calculate different predictive values

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© 2010 Bandars.com

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