GASTROENTEROLOGY 2013;144:918 –925
A Population-based Comparison of Immunochemical Fecal Occult Blood
Tests for Colorectal Cancer Screening
THIBAUT RAGINEL,1,2,3,4 JOSETTE PUVINEL,5 OLIVIER FERRAND,6 VERONIQUE BOUVIER,1,2,3,4 ROMUALD LEVILLAIN,7
ANGELA RUIZ,7 OLIVIER LANTIERI,7 GUY LAUNOY,1,2,3,4 and LYDIA GUITTET1,2,3,4
CLINICAL AT
1
Centre Hospitalier Universitaire (CHU) de Caen, Caen; 2Normandie University, Caen; 3Université de Caen Basse-Normandie (UCBN), Cancers and Preventions,
Caen; 4INSERM U1086, Caen; 5Association Bourbonnaise Interdépartementale de Dépistage des Cancers (ABIDEC), Moulins; 6Action de Dépistage Organisé des
Cancers 18 (ADOC18), Saint-Doulchard; and 7Institut InterRégional pour la Santé (IRSA) de Tours, La Riche, France
See related article, Anderson AE et al, on page 526
in CGH.
BACKGROUND & AIMS: Quantitative fecal immuno-
chemical tests (FITs) identify individuals with colorectal
cancer with greater levels of accuracy than guaiac tests. We
compared the performances of 2 FITs in a population
undergoing screening for colorectal cancer. METHODS:
We collected fecal samples from 19,797 individuals in
France (age, 50⫺74 y) who participated in a colorectal
cancer screening program, from June 2009 through May
2011. Samples were analyzed using the Magstream (Fu-
jirebio Inc, Tokyo, Japan) and OC Sensor (Eiken Chemical
Co, Tokyo, Japan) (2 samples each) FITs, as well as the
Hemoccult II guaiac test (SKD, Villepinte, France) (3 sam-
ples each). Colonoscopies were performed for patients
with positive results from all 3 tests. The cut-off values for
levels of hemoglobin in buffer and stools were 55 ng/mL
and 180 ␮g/g for the Magstream and 150 ng/mL and 30
␮g/g for the OC Sensor, respectively. Results from the
FITs were compared with those from the guaiac test for
cut-off values for stool samples, positivity rates, and the
receiver operating characteristic curve values. The num-
bers needed to screen and the numbers needed to scope to
detect an advanced neoplasia (cancer, adenoma ⱖ10 mm,
or high-grade dysplasia) were calculated. RESULTS: A
positive test result was found in 1224 participants (6.2%);
1075 (87.8%) underwent a colonoscopy examination. Of
these, 334 were found to have advanced neoplasia. Con-
sidering the cut-off values associated with the positivity
rate of Hemoccult II (1.6%), the numbers needed to screen
were 239 for Hemoccult II, 166 for a 1-sample Magstream
FIT, and 129 for a 1-sample OC Sensor FIT; the numbers
needed to scope were 3.3, 2.3, and 1.8, respectively. For the
same false-positive rate as Hemoccult II (0.98%), the true-
positive rates for Magstream and OC Sensor FITs were
0.65% and 0.90% respectively, compared with 0.42% for
Hemoccult II. The OC Sensor FIT had a greater area under
the receiver operating characteristic curve value than the
Magstream FIT. CONCLUSIONS: Based on results from
a large, population-based study, the OC Sensor FIT iden-
tifies patients with colorectal cancer with greater accu-
racy than the Magstream FIT. ClinicalTrials.gov num-
ber: NCT01251666.
Keywords: Colorectal Neoplasm; Early Detection; Sensitiv-
ity; Specificity.
W ith roughly 1 million cases and 500,000 deaths
each year worldwide, colorectal cancer is a major
public health concern, especially in industrialized coun-
tries.1 The natural history of this cancer allows for early
detection. Until now, 2 strategies have been shown to
reduce the mortality associated with this cancer signifi-
cantly: the regular guaiac fecal occult blood test2 and
once-only flexible sigmoidoscopy.3–5
Since the beginning of the 1990s, it has been known
that immunochemical methods allow for improvement of
sensitivity of fecal occult blood tests.6 Automated quan-
titative fecal immunochemical tests (FITs) make adapta-
tion of the cut-off value possible to limit the loss in
specificity. Two randomized controlled trials, conducted
in The Netherlands on roughly 10,000 average-risk indi-
viduals each, found that the OC Sensor FIT (Eiken Chem-
ical Co, Tokyo, Japan) had both better screening perfor-
mances and higher acceptability than the guaiac
Hemoccult II test (SKD, Villepinte, France).7,8 One study
conducted in France on roughly 32,000 subjects found
that the Magstream FIT (Fujirebio Inc, Tokyo, Japan) also
had a better diagnostic accuracy than Hemoccult II.9,10
For both Magstream and OC Sensor FITs, it has been
shown that a gain in both sensitivity and specificity is
possible compared with the guaiac test Hemoccult II,
providing an adequate cut-off value and using a small
number of samples.9,11–13 These results recently were con-
firmed in France.14 An indirect comparison based on a
literature review was in favor of slight superiority of OC
Sensor over Magstream.15 However, this analysis suffered
from limitations inherent to comparison between differ-
ent populations.
Abbreviations used in this paper: FIT, fecal immunochemical test;
FOBT, fecal occult blood test; FPR, false-positive rate; NNScope, num-
ber needed to scope; NNScreen, number needed to screen; ROC, re-
ceiver operating characteristic; TPR, true-positive rate.
© 2013 by the AGA Institute
0016-5085/$36.00
http://dx.doi.org/10.1053/j.gastro.2013.01.042
May 2013
The aim of this study was therefore to compare
directly the screening performances of Magstream and
OC Sensor FITs in the targeted average-risk population,
taking into account the cut-off value and the number
of samples.
Materials and Methods
Study Population and Design
Between June 2009 and May 2011, there were 19,797
residents of 2 French counties (Allier and Cher) who fulfilled
inclusion criteria for the ongoing biennial organized screening
program (aged 50 –74 y, no digestive symptoms or personal or
first-degree relatives with a history of colorectal cancer or ad-
vanced adenoma, no colonoscopy in the past 5 years) who were
enrolled in a study comparing Magstream and OC Sensor FITs.
Participation in the study was suggested at the time of central-
ized invitation. The general practitioners consulted by the pa-
tients checked the inclusion criteria and provided the guaiac
Hemoccult II test (SKD, France) (routine test) together as Mag-
stream and OC Sensor FITs to all subjects agreeing to join the
study. All participants signed a written informed consent.
For the guaiac test, 2 samples per stool on 3 consecutive
bowel movements were required. For each of the FITs, 1 sample
per test on 2 consecutive bowel movements was required. Only
the guaiac test was performed on the first stool. Then, for each
of the last 2 stools sampled, subjects were asked to perform all
3 tests on the same stool, but no order between tests was
specified. In Allier county, in accordance with the ongoing pro-
gram, a specific diet (meatless for 3 days) was recommended.
Subjects performed the 3 tests themselves at home (on the kit
card for Hemoccult II, in OC-Auto sampling bottle for OC
Sensor and in New Hemtube for Magstream), recorded the date
of each bowel movement involved, and sent the 3 tests by mail
to the centralized Institut InterRégional pour la Santé labora-
tory. The Hemoccult II reading was performed by trained staff
without rehydration as planned in the national organized
screening program, and blinded to the results of the FITs.
Magstream samples were analyzed using the Magstream HT
instrument, and OC Sensor samples were analyzed using the OC
Sensor Diana instrument. As recommended, crude results of
Magstream and OC Sensor FITs were standardized by conver-
sion into concentration of hemoglobin in the stools (see the
Supplementary Appendix for conversion details derived from
previous analytic studies).16 –18
Screening was considered positive if the Hemoccult II test was
positive (at least 1 of the 6 slots was positive), or at least 1 of the
2 samples of OC Sensor reported a concentration of hemoglobin
in the stool greater than 30 ␮g/g (eg, 150 ng/mL hemoglobin in
the buffer), or at least 1 of the 2 samples of Magstream reported
a concentration of hemoglobin in the stool greater than 180
␮g/g (eg, 55 ng/mL in the buffer). The study cut-off value for
Magstream was the cut-off value that led, in a former study, to
the same number of false-positive results as Hemoccult II, a
scenario compatible with financial resources and availability of
endoscopists characterizing health care systems such as the
French one.9 A similar scenario was targeted for OC Sensor,
adopting a cut-off value near the manufacturer’s one, limiting
the number of positive results for a 2-sample strategy but allow-
ing comparison with other studies.7,12,19,20
Because Hemoccult II was the routine test in France, if it was
negative and both FITs were either negative or unable to be
analyzed, the screening was considered to be negative. In addi-
COMPARISON OF PERFORMANCES OF 2 FITS 919
tion, if Hemoccult II was not analyzed or not processed and no
FIT was positive, the subject was asked to repeat the Hemoccult
II only, without performing any FIT again.
The global screening test result was sent to both the patient
and general practitioner, without details on each fecal occult
blood test (FOBT) result. If the screening was positive, the
subject was encouraged to undergo a colonoscopy. The colono-
scopy results were recorded following the usual ongoing process
for an organized screening program in the 2 areas. The colono-
CLINICAL AT
scopy findings were classified according to the most advanced
pathologic lesion found. Advanced neoplasias included high-risk
adenomas (adenomas measuring ⱖ10 mm or adenomas with
high-grade dysplasia) and invasive cancers (invasion of malig-
nant cells beyond the muscularis mucosae). Intramucosal carci-
nomas were included in high-risk adenomas. Hyperplasic polyps
were not included as neoplasia. Patients with incomplete colono-
scopy, no invasive cancer diagnosed, and no further exploration
to confirm the absence of any pathologic lesion (double-contrast
barium enema or virtual colonoscopy) were considered as having
no colonoscopy result.
Statistical Analysis
Three strategies were used to compare the performances
of the FITs: at identical cut-off values of hemoglobin concen-
tration in the stools (biochemical point of view), at an identical
positivity rate implying a similar number of colonoscopies (en-
doscopic workload point of view), and for either a similar num-
ber of true-positive or false-positive results (patient’s harm or
benefit point of view).
To this purpose, the performances of each FIT were analyzed,
varying the number of samples analyzed and the positivity cut-
off value. For the 2-sample FIT strategy, the test was positive if
at least one of the samples contained a concentration of hemo-
globin greater than the cut-off value. For the 1-sample FIT
strategy, only the last sample was considered and compared with
the cut-off value. For each FIT, all concentrations of hemoglobin
greater than the cutoff having determined colonoscopy in the
study were assessed as alternative cutoffs. However, the cut-off
value selected by the manufacturer to define Magstream as a
qualitative test is smaller than the cut-off value used in our
study (80 ␮g/g instead of 180 ␮g/g of hemoglobin in the stools).
Many of the subjects with one sample of Magstream between 80
and 180 ␮g/g of hemoglobin in the stools (positive at the
manufacturer’s cut-off value, but negative at the study cut-off
value) were positive for either Hemoccult II, one of the OC
Sensor samples, or the other sample of Magstream at the study
cut-off value and were hence offered a colonoscopy. Therefore,
the performances of one sample Magstream at the manufactur-
er’s cut-off value were derived from the study data, assuming
that the small proportion of missing colonoscopies would have
detected targeted lesions at a similar frequency as the performed
ones (see the Supplementary Appendix). The same extrapolation
was performed for 1-sample OC Sensor FIT at the manufactur-
er’s cut-off value (20 ␮g/g of hemoglobin in the stools).
For each FOBT, the results of colonoscopies of subjects with
a positive test result were classified as true-positive results (sub-
jects with a targeted lesion) or false-positive results (subjects
with no targeted lesion). Then, the true-positive rate (TPR) was
defined as the proportion of true-positive results among the
subjects who performed the FOBT. The false-positive rate (FPR)
was defined as the proportion of false-positive results among the
subjects who performed the FOBT. In practice, the TPR is
directly proportional to the sensitivity of a screening test,
 920 RAGINEL ET AL
whereas the FPR is inversely proportional to its specificity. The
paired design with blinding of details on test results allows one
to draw a receiver operating characteristics (ROC) curve, plotting
the TPR against the FPR.
The number needed to screen (NNScreen) to detect 1 subject
with a targeted lesion was calculated as the inverse of the TPR.
The number needed to scope (NNScope) to detect 1 subject with
a targeted lesion was calculated as the inverse of the proportion
of true-positive results among subjects with a positive test (in-
CLINICAL AT
verse of the positive predictive value). The analysis was con-
ducted considering, first, advanced neoplasias, and, second, in-
vasive cancers as targeted lesions.
Proportions were compared with chi-square tests. A sensitivity
analysis was conducted, first, drawing the ROC curves for detec-
tion of advanced neoplasias excluding all subjects with at least
one nonanalyzable test, and, second, stratified on study area.
Statistical analysis was performed with R 2.12.121 (R Core
Team, Vienna, Austria) for Mac OS 10.6.
The study was approved by the local ethics committee (Co-
mité de Protection des Personnes) and the French sanitary au-
thority (Agence Française de Sécurité Sanitaire des Produits de
Santé). All participants provided written informed consent. The
trial was recorded on clinicaltrials.gov under the identifier
NCT01251666. All authors had access to the study data and
reviewed and approved the final manuscript.
Results
Figure 1 presents the study flow chart. Among the
1224 subjects who were positive for at least one of the
tests, an analyzable colonoscopy was performed for 1075
subjects (87.8%), with a mean time interval between a
positive screening and colonoscopy of 71 days (median, 56
days). No colonoscopy complications were reported. A
total of 334 participants were diagnosed with advanced
neoplasia at colonoscopy.
GASTROENTEROLOGY Vol. 144, No. 5
In Table 1, 16.5% of participants underwent colorectal
cancer screening for the first time. The median and mean
times between the last bowel movement for FOBT and
laboratory analysis were approximately 3 and 4 days, re-
spectively. The rate of nonanalyzable tests decreased from
Magstream (4.4%) to Hemoccult II (2.0%) and OC Sensor
(1.6%) (P ⬍ 10⫺3). A total of 1301 (6.6%) subjects had at
least 1 of the 3 tests nonanalyzable or not performed.
Women and older subjects were significantly more fre-
quent among this population. The positivity rate of
Hemoccult II was 1.6% in both areas. When considering
2 samples at the study cut-off values and only analyz-
able tests, the positivity rates were identical for both
areas for OC Sensor, but higher in Cher than Allier area
for Magstream. The colonoscopy rate did not differ
between tests (P ⫽ .73).
The performances of the 3 FOBTs are compared in
Table 2, for the study conditions and following the man-
ufacturer’s guidelines. In the study conditions, for both
FITs and with only 1 sample, the NNscreen was smaller
than with the guaiac test for detection of invasive cancers,
or advanced neoplasias. Despite an increase in the total
number of colonoscopies, the NNscope for detection of
these lesions was also smaller than with the guaiac test.
For each FIT, adding a second sample at the same cut-off
value decreased the NNscreen, by increasing the number
of colonoscopies at the expense of an increase in the
NNscope. The positivity rate of 1-sample Magstream at
the manufacturer cut-off value was similar to that with
1-sample OC Sensor at the study cut-off value, with a
similar positive predictive value.
Comparison of TPR and FPR for detection of advanced
neoplasias according to the concentration of hemoglobin
Figure 1. Study flow chart.
May 2013 COMPARISON OF PERFORMANCES OF 2 FITS 921

Table 1. Demographic Characteristics and Test Results of Included Subjects

All participants Excluding subjects with at least 1 nonanalyzable test

Allier n (%) Cher n (%) P value Allier n (%) Cher n (%) P value
Sex .14 .19
Men 6649 (44.6) 2125 (43.4) 6266 (45.0) 2002 (43.9)
Women 8252 (55.4) 2771 (56.6) 7665 (55.0) 2563 (56.1)
Age, y ⬍10⫺3 ⬍10⫺3
50–54 2984 (20.0) 920 (18.8) 2828 (20.3) 865 (19.0)

CLINICAL AT
55–59 3226 (21.7) 1051 (21.5) 3045 (21.9) 982 (21.5)
60–64 3591 (24.1) 1340 (27.4) 3380 (24.3) 1265 (27.7)
65–69 2408 (16.2) 843 (17.2) 2240 (16.1) 777 (17.0)
70–74 2692 (18.1) 742 (15.2) 2438 (17.5) 676 (14.8)
Screening round ⬍10⫺2 ⬍10⫺3
First 2526 (17.0) 741 (15.1) 2365 (17.0) 675 (14.8)
Subsequent 12,375 (83.1) 4155 (84.9) 11,566 (83.0) 3890 (85.2)
Test results
Hemoccult II ⬍10⫺3 .98
Positive 238 (1.6) 78 (1.6) 225 (1.6) 74 (1.6)
Negative 14,428 (96.8) 4663 (95.2) 13,706 (98.4) 4491 (98.4)
Nonanalyzable 209 (1.4) 148 (3.0) — —
Not performed 26 (0.2) 7 (0.1) — —
Magstreama ⬍10⫺2 ⬍.05
Positive 451 (3.0) 181 (3.7) 444 (3.2) 173 (3.8)
Negative 13,747 (92.3) 4539 (92.7) 13,487 (96.8) 4392 (96.2)
Nonanalyzable 592 (4.0) 148 (3.0) — —
Not performed 111 (0.7) 28 (0.6)
OC Sensorb .01 .69
Positive 594 (4.0) 207 (4.2) 558 (4.0) 189 (4.1)
Negative 14,038 (94.2) 4633 (94.6) 13,373 (96.0) 4376 (95.9)
Nonanalyzable 217 (1.5) 43 (0.9) — —
Not performed 52 (0.3) 13 (0.3)

NOTE. Characteristics of the population and positivity rates for each test (study cut-off value and for 2-sample FITs).
aTwo-sample Magstream at a cut-off value of 55 ng/mL Hb in the buffer (⬃180 ␮g/g in the stools).
bTwo-sample OC Sensor at a cut-off value of 150 ng/mL Hb in the buffer (30 ␮g/g in the stools).

in the stools is provided in Supplementary Figure 1. For
each FIT, the TPR and FPR decreased as the cut-off value,
expressed as the concentration of hemoglobin in the
stools, increased. Furthermore, adding a second sample of
the same FIT at the same cut-off value increased both the
TPR and the FPR. In the range of cut-off values in which
performances of both FITs were evaluable, the TPR of
Magstream was greater than that of OC Sensor at the
same cut-off value and using the same number of sam-
ples. However, at the same time, the FPR of Magstream
also was greater than that of OC Sensor.
In Table 3, for a similar number of colonoscopies, the
NNscreen for detection of advanced neoplasias was de-
creased by 30% using 1-sample Magstream FIT instead of
the guaiac test (166.4 instead of 238.5). At the same time,
the NNscope also was decreased from 3.3 to 2.3. For the
same total number of colonoscopies, both the NNscreen
and the NNscope associated with 1-sample OC Sensor
FIT were smaller than with 1-sample Magstream. Findings
were similar if the targeted lesion was invasive cancer only.
For both the Magstream and OC Sensor, the same num-
ber of positive subjects could result from use of 1 sample,
or from use of 2 samples at a higher cut-off value. Then,
for a similar number of colonoscopies, the NNscope and
NNscreen for detection of advanced neoplasias were close
with either 1 or 2 samples (providing a higher cut-off
value), for both the Magstream and OC Sensor FITs.
When fixing the positivity rate at a higher level (3.0%),
for both the Magstream and OC Sensor the NNScreen
decreased, and the NNscope increased compared with a
1.6% positivity rate, while staying largely better than
with the guaiac test. Both the NNscope and NNscreen
observed with the OC Sensor were better than with the
Magstream.
Figure 2 compares the ROC curves associated with the
guaiac test, Magstream, or OC Sensor FITs for the detec-
tion of advanced neoplasias. Reading Figure 2 vertically,
for a similar FPR of 9.8‰, the TPR increased from
Hemoccult II (TPR, 4.2‰), to 1-sample Magstream (7.3‰)
and 1-sample OC Sensor (9.7‰). Reading Figure 2 hori-
zontally, for a similar TPR of 4.2‰, the FPR decreased
from Hemoccult II (FPR, 9.8‰) to 1-sample Magstream
(5.1‰) and 1-sample OC Sensor (2.8‰). Globally, the area
below the curve of OC Sensor was greater than that of
Magstream. Similar findings were observed for invasive
cancers. In the range of positivity rates evaluable for both
number of samples given the study design, the perfor-
mances for detection of advanced adenomas observed
with either 1- or 2-sample FITs (at different cut-off values)
 922 RAGINEL ET AL GASTROENTEROLOGY Vol. 144, No. 5

Table 2. Comparison of Clinical Performances of Hemoccult II, Magstream, and OC Sensor Fecal Occult Blood Tests in Study
Conditions, and According to Manufacturer Guidelines (Extrapolated)
Manufacturer cut-off
Study cut-off valuea value

Magstream OC Sensor Magstream OC Sensor

FIT FIT FIT FIT
Guaiac
test 1 sample 2 samples 1 sample 2 samples 1 sample 1 sample
CLINICAL AT

Cut-off value (␮g hemoglobin/g of stools) NA 180 180 30 30 80 20

Cut-off value (ng hemoglobin/mL in the buffer) NA 55 55 150 150 20 100
Positives 316 390 632 551 801 548 694
(positivity rate, %) (1.60) (1.97) (3.19) (2.78) (4.05) (2.77) (3.51)
Colonoscopies 277 344 554 488 712 484 615
(colonoscopy rate, %) (87.7) (88.2) (87.7) (88.6) (88.9) (88.3) (88.6)
Advanced neoplasias 83 146 210 225 290 209 275
(positive predictive value, %) (30.0) (42.4) (37.9) (46.1) (40.7) (43.2) (44.7)
(true-positive rate, %) (0.42) (0.74) (1.06) (1.14) (1.46) (1.06) (1.39)
Number needed to scope 3.3 2.4 2.6 2.2 2.5 2.3 2.2
Number needed to screen 238.5 135.6 94.3 88.0 68.3 94.7 72.0
Invasive cancers 19 28 36 37 44 37 44
(positive predictive value, %) (6.9) (8.1) (6.5) (7.6) (6.2) (7.6) (7.2)
(true-positive rate, %) (0.10) (0.14) (0.18) (0.19) (0.22) (0.19) (0.22)
Number needed to scope 14.6 12.3 15.1 13.2 16.2 13.1 14.0
Number needed to screen 1041.9 707.0 549.9 535.1 449.9 535.1 449.9
False positives 194 198 344 263 422 275 340
(false-positive rate, %) (0.98) (1.00) (1.74) (1.33) (2.13) (1.39) (1.72)
aStudy cut-off value for Magstream is designed to equal the same number of false-positive results as Hemoccult II, as derived from prior studies.
Study cut-off value for OC Sensor is designed to ensure comparability with other studies, while limiting the colonoscopy workload.

were very similar. An increase in TPR was possible by
using 2 samples, at the expense of increased FPR.
Results of the sensitivity analysis (available on request)
did not change the findings.
Discussion
Our results, directly comparing the performances
of the 2 FITs in an average-risk population, strongly
suggest that the OC Sensor outperforms Magstream for
both the detection of invasive cancers alone or ad-
vanced neoplasias as a whole; the 2 tests provide a
substantial improvement in cancer screening in com-
parison with Hemoccult II. Strikingly, for the same
number of positive results, 1-sample OC Sensor nearly
doubled the number of advanced neoplasias detected
compared with the 3-sample guaiac test. For the same

Table 3. Comparison of Clinical Performances of Magstream and OC Sensor FITs for 2 Positivity Rates
1.6% Positivity rate (same as Hemoccult II) 3% Positivity rate

Magstream OC Sensor Magstream OC Sensor

FIT FIT FIT FIT
Guaiac
test 1 sample 2 samples 1 sample 2 samples 2 samples 2 samples
Cut-off value (␮g hemoglobin/g of stools) NA 206 234 68 116 187 48
Cut-off value (ng hemoglobin/mL in the buffer) NA 63 72 340 580 57 240
Positives 316 312 330 316 317 599 595
(positivity rate, %) (1.60) (1.58) (1.67) (1.60) (1.60) (3.03) (3.01)
Colonoscopies 277 273 295 282 285 526 523
(colonoscopy rate, %) (87.7) (87.5) (89.4) (89.2) (89.9) (87.8) (87.9)
Advanced neoplasias 83 119 123 154 160 203 241
(positive predictive value, %) (30.0) (43.6) (41.7) (54.6) (56.1) (38.6) (46.1)
(true positive rate, %) (0.42) (0.60) (0.62) (0.78) (0.81) (1.03) (1.22)
Number needed to scope 3.3 2.3 2.4 1.8 1.8 2.6 2.2
Number needed to screen 238.5 166.4 161.0 128.6 123.7 97.5 82.1
Invasive cancers 19 24 20 31 33 34 37
(positive predictive value, %) (6.9) (8.8) (6.8) (11.0) (11.6) (6.5) (7.1)
(true-positive rate, %) (0.10) (0.12) (0.10) (0.16) (0.17) (0.17) (0.19)
Number needed to scope 14.6 11.4 14.8 9.1 8.6 15.5 14.1
Number needed to screen 1041.9 824.9 989.9 638.6 599.9 582.3 535.1
False positives 194 154 172 128 125 323 282
(false-positive rate, %) (0.98) (0.78) (0.87) (0.65) (0.63) (1.63) (1.42)
May 2013
Figure 2. ROC curves for Hemoccult II, Magstream, and OC Sensor
tests, according to the number of samples of immunochemical tests.
number of unnecessary colonoscopies (false-positive re-
sults), the OC Sensor detected more advanced neopla-
sias than Magstream.
Our study had several limitations. Only subjects posi-
tive for at least one of the tests were explored by colono-
scopy, preventing an estimation of sensitivity and speci-
ficity of each test. Although a minority of studies
evaluating FOBT implied an endoscopy (colonoscopy or
sigmoidoscopy) for all subjects,22,23 this limitation is
shared by most of the studies comparing the performance
of colorectal cancer screening programs, inasmuch as it is
evaluated in the targeted population.7–9,14 Moreover, in
our study, plotting TPR against FPR provided a compre-
hensive version of the ROC curve, with direct and practi-
cal interpretation. Indeed, TPR in participants is the prod-
uct of prevalence of the lesion, the sensitivity of the test,
and the colonoscopy rate of positive subjects, and FPR is
the product of 1 minus the prevalence, 1 minus the
specificity, and colonoscopy rate. The paired design guar-
antees that the prevalence is identical whatever the tests,
whereas the delivery of positive screening results without
specification on which FOBT(s) was(ere) positive guaran-
tees that the colonoscopy rate does not depend on the
test. Thus, comparing TPR or FPR between tests is equiv-
alent to comparing sensitivity and specificity as in relative
ROC curves.9,24
As in other studies, we evaluated indicators such as
positivity rate, detection rate among participants, and
positive predictive values, which reflect the performance
of the tests. To allow for standardization of our results, we
transformed the crude value given by the FIT automats
into concentration of hemoglobin in the stools, but our
conversion equation for Magstream was not perfect.17
Finally, our evaluation of the performances of 1-sample
FIT at the manufacturer’s cut-off value implied the im-
putation of only 13% of the total number of expected
colonoscopies, resulting in reliable results. Too many un-
available colonoscopies prevented us from performing a
COMPARISON OF PERFORMANCES OF 2 FITS 923
similar imputation for 2 samples of FIT at the manufac-
turer cut-off value.
In comparison with Hemoccult II, Magstream FIT
appeared less specific than expected based on our pre-
vious study.9 This could be explained by changes in
automat (Magstream HT instead of Magstream 1000)
and buffer (Magstream NewHemtube instead of Mag-
stream Hemtube) for the Magstream test, or an appar-
CLINICAL AT
ent increase in the specificity of Hemoccult II owing to
dietary restrictions (although debated25) in Allier. In
addition, the present study included subjects with pre-
vious rounds of Hemoccult II, which may have an
impact on its specificity.
The superiority of OC Sensor over Magstream con-
firms previous evidence based on an indirect compari-
son relying on a literature review,15 and laboratory
analyses.17,18 However, this study suggests the superi-
ority of the OC Sensor test, directly comparing the 2
tests in a real-life scenario. The joint increase in sensi-
tivity and the decrease in specificity of Magstream for
the detection of advanced neoplasias compared with
OC Sensor at the same cut-off value expressed in con-
centration of hemoglobin in the stools may be ex-
plained by the poorer precision of the Magstream mea-
surement because a much higher overlap in crude
measurements between different concentrations of he-
moglobin in the feces had been observed for Magstream
than OC Sensor in our in-laboratory analysis.17 Fur-
thermore, OC Sensor is based on latex agglutination
immunoturbidimetry, whereas Magstream is based on
magnetic particle agglutination. Our results confirm
those of other studies that have shown that qualitative
FITs using the same cut-off value expressed in concen-
tration of hemoglobin in the stools may be associated
with different clinical characteristics (adapted from
Brenner et al26), supporting the need for clinical trials,
at least in high-risk subjects, to evaluate future new
FITs.
The superiority of OC Sensor compared with Mag-
stream concerned both the detection of invasive cancers
and high-risk adenomas, hence offering the opportunity
to increase both the reduction in colorectal cancer–spe-
cific mortality and incidence, although not shown. In
addition, the rate of nonanalyzable tests was higher with
Magstream compared with OC Sensor test. This was ex-
plained both by failure to correctly paste the identifying
barcode due to the rounded form of the collecting tube, and
introduction of too much stool in the tube. These difficulties
are consistent with previous findings.18 In our study, how-
ever, and because Hemoccult II is the routine test in France,
nonanalyzable FITs were not repeated, hence overestimating
the rate of nonanalyzable tests.
As suggested by other studies,9,13,14 for moderate posi-
tivity rates we found that both Magstream and OC Sensor
FITs led to identical performances with either 1 of 2
samples (provided a different cut-off value is used),
reflecting equivalence at the population level, rather
than at the level of the subject.10 Differences in bleed-
 924 RAGINEL ET AL
ing pattern between lesions (intensity and intermit-
tence) underlies this finding. When limitation of the
colonoscopy workload is targeted, we would recom-
mend the use of one sample of FIT. Alternatively, when
high positivity rates are affordable for the health care
system, using 2 samples of FIT may increase the detec-
tion rate of advanced neoplasias at an acceptable num-
ber needed to scope.
Concerning the performance of FITs at moderate pos-
CLINICAL AT
itivity rates, our results are clearly in favor of 1-sample OC
Sensor. Selection of the cut-off value then could be ad-
justed by politic decision makers to fit the possibility of
endoscopy. The data presented in this article provide
results for up to a 2.8% positivity rate for 1-sample OC
Sensor (150 ng/mL in the buffer cut-off value which is
equivalent to 30 ␮g/g hemoglobin in the stools), whereas
some studies provide results for lower cut-off values.11–13,20
However, although OC Sensor is more accurate than Mag-
stream, it is also actually more expensive. Even if the costs of
colorectal cancer screening programs are determined mainly
by the number of generated colonoscopies,27 for a fixed
positivity rate, OC Sensor would be more effective (higher
sensitivity), less deleterious (higher specificity), but also more
costly. Cost-effectiveness analyses are required to guide fur-
ther decisions.
Supplementary Material
Note: To access the supplementary material
accompanying this article, visit the online version of
Gastroenterology at www.gastrojournal.org, and at http://
dx.doi.org/10.1053/j.gastro.2013.01.042.
References
1. Parkin DM, Bray F, Ferlay L, et al. Global cancer statistics, 2002.
CA Cancer J Clin 2005;55:74 –108.
2. Hewitson P, Watson Glasziou P, et al. Cochrane systematic review of
colorectal cancer screening using the fecal occult blood test (hemoc-
cult): an update. Am J Gastroenterol 2008;103:1541–1549.
3. Atkin WS, Edwards R, Kralj-Hans I, et al. Once-only flexible sig-
moidoscopy screening in prevention of colorectal cancer: a multi-
centre randomised controlled trial. Lancet 2010;375:1624 –
1633.
4. Segnan N, Armaroli P, Bonelli L, et al. Once-only sigmoidoscopy in
colorectal cancer screening: follow-up findings of the Italian Ran-
domized Controlled Trial—SCORE. J Natl Cancer Inst 2011;103:
1310 –1322.
5. Schoen RE, Pinsky PF, Weissfeld JL, et al. PLCO Project Team.
Colorectal-cancer incidence and mortality with screening flexible
sigmoidoscopy. N Engl J Med 2012;366:2345–2357.
6. Allison JE, Tekawa IS, Ransom LJ, et al. A comparison of fecal
occult-blood tests for colorectal-cancer screening. N Engl J Med
1996;334:155–159.
7. van Rossum LG, van Rijn AF, Laheij RJ, et al. Random comparison
of guaiac and immunochemical fecal occult blood tests for colo-
rectal cancer in a screening population. Gastroenterology 2008;
135:82–90.
8. Hol L, van Leerdam ME, van Ballegooijen M, et al. Screening for
colorectal cancer: randomised trial comparing guaiac-based and
immunochemical faecal occult blood testing and flexible sigmoid-
oscopy. Gut 2010;59:62– 68.
9. Guittet L, Bouvier V, Mariotte N, et al. Performance of immuno-
chemical faecal occult blood test in colorectal cancer screening in
GASTROENTEROLOGY Vol. 144, No. 5
average-risk population according to positivity threshold and
number of samples. Int J Cancer 2009;125:1127–1133.
10. Guittet L, Bouvier V, Guillaume E, et al. Colorectal cancer screen-
ing: why immunochemical faecal occult blood test performs as
well with either one or two samples. Dig Liv Disease 2012;
44:694 – 699.
11. van Rossum LG, van Rijn AF, Laheij RJ, et al. Cutoff determines
the performance of a semi-quantitative immunochemical faecal
occult blood test in a colorectal cancer screening programme. Br J
Cancer 2009;101:1274 –1281.
12. Hol L, Wilschut JA, van Ballegooijen M, et al. Screening for colo-
rectal cancer: random comparison of guaiac and immunochemical
faecal occult blood testing at different cut-off levels. Br J Cancer
2009;100:1103–1110.
13. Park DI, Ryu S, Kim YH, et al. Comparison of guaiac-based and
quantitative immunochemical fecal occult blood testing in a pop-
ulation at average risk undergoing colorectal cancer screening.
Am J Gastroenterol 2010;105:2017–2025.
14. Faivre J, Dancourt V, Manfredi S, et al. Positivity rates and perfor-
mances of immunochemical faecal occult blood tests at different
cut-off levels within a colorectal cancer screening programme. Dig
Liver Dis 2012;44:700 –704.
15. Guittet L, Bailly L, Bouvier V, et al. Indirect comparison of perfor-
mances of two quantitative immunochemical faecal occult blood
tests in a population with average colorectal cancer risk. J Med
Screen 2011;18:76 – 81.
16. Allison JE, Fraser CG, Halloran SP, et al. Comparing fecal immu-
nochemical testing: improved standardization is needed. Gastro-
enterology 2012;142:422– 424.
17. Guittet L, Guillaume E, Levillain R, et al. Analytical comparison of
three quantitative immunochemical fecal occult blood tests for
colorectal cancer screening. Cancer Epidemiol Biomarkers Prev
2011;20:1492–1501.
18. Lamph SA, Bennitt WE, Brannon CR, et al. Evaluation report:
immunochemical faecal occult blood tests. Centre for Evidence-
based Purchasing 2009, Report no. 09042.
19. Castiglione G, Visioli CB, Ciatto S, et al. Sensitivity of latex agglu-
tination faecal occult blood test in the Florence District population-
based colorectal cancer screening programme. Br J Cancer 2007;
96:1750 –1754.
20. Grazzini G, Visioli CB, Zorzi M, et al. Immunochemical faecal
occult blood test: number of samples and positivity cutoff. What is
the best strategy for colorectal cancer screening? Br J Cancer
2009;100:259 –265.
21. R Development Core Team (2010). R: a language and environ-
ment for statistical computing. Vienna, Austria: R Foundation for
Statistical Computing. Available at: http://www.R-project.org/.
22. Allison JE, Sakoda LC, Levin TR, et al. Screening for colorectal
neoplasms with new fecal occult blood tests: update on per-
formance characteristics. J Natl Cancer Inst 2007;99:1462–
1470.
23. Morikawa T, Kato J, Yamaji Y, et al. A comparison of the
immunochemical fecal occult blood test and total colonoscopy
in the asymptomatic population. Gastroenterology 2005;129:
422– 428.
24. Cheng H, Macaluso M. Comparison of the accuracy of two tests
with a confirmatory procedure limited to positive results. Epidemi-
ology 1997;8:104 –106.
25. Konrad G. Dietary interventions for fecal occult blood test screen-
ing: systematic review of the literature. Can Fam Physician 2010;
56:229 –238.
26. Brenner H, Haug G, Hundt S. Inter-test agreement and quantitative
cross-validation of immunochromatographical fecal occult blood
tests. Int J Cancer 2010;127:1643–1649.
27. Berchi C, Bouvier V, Réaud JM, et al. Cost-effectiveness analysis
of two strategies for mass screening for colorectal cancer in
France. Health Econ 2004;13:227–238.
May 2013
Received August 30, 2012. Accepted January 22, 2013.
Reprint requests
Address requests for reprints to: Lydia Guittet, MD, PhD, Inserm
U1086, Cancers and Preventions, CHU Caen, Centre François
Baclesse, Avenue du Général Harris, 14000 Caen, France. e-mail:
guittet-l@chu-caen.fr; fax: 33 (0)2 31 45 86 30.
Acknowledgments
The authors are grateful to all subjects who agreed to join the
study, to the general practitioners who included the patients, to the
endoscopists who performed the colonoscopies, to the members of
the 2 regional associations in charge of colorectal cancer screening,
ADOC18 and ABIDEC, to the Institut InterRégional pour la Santé
COMPARISON OF PERFORMANCES OF 2 FITS 925
laboratory, and to the research team Cancers and Preventions who
were involved in the study.
Conflicts of interest
The authors disclose no conflicts.
Funding
The study was funded by the French National Institute for
Cancer (Institut National du Cancer), and the French National
League against Cancer (Ligue Nationale Contre le Cancer); the
CLINICAL AT
automat analyzers were provided on loan by Eiken (OC Sensor
Diana automat) and Fujirebio (Magstream HT automat)
manufacturers. The sponsors and manufacturers had no role in
the study design or data analysis.