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ORIGINAL ARTICLE

Establishing the reference change values (RCVs)

and validating the delta check auto-verification in a
clinical biochemistry laboratory
Denver Clive Fernandez, Avinash S. S, Malathi M, Shivashankara A. R, Arun Kumar, Pearl Andrea Fernandez1

ABSTRACT
Aims: Establishing the reference change values (RCVs) and validating the delta check auto-verification in the hospital information
system (HIS). Materials and Methods: This study was conducted in the Hospital Laboratory-Biochemistry. Fifty-one parameters were
analyzed in three phases. Phase I: Delta check reference change values were established. Phase II: Delta check auto-verification was
validated in the hospital information system. Phase III: Calculation of test requiring manual verification, true and false positive rates.
Results: Out of all the test results, 1.35% failed the RCV-delta check thus requiring manual verification, and the remaining 98.65%
were auto-verified. Only 0.12% test results were true positives indicating laboratory error, and 1.23% were false positives and were
correlated clinically. Ten percent simulated data results and 0.37% actual patient results were not identified by the newly introduced
HIS. Conclusions: RCV-delta check is a refined form of the delta checks used to analyze acceptable analytical and biological variation
in laboratories. Majority of tests passed the RCV-delta check auto-verification, implying that very few test reports require manual
verification. True positives can be detected in the laboratory. All HISs should be validated before implementing complete auto-verification.
Key Words: Auto-verification, delta check, reference change values (RCVs), turnaround time (TAT)

Introduction Delta check is an important part of a patient test

report check that ensures the release of results with
A large clinical biochemistry laboratory catering to
acceptable biological variation but it does not take into
tertiary care patients is faced with challenges to
account the analytical variations in the lab. Hence, the
dispatch accurate and precise patient test reports
establishment of reference change value (RCV), which
within an acceptable turnaround time (TAT). Reducing
takes into account the analytical as well as intra-individual
the TAT can be achieved by preanalytical, analytical,
variation, is of significance for any medical testing
and postanalytical automation, and linking to
laboratory.[5] RCV/critical difference, is the value that
laboratory information systems (LISs) and Hospital
must be exceeded before a change in consecutive test
information systems (HISs).[1-3] Accuracy and precision
results, is statistically significant, at a predetermined
of reports can be achieved by eternal quality control
(EQC) and internal quality control (IQC), respectively.
Further, checks of patient test reports in the form Department of Biochemistry, Father Muller Medical College,
1
St. Aloysius College Mangalore, Mangaluru, Karnataka, India
of limit check, critical value checks, delta checks,
Address for correspondence: Dr. Denver Clive Fernandez,
and consistency checks can significantly improve
Department of Biochemistry, Father Muller Medical College,
the quality of results.[4] Manual verification of all the Mangaluru, Karnataka, India.
above in medium and large-sized laboratories delays E-mail: drdenverfernandez@gmail.com
the process, and makes applying these checks for all
reports impractical. Auto-verification of these patient
This is an open access article distributed under the terms of the
report checks can minimize the delay.[4]
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License, which allows others to remix, tweak, and build upon the
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How to cite this article: Fernandez DC, Avinash SS, Malathi M,

DOI: Shivashankara AR, Kumar A, Fernandez PA. Establishing the reference
10.4103/0975-9727.199363 change values (RCVs) and validating the delta check auto-verification
in a clinical biochemistry laboratory. Muller J Med Sci Res 2017;8:42-6.

42 © 2017 Muller Journal of Medical Sciences and Research | Published by Wolters Kluwer - Medknow
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Fernandez, et al.: Category: Clinical chemistry/laboratory medicine

probability.[5] RCV brings an objective evidence-based
edge to the interpretation of a patient’s test report when
a previous report is available.
In a large clinical biochemistry lab with an input of more
than 1,000 samples per day, it is absolutely necessary to
establish the RCV. This present study was done in order
to reduce the TAT for the release of accurate and precise
results with very little unacceptable and unexplainable
variation. The RCV and validating the delta check auto-
verification manually according to the CLSI Auto-10A
guidelines,[6] in a clinical biochemistry lab was done.
Materials and Methods
This study was conducted in the Clinical Biochemistry
section of the Hospital Laboratory. Fifty-one parameters
were analyzed.
Institutional ethical clearance was taken before starting the
study. No human or animal subjects were directly involved
in this study. This study was carried out in three phases.
Phase I
The delta check (RCV)[7] was established for each of the
chemistry and immunoassay analytes and was done
based on the following equation:
RCV = 2½ × Z × [CVA2 + CVI2]½
where RCV — Reference Change values[7]
2½ — Variation in present sample is compared with
previous sample
Z — Z-score for 95% confidence interval.
CVA — from the IQC program of our laboratory
CVI — from Westgard database of desired biological
variable[8]
Total variance in the lab,[5] SD2 = preanalytical Standard
Deviation (SD)2 + analytical SD2 + postanalytical SD2
Instead of SD, CV was used as a measure of
dispersion. [5] Since the preanalytical, i.e. sample
collection and centrifugation are standardized, the
preanalytical variation is minimal and was excluded. Only
Analytical CVA and CVI were used for the calculation of
RCV according to Harris and Yasaka. In the IQC, all the
analytes were estimated using IQC dispersed across 6
months. This IQC data was used for calculation of CVA.
IQC controls that are freeze-dried lyophilized powder
stored at –20° were reconstituted with 5 mL distilled water
and restored in aliquots at –20° when required these
aliquots were brought to room temperature by keeping
out for 20 min and then the quality control (QC) run in
the instrument, the similar procedure was followed for
all analytes based on types of control used. CVA was
calculated for all the parameters, using the following
formula: . The respective values were
computed using the formula for RCV and the results
obtained are shown in Table 1.
Phase II
Validation of delta check auto-verification alert in the HIS
was done under standard guidelines, CLSI Auto-10A
guidelines,[6] which include:
1. Using simulated data of patient test result, artificially
generated data (30 values for each analyte) were
entered in HIS and were verified manually.

Table 1: Reference change values (RCV %) of analytes (phase I)

Analyte RCV Analyte RCV Analyte RCV Analyte RCV
P. Glucose 14.45 S. Iron 75.47 HbA1c 12.04 S. TSH 55.05
S. Urea 34.53 S. Total Protein 13.67 S. C3 18.69 S. Ft4 19.67
S. Creatinine 21.57 S. Albumin 15.91 U. MTPU-24 h 98.82 S. T4 17.85
S. Uric acid 25.99 S. Total Bilirubin 61.59 U. Creatinine 67.83 S. T3 20.76
S. HCO3 25.42 S. Bilirubin Direct 102.67 S. Anti-TPO 54.64
S. Calcium 10.78 S. AST 35.18 S. Ferritin 43.16
S. Phosphorous 24.96 S. ALT 54.51 S. LH 65.83
S. Magnesium 27.48 S. ALP 20.61 S. FSH 32.77
S. Cholesterol 20.27 S. GGT 38.52 S. Prolactin 65.43
S. Triglyceride 58.59 S. Lactate 75.79 S. TPSA 52.75
S. HDL 21.57 S. Sodium 4.94 S. AFP 36.6
S. LDL 22.99 S. Potassium 14.57 S. CA 125 70.83
S. CK 63.86 S. Chloride 6.89 S. CA 15-3 24.95
S. LDH 25.89 CK-MB Activity 55.82 S. CA 19-9 50.4
S. Amylase 26.22 S. CRP 117.49 S. Cortisol 61.63
S. Lipase 90.76 S. RF 26.23

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Fernandez, et al.: Category: Clinical chemistry/laboratory medicine

2. Actual patient values spanning over a month for each Table 2: Validation of RCV (phase II)
chemistry and immunoassay analyte were run in the Validation Total Manual and his His percentage
system. The data generated were verified manually. tests data mismatch error (%)
Simulated patient data 200 20 10
Validation of HIS with manual cross-checking was done Actual patient reports 810 3 0.37
to ensure the systems reliability.[4] Here the patient test HIS = Hospital information system

values, simulated/actual values were fed in the test site for

a patient, subsequent reports were generated with different
Table 3: Results of phase III
values at a different time/date. Values that failed the RCV- Data verification Number Percentage (%)
delta check appeared with a yellow background in the HIS. Total number of samples 142 —
The values that matched with manual verification were Total number of tests 810 —
concluded as validated, and values that did not match with Total number of delta pass (AV) 799 98.65
manual verification were concluded as validation failed. Total number of delta fail (MV) 11 1.35
The results obtained are mentioned in Table 2. Total number of False Positives 10 1.23
Total number of True Positives 1 0.12
AV = Auto-verified, MV = Manually verified
Phase III
Using the decision-making algorithm according to the remaining 98.65% were auto-verified [Table 2]. This
CLSI Auto-10A guidelines and calculating the percentage implies that 1.35% patient test results fail the delta check
of test requiring manual verification, true positive and when RCV are used, nevertheless, delta check is only a
false positive rates of the reporting were generated. part of sample check and does not eliminate the need for
limit, critical and consistency checks which need to be
True positives are errors made in specimen identification, established and validated. Amongst the 1.35% delta fail
test performance, or test result reporting, which are 0.12% were true positives refer Table 3. True positives
correctable errors in the lab. False positives are changes are errors identified in the laboratory, while the remaining
ascribable to response in disease or therapy. The 1.35% were correlated clinically, indicating that they were
percentage of tests that were auto-verified by RCV-delta false positives. Moreover, 10% of actual patient result
check alone and the percentage requiring manually
and 0.37% of simulated data result were not picked up
verified were determined by checking with patient
by the newly introduced HIS in detecting delta errors.
requisitions through the following algorithm based on
the CLSI Auto10-A guidelines.[9]
Discussion
Most tertiary care laboratories rely on manual verification
alone to validate test reports; this increases the TAT
in medium- to large-sized laboratories and leads to
inconsistent quality.

Delta check is an important part of sample check that

ensures release of reports with acceptable variation.
There are four types of delta check: Delta difference, delta
percent change, rate difference, and rate percent change.
The delta check has been considered a recognized
form of quality assurance.[5] But it does not account for
analytical variation in the laboratory, in present laboratory
practice the analytical variation is readily available as
coefficient of variation (CV) from the IQC program. RCV
accounts for this analytical variation as CVA as well as
the intra-individual variation (CVI), and is known to be a
Results refined form of the delta check.[5] In this study, as a part
The RCV was established and the values obtained are of phase I, we established the RCV using the formula as
mentioned in Table 1. mentioned above for 51 analytes done in our laboratory.

Out of all the inpatient test results, 1.35% failed the Using these established RCV for checking patient test
RCV-delta check thus requiring manual verification; the report is a sign of good laboratory practice, but for most

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Fernandez, et al.: Category: Clinical chemistry/laboratory medicine
tertiary care centers this is not practical with the given
sample load. Hence, it is necessary to implement auto-
verification. Auto-verification maintains the quality of test
reports and significantly reduces the TAT. Here we entered
the RCV into the HIS, test site followed by the live site.
Auto-verification systems dispatch patient test reports
after performing appropriate predefined checks without
the need of manual validation. Therefore, before auto-
verification is implemented, it needs to be validated.[6]
The guideline[6] also recommends a two-step validation,
with simulated data and actual patient test results.
Simulated data help check this system across the
entire analytical measuring range for robustness of
performance and helps pick up errors not detectable
by using patient test results alone. Validation with
simulated data revealed 10% error in the HIS, whereas
validation with patient test results revealed 0.37%
errors, This discrepancy was seen because, validation
with simulated data tests this system across it’s
analytical measuring range (AMR) thereby helps in
detecting minute errors, these may not be seen in day-
to-day practice but need to be identified and corrected.
The errors identified were taken constructively by the
HIS team and corrected.
Approximately, 1.35% of test results failed the delta
check and required manual verification. Remaining
98.65% were auto-verified when the RCV-delta check
was used alone, further checks of these patient reports
in the form of limit, critical, and consistency checks
are mandatory for complete auto-verification. [4,6]
Nevertheless, this clearly implies that very few test
reports need manual validation, this is supported by
a study done by Shih et al., who demonstrated that
80% test reports can be auto-released and the TAT
is shortened. [4] Their study was conducted using a
middleware and a dedicated auto-verification system.
Their delta checks were based on the four types of
delta checks as follows: Delta difference, delta percent
change, rate difference, and rate percent change.[5] In
our study, we used RCV as a form as delta check and
observed it to be a form of delta percent change; our
validation was performed using the HIS. We observed a
higher auto-verification rate of 98.65% as we performed
only the RCV-delta check. The purpose of delta check
is to detect true positives. True positives are errors that
occur in the laboratory[9] (for example, specimen mix-up,
calibration errors, and typing errors). The true positive
rate was 0.12%. False positives are changes occurring
in patient test report either due to disease or due to
response to treatment; these correlate clinically and is
not the main purpose of the delta check. The common
false positives encountered were cases of hypokalemia
Muller Journal of Medical Sciences and Research | Vol 8 | Issue 1 | January - June 2017 45
on treatment, nephrotic syndrome, Chronic Kidney
Disease (CKD) patients on dialysis, and hepatic failure.
RCV-delta check was therefore a better model of the delta
checks, which was established and validated in the HIS.
All HISs need to be validated before the implementation.
Auto-verification drastically reduces the TAT.
Standardization of patient test result verification with RCV-
delta percentage change and auto-verification under the
CLSI Auto-10A guidelines can produce quality reports
consistently even as the test load increases with time.
Limitations
1. One percent error was present in the HIS with actual
patient results were tested.
2. Ten percent error was present with simulated data.
3. For establishing the RCV-delta check, we have used
analytical CV. For analytes where analytical CV is
greater than allowable CV, the established RCV may
be broader and may fail to detect true positives.
4. Large number of actual patient test results need to
be checked over a longer duration of time.
5. Manual verification for the detection of false
negatives was not done.
Financial Support and Sponsorship
Nil.
Conflicts of Interest
This study was presented as a poster in the South
Regional Conference of the Association of Clinical
Biochemists of India 2014.
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