Reference Ranges PDF

Claudia Schäfer, CIR, Penzberg  4486 July 2017
elecsysrefranges.doc
Elecsys Reference Ranges
1 Thyroid Assays: ............................................................................................................................ 4

1.1 Elecsys FT3 III ........................................................................................................................ 4
1.2 Elecsys FT4 II ......................................................................................................................... 5
1.3 Elecsys T3 ............................................................................................................................. 5
1.4 Elecsys T4 ............................................................................................................................. 5
1.5 Elecsys TSH............................................................................................................................. 6
1.6 Elecsys T-uptake ................................................................................................................... 6
1.7 Elecsys Calcitonin ................................................................................................................. 6
1.8 Elecsys Tg II ........................................................................................................................... 6
1.9 Elecsys Anti-Tg ...................................................................................................................... 7
1.10 Elecsys Anti-TPO ................................................................................................................... 7
1.11 Elecsys Anti-TSHR ................................................................................................................. 7
2 Cardiac: ........................................................................................................................................ 9
2.1 Elecsys CK-MB STAT............................................................................................................... 9
2.2 Elecsys Digoxin ..................................................................................................................... 9
2.3 Elecsys Digitoxin ................................................................................................................... 9
2.4 Elecsys Myoglobin STAT ....................................................................................................... 9
2.5 Elecsys proBNP II ................................................................................................................ 10
2.6 Elecsys Troponin I ............................................................................................................... 12
2.7 Elecsys Troponin T hs ......................................................................................................... 12
3 Fertility Assays: .......................................................................................................................... 14
3.1 Elecsys ACTH....................................................................................................................... 14
3.2 Elecsys AMH ....................................................................................................................... 14
3.3 Elecsys Cortisol II ................................................................................................................ 16
3.4 Elecsys DHEAS .................................................................................................................... 17
3.5 Elecsys Estradiol III ............................................................................................................. 18
3.6 Elecsys FSH ......................................................................................................................... 20
3.7 Elecsys LH ........................................................................................................................... 22
3.8 Elecsys Progesterone III...................................................................................................... 25
3.9 Elecsys Prolactin II .............................................................................................................. 26
3.10 Elecsys SHBG ...................................................................................................................... 26
3.11 Elecsys Testosterone II ....................................................................................................... 27
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3.12 Elecsys HCG STAT ............................................................................................................... 32
3.13 Elecsys HCG+ .................................................................................................................... 32
4 Diabetes:.................................................................................................................................... 35
4.1 Elecsys C-Peptide ................................................................................................................. 35
4.2 Elecsys Insulin ...................................................................................................................... 35
5 Preeclampsia: ............................................................................................................................ 36
5.1 Elecsys PlGF /sFlt-1 .............................................................................................................. 36
6 Tumor Marker: .......................................................................................................................... 38
6.1 Elecsys AFP .......................................................................................................................... 38
6.2 Elecsys CA 125 II .................................................................................................................. 38
6.3 Elecsys CA 15-3 II ................................................................................................................. 39
6.4 Elecsys CA 19-9 .................................................................................................................... 40
6.5 Elecsys CA 72-4 .................................................................................................................... 40
6.6 Elecsys CEA .......................................................................................................................... 40
6.7 Elecsys Cyfra 21-1 ................................................................................................................ 41
6.8 Elecsys HE4 .......................................................................................................................... 41
6.9 Elecsys ProGRP .................................................................................................................... 45
6.10 Elecsys free PSA ................................................................................................................... 48
6.11 Elecsys NSE .......................................................................................................................... 50
6.12 Elecsys total PSA .................................................................................................................. 50
6.13 Elecsys S 100 ........................................................................................................................ 52
6.14 Elecsys SCC .......................................................................................................................... 54
7 Down Syndrome Screening: ...................................................................................................... 60
7.1 Elecsys free ßhCG ................................................................................................................ 60
7.2 Elecsys PAPP-A..................................................................................................................... 61
8 Anemia: ..................................................................................................................................... 64
8.1 Elecsys Ferritin ..................................................................................................................... 64
8.2 Elecsys Folate III................................................................................................................... 64
8.3 Elecsys Folate RBC ............................................................................................................... 65
8.4 Elecsys Vitamin B12 II .......................................................................................................... 66
9 Bone Marker: ............................................................................................................................. 67
9.1 Elecsys -CrossLaps ............................................................................................................. 67
9.2 Elecsys hGH ......................................................................................................................... 67
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9.3 Elecsys N-MID Osteocalcin .................................................................................................. 68
9.4 Elecsys PTH .......................................................................................................................... 68
9.5 Elecsys PTH (1-84) ............................................................................................................... 68
9.6 Elecsys total P1NP ............................................................................................................... 69
9.7 Elecsys Vitamin D total ........................................................................................................ 70
10 Varia: ......................................................................................................................................... 72
10.1 Elecsys IgE II ......................................................................................................................... 72
11 Rheumatoid Arthritis: ................................................................................................................ 73
11.1 Elecsys Anti-CCP .................................................................................................................. 73
12 Sepsis: ........................................................................................................................................ 75
12.1 Elecsys BRAHMS Procalcitonin ............................................................................................ 75
12.2 Elecsys IL-6........................................................................................................................... 76
13 ISDs: ........................................................................................................................................... 77
13.1 Elecsys Cyclosporine ............................................................................................................ 77
13.2 Elecsys Everolimus............................................................................................................... 77
13.3 Elecsys Sirolimus.................................................................................................................. 78
13.4 Elecsys Tacrolimus ............................................................................................................... 78
14 Alzheimer’s Disease Diagnosis: ................................................................................................. 78
14.1 Elecsys ß-Amyloid (1-42) CSF............................................................................................... 78
15 Hepatitis: ................................................................................................................................... 81
15.1 Elecsys Anti-HAV.................................................................................................................. 81
15.2 Elecsys Anti-HAV IgM .......................................................................................................... 82
15.3 Elecsys Anti-HBc .................................................................................................................. 82
15.4 Elecsys Anti-HBc IgM ........................................................................................................... 82
15.5 Elecsys Anti-HBe .................................................................................................................. 83
15.6 Elecsys HBeAg ...................................................................................................................... 83
15.7 Elecsys Anti-HBs II................................................................................................................ 83
15.8 Elecsys HBsAg II ................................................................................................................... 83
15.9 Elecsys HBsAg II quant II ...................................................................................................... 84
15.10 Elecsys Anti-HCV II ............................................................................................................... 84
16 Sexually transmitted diseases: .................................................................................................. 86
16.1 Elecsys HIV Ag ...................................................................................................................... 86
16.2 Elecsys HIV combi PT ........................................................................................................... 86
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16.3 Elecsys HTLV-I/II .................................................................................................................. 86
16.4 Elecsys Syphilis .................................................................................................................... 87
17 TORCH: ...................................................................................................................................... 89
17.1 Elecsys CMV IgG .................................................................................................................. 89
17.2 Elecsys CMV IgG Avidity ...................................................................................................... 89
17.3 Elecsys CMV IgM.................................................................................................................. 90
17.4 Elecsys HSV-1 IgG ................................................................................................................ 90
17.5 Elecsys HSV-2 IgG ................................................................................................................ 91
17.6 Elecsys Rubella IgG .............................................................................................................. 91
17.7 Elecsys Rubella IgM ............................................................................................................. 92
17.8 Elecsys Toxo IgG .................................................................................................................. 92
17.9 Elecsys Toxo IgG Avidity ...................................................................................................... 93
17.10 Elecsys Toxo IgM ................................................................................................................. 94
1 Thyroid Assays:
Please note that within the attached brochure Elecsys® Thyroid Tests – “Reference Intervals
for Children and Adults” reference intervals for the entire thyroid tests are summarized that
Roche offers for the Elecsys® 2010 / cobas e 411 / MODULAR ANALYTICS <E> / cobas e
601/2 automated immunoassay analyzers for children and adults and pregnant women.
Printed brochures can be ordered with Cat.no. 04625889990 (German) and cat.no.
04640292001 (English).
This booklet contains also results of a detailed study about influencing factors on thyroid
parameters in a well characterized reference group of adults. Different inclusion and
exclusion criteria were applied (e.g. sonographic results (thyroid volume and density) as well
as criteria according to the guidelines of the National Academy of Clinical Biochemistry
(NABC).
1.1 Elecsys FT3 III
Expected values
Euthyroid: 3.1-6.8 pmol/L (2.0-4.4 pg/mL)
These values correspond to the 2.5th and 97.5th percentiles of results
obtained from a total of 5366 healthy test subjects examined.
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For detailed information about reference intervals in children, adolescents
and pregnant women, refer to the brochure “Reference Intervals for Children
and Adults”, REF English: 04640292, German: 04625889.
This booklet also contains results of a detailed study about influencing factors
on thyroid parameters in a well characterized reference group of adults.
Different inclusion and exclusion criteria were applied (e.g. sonographic results
(thyroid volume and density) as well as criteria according to the guidelines
of the National Academy of Clinical Biochemistry - NACB)
1.2 Elecsys FT4 II
Expected values
Euthyroid: 12-22 pmol/L (0.93-1.7 ng/dL)
These values correspond to the 2.5th and 97.5th percentile of results
from a total of 801 healthy test subjects studied.
Status: MCE Reference Range Thyroid, Status 1st quarter 1998.
For detailed information about reference intervals in children, adolescents

and pregnant women, refer to the brochure “Reference Intervals for Children
and Adults”, REF English: 04640292, German: 04625889.
This booklet also contains results of a detailed study about influencing factors
on thyroid parameters in a well characterized reference group of adults.
Different inclusion and exclusion criteria were applied (e.g. sonographic results
(thyroid volume and density) as well as criteria according to the guidelines
of the National Academy of Clinical Biochemistry - NACB).
1.3 Elecsys T3
Elecsys T3 2.5th - 97.5th percentile

n nmol/l ng/ml
Adults
euthyroid 514 1.3 - 3.1 0.8 - 2.0
st
Status: MCE Elecsys 2010, status 1996, verified 1 quarter 1998.
1.4 Elecsys T4
Measurements with Elecsys® T4 on 2526 samples from euthyroid test subjects in Germany
and Japan yielded the following values (2.5-97.5th percentile):
Elecsys T4 2.5th - 97.5th percentile

n nmol/l µg/dl
Adults
euthyroid 2526 66 - 181 5.1 – 14.1
FT4 Index (T4/TBI) calculated from 825 serum samples from euthyroid test subjects
measured with Elecsys® T4 and Elecsys® T-uptake (2.5-97.5th percentile):
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62-164 nmol/l or 4.8-12.7 µg/dl
Following values were determined for the 99% percentile range from 275 serum and plasma
samples from healthy test subjects in USA:
59-154 nmol/l or 4.6-12.0 µg/dl
FT4 Index:
57-147 nmol/l or 4.4-11.4 µg/dl
1.5 Elecsys TSH
Elecsys TSH 2.5th - 97.5th percentile

n µIU/ml
Adults
euthyroid 516 0.27 - 4.2
1.6 Elecsys T-uptake
Elecsys® T-uptake results (TBI) calculated in 974 serum samples from euthyroid subjects in
Japan, Belgium and Germany:
TBI: Median 1.0 (range: 2.5th-97.5th percentile): 0.8-1.3
FT4 Index:
Elecsys® T4/TBI results calculated in 825 serum samples from euthyroid subjects in
Germany and Japan (range: 2.5th-97.5th percentile): 62-164 nmol/l or 4.8-12.7 µg/dl.
The following values were determined for the 99th percentile range of results in a total of 275
serum and plasma samples from healthy subjects in the USA:
57-147 nmol/l or 4.4-11.4 µg/dl.
Values < 0.8 are indicative of hyperthyroidism or low TBG concentrations while values > 1.3
are indicative of hypothyroidism or elevated TBG concentrations.
1.7 Elecsys Calcitonin

Upper limits of reference ranges are provided as the 97.5th percentile.
Cohort N 97.5th percentile Lower limit of 95% Upper limit of 95th
confidence interval confidence interval
Apparently 166 6.39 pg/mL 5.64 pg/mL 9.82 pg/mL
healthy females
Apparently 160 10.2 pg/mL 8.31 pg/mL 14.3 pg/mL
healthy males
1.8 Elecsys Tg II
3.5-77 ng/ml
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These values correspond to the 2.5th and 97.5th percentiles of results obtained from a total of
478 healthy Caucasian subjects (254 males, 224 females).
1.9 Elecsys Anti-Tg
Studies conducted with Elecsys® Anti-TG in 5 clinical centers covering a total of 392 healthy
subjects (MCE Elecsys® Anti-TG, status October 2001) confirmed the currently used
threshold value of 115 IU/ml; this values corresponds to the 94th percentile.
1.10 Elecsys Anti-TPO
Extended studies with Elecsys® Anti-TPO performed on samples from 208 healthy test
subjects in 3 clinical centers in Austria and Germany showed a borderline value for 34 IU/ml
for 95% of the results.
1.11 Elecsys Anti-TSHR
In an external study using the Elecsys Anti-TSHR assay on samples from 436 apparently
healthy individuals, 210 patients with thyroid diseases* without diagnosis of Graves’ disease,
and 102 patients with untreated Graves’ disease an optimal cut-off of 1.75 IU/l was
determined. At this cut-off the sensitivity was calculated at 96% and the specificity at 99%.
The calculated receiver operating characteristic (ROC) curve had an area under the curve
(AUC) of 0.99. The upper limits of anti-TSHR values in the cohorts of healthy individuals and
patients with out diagnosis of Graves’ disease were 1.22 IU/l and 1.58 IU/l, respectively
(97.5th percentiles).
* 91 subacute thyroiditis, 45 adenomatous goiter, 27 Hashimotos disease, 32 painless

thyroiditis, 7 autonomously functioning thyroid nodules, 1 toxic multinodular goiter, 7 others.
Each laboratory should investigate the transferablility of the expected values to its own
patient population and if necessary determine its own reference ranges.
For diagnostic purposes, the results should always be assessed in conjunction with the
patient´s medical history, clinical examination and other findings.
Used Documents:
Assay Method sheet (or Product Information)

FT3 III 1212/01
FT4 II 1212/01
T3 0811/20
T4 1011/16
TSH 0911/20
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T-uptake 1111/18
Calcitonin 0213/01
Tg II 0313/01
Anti-Tg 0911/02
Anti-TPO 0811/02
Anti-TSHR 0911/09
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2 Cardiac:
2.1 Elecsys CK-MB STAT
Elecsys CK-MB assay (4th generation). The calculation is based on samples

from 879 apparently healthy volunteers (463 women, 416 men).
n Median 97.5th percentile 99th percentile

ng/ml ng/ml ng/ml
Women 463 4.39 3.61 4.88

Men 416 1.72 4.87 6.22
When myocardial infarction is suspected the diagnostic strategy proposals in the consensus
document of European and American cardiologists should in general be followed.
2.2 Elecsys Digoxin
The usual therapeutic range for digoxin is 0.9 to 2.0 ng/ml (1.2-2.6 nmol/l). Concentrations
above 2.0 ng/ml (2.6 nmol/l) are generally considered toxic. Some overlap of toxic and non-
toxic values have been reported. Therefore, clinical diagnosis should be based on clinical
and laboratory data. Each laboratory should establish and acceptable reporting format and
identify procedures for the reporting of abnormal results.
2.3 Elecsys Digitoxin
In the literature, the mean therapeutic serum level for digitoxin is indicated as being 13-39
nmol/l or 10-30 ng/ml.
Since the therapeutic and the toxic serum levels can overlap, the monitoring of the glycoside
levels as well as the clinical findings must be taken into consideration to clarify a possible
digitalis intoxication. See also the „Limitations – interference“ section.
2.4 Elecsys Myoglobin STAT
In studies with Elecsys Myoglobin STAT on 2162 healthy test subjects the following data
were obtained:
Number 2.5th-97.5th Percentile

Men 1030 28-72 ng/ml
Women 1132 25-58 ng/ml
Data (status: July 1999) combined from: Multicenter Evaluation of Myoglobin STAT, April
1999 and International Elecsys 1010 Study, Cardiac markers, March 1999.
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2.5 Elecsys proBNP II
Interpretation of NT-proBNP values

With increasing age atherosclerosis and aging processes of the heart (e.g. fibrosis) result in
cardiac dysfunction. Development of cardiac dysfunction is individually different and clinically
asymptomatic in is early stages. NT-proBNP levels reflect cardiac function or dysfunction
respectively. With increasing of age elevated levels of NT-proBNP are more frequently found
in apparently healthy individuals, thus reflecting the increasing frequency of cardiac
dysfunction.
NT-proBNP values need to be interpreted in conjunction with the medical history, clinical
findings and other information (e.g. imaging, laboratory findings, accompanying disorders,
treatment effects).
Cutoff values
A number of studies support a decision threshold for NT-proBNP of 125 pg/ml. NT-proBNP
values below 125 ng/ml exclude cardiac dysfunction with high level of certainty in patients
with symptoms suggestive of heart failure e.g. dyspnea. NT-proBNP values above 125 pg/ml
may indicate early cardiac dysfunction and are associated with an increased risk of cardiac
complications (myocardial infarction, heart failure, death).
Recommended cutoffs in patients with diagnosed stable chronic heart failure

Patients with stable heart failure (n=721) were compared to the reference group (n=2264).
ROC plot analysis at the cutoff value of 125 pg/ml showed a sensitivity of 88%, a specificity
of 92%, a negative predictive value (NPV), and a positive predictive value (PPV)= of 96.7%
and 80,6% respectively.
Expected values
NT-proBNP concentrations in the reference group are shown in the following tables. The
most appropriate decision threshold apparent from these distribution is 125 pg/ml.
Reference group
The circulating NT-proBNP concentration was determined in samples from 1981 blood
donors aged between 18 and 65 as well as 283 elderly patients aged between 50 and 90,
both populations without known cardiac risks, symptoms or medical history.
The descriptive statistics for NT-proBNP concentrations (pg/ml) in the reference group are
shown in the following table:
All
Age 18- 45 45-54 55-64 64-74 ≥ 75 Total
(years)
N 1323 408 398 102 33 2264
Mean 35.6 49.3 72.6 107 211 50.3
SD 30.2 63.3 84.4 85.9 152 62.4
Median 20.4 30.7 47.3 85.1 174 27.9
95th 97.3 121 198 285 526 149
percentile
97th 115 172 263 349 738 196
percentile
In the pediatric population aged between 1 and 18 the following NT-proBNP values were
obtained using the Elecsys proBNP II assay.
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Age (years) N NT-proBNP (ng/L)

75th percentile 97.5th percentile
1-3 13 231 320
4-6 21 113 190
7-9 32 94 145
10 11 73 112
11 69 93 317
12 21 95 186
13 23 114 370
14 18 68 363
15 24 74 217
16 24 85 206
17 24 71 135
18 12 53 115
Correlation of NT-proBNP with NYHA classification in patients diagnosed with CHF

NT-proBNP values (pg/ml) for patients with restricted left ventricular ejection fraction
(majority under therapy).
NYHA functional class

NYHA NYHA I NYHA II NYHA III NYHA IV
classification
N 182 250 234 35
Mean 1016 1666 3029 3465
SD 1951 2035 4600 4453
Median 342 951 1571 1707
5th percentile 33.0 103 126 148
95th percentile 3410 6567 10,449 12,188
% > 125 pg/ml 78.6 94.0 95.3 97.1
Patients presenting acute dyspnea – ICON (International Collaborative of NT-proBNP)

study
NT-proBNP concentrations were determined in samples from 1256 patients presenting with
acute shortness of breath to emergency departments at four hospitals. This population
included patients with a prior history of hypertension, coronary artery disease, myocardial
infarction, heart failure, or pulmonary disease. 720 subjects were found to be suffering from
acute exacerbation of heart failure, while the remainder were determined to present dyspnea
due to other causes. The descriptive statistics for NT-proBNP concentrations (pg/ml) for both
groups are shown in the following table:
ICON Acute dyspnea without acute heart Acute dyspnea with acute heart failure
failure
Age < 50 50-75 > 75 < 50 50-75 > 75
(years)
Mean 163 500 1209 7947 7964 10,519
SD 484 1239 2703 9093 12,892 15,961
Median 42 121 327 5044 3512 5495
5th 5 10 24 393 416 658
percentile
25th 16 44 139 2257 1608 2154
percentile
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95th 104 402 910 9825 9262 11,900
percentile
97.5th 778 2101 7916 36,201 29,089 35,183
percentile
Min. 1 1 2 196 38 17
Max. 4386 10,467 15,725 43,177 117,390 117,390
N 150 281 105 33 251 436
Result interpretation in patients presenting acute dyspnea

By using the optimal cutoffs established by the ICON study group and shown in the table
below, physicians can increase the specificity and accuracy for diagnosing heart failure in
patients presenting acute dyspnea in the emergent setting.
Category Optimal Sensitivity Specificity PPV NPV Accuracy

cut-point % % % % %
pg/mL
Rule in
cut-point
< 50 years 450 97 93 79 99 94
(n=184)
50-75 900 90 82 83 88 85
years
(n=537)
> 75 years 1800 85 73 92 55 83
(n=535)
Rule out
cut-point
All patients 300 99 60 77 98 83
2.6 Elecsys Troponin I
In studies performed with the Elecsys Troponin I assay involving 839 healthy volunteers in 4
US sites and 2 EU sites, the upper reference limit (99th percentile) for cTnI was < 0.16 µg/l
(ng/ml) (95% confidence interval 0.12-0.60).
The lowest concentration with a CV less than or equal to 10% with the Elecsys Troponin I
assay was 0.30 µg/l (ng/ml).
Due to the release kinetics of cTnI, a result below the decision limit within the first hours of
the onset of symptoms does not rule out myocardial infarction with certainty. If myocardial
infarction is still suspected, repeat the test at appropriate intervals.
Factors associated with elevated values

Published clinical studies have shown elevations of cTnI in patients with myocardial injury, as
seen in unstable angina pectoris, cardiac contusions, and heart transplants.
2.7 Elecsys Troponin T hs
In studies performed with the Elecsys Troponin T hs assay involving 533 healthy volunteers,
the upper reference limit (99th percentile) for troponin T was 14 ng/L (pg/ml), 95% confidence
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interval 12.7-24.9 ng/L (pg/mL). The lowest concentration with a CV less than or equal to
10% (LoQ) with the Elecsys Troponin T hs assay was 13 ng/L (pg/ml).
Based on the WHO criteria for the definition of AMI from the 1970’, the cutoff (clinical
discriminator) value for troponin T is 0.1 µg/L (ng/ml) 100 ng/L (pg/ml) as determined from
ROC analysis in results with an earlier test generation of the Elecsys Troponin T assay.
The WHO definition of AMI has been recently updated and takes into consideration the
ESC/ACC/AHA/WHF definition recommending the detection of a rise and/or fall of cardiac
troponin in the clinical setting of myocardial ischemia using the 99th percentile troponin cutoff
value.
Due to the release kinetics of cardiac troponin T, an initially test result < 99th percentile with
the first hours of the onset of symptoms does not rule out myocardial infarction with certainty.
If myocardial infarction is still suspected, repeat the test at appropriate intervals (6-12 hours
after initial assessment).
It is important to obtain a careful history and a precise description of the symptoms. A

physical examination with particular attention to the possible presence of cardiac contusion,
acute and chronic heart failure, aortic dissection, aortic valve disease, hypertrophic,
cardiomyopathy, tachy- or bradyarrhythmias, apical ballooning syndrome, rhabdomyolysis
with cardiac injury, pulmonary embolism, severe pulmonary hypertension, acute neurological
disease, infiltrative diseases, drug toxicity, respiratory failure, sepsis, burns is required.
An electrocardiogram is recorded for allowing differentiation of patients with suspicion of ACS

(ST-segment elevation or ST-segment changes but without persistent ST-segment elevation
or normal ECG).
Laboratory assessment should include markers of myocardial damage, preferably cardiac

troponin. If concentration of troponin or cardiac enzymes rise, irreversible cell damage will
have occurred and these patients must be regarded as having had myocardial infarction as
defined by the consensus conference. Finally a second cardiac troponin measurement
should be obtained after 6 to 12 hours.
Factors Associated with Elevated Values

Published clinical studies have shown elevations of troponin T in patients with myocardial
injury, as seen in unstable angina pectoris, cardiac contusions and heart transplants.
Elevations have also been seen in patients with rhabdomyolysis and polymyositis.
Each laboratory should investigate the transferablility of the expected values to its own

CK-MB 0812/03
Digoxin 0512/18
Digitoxin 0612/11
Myoglobin 0812/14
proBNP II 0512/07
Troponin I 0712/05
Troponin T hs 0512/05
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3 Fertility Assays:
3.1 Elecsys ACTH
Studies with the Elecsys ACTH assay using plasma samples from 354 apparently healthy
adults gave the following results (5th-95th percentile):
7.2-63.6 pg/ml (1.6-13.9 pmol/l)
The plasma samples were drawn between 7-10 a.m.
ACTH concentrations vary considerably depending on physiological conditions. Therefore,

ACTH results should always be evaluated together with simultaneously measured cortisol
concentrations.
3.2 Elecsys AMH
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3.3 Elecsys Cortisol II
In studies with the Elecsys Cortisol II assay, the following values were
determined using samples from 150 self-reported healthy individuals, aged
21 years or older. Exclusion criteria were: pregnancy, lactation, use of oral
contraceptives and medication with cortisone/cortisol (5th‑95th percentile):
Morning hours 6‑10 a.m.: 172‑497 nmol/L (6.24‑18.0 μg/dL), n = 146
Afternoon hours 4‑8 p.m.: 74.1‑286 nmol/L (2.69‑10.4 μg/dL), n = 150
No statistical difference was observed between males and females.
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Cortisol in saliva
In studies with the Elecsys Cortisol II assay, the following values were
determined using saliva samples from the same 150 individuals described
above. Again, no gender specific differences were seen (5th‑95th percentile):
Morning hours 6‑10 a.m.: < 21.6 nmol/L (< 0.783 μg/dL), n = 147
3.4 % < 1.50 nmol/L, n = 5
Afternoon hours 4‑8 p.m.: < 6.70 nmol/L (< 0.243 μg/dL), n = 149
24.8 % < 1.50 nmol/L, n = 37
Midnight ± 30 minutes: < 5.74 nmol/L (< 0.208 μg/dL), n = 150
72.0 % < 1.50 nmol/L, n = 108
3.4 Elecsys DHEAS
Extended studies with Elecsys® DHEAS conducted in two clinical centers in Germany
covering a total of 519 samples from female individuals, a total of 489 samples from male
individuals and a total of 269 samples from children gave the following values for the age
groups listed below (study protocols no.: C00P032 and P01P005 – status 5/01 to 11/01):
Elecsys DHEAS 50th percentile 5-95th percentile

n µg/dl µmol/l µg/dl µmol/l
Females
10-14 years 73 123 3.34 33.9 - 280 0.92 - 7.60
15-19 years 55 157 4.26 65.1 - 368 1.77 - 9.99
20-24 years 36 238 6.46 148 - 407 4.02 - 11.0
25-34 years 64 183 4.96 98.8 - 340 2.68 - 9.23
35-44 years# 85 161 4.38 60.9 - 337 1.65 - 9.15
45-54 years# 89 121 3.28 35.4 - 256 0.96 - 6.95
55-64 years 59 76.7 2.08 18.9 - 205 0.51 - 5.56
65-74 years 29 64.4 1.75 9.40 - 246 0.26 - 6.68
> 75 years 29 60.9 1.65 12.0 - 154 0.33 - 4.18
# Effects of the menopause on the results obtained for the women of the corresponding age
groups were tested and found to be negligible.

Males
10-14 years 74 101 2.74 24.4 - 247 0.66 - 6.70
15-19 years 67 279 7.57 70.2 - 492 1.91 - 13.4
20-24 years 28 353 9.58 211 - 492 5.73 - 13.4
25-34 years 60 283 7.68 160 - 449 4.34 - 12.2
35-44 years 70 221 6.00 88.9 - 427 2.41 - 11.6
45-54 years 45 219 5.94 44.3 - 331 1.20 - 8.98
55-64 years 69 138 3.75 51.7 - 295 1.40 - 8.01
65-74 years 55 90.2 2.45 33.6 - 249 0.91 - 6.76
> 75 years 21 56.2 1.53 16.2 - 123 0.44 - 3.34

Children
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< 1 week 37 280 7.60 108 - 607 2.93 - 16.5
1-4 weeks 25 144 3.91 31.6 - 431 0.86 - 11.7
1-12 month 69 21.6 0.59 3.3 - 123.6 0.09 - 3.35
1-4 years 59 5.0 0.14 0.47 - 19.4 0.01 - 0.53
5-10 years 79 23.1 0.63 2.8 - 85.2 0.08 - 2.31
DHEA-S values of newborns are strongly influenced by maternal hormonal exchange via
placenta.
3.5 Elecsys Estradiol III
The reference ranges were determined in a Caucasian population.
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3.6 Elecsys FSH
Elecsys FSH Percentile

n 50%
5th - 95th
** lower detection limit - 95% percentile
mIU/ml
Men 319 4.6
1.5 - 12.4
Woman
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Follicular phase 376 6.9
3.5 - 12.5
Ovulat. Phase 56 12.3
4.7 - 21.5
Luteal Phase 349 3.6
1.7 - 7.7
Postmenopause 181 67.0
25.8 - 134.8
LH/FSH Quotient: Quotients were calculated from Elecsys® LH and FSH results on samples
from healthy women of child-bearing age. The following medians were found:
Follicular phase: 0.82 (n = 315)

Luteal phase: 1.12 (n = 279)
Elecsys FSH Percentile

n 50%
5th - 95th
** lower detection limit - 95%
percentile
mIU/ml
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Children (males and females)
< 24 hours 9 0.1
<0.1** - 0.8
day 1 32 <0.1
<0.1** - 0.8
day 2 46 <0.1**
<0.1** - 0.8
day 3 55 0.1
<0.1** - 2.4
day 4 35 0.3
<0.1** - 2.3
day 5 23 0.3
<0.1** - 3.4
day 6 9 0.4
<0.1** - 4.5
day 7 9 2.0
0.2 - 21.4
day 8-30 14 2.8
<0.1** - 22.2
Children females
>1-12 month 1 3.5
-
1-5 years 34 2.0
0.2 - 11.1
6-10 years 37 2.0
0.3 - 11.1
11-13 years 35 4.8
2.1 - 11.1
14-17 years 45 5.7
1.6 - 17.0
Children males
>1-12 month 1 1.7
-
1-5 years 39 0.9
0.2 - 2.8
6-10 years 41 0.8
0.4 - 3.8
11-13 years 10 2.3
0.4 - 4.6
14-17 years 65 4.8
1.5 - 12.9
3.7 Elecsys LH
Elecsys LH Percentile
n 50%
5th - 95th
percentile
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mIU/ml
Men 322 4.0
1.7 - 8.6
Woman
Follicular phase 316 5.9
2.4 - 12.6
Ovulat. Phase 56 30.8
14.0 - 95.6
Luteal Phase 280 4.3
1.0 - 11.4
Postmenopause 132 29.1
7.7 - 58.5
LH/FSH Quotient: Quotients were calculated from Elecsys® LH and FSH results on samples
from healthy women of child-bearing age. The following medians were found:
Follicular phase: 0.82 (n = 315)

Luteal phase: 1.12 (n = 279)
Elecsys LH Percentile
n 50%
5th - 95th
percentile
mIU/ml
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Children (males and females)
< 24 hours 13 <0.1**
<0.1** - 1.0
day 1 36 <0.1**
<0.1** - 0.8
day 2 48 <0.1**
<0.1** - 0.6
day 3 64 0.1
0<.1** - 2.7
day 4 35 <0.1**
<0.1** - 1.7
day 5 25 0.5
<0.1** - 3.1
day 6 10 0.5
0.4 - 6.4
day 7 9 1.4
<0.1** - 5.6
day 8-30 21 2.5
<0.1** - 7.8
Children females
>1-12 month 14 <0.1**
<0.1** - 0.4
1-5 years 56 <0.1**
<0.1** - 0.5
6-10 years 58 <0.1**
<0.1** - 3.1
11-13 years 53 2.6
<0.1** - 11.9
14-17 years 56 6.0
0.5 - 41.7
Children males
>1-12 month 22 <0.1**
<0.1** - 0.4
1-5 years 63 <0.1**
<0.1** - 1.3
6-10 years 58 <0.1**
<0.1** - 1.4
11-13 years 23 0.9
0.1 - 7.8
14-17 years 76 3.7
1.3 - 9.8
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3.8 Elecsys Progesterone III
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3.9 Elecsys Prolactin II
A study with the Elecsys Prolactin II assay was performed using samples from 300
apparently healthy blood doners. The following results were obtained:
50% 2.5-97.5% 50% 2.5-97.5%

n µIU/ml ng/ml
Men 102 155 86-324 7.30 4.04-15.2
Woman 198 225 102-496 10.6 4.79-23.3
(not
pregnant)
3.10 Elecsys SHBG
Expected values
The following table shows the results obtained from a group of 415 males and
343 females using the Elecsys SHBG assay. All subjects were apparently
healthy, non-obese (BMI, body mass index ≤ 30), non-pregnant adults without
intake of any contraceptive or relevant prescription drugs (study number
CIM 000669). Blood samples (fasting) were taken between 6.30 am and
2.00 pm. This clinical study focusing on the Elecsys Testosterone II assay
included measurements in parallel using the Elecsys SHBG assay.
Please refer to the Elecsys Testosterone II method sheet for SHBG
values in combination with testosterone.
SHBG
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SHBG (nmol/l)
n Median 5th - 95 th percentile
Males (20-49 years) 241 33.2 18.3-54.1
Males (≥ 50 years) 174 40.6 20.6-76.7
Females (20-49 years) 166 67.8 32.4-128
Females (≥ 50 years) 177 62.4 27.1-128
3.11 Elecsys Testosterone II
Expected values
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3.12 Elecsys HCG STAT
Results from a multicenter study in 5 clinical centers in Belgium, France, and Germany with
Elecsys® HCG STAT (cat.no. 03300811) in specimen from healthy individuals are listed
below (Study No. BO1PO19, status March 2003):
 1 mIU/ml HCG for 97.5% of the values obtained from 182 healthy, non-pregnant
premenopausal women. The corresponding upper 95% confidence limit ranges up to 4.9
mIU/ml.
 7 mIU/ml HCG for 97.5% of the values obtained from 143 healthy, postmenopausal
women. The corresponding upper 95% confidence limit ranges up to 8.1 mIU/ml
The following HCG-values were determined during pregnancy (weeks of pregnancy

completed following the start of the last menstruation cycle): Data are given only for the
weeks of gestation for which the case numbers (n) were greater than 10.
weeks of HCG IU/ml
gestagation n Median Range 5th - 95th
percentile
3 25 18.7 5.4 – 72
4 43 135 10.2 – 708
5 23 1420 217 – 8245
6 19 3475 152 – 32,177
7 13 35,873 4059 – 153,767
8 23 83,603 31,66 – 149,094
9 23 104,475 59,109 – 135,901
10 20 85,304 44,186 – 170,409
12 17 61,730 27,107 – 201,615
14 20 37,082 24,302 – 93,646
15 546 28,696 12,540 – 69,747
16 766 24,346 8904 – 55,332
17 190 22,064 8240 – 51,793
18 64 22,464 9649 – 55,271
3.13 Elecsys HCG+
Results from a multicenter study in clinical centers in Belgium, France and Germany with
Elecsys® HCG+ (cat.no. 03271749) are listed below (study no. BO1PO19, status March
03).
Serum samples from healthy individuals:
  1 mIU/ml HCG for 97.5% of the values obtained from 181 healthy, non-pregnant
premenopausal women. The corresponding upper 95% confidence limit range up to 5.3
mIU/ml.
  7 mIU/ml HCG for 97.5% of the values obtained from 143 healthy, postmenopausal
women. The corresponding upper 95% confidence limit ranges up to 8.3 mIU/ml.
 < 2 mIU/ml HCG for 97.5% of the values obtained from 290 men. The corresponding upper
95% confidence limit ranges up to 2.6 mIU/ml.
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 During pregnancy (weeks of pregnancy - defined as complete week of pregnancy
beginning with the start of the last menstruation phase) the following values have been
determined.
Data are given only for the weeks of gestation for which the case numbers (n) were greater
than 10.
weeks of HCG mIU/ml

pregnancy n Median Range 5th - 95th perc.
3 25 17.5 5.8 - 71.2
4 43 141 9.5 - 750
5 23 1398 217 - 7138
6 19 3339 158 - 31,795
7 13 39,759 3697 - 163,563
8 23 90,084 32,065 - 149,571
9 23 106,257 63,803 - 151,410
10 20 85,172 46,509 - 186,977
12 17 66,676 27,832 210,612
14* 67 34,440 13,950 -
62,530
15* 666 28,962 12,039 - 70,971
16* 766 23,930 9040 56,451
17* 190 20,860 8175 - 55,868
18* 64 19,817 8099 - 58,176
* For the gestational weeks 14 to 18, which are the relevant weeks for the trisomie 21 risk
assessment, the values from serum samples for 1753 pregnant women in total were
evaluated from measurements with Elecsys® HCG+ and Elecsys® AFP in the 5 clinical
centers. The maternal age and weight and the gestational age in days was given for each
sample.
The individual results were analyzed for normal distribution of the log MOM (Multiple of
Median) values. The standard deviations of the MoM values are comparable to published
data. Median values and the 5th and 95% percentile were calculated for the completed
gestational weeks – see within the table above.
Distribution of Elecsys® HCG+ results from healthy subjects and patients with benigne and
malignant diseases.
The results from patients with benigne and malignant diseases are summarized data from
measurements with Elecsys® HCG+ (cat.no. 03271749) and Elecsys® HCG+ (cat.no.
11973193).
Concentration N Percent (%)

mIU/ml 2 >2 -  7 >7 -  100 > 100 > 1000
Healthy subjects 614
Males 290 97.9 2.1 0 0 0
Females 181 98.1 1.1 0 0 0
premenopausal
Females 143 53.1 46.2 0.7 0 0
postmenopausal
Malignant 839
diseases
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Chorioncarcinom 64 10.9 10.9 21.9 10.9 45.3
a
Seminoma 29 89.7 3.4 6.9 0 0
Germ cell tumor 109 78.0 3.7 0.9 5.5 11.9
Yolk sac tumor 45 20.0 6.7 22.2 8.9 42.2
Ovarian cancer 38 76.3 18.4 5.3 0 0
Gestational 169 19.5 10.7 29.6 20.1 20.1
trophoblastic
diseases
Mole 72 1.4 4.2 26.4 27.8 40.3
Others 313 52.7 13.1 8.6 11.8 13.7
Note: For prenatal testing it is recommended that the median values be re-evaluated
periodically (1 to 3 years) and whenever methodology changes.
Each laboratory should investigate the transferability of the expected values to its own
patient population and if necessary determine its own reference range.
Used Documents:

ACTH 1211/07
AMH 0714/01
Cortisol II 0615/01
DHEAS 0912/16
Estradiol III 0415/02
FSH 0412/18
LH 0412/18
Progesterone III 0316/01
Prolactin II 0312/05
SHBG 0512/10
Testosterone II 1213/08
HCG STAT 0412/15
HCG+ß 0412/15
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4 Diabetes:
4.1 Elecsys C-Peptide
Studies with Elecsys® C-Peptide were performed using serum samples from
apparently healthy fasting males and females, and 24 h urine samples from
apparently healthy individuals.
The following results were obtained:
C-Peptide in Median 5th - 95th Unit

percentile
Serum / plasma 1,96 1,1 – 4,4 ng/mL

n= 96
0,65 0,37 – 1,47 nmol/L
24 h urine 54,8 17,2 – 181 ng/24 h

n= 79
18,3 5,74 – 60,3 nmol/24 h
4.2 Elecsys Insulin
Studies with Elecsys® Insulin conducted in a clinical center in Germany with samples from
57 healthy, fasting individuals gave the following results (5th – 95% percentile range):
2.6 – 24.9 µU/ml (17.8 – 173 pmol/l)
Status: Elecsys® Insulin MCE on Elecsys® 1010/2010, Study no.: B99P027 of 29 March
2001.
Used Documents:

C-Peptide 0412/08
Insulin 0412/13
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5 Preeclampsia:
5.1 Elecsys PlGF /sFlt-1
The following results were obtained in the Prospective Multicenter Study:

Diagnosis of Preeclampsia by means of the Elecsys sFlt‑1 assay and the
Elecsys PlGF assay (Roche study No. CIM RD000556/X06P006).
To define the reference ranges for normal pregnancies, 877 normotensive
pregnant women from 9 sites in Europe (Germany, Spain, Austria, Czech
Republic, Switzerland) provided samples at 1685 visits. All women had a
singleton pregnancy with normal pregnancy outcome (i.e. no PE/HELLP, no
intrauterine growth restriction). For each sample the levels of sFlt‑1 and
PlGF were determined in parallel and the sFlt‑1/PlGF ratio was calculated.
Weeks of gestation: defined as completed weeks of pregnancy beginning
with the start of the last menstruation cycle.
The following results were obtained:
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Used Documents:

PlGF 0813/06
sFlt-1 0813/06
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6 Tumor Marker:
6.1 Elecsys AFP
Results of following studies using Elecsys® AFP see below:
a) Multicenter study „Elecsys® 2010“ status September 1997 and reference range study in
Germany and France, data evaluated in September 1998.
Following AFP values were found in serum samples from 646 healthy test subjects:
 5.8 IU/ml or  7.0 ng/ml for 95% of the results
 11.3 IU/ml or  13.6 ng/ml for 100% of the results.
AFP median values for completed weeks of pregnancy (defined as completed weeks of
pregnancy beginning with the start of the last menstruation phase).
Weeks 14 15 16 17 18 19
n 382 1782 2386 975 353 146
ng/ml 27.9 30.9 36.1 40.4 48.3 54.8
IU/ml 23.2 25.6 30.0 33.5 40.1 45.5
b) Multicenter study to determine reference values for evaluating the risk of trisomy 21 in
maternal serum (study No. BO1P019, status March 2003).
Values from serum samples of 1753 pregnant women in total (relevant gestational weeks 14
to 18) were evaluated.
Measurements with Elecsys® HCG+β and Elecsys® AFP were conducted in 5 clinical
centers in Belgium, France, and Germany.
The gestational age in days determined by ultrasound was given for each sample. From a
log-linear regression analysis of all 1753 AFP-values versus gestational age the following
median values were calculated for the middle of the respective weeks (e.g. week 14 + 3
days):
Weeks 14 15 16 17 18
IU/ml 20.9 24.0 27.6 31.7 36.4
ng/ml 25.3 29.0 33.3 38.3 44.0
Note: For prenatal testing it is recommended that the median values be re-evaluated
periodically (1 to 3 years) and whenever methodology changes.
The transferability of the reference values to plasma samples has not been verified.
6.2 Elecsys CA 125 II
Studies using the Elecsys CA 125 II assay in 593 samples from healthy females (pre- and
postmenopausal) yielded a value of 35 U/ml (95th percentile). Values > 35 U/ml indicate an
increased probability for residual or recurrent ovarian carcinoma in patients treated for
primary epithelial invasive ovarian cancer.
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6.3 Elecsys CA 15-3 II
Results of a multicenter study in clinical centers in USA, Spain and Germany (status 12/99)
as follows:
Healthy subjects:
Using Elecsys CA 15-3, 95% of the results obtained in 272 samples from healthy subjects
were  25 U/ml.
Patients with benign diseases and pregnant women:

Relative distribution of CA 15-3 concentrations in patients with benign disease and
pregnancy
Subjects total > 25 U/ml 25-50 U/ml 50-200 U/ml > 200 U/ml
N Classification in percent (%)
Liver, 109 84 16 0 0
pancreas, gall
bladder
Breast 58 88 12 0 0
Gynecological 42 83 12 5 0
diseases
Renal failure 37 81 19 0 0
Urological 34 82 18 0 0
diseases
Bacterial 28 96 4 0 0
infection
Pregnancy 34 97 0 3 0
Patients with malignant disease (other than breast):

Relative distribution of CA 15-3 concentrations in individuals with malignancy other than
breast
Subjects > 25 U/ml 25-50 U/ml 50-200 U/ml > 200 U/ml
total
Stomach- 36 75 14 8 3
Carcinoma
Hepatocellular- 37 60 32 3 5
Carcinoma
Lung- 38 82 13 5 0
Carcinoma
Ovarian- 34 47 21 29 3
Carcinoma
Gynecological 5 40 20 40 0
Carcinoma
Prostate- 48 79 17 4 0
Carcinoma
Colorectal- 40 93 7 0 0
Carcinoma
Pancreatic- 40 65 33 2 0
Carcinoma
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Patients with breast cancer:

Relative distribution of CA 15-3 concentrations in patients with breast malignancy. The
staging of patients according to UICC criteria was performed at primary diagnosis before any
treatment. The patients diagnosed with recurrent disease had developed metastases (M1).
Subjects > 25 U/ml 25-50 U/ml 50-200 U/ml > 200 U/ml
total
UICC I 56 88 12 0 0
UICC II 126 85 13 2 0
UICC III 77 53 30 14 3
UICC IV 24 25 17 37 21
Recurrent 75 15 25 36 24
Disease
6.4 Elecsys CA 19-9
In samples from 381 healthy test subjects (n = 187) and blood donors (n = 194), the following
values were obtained:
27 U/ml for 95% of the results
34 U/ml for 97.5% of the results
39 U/ml for 99% of the results
6.5 Elecsys CA 72-4
Extended studies with Elecsys® CA 72-4 in clinical centers in Belgium, Germany and
company internal studies gave the following results for a total of 635 healthy subjects:
6.9 U/ml (95% percentile)

5.6 – 8.2 U/ml (95% confidence range)
Status: Elecsys® CA 72-4 multicenter studies; study no. B99P026, 7/2001
6.6 Elecsys CEA
Studies with the Elecsys® CEA assay were performed on 352 healthy subjects. The
following results were obtained:
All subjects Non-smokers Smokers

(past/never smokers) (current)
Age 20-69  40 20-69  40 20-69  40
(years)
95% 4.7 5.2 3.8 5.0 5.5 6.5
percentile
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N 352 203 242 154 110 49
6.7 Elecsys Cyfra 21-1
The cutoff limit is 3.3 ng/ml. Specificity, as determined on a group of patients with benign
lung diseases (n = 526) is 95%.
Clearly elevated CYFRA 21-1 concentrations can also be found in samples from patients
with acute pneumonia, tuberculosis and intersistal pulmonary diseases. Concentrations
above the reference ranges are also observed in cases of liver cirrhosis and renal failure.
6.8 Elecsys HE4
A study in one clinical center in Germany with the Elecsys HE4 assay on sera
from 358 apparently healthy women yielded the following results:
HE4 (pmol/L)
Age (years) N Median 95th percentile
< 40 127 42.0 60.5
40-49 65 44.3 76.2
50-59 60 47.9 74.3
60-69 60 55.0 82.9
≥ 70 46 62.1 104
The distribution in percentage (%) of HE4 assay values determined in two clinical centers in
Spain and Germany with the Elecsys HE4 assay in 896 female specimens is summarized in
the table below:
Elecsys HE4 values (pmol/L)

0.0- 70.1- 140.1- 500.1-
> 1500
70.0 140 500 1500
N (percentage distribution)
Apparently healthy
76 13 1 0 0
Premenopausal 90
(84.4 %) (14.4 %) (1.1 %) (0.0 %) (0.0 %)
63 40 3 0 0
Postmenopausal 106
(59.4 %) (37.7 %) (2.8 %) (0.0 %) (0.0 %)
Benign conditions
160 16 1 0 0
Premenopausal 177
(90.4 %) (9.0 %) (0.6 %) (0.0 %) (0.0 %)
Postmenopausal 102 62 31 9 0 0
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(60.8 %) (30.4 %) (8.8 %) (0.0 %) (0.0 %)
50 0 0 0 0
Pregnancy 50
(100 %) (0.0 %) (0.0 %) (0.0 %) (0.0 %)
16 6 6 7 0
Non-gynecological disease 35
(45.7 %) (17.1 %) (17.1 %) (20.0 %) (0.0 %)
9 11 3 0 0
CHFb 23
(39.1 %) (47.8 %) (13.0 %) (0.0 %) (0.0 %)
Cancer
Ovarian cancer 12 7 13 5 2
39
Premenopausal (30.8 %) (17.9 %) (33.3 %) (12.8 %) (5.1 %)
Ovarian cancer 10 19 34 28 6
97
Postmenopausal (10.3 %) (19.6 %) (35.1 %) (28.9 %) (6.2 %)
18 20 9 1 1
Endometrial cancer 49
(36.7 %) (40.8 %) (18.4 %) (2.0 %) (2.0 %)
22 19 5 1 0
Breast cancer 47
(46.8 %) (40.4 %) (10.6 %) (2.1 %) (0.0 %)
19 20 6 1 0
Gastrointestinal cancer 46
(41.3 %) (43.5 %) (13.0 %) (2.2 %) (0.0 %)
5 7 10 1 0
Lung cancer 23
(21.7 %) (30.4 %) (43.5 %) (4.3 %) (0.0 %)
3 4 4 1 0
Bladder cancer 12
(25.0 %) (33.3 %) (33.3 %) (8.3 %) (0.0 %)
b) CHF = congestive heart failure
In this study 84 % of the apparently healthy premenopausal women had an Elecsys HE4
assay value at or below 70 pmol/L and 97 % of the apparently healthy postmenopausal
women had an Elecsys HE4 assay value at or below 140 pmol/L. In this study the 95th
percentiles for the apparently healthy pre- and postmenopausal women (all ages) were 92.1
pmol/L and 121 pmol/L, respectively.
Monitoring of disease status in patients diagnosed with ovarian cancer

The effectiveness of the Elecsys HE4 assay as an aid in monitoring of disease status in
ovarian cancer patients was determined by assessing changes in HE4 levels in serial serum
samples from 100 patients compared to changes in disease status. A study involving a total
of 375 pairs of observations was undertaken with ≥ 3 blood withdrawals per patient. A
positive change HE4 was defined as an increase in the value that was at least 20 % greater
than the previous value of the test. 58.0 % (29/50) of the patient samples with a positive
change correlated with the disease progression while 84.0 % (273/325) of the patient serial
samples with no significant change in HE4 value correlated with no progression. The total
concordance was 80.5 % (302/375). The following table presents the data in a 2x2 format.
Change in disease state per sequential pair

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Increase in HE4 concentration Progression No progression Total
> 20 % 29 52 81
≤ 20 % 21 273 294
Total 50 325 375
Risk estimation in patients with pelvic mass

The effectiveness of the Elecsys HE4 assay in combination with the Elecsys CA 125 II assay
for risk estimation of epithelial ovarian cancer of patients presenting with pelvic mass was
determined in an international multi-center clinical trial using repository samples. An
algorithm (ROMA = Risk of Ovarian Malignancy Algorithm) was developed for estimation of
the risk of epithelial ovarian cancer. The algorithm takes into account the HE4 and CA 125
values as well as the menopausal status of the patient. The algorithm calculates a predictive
probability of finding epithelial ovarian cancer on surgery.
Calculation of Predictive Index (PI)

A Predictive Index is calculated for premenopausal and postmenopausal patients separately
using equations (1) and (2) below. To calculate the PI, the assay values obtained from the
Elecsys HE4 assay and the Elecsys CA 125 II assay are inserted into the equations below,
depending on the menopausal status of the women.
(1) Premenopausal: PI = -12.0 + 2.38*LN[HE4] + 0.0626*LN[CA125]

(2) Postmenopausal: PI = -8.09 + 1.04*LN[HE4] + 0.732*LN[CA125]
where, LN = Natural Logarithm. Do not use LOG = Log10.
Calculation of ROMA value

To calculate the ROMA value (i.e. predictive probability), insert the calculated value for PI
into equation (3):
(3) ROMA value (%) = exp(PI) / [1 + exp(PI)] * 100

where, exp(PI) = ePI
NOTE: These equations were used for the calculation of ROMA values with the Elecsys HE4
assay from 28.8-3847 pmol/L and with the Elecsys CA 125 II assay from 6.42-5000 U/mL.
The examples below should be used in order to validate calculations of PI and ROMA before
reporting patient results:
Menopausal status Elecsys values PI calculation PI ROMA

HE4 CA 125 II
%
(pmol/L) (U/mL)
Premenopausal 37.5 74.9 -12.0 + (2.38*3.624) + (0.0626*4.316) -3.10388 4.29
387 21.8 -12.0 + (2.38*5.957) + (0.0626*3.082) 2.371517 91.5
Postmenopausal 66.7 11.3 -8.09 + (1.04*4.200) + (0.732*2.425) -1.94683 12.5
383 22.7 -8.09 + (1.04*5.948) + (0.732*3.122) 0.381799 59.4
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Stratification into low risk and high risk groups
In a study a total of 384 repository patient samples were included and the predictive
probability for ovarian cancer as well as the ability for separation into a low and a high risk
group based on ROMA values were determined.
The risk of ovarian malignancy algorithm was used to stratify women into risk groups for
finding epithelial ovarian cancer. The following cut-points were used in order to provide a
specificity level of 75 % for the Elecsys HE4 and Elecsys CA 125 II assay combination:
Premenopausal women
ROMA value ≥ 11.4 % = high risk of finding epithelial ovarian cancer
ROMA value < 11.4 % = low risk of finding epithelial ovarian cancer
Postmenopausal women
ROMA value ≥ 29.9 % = high risk of finding epithelial ovarian cancer
ROMA value < 29.9 % = low risk of finding epithelial ovarian cancer
The risk stratification of all 384 patients (194 pre- and 190 postmenopausal) presenting with
pelvic mass using the ROMA values for the Elecsys HE4 and Elecsys CA 125 II assay
combination is shown in the following table:
Premenopausal patients Postmenopausal patients

Patient groups presenting with pelvic mass ROMA ROMA ROMA ROMA
N N
< 11.4 % ≥ 11.4 % < 29.9 % ≥ 29.9 %
6 10 6 10
Stage I-II EOCc 16 16
(37.5 %) (62.5 %) (37.5 %) (62.5 %)
7 14 9 25
Stage I-IIIC EOCd 21 34
(33.3 %) (66.7 %) (26.5 %) 73.5 %)
7 18 10 43
Stage I-IV EOC 25 53
(28.0 %) (72.0 %) (18.9 %) (81.1 %)
1 8 4 33
Stage III-IV EOC 9 37
(11.1 %) (88.9 %) (10.8 %) (89.2 %)
2 10 2 42
Unstaged EOC 12 44
(16.7 %) (83.3 %) (4.5 %) (95.5 %)
118 39 71 22
Benign 157 93
(75.2 %) (24.8 %) (76.3 %) (23.7 %)
c) EOC = epithelial ovarian cancer

d) Stage I-IIIB and Stage I-IIIC (omentum negative, lymph node positive) EOC
The sensitivity for stratifying patients with stage I-IV epithelial ovarian cancer into the high
risk group was 84.3 % at the set specificity of 75 %, such that 75.6 % of women with benign
pelvic mass were classified into the low risk group. The positive and negative predictive
values were 64.9 % and 90 % respectively.
AUC (95 %-CI):

Premenopausal women = 0.858 (0.779-0.937)
Postmenopausal women = 0.923 (0.885-0.962)
The following has to be taken into consideration
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The level of HE4 cannot be used as absolute evidence for the presence or absence
of malignant disease and the Elecsys HE4 assay should not be used as a cancer
screening test.
Elecsys HE4 results should be used in conjunction with other clinical data; e.g.
symptoms, medical history, etc.
If the Elecsys HE4 results are inconsistent with clinical evidence, additional testing is
suggested to confirm the result.
Elecsys HE4 results should not be used interchangeably with other manufacturers’
methods for HE4 determinations.
Elecsys CA 125 II results should not be used interchangeably with other

manufacturers’ methods for CA 125 determinations in the ROMA calculation.
Patients with confirmed ovarian cancer may have Elecsys HE4 assay values in the
same range as healthy women. Certain histological types of ovarian cancer (e.g.
mucinous or germ cell tumors) rarely express HE4, therefore the use of the Elecsys
HE4 assay is not recommended for monitoring of patients with known mucinous or
germ cell ovarian cancer.5 Conversely, elevated levels of HE4 antigen may be
present in individuals with renal, liver and non-malignant diseases.
 The ROMA has not been validated for the following patient groups: patients
previously treated for malignancy, patients currently being treated with chemotherapy,
and patients less than 18 years of age. Failure of the Elecsys HE4 assay and/or the
Elecsys CA 125 II assay to perform as indicated, or error in the calculation of results,
could lead to inaccurate risk assessment and improper management of the patient.
Specifically, a falsely low result of the assay(s) could result in a determination that the
patient is at lower risk of having epithelial ovarian cancer, which could triage the
patient to a less specialized level of care.
6.9 Elecsys ProGRP
A study in Germany with the Elecsys ProGRP assay on 698 samples from apparently healthy
caucasian adults (336 males, 362 females) aged between 18 and 79 years yielded the
following results (Roche study No. RD001525 and RD000788)
ProGRP (pg/mL)
5th Median 95th 97.5th
Percentile percentile percentile
(95 % CIb)) (95 % CI)
Serum 25.3 40.3 69.2 77.8
(63.8- (74.6-
Li-heparin plasma 25.7 41.4 75.3)
68.0 99.6)
77.0
(63.7- (73.0-
EDTA plasma 22.2 35.5 74.5)
59.5 101.1)
68.1
(55.8- (64.1-
b) CI = confidence interval
65.3) 84.9)
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Each laboratory should investigate the transferability of the expected
values to its own patient population and if necessary determine its
own reference ranges.
ProGRP values in apparently healthy individuals and different
types of benign and malignant disorders
The distribution in percentage (%) of ProGRP assay values
determined in 4 clinical centers in Europe with the Elecsys ProGRP
assay in 2163 serum samples is summarized in the table below:
Elecsys ProGRP values (pg/mL)
Total < 3.0 3.0-50 50.1-100 100.1-200 > 200
N N N N N
(%) (%) (%) (%) (%)
Apparently healthy
Smokers 174 0 140 34 0 0
(0) (80.5) (19.5 (0) (0)
Past smokers 61 0 46 ) 15 0 0
(0) (75.4) (24.6 (0) (0)
Non smokers 463 0 347 ) 108 8 0
(0) (74.9) (23.3 (1.7) (0)
Benign conditionsc) )
Benign lung 35 0 31 4 0 0
diseases (0) (88.6) (11.4 (0) (0)
Renal diseases 29 0 4 ) 6 13 6
(0) (13.8) (20.7 (44.8 (20.7
Other benign 120 0 100 ) 20 ) 0 ) 0
diseases (0) (83.3) (16.7 (0) (0)
Cancer )
SCLC 185 0 33 24 17 111
(0) (17.8) (13.0 (9.2) (60.0
NSCLC 752 0 543 ) 182 14 ) 13
(0) (72.2) (24.2 (1.9) (1.7)
NSCLC/SCLC 7 0 1 ) 2 0 4
mix (0) (14.3) (28.6 (0) (57.1
) )
Elecsys ProGRP values (pg/mL)

Total < 3.0 3.0-50 50.1-100 100.1-200 > 200
N N N N N
(%) (%) (%) (%) (%)
Mesothelioma 27 0 24 3 0 0
(0) (88.9) (11.1) (0) (0)
Thyroid 15 0 2 1 0 12
medullary (0) (13.8) (6.7) (0) (80.0)
Neuroendocrine 23 0 10 6 2 5
carcinoma (0) (43.5) (26.1) (8.7) (21.7)
Breast 53 0 40 12 0 1
(0) (75.5) (22.6) (0) (1.9)
Ovarian 36 0 25 8 2 1
(0) (69.4) (22.2) (5.6) (2.8)
Prostate 32 0 18 9 5 0
(0) (56.3) (28.1) (15.6) (0)
Colorectal 61 0 43 15 3 0
(0) (70.5) (24.6) (4.9) (0)
Other 90 0 67 18 5 0
malignanciesd) (0) (74.4) (20.0) (5.6) (0)
c) Other benign diseases contain liver-, metabolic-, autoimmune- and inflammatory diseases. Benign lung diseases contain pneumonia, asthma, COPD and tubercolosis.
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d) Other malignancies contain renal-, liver-, pancreatic-, gastrointestinal-, stomach- and cervical tumors, carcinoids and lymphoma
Use of ProGRP for the primary differential diagnosis in lung cancer The differentiation ability of ProGRP regarding SCLC vs.
NSCLC was investigated in a study on 944 patients, (185 SCLCs, 752 NSCLCs and 7
NSCLC/SCLC mix) and ProGRP levels were correlated with histology. The
istribution of values is shown in the box‑plot and the 2 x 2 table below
N N Total
NSCLC SCLC
ProGRP ≤ 85.7 pg/mL 714 51 765

ProGRP > 85.7 pg/mL 38 134 172
Total 752 185 937
The cutoff value for a specificity of 95 % (based on NSCLC collective) was
85.7 pg/mL. The correlation of Elecsys ProGRP values and stage for 168
patients with SCLC is shown in the following table:
Clinical condition N 5th Median 95th

percentile ProGRP percentile
pg/mL pg/mL pg/mL
Stage I-II 11 17.9 75.9 781
SCLC
Stage III 57 28.4 301 2985
SCLC
Stage IV 100 32.5 585 21830
SCLC
Stage I-IV 752 15.8 38.6 85.7
NSCLC
SCLC/ NSCLC mix 7 33.5 416 25240
Benign lung disease 35 14.0 32.6 54.8
The sensitivity of ProGRP in patients with stage I-IV SCLC vs.
NSCLC and vs. benign lung diseases at the set specificity of 95 % as
well as the area under the curve (AUC) values are shown in the table
below.
Cut-off Sensitivity AUC

(pg/mL) (%) (95 % CI)
SCLC vs. NSCLC 85.7 72.4 0.872
(0.837-
0.907)
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SCLC vs. benign 54.8 80.0 0.922
diseases (0.886-
The following has to be taken into consideration 0.957)
▪ If the ProGRP results are inconsistent with clinical evidence,

additional testing is suggested to confirm the result.
▪ For diagnostic purposes, results should be used in
conjunction with other data; e.g., symptoms, results of other
tests, clinical impressions, etc.
▪ Report the results in conjunction with the sample type.
▪ Increased concentrations of ProGRP have been observed in
patients with renal dysfunction. There is a significant correlation
between serum ProGRP levels and serum creatinine
concentrations in patients with renal dysfunction. The evaluation
of serum creatinine levels should be considered in cases of high
ProGRP levels that are not consistent with diagnostic and clinical
characteristics of the patient.
▪ ProGRP levels, regardless of value, should not be interpreted
as absolute evidence for the presence or absence of malignant
disease. In patients with suspected or known cancer, other tests
and procedures must also be considered for diagnosis and good
management.
▪ The concentration of ProGRP in a given specimen,
determined with assays from different manufacturers, can
vary due to differences in assay methods, calibration, and
reagent specificity.
6.10 Elecsys free PSA
A multicenter study was performed using samples from men (aged  50) referred to
urologists for evaluation of prostate cancer. 1143 of the referred men had normal DRE that
were not suspicious for prostate cancer (DRE normal cohort). Samples were evaluated using
the Elecsys total PSA and free PSA immunoassays in parallel on the Elecsys 2010 and
1010 immunoassay analyzers. A subset of these samples was evaluated on the Elecsys
E170 MODULAR ANALYTICS Immunoassay Analyzer. No significant differences between
the three platforms were observed.
All patients underwent a transrectal prostate biopsy. Of the 1143 men with normal DRE, 664
men had tPSA results between 4-10 ng/ml on the Elecsys 2010 (tPSA 4-10: DRE normal
cohort). The racial composition of PSA 4-10: DRE normal cohort was 84.5% Caucasian,
11.5% Black non-Hispanic, 2.6% Hispanic-Mexican, and 1.4% other. The median age was
66 years. The distribution of fPSA, tPSA, and ratio fPSA/TPSA (% fPSA) values by biopsy
results for this cohort is shown in table 1.
Table 1: PSA statistics y biopsy outcome (benign, malignant)

Elecsys 2010 Biopsy Number Mean Median Min. Max. Stand.
result ng/ml ng/ml ng/ml ng/ml error of
mean
fPSA Benign 463 1.19 1.11 0.26 4.14 0.02
Malignant 201 1.00 0.92 0.34 2.39 0.03
Total 664 1.13 1.06 0.26 4.14 0.02
tPSA Benign 463 6.10 5.68 3.95 10.00 0.07
Malignant 201 6.42 6.10 3.95 10.00 0.11
Total 664 6.20 5.84 3.95 10.00 0.06
% fPSA Benign 463 19.72 19.2 5.1 53.4 0.32
Malignant 201 16.00 15.2 5.2 35.8 0.42
Total 664 18.60 18.0 5.1 53.4 0.27
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A comparison of the mean % fPSA for the benign and malignant biopsy groups indicated that
the difference is significant.
The % fPSA result may be used in evaluating the need for prostate biopsy in one of two
ways:
1. The relative risk of prostate cancer in an individual men may be considered, or
2. Patients may be managed using a single cutoff approach.
1. Individual risk assassment

There is an increased probability of detecting PCA as the PSA level increases. Of interest is
that in an urologically referred cohort there is a 12% to 22% risk of PCA in men whose tPSA
is < 4.0 ng/ml. The tPSA range of 4-10 ng/ml has been described in references 9 and 10 s
the diagnostic "gray zone". It is in this area that the % fPSA to tPSA ratio is of utility.
Table 2: Probability of detecting PCA on needle biopsy in urologically referred men with DRE
results not suspicious for prostate cancer
tPSA Probability of PCA (%) 95% confidence interval
ng/ml
< 4.0 17.1 12.4 - 21.6
4.0-10.0 30.3 26.8 - 33.8
> 10.0 49.1 42.5 - 55.7
The probability of finding prostate cancer PCA with tPSA in the gray zone (4-10 ng/ml)
increases with increasing age and with decreasing fPSA/tPSA ratios - see table 3. The
probabilities presented in table 3 wee estimated from a loglinear model.
Table 3: Probability of finding PCA on needle biopsy by age in years and % fPSA on
Elecsys® 2010
Probability of finding PCA on needle biopsy by age in years (95% confidence interval)
% fPSA ratio 50-59 60-69  70
 10 49.2 (12.4-86.9) 57.7 (17.9-89.3) 64.5 (30.4-88.3)
11-18 26.9 (5.7-68.9) 33.9 (8.6-73.7) 40.8 (15.8-71.7)
19-25 18.3 (3.5-57.9) 23.9 (5.4-63.4) 29.7 (10.1-61.1)
> 25 9.1 (3.1-23.7) 12.2 (4.7-28.1) 15.8 (9.0-26.1)
2. Single cutoff
Alternatively, a single cutoff may be used for men in all age groups. Sensitivities (% of PCA
detected) and specificities (% of biopsies avoided in men without PCA) for various % fPSA
cutoffs are shown in table 4. A cutoff of 25% results in the detection of 92.5% of prostate
cancers and avoids unnecessary biopsy in 20.3% of men without prostate cancer. Virtually
all (99%) of prostate cancers are detected with a cutoff of 30%, but only 8.9% of men without
prostate cancer are spared biopsy.
Table 4: Argeement with biopsy at various % fPSA cutoffs on Elecsys® 2010

Benign biopsies
free PSA Number of patients with Agreement 95% confidence
% negative biopsy identified at at cutoff, % interval
cutoff (total = 463)
23 141 30.4 (26.3-34.9)
25 94 20.3 (6.7-24.3)
27 65 14.0 (11.0-17.5)
30 41 8.9 (6.4-11.8)
53 1 0.2 (0.0-1.2)
Malignant biopsies
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free PSA Number of patients with Agreement 95% confidence
% positive biopsy identified at at cutoff, % interval
cutoff (total = 201)
23 173 86.1 (80.5-90.5)
25 186 92.5 (88.0-95.8)
27 192 95.5 (91.7-97.9)
30 199 99.0 (96.4-99.9)
53 201 100.0 (98.2-100.0)
6.11 Elecsys NSE
Studies conducted with Elecsys® NSE in 3 clinical centers in Germany and Roche-inhouse
covering a total of 547 healthy subjects gave the following results:
16.3 ng/ml (95% percentile)

15.7 – 17.0 ng/ml (95% confidence range)
Status: Elecsys® NSE Multicenter Evaluation; study no. B99P005, 7/2001
6.12 Elecsys total PSA
Expected values in normal healthy males

a) Studies in two clinical centers in the Netherlands and Germany with Elecsys® total PSA
on sera from 244 healthy men of various age groups yielded the following results:
tPSA (ng/ml)
Age (years) n Median 95th percentile
< 40 45 0.57 1.4
40-50 42 0.59 2.0
50-60 107 0.75 3.1
60-70 41 1.65 4.1
>70 9 1.73 4.4
b) The distribution of tPSA results was measured in a cohort of 395 normal healthy males
aged 50-94 years (results of a study in the USA). The subsequent table presents the tPSA
values as measured on the Elecsys® 2010 immunoassay analyzer.
tPSA (ng/ml)
Age (years) n Median 95th percentile
50-59 154 0.81 3.89
60-69 131 0.95 5.4
>70 110 1.11 6.22
tPSA values in detection of prostate cancer

A multicenter cohort study was performed to demonstrate the effectiveness of the Elecsys®
total PSA Immunoassay when used in conjunction with digital rectal examination (DRE) as
an aid in the detection of prostate cancer in men 50 years of age or older. A total of 1121
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serially accrued men fifty years of age or older participated n the study. The mean age of the
cohort was 66.4 years (95% confidence interval = 65.9 to 66.8 years).
Distribution of tPSA values by biopsy result and digital rectal examination result
Prostate biopsy result: benign
tPSA (ng/ml)
DRE result n Median Minimum Maximum
Normal 375 5.8 0.4 75.8
Pathological 355 4.9 0.3 29.6
Total 730 5.4 0.3 75.8
Prostate biopsy result: malignant

tPSA (ng/ml)
DRE result n Median Minimum Maximum
Normal 146 7.2 2.5 122.1
Pathological 245 7.8 0.5 778.5
Total 391 7.4 0.5 778.5
Utility of tPSA in detection of prostate cancer.

As shown in the table below, within this cohort of 1221 males, 391 (34.9%) prostate cancers
were detected by biopsy. Abnormal digital rectal examination (DRE) results were reported for
245 (62.7%) of the 391 prostate cancers while tPSA results above 4 ng/ml were reported for
336 (85.9%) cancers for the Elecsys® 2010 immunoassay analyzer. Of the 391 men
diagnosed with cancer, 379 (96.9%) had either an abnormal DRE result or a tPSA value
above 4.0 ng/ml.
The positive predictive value for the Elecsys® total PSA immunoassay on the Elecsys® 2010
immunoassay analyzer was 0.39 using 4.0 ng/ml as a cutoff (maligne prostatabiopsie + tPSA
> 4.0 ng/ml: n=336 /tPSA > 4.0 ng/ml: n=862).
Results for digital rectal examination and tPSA as referred to prostate cancers detected by
biopsy in a cohort of:
1121 males 50 years older referred to an urologist for prostate evaluation.
Total DRE+* PSA+** PSA+ or PSA+ and PSA+ and PSA- and
DRE+ DRE+ DRE-*** DRE+****
Total 1121 600 862 1037 425 437 175
number
No. of 391 245 336 379 202 134 43
malignant
prostate
biopsies
% positive 34.9 40.8 39.0 36.5 47.5 30.7 24.6
biopsies
* abnormal DRE ** tPSA value > 4 ng/ml *** normal DRE **** tPSA value < 4 ng/ml
Analysis of tPSA values was performed with Elecsys® 2010 and Elecsys® 1010 and gave
similar results.
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6.13 Elecsys S 100
Apparently healthy adults and patients with malignant melanoma

Measurements using Elecsys® S 100 in samples from apparently healthy adults in 2 centers
(Munich) and in group of internal healthy volunteers and patients suffering from malignant
melanoma in different tumor stages under follow-up investigation revealed the following
values:
Group Subgroup No. of Median µg/l 95% No. of

samples percentile samples
(patient) above cutoff
(> 0.105 µg/l)
Apparently healthy adults 206 (206) 0.046 0.105 10 of 206
(4.9%)
Malignant No evidence 821 (408) 0.044 0.109 45 of 821
melanoma of disease (5.5%)
patients (all Regional 32 (24) 0.047 0.120 4 of 32
stages under lymph node (12.5%)
follow up metastases
investigation) Skin / distant 21 (15) 0.093 0.511 10 of 21
lymph node (47.6%)
metastases
Distant / 70 (48) 0.077 0.759 30 of 70
visceral (42.9%)
metastases
Percentile 2.5 5 25 50 75 95 97.5 100

(%)
S 100 µg/l 0.020 0.020 0.030 0.046 0.061 0.105 0.125 1.135
The classification of the clinical samples were made accordingly to the stage of disease
which was present at the point of time the sample was taken. This metastasis stage groups
can but must not be the same as the stage at primary diagnosis.
The metastasis groups are defined as follows:
 Met-group 1 = tumor free, no evidence of disease

 Met-group 2 = regional lymph node metastasis
 Met-group 3 = skin/distant lymph node metastasis
 Met-group 4 = Distant/visceral metastasis
The following values were measured using the Elecsys® S 100 in 944 serum samples of
patients suffering from malignant melanoma of different metastasis stages.
Percentile 2.5 5 25 50 75 95 97.5 100

(%)
S 100 µg/l 0.011 0.015 0.030 0.044 0.060 0.109 0.170 5.010
Met 1
S 100 µg/l 0.012 0.019 0.033 0.058 0.183 0.661 1.150 2.980
Met 2-4
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The table below shows sensitivity and specificity, as well as positive and negative predictive
values (PPV, NPV) in values in the range of 0.05 and 0.19 µg/l resulting from measurements
in malignant melanoma patients in different stages.
Value µg/l Met group 1 Met group PPV NPV Sensitivity Specificity
2-4
0.07 54 5 0.30 0.91 0.48 0.83
0.08 39 2 0.38 0.92 0.45 0.89
0.09 14 2 0.47 0.92 0.43 0.93
0.10 12 6 0.50 0.91 0.41 0.94
0.11 10 3 0.54 0.91 0.36 0.95
0.12 6 2 0.58 0.91 0.34 0.96
0.13 6 2 0.62 0.91 0.33 0.97
0.14 0 1 0.64 0.90 0.32 0.97
0.15 1 0 0.63 0.90 0.31 0.97
0.16 1 4 0.62 0.90 0.28 0.97
0.17 3 1 0.63 0.90 0.27 0.98
0.18 0 1 0.66 0.90 0.27 0.98
0.19 1 3 0.65 0.90 0.25 0.98
The table below shows the number of samples above the cutoff value of 0.105 µg/l.
Individuals No of samples above cutoff %

Apparently healthy 10 of 206 4.9
No evidence of disease 45 of 821 5.5
Regional lymph node 4 of 32 12.5
metastases
Skin / distant LN metastases 10 of 21 47.6
Distant / visceral metastases 30 of 70 42.9
Adults with potential brain injury

Elecsys® S100 values were assessed within 3 hours after traumatic event in patients
presenting with minor traumatic brain injury (GCS 13-15-Glasgow Coma Score) and at least
one symptom. CCT (cranial computer tomography) was performed within 6 hours after
traumatic event. When using the 95% percentile value of the apparently healthy persons
(0.105 µg/l) as the cutoff, the following results were obtained for the Elecsys® S100
compared to the CCT reference:
NPV (negative predictive value) 99.7%, PPV (positive predictive value) 11%, sensitivity
98.8%, and specificity 32.9% (confidence interval 95%: NVP 99.1-100%, PPV 8.8-13.3%,
sensitivity 96.5-100%, specificity 30-35.9%).
CCT positive CCT negative Total

Elecsys® S100 positive 83 670 753
Elecsys® S100 negative 1d 329 330
Total 84 999 1083
d
0.098 µg/l
Please check the product information for further information.
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6.14 Elecsys SCC
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AFP 0911/10
CA 125 II 1014/01
CA 15-3 II 0512/16
CA 19-9 0911/20
CA 72-4 0312/10
CEA 0512/20
Cyfra 21-1 0812/15
HE4 0612/05
NSE 0812/11
ProGRP 0913/01
free PSA 0211/10
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total PSA 0510/07
S100 0510/07
SCC 0316/02
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7 Down Syndrome Screening:
7.1 Elecsys free ßhCG
Expected values and clinical performance

The following results were obtained with the Elecsys free ßhCG:
1. Reference range study using a panel of samples from 500 healthy non-pregnant donors
(Roche study No. R04P026)
All results were below the lower detection limit of < 0.1 IU/L.
2. Perfomance evaluation study of the Elecsys free βhCG assay and the Elecsys PAPP-A
assay in first trimester trisomy 21 risk assessment (Roche study No. B05P020, status May
2011 and Roche study No. CIM 000950 status May 2011) Measurements with the Elecsys
free βhCG assay and the Elecsys PAPP-A assay were conducted in 6 clinical centers in
Belgium, Switzerland, Denmark, England and Germany. Median values (gestational weeks
8+0 to 14+0) were calculated from log-linear regression analysis of 4842 free βhCG values
for the middle of the respective week (week n+3). Gestational age was calculated from
ultrasound crown-to-rump length (CRL) according to Robinson.
patient population and if necessary determine its own reference ranges. For prenatal testing
it is recommended that the median values be re-evaluated periodically.
Clinical performance data

In total, 2629 samples from clinical routine with known outcome were examined. 107 out of
the 2629 samples were from pregnancies with confirmed Down syndrome. All samples were
measured in parallel with FMF (Fetal Medicine Foundation) certified PAPP-A and free βhCG
tests. Risk calculation was performed using the software SsdwLab version 5.0. This software
makes use of an algorithm described by Palomaki et al. by means of the mathematical
calculations for Gaussian multivariate distribution as already published. Risk analysis is
based on maternal age, nuchal translucency as well as on the results of the biochemical
parameters, corrected by different factors such as maternal weight, smoking and ethnic
background of the pregnant woman. Individual risk calculation The calculation of a woman’s
individual risk of carrying a single fetus affected
by trisomy 21 was assessed without consideration of nuchal translucency (NT) data to
demonstrate the performance of the biochemical methods. Maternal weight and smoking
behavior were taken into account as correction factors. Concordance of risk analysis compared
to a competitor method was examined using the cutoff value established in the participating
laboratory.
It is the responsibility of the user to choose the cutoff which
will apply for further procedures.
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7.2 Elecsys PAPP-A
Expected values and clinical performance

The following results were obtained with the Elecsys PAPP-A assay:
1. Reference range study using a panel of samples from 500 healthy non-pregnant donors
(Roche study No. R04P026)
< 7.15 mIU/L (95% percentile)
2. Performance evaluation study of the Elecsys PAPP-A assay and the Elecsys free ßhCG
assay in first trimester trisomy 21 risk assessment (Roche study No. B05P020, status July
2007)
Measurements with the Elecsys free ßhCG assay and the Elecsys PAPP-A assay were
conducted in 4 clinical centers in Belgium, Switzerland, and Germany. Median values
(gestational weeks 11-14) were calculated from log-linear regression analysis of 3270 PAPP-
A values for the middle of the respective week. Estational age was calculated from
ultrasound crown-to-rump length (CRL) according to Robinson.
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Gestational 11 12 13 14
week
Number of 206 623 1384 1057
samples
Median 1337 1919 2926 4358
(mIU/L)
For prenatal testing it is recommended that the median values be re-evaluated periodically.
Clinical performance data

In total, 1079 samples from clinical routine with known outcome were examined. 32 out of the
1079 samples were from pregnancies with confirmed Down syndrome. All samples were
measured in parallel with FMF (Fetal Medicine Foundation) certified PAPP-A and free ßhCG
tests. Risk calculation was performed using the software SsdwLab version 5.0. This software
makes the use of an algorithm described by Palomaki et al by means of the mathematical
calculations for Gaussian multivariate distribution as already published. Risk analysis is
based on maternal age, nuchal translucency as well as on the results of the biochemical
parameters, corrected by different factors like e.g. maternal weight, smoking and ethnic
background of the pregnant woman.
Individual risk calculation

The calculation of a woman’s individual risk of carrying as single fetus affected by trisomy 21
was assessed without consideration of nuchal translucency (NT) data to demonstrate the
performance of the biochemical methods. Maternal weight and smoking behaviour were
taken into account as correction factors. Concordance of risk analysis compared to
competitor method combination was examined using the cut-off value already established in
the participating laboratory.
It is the responsibility of the user to choose the cut-off which will apply for further procedures.
Concordance analysis data
A. Concordance analysis in unaffected pregnancies (n=1047)
Risk > cut-off (Roche*) Risk < cut-off (Roche*)
Risk > cut-off (competitor**) 55 (5.2%) 26 (2.5%)
Risk < cut-off (competitor**) 6 (0.6%) 960 (01.7%)
In 1047 unaffected samples the Roche methods correctly classified 986 samples (specificity:
94.2%) in comparison to 966 (specificity: 92.3%) correctly classified by the competitor
methods.
B. Detection rate in confirmed trisomy 21 pregnancies (n=32)

Risk > cut-off (Roche*) Risk < cut-off (Roche*)
Risk > cut-off (competitor**) 21 (65.6%) 0
Risk < cut-off (competitor**) 3 (9.4%) 8 (25%)
In 32 affected samples the Roche methods showed a detection rate of 75% (24/32) in
comparison of 65.6% (21/32) obtained with the competitor method.
* Combination of results from the Elecsys PAPP-A assay and the Elecsys free ßhCG
* Combination of results from the competitors PAPP-A and free ßhCG
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Free ßhCG 0812/06
PAPP-A 0411/03
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8 Anemia:
8.1 Elecsys Ferritin
Results of a study with Enzymun-Test® Ferritin on samples from 224 healthy test subjects
(104 women - mainly premenopausal - and 120 men) are given below. The values
correspond to the 5th and 95th percentiles.
Men, aged 20-60 years: 30-400 ng/ml
Women, aged 17-60 years: 13-150 ng/ml
Ferritin (ng/ml) in children (n total = 427)
3 - 30 1 - 12 1-6 7 - 12 13 - 18 >19
Parameter < 3 days
days mth years years years years
Percentile
0 149,0 32,99 21,45 8,54 5,48 8,97 13,25
2,5 149,0 32,99 21,45 9,67 6,75 13,25 13,25
5 149,0 42,42 26,08 10,90 9,94 15,69 13,25
10 158,5 88,31 46,44 13,68 13,50 21,06 15,58
25 190,2 117,60 84,89 19,62 20,18 25,50 22,80
50 262,4 206,3 129,75 25,05 27,13 33,68 49,40
75 306,3 271,9 191,0 45,41 40,54 45,04 111,70
90 413,7 334,6 277,9 73,12 59,59 59,69 114,70
95 1351,0 509,2 287,6 92,24 71,70 92,4 149,4
97,5 1351,0 834,7 597,3 117,70 84,0 110,6 149,4
100 1351,0 834,7 597,3 148,90 177,7 156,5 149,4
Number 12 33 26 82 157 106 11
8.2 Elecsys Folate III
Referring to “The American Journal of Clinical Nutrition” serum folate (folic acid) values were
found as follows:
Sex Age N Median 2.5th-27.5th percentile

years nmol/L ng/ml nmol/L ng/ml
Both all 23345 29.5 10.4 10.4-78.9 4.6-34.8
Male all 11387 27.9 12.3 10.2-73.0 4.5-32.2
Female all 11958 30.1 13.3 10.9-84.5 4.8-37.3
Both 4-11 3595 39.0 17.2 19.5-85.4 8.6-37.7
Both 12-19 6390 27.4 12.1 11.3-61.6 5.0-27.2
Both 20-59 8689 26.3 11.6 10.0-70.2 4.4-31.0
Both ≥ 60 4671 37.6 16.6 12.7-103.8 5.6-45.8
These values were obtained in the USA during the National Health and Nutrition Examination
Survey (NHANES), 1999-2004.
The values shown below were performed on samples from an apparently healthy population,
using the Elecsys Folate III assay.
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Europe: The calculation is based on 290 sera (96 men, 194 women). The age range was
between 18 and 65 years. Pregnant or lactating women were excluded. The reference
population was selected according to normal homocysteine values.
Australia: The calculation is based on 345 sera (217 men, 128 women). The age reange was
between 18 and 65 years. Pregnant women were excluded. The reference population was
selected according to normal homocysteine values.
Country N Median 2.5th-27.5th percentile

nmol/L ng/ml nmol/L ng/ml
Europe 290 21.7 9.57 10.4-42.4 4.6-18.7
Australia 345 23.9 10.6 12.0-43.9 5.3-19.3
Please note: These values should only be used as a guideline.

It should be taken into consideration that differences in the expected values may exist with
respect to population and dietary status.
Folate deficient sample values

25 samples considered to be deficientb in serum folate concentration were assessed using
the Elecsys Folate III assay. All samples were found to be below the 2.5th percentile as given
in the table above.
b) Folate deficiency was assessed by measurement of serum folate by two commercially

available folate assays.
8.3 Elecsys Folate RBC
The values shown below were measured on samples from an apparently healthy population,
using the Elecsys Folate III/RBC application. The values can be applied for the Elecsys
Folate RBC assay on all Elecsys and cobas e analyzers. The calculation is based on 290
sera (96 men, 194 women) from an European population and on 202 sera (59 men, 143
women) from an Australian population, respectively. The age range was between 18 and 65
years. Pregnant or lactating women were excluded. The reference population was selected
according to normal homocysteine values. The following values were obtained:
Whole blood folate (from hemolysate sample)

Country Median 2.5th-97.5th percentile
N nmol/l ng/ml nmol/l ng/ml
Europe 290 673 296 418-1212 212-534
Australia 202 878 387 546-1324 241-584
RBC folate (folate in erythrocyte fraction)

Country Median 2.5th-97.5th percentile
N nmol/l ng/ml nmol/l ng/ml
Europe 290 1657 730 1187-2854 523-1257
Australia 202 2149 948 1426-3294 629-1453
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8.4 Elecsys Vitamin B12 II
Because differences may exist with respect to population and dietary status, it is
recommended that normal ranges be determined by each laboratory over a suitable period of
time and in a statistically significant number of assays before clinical significance is attached
to the results of these tests.
The values shown below were performed on samples from an apparently healthy population,
using the Elecsys Vitamin B12 II assay. The calculation is based on 135 sera (68 men, 67
women). The age range was between 20 and 78 years. Pregant women wer excluded. The
reference population was selected according to normal homocysteine values.
N Median Range (2.5-97.5 perc.)

pg/ml pmol/l pg/ml pmol/l
135 425 314 197-771 145-569
These values should only be used as a guideline.

Ferritin 0312/12
Folate III 0712/10
Folate RBC 1011/01
Vitamin B12 II 0515/01
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9 Bone Marker:
9.1 Elecsys -CrossLaps
The following values have been obtained from studies with Elecsys® -CrossLaps in healthy
test subjects:
n Mean SD Mean + 2SD

ng/ml (pg/ml) ng/ml (pg/ml) ng/ml (pg/ml)
Males
30-50 years 165 0.3 (300) 0.142 (142) 0.584 (584)
>50-70 years 109 0.304 (304) 0.2 (200) 0.704 (704)
> 70 years 365 0.394 (394) 0.23 (230) 0.854 (854)
Females
Premenopausal 254 0.299 (299) 0.137 (137) 0.573 (573)
postmenopausal 429 0.556 (556) 0.226 (226) 1.008 (1008)
Status: Males, MCE study, 2/2000

Females, follow up tests of samples from the OFELY study.
Please check the method sheet regarding
- Monitoring in a placebo control group

- Monitoring during antiresorptive therapy
9.2 Elecsys hGH

Expected values
Basal levels of hGH do not have a diagnostic relevance and stimulation tests are needed
(see above) to assess a growth hormone disorder. Therefore the following values from
healthy subjects are for information only and should not be used for diagnostic purposes.
Girls (n = 43) Boys (n = 86)
Percentiles
0-10 years, median: 5 years 0-10 years, median: 5 years
hGH (ng/mL)
5 0.120 0.094
50 0.689 0.814
95 7.79 6.29
Girls (n = 38) Boys (n = 33)
Percentiles
hGH (ng/mL)
5 0.123 0.077
50 0.432 0.322
95 8.05 10.8
Percentiles Women (n = 150) Men (n = 149)
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hGH (ng/mL)
5 0.126 < 0.030
50 0.944 0.119
95 9.88 2.47
9.3 Elecsys N-MID Osteocalcin
The reference ranges are test-dependent.

Completed studies with Elecsys N-MID Osteocalcin have revealed the following ranges in
ng/ml.
Number 50% percentile 5-95% percentile

ng/ml ng/ml
Healthy women
premenopausal, > 20 108 23 11-43
years 102 27 15-46
postmenopausal (no HRT) 120 27 13-48
Osteoporosis patients
Healthy men
18 - < 30 years 183 40 24-70
30 – 50 years 179 25 14-42
> 50-70 years 125 24 14-46
Study protocol No. 9905 – 8/2000

In patients with renal failure the osteocalcin values can be elevated, both directly, due to
impaired clearance and indirectly, due to renal osteodystrophy.
9.4 Elecsys PTH
15-65 pg/ml (1.6-6.9 pmol/l)
9.5 Elecsys PTH (1-84)
Expected values
Normal values in apparently healthy individuals
The normal value range was determined in a clinical study using 596
samples from apparently healthy individuals. The reference population
was selected according to normal clinical chemistry parameters,
normal hematology results, no vitamin D intake and normal calcium
values as detemined by flame photometry. The values given are only
indicative and may vary from other published data.
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N = 596 PTH (1-84) range
pg/ml pmol/l
Mean 31.3 3.32
2.5th percentile 14.9 1.58
97.5% percentile 56.9 6.03
The subgrouping of the above cohort according to the vitamin D (25-OH)

level shows the inverse relationship between the concentrations of
PTH (intact) and PTH (1-84) and vitamin D (25-OH).
N Vitamin D PTH intact median PTH (1-84) median

(25-OH)
ng/ml pg/ml pmol/l pg/ml pmol/l
339 ≤ 20 41.4 4.39 32.2 3.42
157 ≥ 20 and < 37.0 3.92 29.0 3.07
30
100 ≥ 30 33.0 3.49 24.9 2.64
Each laboratory should investigate the transferability of the expected values to

its own patient population and if necessary determine its own reference ranges.
9.6 Elecsys total P1NP
Sera taken from 573 healthy female volunteers who had been enrolled in a study of
determinants of bone loss (OFELY) were measured for total P1NP levels. The following
results were obtained.
Post-menopausal Pre-menopausal
All HRTb yes HRT no All
N 444 154 290 129
5th percentile 16.27 14.28 20.25 15.13
Median 37.09 28.48 42.94 27.8
Mean 40.43 31.74 45.05 30.1
95th percentile 73.87 58.92 76.31 58.59
b
HRT = patients receiving hormone replacement therapy
Please note that within the method sheet and product information are two additional figures.
Figure 1: Frequency of total P1NP concentrations (µg/l or ng/ml) observed in normal,
untreated, pre-(n=129) and post-(n=290) menopausal women.
Figure 2: The effect of hormone replacement therapy on total P1NP (µg/l or ng/ml)
concentration frequency distribution in treated („HRT yes“; n = 154) and untreated („HRT no“;
n = 290) post-menopausal women.
The measurement of total P1NP shows minimal circadian or seasonal variation (approx. 6%)
and food intake or diet show no detectable influence upon serum levels.
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Significantly elevated serum total P1NP levels are associated with the presence of metastatic
bone disease and may also be seen in patients with renal insufficiency. Diseases associated
with secondary bone disease may have an effect upon levels of total P1NP.
9.7 Elecsys Vitamin D total
Expected values
Due to different standardizations between methods, result
variation may arise. Clinical assessment should be taken into
consideration when interpreting results.
Health based reference values (recommended for use):

Currently there is no standard definition of the optimal vitamin D status.
Many specialists consider the commonly used population based reference
values too low. Health based reference values are recommended to
replace population based reference values.
There is a consensus opinion that the minimal vitamin D (25-OH) level for
bone health is between 20-32 ng/mL (50-80 nmol/L).
A more recent consensus of experts leads to the conclusion that
for general health a desirable concentration of vitamin D (25-OH)
is ≥ 30 ng/mL (≥ 75 nmol/L).
Population based reference values (for information only):

It should be taken into consideration that differences in vitamin D
levels may exist with respect to gender, age, season, geographical
latitude and ethnic groups.
Each laboratory should investigate the transferability of the expected values to
its own patient population and if necessary determine its own reference ranges.
Population based reference ranges should not be taken as clinical cutoff
to recommend or dissuade from vitamin D supplementation. Guidance for
supplementation should be taken from recent literature.
A reference range study was conducted with samples from apparently
healthy individuals of Caucasian heritage. The age range was 20-77
years. Samples were collected between November and July.
The values given are for information only and may vary from other published data.
Gender
All Female Male Unit
N 453 252 201
Mean 20.6 21.6 19.4 ng/ml
2.5% percentile 5.26 6.23 4.92 ng/ml
97.5% percentile 47.0 49.9 42.7 ng/ml
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-CrossLaps 1211/12
hGH 0211/02
N-MID Osteocalcin 1211/14
PTH 1012/22
PTH (1-84) 1012/02
total P1NP 0812/09
Vitamin D total 0812/04
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10 Varia:
10.1 Elecsys IgE II
The IgE concentrations in healthy, non-atopic test subjects are greatly dependent on age.
The lowest values are found in neonates. Normal values reach a maximum in the 9-13 age
group and decrease once more in adults.
Recommended threshold values:
Age group IU/ml ng/ml

Neonates 1.5 3.6
Infants in 1st year of life 15 36
Children aged 1-5 years 60 144
Adults 100 240

IgE II 0312/06
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11 Rheumatoid Arthritis:
11.1 Elecsys Anti-CCP
In an external study using the Elecsys Anti-CCP assay on samples from 420 asymptomatic
healthy individuals, 792 confirmed RA patients and 907 patients with other rheumatic and
non-rheumatic disorders an optimal cut-off of 17 U/ml was determined; samples with a
concentration  17 U/ml being considered positive for anti-CCP (for details see section
“Clinical Sensitivity and Specificity”).
Clinical Sensitivity and Specificity

In cohorts of 792 confirmed RA patients, 420 asymptomatic healthy individuals and 907
patients with other rheumatic and non-rheumatic disorders an optimal cut-off o 17 U/ml was
determined. At this cut-off the sensitivity was calculated to be 67.4%, with a specificity of
97.0%. The area under the receiver operating characteristic (ROC) curve was 0.85.
The health status of 420 asymptomatic healthy volunteers (213 men, 207 women) was
defined by normal results for a standard clinical chemistry and hematology profile and a brief
medical examination. A family history of rheumatic/automimmune disorders was excluded
through a medical questionnaire.
The cohort of established RA patients consisted of patients with unknown disease duration
as well as patients with a known disease duration of more than 2 years or less than 2 years.
Disease duration was measured from the time point of RA diagnosis by an experienced
rheumatologist.
N Number of samples Sensitivity %

found positive with
the Elecsys Anti-CCP
assay
RA samples in total 792 534 67.4
RA, > 2 years 378 273 72.2
Clinical specificity
N Number of samples Specificity %

found positive with
the Elecsys Anti-
CCP assay
Non-RA samples in 1327 40 97.0
total
Healthy 420 4 99.0
Non-RA disease in 907 36 96.0
total
Non-RA disease
subsets:
Connective tissue 166 9 94.6
diseases
Vasculitides 47 4 91.5
Spondyloarthropathies 146 8 94.5
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Other rheumatic 108 2 98.1
diseases
Inflammatory bowel 52 0 100
diseases
Non-rheumatic 31 2 93.5
autoimmune diseases
Renal failure 31 1 96.8
Liver cirrhosis 26 2 92.3
Infectious diseases 300 8 97.3

Anti-CCP 0611/04
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12 Sepsis:
12.1 Elecsys BRAHMS Procalcitonin
Expected values
Reference range
A study performed with the Elecsys BRAHMS PCT assay using 492 samples from apparently
healthy males (245) and females (247) revealed the following normal value:
0.046 ng/ml (95% percentile).
Clinical cut-off
Results obtained with the Elecsys BRAHMS PCT assay are in agreement with the literature.
A study performed on samples from patients admitted to an ICU (intensive care unit) showed
that PCT values:
< 0.5 ng/ml represent a low risk of severe sepsis and / or septic shock
> 2 ng/ml represent a high risk of severe sepsis and/or septic shock
Clinical Performance
Clinical studies were conducted on samples from 283 ICU patients. The patients were
classified into categories based on ACCP/SCCM (American College of Chest
Physicians/Society of Critical Care Medicine) consensus criteria on their first day of ICU
admission: SIRS (systemic inflammatory response syndrome), sepsis, severe sepsis and
septic shock.
The PCT values of the patients with SIRS (95) or sepsis (n=71) compared to patients with
severe sepsis (n=60) or septic shock (n=57) were as follows:
Results with a cut-off at 0.5 ng/ml
Clinical Classification
Elecsys BRAHMS PCT SIRS Severe sepsis/ Total
septic shock
< 0.5 ng/ml 63 5 68
 0.5 ng/ml 32 112 144
Total 95 117 212
Based on the above data the sensitivity was 96%, the specificity 66%, the positive predictive
value 78% and the negative predictive value 93%.
Elecsys BRAHMS PCT SIRS Sepsis Total
< 0.5 ng/ml 63 25 88
 0.5 ng/ml 32 46 78
Total 95 71 166
Results with a cut-off at 2 ng/ml
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Elecsys BRAHMS PCT SIRS Severe sepsis/ Total
septic shock
< 2 ng/ml 88 18 106
 2 ng/ml 7 99 106
Total 95 117 212
Elecsys BRAHMS PCT SIRS Sepsis Total
< 2 ng/ml 88 55 143
 2 ng/ml 7 16 23
Total 95 71 166
12.2 Elecsys IL-6
In an external study using the Elecsys IL-6 assay on samples from 817 apparently healthy
individuals a reference range of 7 pg/ml (95% percentile) was determined.

BRAHMS Procalcitonin 0712/07
IL-6 0512/05
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13 ISDs:
13.1 Elecsys Cyclosporine
No firm therapeutic range exists for cyclosporine in whole blood. The

complexity of the clinical state, individual differences in sensitivity to
immunosuppressive and nephrotoxic effects of cyclosporine,
coadministration of other immunosuppressants, type of transplant, time
post-transplant, and a number of other factors contribute to different
requirements for optimal blood levels of cyclosporine. Individual
cyclosporine values cannot be used as the sole indicator for making
changes in the treatment regimen. Each patient should be thoroughly
evaluated clinically before treatment adjustments are made, and each
assay user must establish his or her ranges based on clinical experience.
These ranges will vary according to the commercial in vitro diagnostic test
used. Ranges must be established for each commercial test used.
13.2 Elecsys Everolimus
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13.3 Elecsys Sirolimus
13.4 Elecsys Tacrolimus

No firm therapeutic range exists for tacrolimus in whole blood. The
complexity of the clinical state, individual differences in sensitivity to
immunosuppressive and nephrotoxic effects of tacrolimus, coadministration
of other immunosuppressants, type of transplant, time post-transplant, and
a number of other factors contribute to different requirements for optimal
blood levels of tacrolimus. Individual tacrolimus values cannot be used as
the sole indicator for making changes in the treatment regimen. Each
patient should be thoroughly evaluated clinically before treatment
adjustments are made, and each assay user must establish his or her
ranges based on clinical experience.
These ranges will vary according to the commercial in vitro diagnostic test
used. Ranges must be established for each commercial test used.

Cyclosporine 0913/01
Everolimus 0316/01
Sirolimus 0316/01
Tacrolimus 0913/02
14 Alzheimer’s Disease Diagnosis:
14.1 Elecsys ß-Amyloid (1-42) CSF

Clinical performance
Each laboratory should investigate the transferability of the expected values
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to its own patient population.
Concordance with PET visual read was assessed in a retrospective study (Roche study number RD002145) based
on samples from the BioFINDER cohort.16 The primary analysis population consisted of 277 mild cognitive
symptoms (MCS) patients for whom banked CSF samples and PET scan results were available (PET tracer: [18F]‑
Flutemetamol). Of the 277 patients, 120 had subjective cognitive deficiency (SCD), 153 MCI and for 4 patients no
assignment was available. The average age was 70 years(range 59‑80 years), 42 %/ 58 % of patients were
female/male and 45 %/ 54 % of patients were ApoE4 carriers/non-carriers. The amyloid PET
scans were read by three independent trained readers and majority voting
was used to call the image positive or negative, resulting in 110 (40 %)
positive, and 167 (60 %) negative PET reads. As the BioFINDER study
used a different pre-analytical handling procedure, an adjustment factor
was determined in study RD002575. The resulting cutoff after adjustment
was as follows:
▪ Elecsys β‑Amyloid (1‑42) CSF ≤ 1000 pg/mL - test result positive

▪ Elecsys β‑Amyloid (1‑42) CSF > 1000 pg/mL - test result negative
Based on the selected cutoff, agreement with the PET scan results was as follows:
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PPA (sensitivity) and NPA (specificity) as a function of cutoff

x: β‑AMYLOID (1‑42) (pg/mL), ROCHE pre-analytical handling procedure
z: β‑AMYLOID (1‑42) (pg/mL), BioFINDER pre-analytical handling
procedure
y: agreement (%)
A: NPA (specificity) (%)
B: PPA (sensitivity)

ß-Amyloid (1-42) CSF 0517/01
15 Hepatitis:
15.1 Elecsys Anti-HAV
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Interpretation of the results
Samples with concentrations < 20 IU/l are not reactive in the Elecsys® Anti-HAV test.
Samples with concentrations  20 IU/l are reactive in the Elecsys® Anti-HAV test.
Concentrations > 20 IU/l indicate an existing or past hepatitis A infection or the presence of
anti-HAV antibodies after hepatitis A vaccination.
15.2 Elecsys Anti-HAV IgM

Samples having a cutoff index  1.0 are reactive with Elecsys® Anti-HAV IgM test. These
samples are considered positive for anti-HAV IgM.
Samples with a cutoff index < 1.0 are non-reactive with Elecsys® Anti-HAV IgM test. These
samples are considered negative.
The cutoff is selected such that the anti-HAV IgM concentration is above the cutoff index
when an acute HAV infection is present. In case of a past hepatitis A infection, the anti-HAV
concentration is usually below the cutoff index of 1.0. In the course of most acute hepatitis A
infections, the anti-HAV IgM concentration decreases within 3-4 months after onset of the
first symptoms and can then no longer be detected. Anti-HAV IgM antibodies are persistent
only in exceptions and can then be detected beyond this period.
15.3 Elecsys Anti-HBc

Samples having a cutoff index > 1.0 are non-reactive in the Elecsys anti-HBc test. These
samples are deemed negative for anti-HBc and do not need further testing.
Samples having a cutoff index  1.0 are reactive in the Elecsys Anti-HBc test. All samples
found to be reactive in the initial test must be retested in duplicate with Elecsys Anti-HBc
assay. If the results in the follow-up test are "non-reactive" in both cases, then the sample is
deemed negative for anti-HBc. If at least one of the repeat measurements is "reactive", then
the sample is deemed repeatedly reactive.
15.4 Elecsys Anti-HBc IgM

Samples with a cutoff index  1.0 are reactive in the Elecsys® Anti-HBc IgM test. These
samples are considered positive for anti-HBc IgM. Samples with a cutoff index < 1.0 are non-
reactive in the Elecsys® Anti-HBc IgM test. These samples are considered negative.
Note: According to the recommendations of the Paul-Ehrlich-Institute, Langen (Germany), an
equivocal range should be allowed for the in the assessment of results from anti-HBc tests.
For Elecsys® Anti-HBc IgM the equivocal cutoff index range is 0.9-1.1.
The cutoff (cutoff index 1.0) was set to approx. 100 PEI U/ml. In acute HBV infections the
anti-HBc IgM level is generally far above this limit. After recovery from hepatitis B disease the
anti-HBc levels are below this. Chronic hepatitis can produce values in the vicinity of the
cutoff.
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15.5 Elecsys Anti-HBe

Samples with a cutoff index > 1.0 are non-reactive in the Elecsys® Anti-HBe test. These
samples are considered negative for anti-HBE and do not need further testing.
Samples with a cutoff index  1.0 are reactive in the Elecsys® Anti-HBe test.
Anti-HBe could be detected in samples from 210 (83.7%) out of 251 samples from persons
with chronic or past HBV infections. 14 (1.4% out of 1000 samples of randomly selected
blood donors were reactive for anti-HBe.
15.6 Elecsys HBeAg

Samples having a cutoff index < 1.0 are non-reactive in the Elecsys HBeAg test. These
samples are deemed negative for HBeAg.
Samples having a cutoff index  1.0 are reactive in the Elecsys HBeAg test. These samples
are deemed positive for HBeAg.
15.7 Elecsys Anti-HBs II

Samples with concentrations < 10 IU/l are considered non-reactive in the Elecsys Anti-HBs
test. Samples with concentrations  10 IU/l are considered reactive in the Elecsys Anti-HBs
test.
Note: Due to the diversity of the antibodies, the measured anti-HBs value can vary
depending on the testing procedure used. Results obtained form a single sample using tests
from different manufacturers can therefore differ by up to a factor of 4 (or even a factor of 10
in rare cases). If there is a change in the assay procedure during the monitoring of
vaccination protection, then the anti-HBs values obtained upon changing over to the new
method must be confirmed by parallel measurements by both methods.
Vaccination strategies in certain risk groups are based on the measured anti-HBs
concentration. Respective recommendations are given by national or regional guidelines.
15.8 Elecsys HBsAg II

Samples with a cutoff index < 0.9 are non-reactive in Elecsys® HBsAg II test. These samples
are considered negative for HBsAg and do not need further testing.
Samples having a cutoff index in the range  0.9 to < 1.0 are considered borderline in the
Elecsys® HBsAg II test. Samples with a cutoff index  1.0 are considered reactive. All initially
reactive or borderline samples must be redetermined in duplicate with Elecsys® HBsAg II
test. If these samples yield mean cutoff index values of < 0.9 in either of the redeterminations
are considered repeatedly reactive. Repeatedly reactive samples must be investigated using
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an independent neutralization test (Elecsys® HBsAg Confirmatory Test). Samples confirmed
by neutralization with human anti-HBs are regarded as positive for HBsAg.
15.9 Elecsys HBsAg II quant II
Expected values
From 611 samples obtained from a multicenter-evaluation the following values have been
reported:
IU/mL MCE (n = 611) % of total
<1 17 2.78
1-<10 20 3.27
10-<100 35 5.73
100-<1000 127 20.8
1000-<10000 239 39.1
10000-<100000 147 24.1
100000-<1000000 26 4.26
The final result was determined from the first measurement in 70.0 % of the samples on the
Elecsys 2010 and cobas e 411 analyzers (1:100 dilution) and 85.6 % of the samples on the
MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 analyzers (1:400 dilution).
15.10 Elecsys Anti-HCV II

Samples with a cutoff index < 0.9 are non reactive in the Elecsys® Anti-HCV II assay.
Samples with a cutoff-index  0.9 and < 1.0 are considered borderline in the Elecsys® Anti-
HCV II assay.
Samples with a cutoff-index  1.0 are reactive in the Elecsys® Anti-HCV II assay.
All initially reactive or borderline samples should be redetermined in duplicate using the
Elecsys Anti-HCV II assay. If no reactivity is found in both cases, the sample is negative for
anti-HCV. If the result from either of the two measurements is reactive or borderline then the
sample is repeatedly reactive. Repeatedly reactive samples must be investigated by
supplemental methods (e.g. immunoblot or detection of HCV RNA). If one or both
measurements remain borderline the analysis of a follow-up sample is recommended.

Anti-HAV 0712/09
Anti-HAV IgM 1012/12
Anti-HBc 0610/20
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Anti-HBc IgM 0212/14
Anti-HBe 0610/13
HBeAg 0610/15
Anti-HBs II 1015/01
HBsAg II 1112/11
HBsAg II quant II 0415/01
Anti-HCV II 1211/02
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16 Sexually transmitted diseases:
16.1 Elecsys HIV Ag
Samples with a cutoff index < 0.9 are non-reactive in the Elecsys® HIV Ag test. These
samples are considered negative for HIV Ag and no not need further testing.
Samples with a cutoff index in the range  0.9 to < 1.0 are considered borderline for HIV Ag
in the Elecsys® HIV Ag test.
All initially reactive or borderline samples must be retested in duplicate with the Elecsys®
HIV Ag test. If these samples yield mean cutoff index values of < 0.9 upon redetermination,
then they are deemed negative for HIV Ag. Initially reactive or borderline samples with a
cutoff index  0.9 either of the redeterminations are considered repeatedly reactive.
Repeatedly reactive samples must be investigated using an independent neutralization test
(Elecsys® HIV Ag Confirmatory Test). Samples confirmed by neutralization with human anti-
HIV antibodies are regarded as positive for HIV Ag.
Diagnosis of existing HIV infection: In the event of an isolated positive HIV antigen test, the
HIV infection should be confirmed in follow-up samples and by the anti-HIV screening test. A
negative result does not completely rule out the possibility of infection with the HI-virus.
In randomly selected blood donors (from a blood bank in Salzburg), the number of repeatedly
reactive samples in the Elecsys HIV Ag test was < 0.2%. Using the Elecsys HIV Ag test,
the presence of HIV Ag was demonstrated in 327 out of 329 cases of HIV-reactive samples.
16.2 Elecsys HIV combi PT

Samples with a cutoff index < 0.90 are non-reactive in the Elecsys HIV combi PT test. These
samples are considered negative for HIV-1 Ag and HIV-1/-2 specific antibodies and do not
need further testing. Samples having a cutoff index in the range ≥ 0.90 to < 1.0 are
considered borderline in the Elecsys® HIV combi PT test.
Samples with a cutoff index ≥ 1.0 are considered reactive in the Elecsys® HIV combi PT test.
All initially reactive or borderline samples must be redetermined in duplicate with the Elecsys
HIV combi PT test. If cutoff index values are < 0.90 are found in both cases, the samples are
considered negative for HIV-1 Ag and HIV-1/-2 specific antibodies. Initially reactive or
borderline samples giving cutoff index values of ≥ 0.90 in either of the redeterminations are
considered repeatedly reactive. Repeatedly reactive samples must be confirmed according
to recommended confirmatory algorithms. Confirmatory tests include Western Blot and HIV
RNA tests.
16.3 Elecsys HTLV-I/II
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Samples with a cutoff index < 1.00 are non-reactive in the Elecsys® HTLV-I/II assay. These
samples are considered negative for HTLV-I/II specific antibodies and do not need further
testing.
Samples with a cutoff index ≥ 1.00 are considered reactive in the Elecsys HTLV-I/II assay.
All initially reactive samples should be redetermined in duplicate with the Elesys HTLV-I/II
assay. If cutoff index values are found in both cases, the samples are considered negative
for HTLV-specific antibodies. Initially reactive samples giving cutoff index values of ≥ 1.00 in
either of the redeterminations are considered repeatedly reactive.
Repeatedly reactive samples must be confirmed according to recommended confirmatory
algorithms. Confirmatory tests include Western Blot and HTLV PCR tests.
16.4 Elecsys Syphilis
Clinical sensitivity
A total of 924 samples from patients with suspected syphilis infection
(diagnostic routine and blood screening) from Europe and Asia were tested
with the Elecsys Syphilis assay. Four additional samples were excluded
due to probable handling errors with banked samples. 922 samples were
found to be positive for anti-syphilis antibodies (either clinically defined or
confirmed by FTA-Abse) and other anti-syphilis assays). Two samples were
found to be indeterminate. Overall, 922 samples were found to be
repeatedly reactive (RR) with the Elecsys Syphilis assay. The two
indeterminate samples were found to be non‑ reactive with the Elecsys
Syphilis assay. The resulting sensitivity of confirmed positive samples is
100 %. The 95 % lower confidence limit was 99.60 %.
Cohort N Confirmed Indeterm- False Sensitivity

positive inate negative g)
samples samples samples f) %
Primary 101 101 0 0 100

syphilis
Secondary 124 124 0 0 100
syphilis
Latent 470 470 0 0 100
syphilis
Syphilis, 229 227 2 0 100
stage of the
disease
unknown
Totalh) 924 922 2 0 100
f) Elecsys Syphilis assay (RR)
g) Sensitivity of confirmed positive samples
h) Four additional samples were excluded
due to probable handling errors with
banked samples. e) FTA (Fluorescent
Treponemal Antibody) - Abs (absorption)
Clinical specificity
A total of 8079 samples (diagnostic routine and blood screening) from Europe and Asia
were tested with the Elecsys Syphilis assay. 14 samples were found to be positive for anti-
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syphilis antibodies (confirmed by FTA-Abs and other anti-syphilis assays), 8063 samples
were found to be negative and 10 samples were found to be repeatedly false reactive with
the Elecsys Syphilis assay (negative in FTA-Abs and other anti-syphilis assays). The
resulting specificity in the study is 99.88 %. The 95 % lower confidence limit was 99.77 %.
Cohort N Confirmed Confirmed False Specificit
positive negative positive y
samples samples samplesi) %
Diagnostic 3500 14 3486 7 99.80
routine
Blood donor
samples 4579 0 4577* 3 99.93
samples
Overall spe- 8079 14 8063* 10 99.88
cificity for
all samples
(routine
cohorts and
blood dona-
tions)
i) Elecsys Syphilis assay (RR)
* Two samples were excluded due to indeterminate confirmation results.

HIV Ag 0712/11
HIV combi PT 1212/03
Syphilis 0114/01
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17 TORCH:
17.1 Elecsys CMV IgG

Results obtained with the Elecsys CMV IgG assay can be interpreted as follows:
Non-reactive: < 0.5 U/ml
Indeterminate: 0.5 - < 1.0 U/ml
Reactive: ≥ 1.0 U/ml
Samples with concentrations < 0.5 U/ml are considered as non-reactive in the Elecsys CMV
IgG assay. These individuals are considered not to be infected with CMV and therefore
susceptible to primary infection.
Samples with concentrations between 0.5 U/ml and < 1.0 U/ml are considered indeterminate.
These samples should be retested. In case the result is still indeterminate, a second sample
should be collected e.g. within 2 weeks. Samples with concentrations ≥ 1.0 U/ml are
considered positive for IgG antibodies to CMV and indicate either acute or past infection.
Such individuals are potentially at risk of transmitting the virus (e.g. mother to fetus) but are
at current not necessarily contagious.
For the diagnosis of acute CMV infection further tests have to be performed e.g the
determination of CMV IgM antibodies and the CMV IgG avidity. A positive IgM result in
combination with a low avidity index for IgG is a string indication of a primary infection. The
diagnosis may be supported by a significant increase of the CMV IgG antibody titer from a
first to a second sample taken e.g. within 3-4 weeks.
Note:
An indeterminate or low positive result may already indicate an early acute CMV infection
(also if the sample is non-reactive for CMV IgM antibodies).
The prevalence of IgG antibodies to CMV varies considerably depending upon geographical
location and socioeconomic status of the population studied. The Elecsys CMV IgG assay
was used to test 616 samples from clinical routine in Germany (site 1) and 520 samples from
clinical routine in Israel (site 2). Out of these 334 (54.2%, Germany) and 415 samples
(79.8%, Israel) were found positive or indeterminate with the Elecsys CMV IgG assay.
A distribution of these values is given in the following table:
U/ml Site 1, Germany, n = 616 Site 2, Israel, n = 520

N % of total N % of total
< 0.5 282 45.8 105 20.2
0.5-<1 4 0.6 2 0.4
 1-<10 15 2.4 2 0.4
10-<100 62 10.1 71 13.7
100-<300 91 14.8 114 21.9
300-<500 65 10.6 84 16.2
<500 97 15.0 142 27.3
17.2 Elecsys CMV IgG Avidity

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Results obtained with the Elecsys CMV IgG Avidity assay are interpreted as follows:
Avidity Interpretation
< 45.0 Avi% low avidity
45.0 – 54.9 Avi% gray-zone
≥ 55.0 Avi% high avidity
No clinical interpretation can be deduced from a gray-zone result. It is recommended to take

a follow-up sample within an appropriate period of time (e.g. 2-4 weeks) and repeat testing.
Elecsys CMV IgG Avidity results should be used in conjunction with the patients`s medical
history, clinical symptoms and other laboratory tests, e.g. CMV-specific IgG and IgM results.
In case of a CMV IgG avidity result discordant to the patient’s medical history, clinical
symptoms and other laboratory tests, e.g.CMV-specific IgG and IgM results, further tests
should be performed to verify the results and testing of a follow up sample is recommended.
The CMV IgG avidity results in a given specimen, as determined by assays from different
manufacturers, can vary due to differences in assay methods and reagents used. Therefore,
the results reported by the laboratory to the phyician should include: “The following results
were obtained with the Elecsys CMV IgG avidity assay. Results from assays of other
manufacturers cannot be used interchangeably.”.
Avidity results up to 110 Avi% can occur due to the assay inherent variance and are
interpreted as high avidity results. For avidity > 110 Avi%, it is advised to predilute the
sample and repeat both measurements to calculate a new avidity (Avi%).
17.3 Elecsys CMV IgM

Results obtained with the Elecsys CMV IgM assay can be interpreted as follows:
Non-reactive: < 0.7 COI
Indeterminate: ≥ 0.7 - < 1.0 COI
Reactive: ≥ 1.0 COI
Samples with a cutoff index < 0.7 are non-reactive in the Elecsys CMV IgM assay.
Samples with a cutoff index between ≥ 0.7 and < 1.0 COI are considered indeterminate. The
sample should be retested. In case the result is still indeterminate, a second sample should
be tested e.g. within the following 2-3 weeks.
Samples with a cutoff index ≥ 1.0 are reactive in the Elecsys CMV IgM assay. The magnitude
of the measured result in a given specimen, as determined by assays from different
manufacturers, can vary due to differences in reagents and assay methods.
17.4 Elecsys HSV-1 IgG

Gray-zone: ≥ 0.6 - < 1.0 COI
Samples with a cutoff index < 0.6 are non-reactive in the Elecsys HSV-1 IgG
assay. These samples are considered negative for HSV-1 IgG-specific
antibodies and do not need further testing.
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Samples with a cutoff index between ≥ 0.6 and < 1.0 are considered as gray-zone samples.
The samples should be retested. In case the result is still gray-zone, a second sample should
Samples with a cutoff index ≥ 1.0 are considered reactive in the Elecsys HSV-1 IgG assay.
The HSV-1 IgG results in a given specimen, as determined by assays from different
17.5 Elecsys HSV-2 IgG

Gray-zone: ≥ 0.51 - < 1.0 COI
Samples with a cutoff index < 0.51 are non-reactive in the Elecsys HSV-2 IgG
assay. These samples are considered negative for HSV-2 IgG-specific
antibodies and do not need further testing.
Samples with a cutoff index between ≥ 0.51 and < 1.0 are considered as gray-zone samples.
The samples should be retested. In case the result is still gray-zone, a second sample should
Samples with a cutoff index ≥ 1.0 are considered reactive in
the Elecsys HSV-2 IgG assay.
The HSV-2 IgG results in a given specimen, as determined by assays from different
17.6 Elecsys Rubella IgG

Results obtained with the Elecsys Rubella IgG assay can be interpreted as follows:
Non-reactive: < 10 IU/ml
Reactive: ≥ 10 U/ml
The NCCLS subcommittee on Rubella Serology recommended 10 IU/ml as the cutoff level.
A result < 10 IU/ml is considered to be non-reactive.
A result ≥ 10 IU/ml is considered to be positive for IgG antibody to Rubella virus.
The presence of IgG antibodies to Rubella virus is an indication of previous exposure to the
virus, either by prior infections or by vaccination.
Patients suspected of acute Rubella infection should be tested for the presence of Rubella-
specific IgM. The diagnosis of acute Rubella IgG antibody titer from a first to a second
sample.
The Elecsys Rubella IgG assay was used to test 560 samples from clinical routine in France
(site 1) and 1000 samples from clinical routine in Germany (site 2). A distribution of these
values is given in the following table.
IU/ml Site 1, France, n = 560 Site 2, Germany, n = 1000
<5 32 5.7 19 1.9
5-<10 5 0.9 2 0.2
10-<20 13 2.3 12 1.2
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20-<50 34 6.1 47 4.7
50-<100 56 10 82 8.2
100-<300 244 43.6 541 54.1
300-<500 105 18.8 151 15.1
>500 71 12.7 146 14.6
17.7 Elecsys Rubella IgM

Results obtained with the Elecsys Rubella IgM assay can be interpreted as follows:
Samples with a cutoff index < 0.8 are non-reactive in the Elecsys Rubella IgM assay.
Samples with a cutoff index between ≥ 0.8 - < 1.0 are considered indeterminate. The sample
should be retested. In case the result is still indeterminate, a second sample should be
collected e.g. within 1 week. A significant increase of the Rubella IgG antibody titer from a
first to a second sample supports the diagnosis of acute Rubella infection.
Samples with a cutoff index ≥ 1.0 are reactive in the Elecsys Rubella IgM assay.
The magnitude of the measured result above the cutoff is not indicative of the total amount of
antibody present in the sample.
The anti-Rubella IgM results in a given specimen, as determined by assays from different
17.8 Elecsys Toxo IgG
The cutoff for the Elecsys Toxo IgG assay was established by measuring a total of 2645
samples from clinical routine in a multi-center study at 5 European study sites in France,
Switzerland and Germany. The majority of samples were from pregnant women who were
tested for toxoplasma during pregnancy screening. The distribution of positive, equivocal and
negative results was compared to results from various reference assays and the cutoffs were
set as noted below. This setting revealed an excellent separation of negative and positive
samples exhibiting only 14 equivocal results out of 2645. The cutoff was verified internally
with an additional set of 2121 samples and applied to the performance evaluation studies
described below.

Results obtained with the Elecsys Toxo IgG assay can be interpreted as follows:
Non-reactive: < 1 IU/ml
Equivocal: ≥ 1 - < 3 IU/ml
Reactive: ≥ 3 U/ml
Samples with concentrations < 1 IU/ml are considered non-reactive in the Elecsys Toxo
assay.
Samples with concentrations between 1 IU/ml and < 3 IU/ml are considered equivocal. The
sample should be retested. In case the result is still equivocal, a second sample should be
collected e.g. within 2 weeks. Samples with concentrations ≥ 3 U/ml are considered positive
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for IgG antibodies to T. gondii. The diagnosis of acute Toxoplasma infection may be
supported by a significant increase of the Toxo IgG antibody titer from a first to a second
sample taken e.g. within 2 weeks and in addition by Toxoplasma-specific IgM results. To
obtain additional serological data to aid in the diagnosis of a recent infection, the laboratory is
advised to evaluate the samples for the presence of a significant level of IgM antibody to T.
gondii. For additional information concerning the interpretation of Toxoplamsa serology
results, refer to CLSI document M36-A.
The prevalence of IgG antibodies to T. gondii varies considerably depending upon

geographical location and age of the population studied. The Elecsys Toxo IgG assay was
used to test 996 samples from clinical routine in France (site 1) and 1001 samples from
clinical routine in Germany (site 2). Out of these 231 (23.2%, France) and 376 (37.6%,
Germany) were found positive or indeterminate with the Elecsys Toxo IgG assay. A
distribution of these values is given in the following table.
IU/ml Site 1, France, n = 996 Site 2, Germany, n = 1001

<1 765 76.8 625 62.5
1-<3 1 0.1 9 0.9
3-<10 1 0.1 3 0.3
10-<100 26 2.61 46 4.6
100-<300 79 7.93 158 15.8
300-<650 83 8.33 99 9.9
>650 41 4.12 61 6.1
17.9 Elecsys Toxo IgG Avidity

Results obtained with the Elecsys Toxo IgG Avidity assay are interpreted as follows:
Avidity (Avi%) Interpretation

< 70 low avidity
70-79 gray-zone
≥ 80 high avidity
No clinical interpretation can be deduced from a low or gray-zone result.

The recommendation in these cases is to take a follow-up sample within an
appropriate period of time (e.g. 2-4 weeks) and repeat testing. Elecsys Toxo IgG
Avidity results should be used in conjunction with the patient’s medical history,
clinical symptoms, and other laboratory tests, e.g. Toxo-specific IgG and IgM
results. If a Toxo IgG avidity result is discordant with the patient’s medical
history, clinical symptoms and other laboratory tests, e.g. Toxo-specific IgG and
IgM results, further tests should be performed to verify the result and testing of
a follow-up sample is recommended. The Toxo IgG avidity results in a given
specimen, as determined by assays from different manufacturers, can vary
due to differences in assay methods and reagents used. Therefore, the results
reported by the laboratory to the physician should include the statement:
“The following results were obtained using the Elecsys Toxo IgG Avidity
assay. Results from assays provided by other manufacturers cannot be used
interchangeably.” In rare cases a value of 0 % avidity or negative percentage
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avidity might be observed; these results are classified as low avidity.
17.10 Elecsys Toxo IgM

Results obtained with the Elecsys Toxo IgM assay can be interpreted as follows:
Samples with a cutoff index < 0.8 are non-reactive in the Elecsys Toxo IgM assay.
Samples with a cutoff index between ≥ 0.8 - < 1.0 are considered indeterminate. The sample
should be retested. In case the result is still indeterminate, a second sample should be tested
e.g. within 2-3 weeks.
Samples with a cutoff index ≥ 1.0 are reactive in the Elecsys Toxo IgM assay.
The magnitude of the measured result above the cutoff is not indicative of the total amount of
antibody present in the sample.
The anti-Toxoplasma IgM results in a given specimen, as determined by assays from
different manufacturers, can vary due to differences in reagents and assay methods.

CMV IgG 1012/06
CMV IgG Avidity 0712/03
CMV IgM 0712/05
HSV-1 IgG 1211/02
HSV-2 IgG 1211/02
Rubella IgG 1012/06
Rubella IgM 1012/07
Toxo IgG 0612/10
Toxo IgG Avidiy 0712/03
Toxo IgM 1211/07
For this document are the contents of the current Elecsys reagent kit method sheets
and product information used. The used method sheets versions are listed above.
Original datas are available in the corresponding method sheets and product
information.
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Claudia Schäfer, CIR, Penzberg  4486 July 2017

Elecsys Reference Ranges

1 Thyroid Assays: ............................................................................................................................ 4

Elecsys Reference Ranges

Elecsys Reference Ranges

Elecsys Reference Ranges

1.1 Elecsys FT3 III

Elecsys Reference Ranges

1.2 Elecsys FT4 II

For detailed information about reference intervals in children, adolescents

Elecsys T3 2.5th - 97.5th percentile

Elecsys T4 2.5th - 97.5th percentile

Elecsys Reference Ranges

1.5 Elecsys TSH

Elecsys TSH 2.5th - 97.5th percentile

1.6 Elecsys T-uptake

1.7 Elecsys Calcitonin

Elecsys Reference Ranges

1.9 Elecsys Anti-Tg

1.10 Elecsys Anti-TPO

1.11 Elecsys Anti-TSHR

* 91 subacute thyroiditis, 45 adenomatous goiter, 27 Hashimotos disease, 32 painless

Assay Method sheet (or Product Information)

Elecsys Reference Ranges

Elecsys Reference Ranges

2.1 Elecsys CK-MB STAT

Elecsys CK-MB assay (4th generation). The calculation is based on samples

n Median 97.5th percentile 99th percentile

Women 463 4.39 3.61 4.88

2.2 Elecsys Digoxin

2.3 Elecsys Digitoxin

2.4 Elecsys Myoglobin STAT

Number 2.5th-97.5th Percentile

Elecsys Reference Ranges

2.5 Elecsys proBNP II

Interpretation of NT-proBNP values

Recommended cutoffs in patients with diagnosed stable chronic heart failure

Elecsys Reference Ranges

Age (years) N NT-proBNP (ng/L)

Correlation of NT-proBNP with NYHA classification in patients diagnosed with CHF

NYHA functional class

Patients presenting acute dyspnea – ICON (International Collaborative of NT-proBNP)

Elecsys Reference Ranges

Result interpretation in patients presenting acute dyspnea

Category Optimal Sensitivity Specificity PPV NPV Accuracy

2.6 Elecsys Troponin I

Factors associated with elevated values

2.7 Elecsys Troponin T hs

Elecsys Reference Ranges

It is important to obtain a careful history and a precise description of the symptoms. A

An electrocardiogram is recorded for allowing differentiation of patients with suspicion of ACS

Laboratory assessment should include markers of myocardial damage, preferably cardiac

Factors Associated with Elevated Values

Assay Method sheet (or Product Information)

Elecsys Reference Ranges

3.1 Elecsys ACTH

ACTH concentrations vary considerably depending on physiological conditions. Therefore,

3.2 Elecsys AMH

Elecsys Reference Ranges

Elecsys Reference Ranges

3.3 Elecsys Cortisol II

Elecsys Reference Ranges

3.4 Elecsys DHEAS