SYSTEMATIC REVIEW AND META-ANALYSIS

Pooled rates of adenoma detection by colonoscopy in

asymptomatic average-risk individuals with positive fecal
immunochemical test: a systematic review and meta-analysis
Babu P. Mohan, MD,1 Shahab R. Khan, MBBS,2 Evan Daugherty, MD,3 Saurabh Chandan, MD,4
Suresh Ponnada, MD, MPH,5 Antonio Facciorusso, MD,6 Lena L. Kassab, MD, MBA,7
Ravishankar Asokkumar, MBBS, MRCP,8 Douglas G. Adler, MD9

Salt Lake City, Utah; Boston, Massachusetts; Omaha, Nebraska; Roanoke, Virginia; Rochester, Minnesota; Denver,
Colorado, USA; Foggia, Italy; Singapore

GRAPHICAL ABSTRACT

Background and Aims: Current adenoma detection rate (ADR) benchmarks for colonoscopy in individuals pos-
itive for a fecal immunochemical test (FIT) are 45% in men and 35% in women. These are based on weak, low-
quality evidence. We performed a meta-analysis to ascertain the pooled ADR in FIT-positive colonoscopy.
Methods: Major databases like PubMed, EMBASE, and Web of Science were searched in October 2021 for studies
reporting on ADR of colonoscopy in a FIT-positive population. Meta-analysis was performed by standard method-
ology using the random-effects model. Heterogeneity was assessed by I2 and 95% prediction interval statistics.
Results: Thirty-four high-quality studies that included more than 6 million asymptomatic average-risk individuals
were analyzed; 2,655,345 individuals completed a screening FIT test. The pooled FIT screening rate was 69.8%
(95% CI, 62.8-76.1), the pooled FIT positivity rate was 5.4% (95% CI, 4.3-6.9), and the colonoscopy completion
rate was 85% (95% CI, 82.8-86.9). The pooled ADR was 47.8% (95% CI, 44.1-51.6), pooled advanced ADR was
25.3% (95% CI, 22-29), and the pooled colorectal cancer detection rate was 5.1% (95% CI, 4.4-5.9). The pooled
ADR in men was 58.3% (95% CI, 52.8-63.6) and in women was 41.9% (95% CI, 36.4-47.6). The pooled ADR
with qualitative FIT assessment was 67.7% (95% CI, 50.7-81), with 1-stool sample FIT was 52.8% (95% CI, 48.8-
56.8), and at a cutoff threshold of 100 ng hemoglobin/mL was 52.1% (95% CI, 47-57.1). Based on time-period cu-
mulative analysis, the ADR improved over time from 30.5% (95% CI, 24.6-37.2) to 47.8% (95% CI, 44.1-51.6).
Conclusions: This meta-analysis supports the current ADR benchmarks for colonoscopy in FIT-positive individ-
uals. Excellent pooled ADR parameters were demonstrated with qualitative assessment of 1 stool sample at a test
cutoff value of 100 ng hemoglobin/mL, and ADR per endoscopist improved over time. (Gastrointest Endosc
2022;96:208-22.)

(footnotes appear on last page of article)

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Mohan et al
Colorectal cancer (CRC) is the second leading cause of
cancer death worldwide, with increasing incidence among
young patients.1 The recent statement by the U.S.
Preventive Services Task Force recommends screening
colonoscopy in asymptomatic individuals over age 45
years, instead of the previous recommendation of 50
years.2 Screening colonoscopy has been shown to reduce
the incidence of CRC and CRC-related mortality; however,
this depends, to a large extent, on a high-quality colono-
scopic examination.3,4
A well-accepted colonoscopy quality indicator is the ade-
noma detection rate (ADR), which is defined as the propor-
tion of patients who have 1 or more adenoma detected per
examination. Suboptimal detection of adenomas, in terms of
a low ADR, has been translated to poor-quality colonoscopy
and has been shown to correlate with an increased risk of
interval CRC.5,6 Professional societies recommend a
physician-related ADR of 30% for men, 20% for women,
and an overall ADR of 25% in regular screening colonoscopy
of asymptomatic average-risk individuals.7
Checking stool for blood, specifically hemoglobin, is an
acceptable noninvasive screening modality for CRC in
average-risk asymptomatic individuals.8 The fecal
immunochemical test (FIT) uses hemoglobin-specific im-
munoglobulins that bind to hemoglobin present in stool.
The test is interpreted as positive or negative based on
the test kit cutoff threshold set by the manufacturer. FIT
has a reported sensitivity of 79% and specificity of 94%
for CRC and is the predominant CRC screening modality
worldwide because of its lower cost and noninvasive
nature.8,9
FIT-positive individuals are advised to undergo colonos-
copy, and the prevalence of adenomas and/or CRC are ex-
pected to be higher in this cohort as compared with the
general asymptomatic screening population. Therefore,
professional societies have suggested a higher ADR
threshold for physicians performing colonoscopy in FIT-
positive individuals.10 However, the benchmarks are
based on low-quality evidence, and professional societies
slightly differ on the recommended threshold. The U.S.
Multi-Society Task Force on CRC prevention proposed an
ADR benchmark of 35% for women and 45% for men
in the FIT-positive asymptomatic population.11
To ensure uniform quality among centers after orga-
nized screening programs, a reliable ADR measure needs
to be established in FIT-positive colonoscopy. To this
end, we conducted this systematic review and meta-
analysis to estimate the pooled threshold of ADR in the
FIT-positive asymptomatic population undergoing
colonoscopy.
METHODS
Search strategy
We conducted a comprehensive search of PubMed, EM-
BASE, and Web of Science databases (earliest inception to
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ADR in FIT-positive colonoscopy
October 2021). Key words used in the literature search
were a combination of “screening colonoscopy,” “FIT-pos-
itive,” and “adenoma detection.” The search was restricted
to studies of human subjects that were published in peer-
reviewed journals. An experienced medical librarian
conducted the literature search, and the search strategy
is provided in Appendix 1 (available online at www.
giejournal.org). We followed the updated Preferred
Reporting items for Systematic Reviews and Meta-
Analyses guidelines and Meta-analysis Of Observational
Studies in Epidemiology checklist (see Appendix 2 and
Appendix 3, respectively, available online at www.
giejournal.org).12,13
Two authors (B.P.M. and S.C.) independently reviewed
the titles and abstracts of candidate studies identified in
the primary search and excluded studies that did not
address the research question of interest, based on prespe-
cified exclusion and inclusion criteria. The full text of the
remaining articles was reviewed to determine whether it
contained relevant information. Any discrepancy in article
selection was resolved by consensus and in discussion
with a co-author (A.F.). The bibliographic section of the
selected articles and the systematic and narrative articles
on the topic were manually searched for additional rele-
vant articles.
Study selection
We included studies that reported on adenoma detec-
tion parameters in average-risk asymptomatic individuals
undergoing colonoscopy based on a positive screening
FIT test. Inclusion was strictly restricted to studies based
on data that longitudinally evaluated the study cohort.
Studies irrespective of prospective or retrospective design,
qualitative or quantitative assessment of FIT kit, the com-
mercial brand of FIT kit used, test cutoff threshold, num-
ber of samples collected, study geography, and language
were included as long as they provided data needed for
the analysis.
Exclusion criteria were studies that evaluated
intermediate-risk and/or high-risk individuals, FIT assess-
ment of a study cohort that was already scheduled to un-
dergo colonoscopy, studies of patients undergoing stool
sampling on the day of colonoscopy and/or after colonos-
copy, studies that used colonoscopy results to “back-track”
the FIT data, studies that primarily assessed test-kit accu-
racy parameters to ascertain cutoff thresholds, and confer-
ence abstracts.
Studies that compared FIT with other screening
methods, such as guaiac-based fecal occult blood test
and/or colonoscopy, were included if the data pertaining
to the FIT cohort met the above inclusion and exclusion
criteria. For multiple publications from the same cohort
and/or overlapping cohorts, data from the most recent
and/or most appropriate comprehensive report were
included. Primary study authors were contacted via email
for clarifications, if needed.
Volume 96, No. 2 : 2022 GASTROINTESTINAL ENDOSCOPY 209
ADR in FIT-positive colonoscopy
Data abstraction and quality assessment
Data on study-related outcomes in the individual studies
were abstracted onto a standardized form by 2 authors
(S.R.K. and E.D.) independently, and 2 authors (S.C. and
B.P.M.) did the quality scoring independently. The
Newcastle-Ottawa scale for cohort studies was used to
assess the quality of studies.14 This quality score
consisted of 8 questions, the details of which are
summarized in Supplementary Table 1 (available online
at www.giejournal.org). A score of >5, 3 to 5, and <3 was
considered suggestive of high quality, medium quality
and low quality, respectively.
Outcomes assessed
The pooled outcomes assessed were FIT screening rate,
FIT positivity rate, colonoscopy completion rate, ADR,
advanced ADR (aADR), 10 mm ADR, CRC detection
rate (CRCDR), and polyp detection rate (PDR). Based on
data availability, pooled results for ADR parameters were
segregated by gender (male and female), and a time-
period cumulative analysis of ADR stratified by the year
of publication of the studies was performed. Based on
data availability and feasibility, subgroup analyses were
planned based on the number of stool samples collected,
test cutoff thresholds, brand of testing kit, study type (pop-
ulation-based studies, prospective), and study geography
(Americas, Asia, Europe).
Statistical analysis
We used meta-analysis techniques using the logit trans-
formation to calculate the pooled proportions along with
the corresponding 95% confidence interval (CI), following
the methods suggested by DerSimonian and Laird,15
and the random-effects model was used. When the inci-
dence of an outcome was zero in a study, a continuity
correction of .5 was added to the number of incident cases
before statistical analysis.16 We assessed heterogeneity
between study-specific estimates by using the Cochran Q
statistical test for heterogeneity; 95% prediction interval,
which deals with the dispersion of the effects; and the I2
statistic.17-19 In this, values of <30%, 30% to 60%, 61% to
75%, and >75% were suggestive of low, moderate, substan-
tial, and considerable heterogeneity, respectively.20
Publication bias was ascertained, qualitatively, by visual
inspection of the funnel plot and quantitatively by the
Egger test.21 All analyses were performed using
Comprehensive Meta-Analysis software, version 3 (BioStat,
Englewood, NJ, USA).
Ethics statement
This is a meta-analysis of published studies and data,
and this type of study does not involve active human par-
ticipants and/or animals. Therefore, formal consent,
informed consent, institutional review board approval,
and ethics approval are not applicable and/or not required.
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Mohan et al
RESULTS
Search results and population characteristics
From an initial 9648 article references, 5138 were
screened after removal of duplicates and conference ab-
stracts. One hundred four full-length articles were evalu-
ated in detail, and 34 studies were included in the final
analysis.22-55 A schematic diagram of study selection is illus-
trated in Figure 1.
The intention-to-screen population included 6,624,020
asymptomatic average-risk individuals. Of these,
2,655,345 individuals completed a screening FIT. Patient
age for inclusion was primarily based on local screening
programs. Eligible age for inclusion was 40 years in
studies by Nakama et al,44 Itoh et al,36 and Castiglione
et al25; 45 years in the study by Levin et al42; and 50
years in the remaining studies. Baseline study and
population characteristics are summarized in Table 1, and
gender-based outcomes are summarized in Table 2.
Histologic classification of polyps and CRC were based
on World Health Organization criteria. An advanced
adenoma was defined as 10 mm, or with high-grade
dysplasia, or villous component >20%.
Characteristics and quality of included studies
Twenty-five studies analyzed population-based
data,22,25-29,31-35,37,40-42,44,45,47-54 and, based on the New-
Castle Ottawa scoring system to assess the quality of
studies, all included studies were considered to be high
quality.22-55 The detailed assessment of study quality is
summarized in Supplementary Table 1 (available online
at www.giejournal.org).
Pooled outcomes
Pooled FIT screening and adenoma detection.
Much of the asymptomatic population completed a FIT
screening as requested by their primary care physician.
The pooled FIT screening rate in the target population
was 69.8% (95% CI, 62.8-76.1). Among the screened popu-
lation, the pooled FIT positivity rate was 5.4% (95% CI, 4.3-
6.9). The pooled colonoscopy completion rate was 85%
(95% CI, 82.8-86.9).
The pooled ADR in FIT-positive asymptomatic individ-
uals was 47.8% (95% CI, 44.1-51.6) (Fig. 2). The pooled
aADR was 25.3% (95% CI, 22-29) and the pooled CRCDR
5.1% (95% CI, 4.4-5.9). The pooled ADR for
polyps 10 mm was 33.2% (95% CI, 24-43.8)
(Supplementary Fig. 1, available online at www.
giejournal.org) and the pooled PDR 63.1% (95% CI, 58-
67.9) (Supplementary Fig. 2, available online at www.
giejournal.org).
Pooled ADR by gender. Seven studies reported
gender-based ADRs in asymptomatic average-risk individ-
uals who underwent colonoscopy based on a positive
FIT.27,30,37,43,49,54,55 Data were reported for 40,330 men
www.giejournal.org
Mohan et al ADR in FIT-positive colonoscopy

Total studies found on literature

Identification
search, N=9648;
After de-duplication N=5138

Irrelevant records excluded

by reading study title and
abstract, n=5009
Screening

Records screened
(n = 129)

Records excluded based on

eligibility criteria (guidelines
papers, studies assessing novel
tools to improve ADR, review
papers), n=25

Full-text articles assessed

Eligibility

for eligibility
(n = 104)
• Studies on multi-target stool
DNA analysis: 15
• Studies assessing the accuracy
parameters of FIT test: 31
• Studies with indirect
statistical data on ADR: 13
• Studies with non-longitudinal
Studies included in data = 11
Included

quantitative synthesis
(meta-analysis)
(n = 34)

Figure 1. Study selection flowchart.

and 39,350 women. In men, the pooled ADR was 58.3%
(95% CI, 52.8-63.6) (Supplementary Fig. 3, available
online at www.giejournal.org), aADR was 27.5% (95% CI,
16.9-41.4), and CRCDR was 6.6% (95% CI, 5.7-7.7). In
women, the pooled ADR was 41.9% (95% CI, 36.4-47.6)
(Supplementary Fig. 4, available online at www.
giejournal.org), aADR was 16.5% (95% CI, 9.9-26.2), and
CRCDR was 5.4% (95% CI, 4.3-6.8).
Change in pooled ADR by time. A time-period
change in the ADR by endoscopists was assessed by means
of cumulative meta-analysis stratified by the year of publi-
cation of the included studies. The earliest published study
was in 1996 and the latest was published in 2020. Based on
time-period cumulative analysis, the pooled ADR improved
from 30.5% (95% CI, 24.6-37.2) to 47.8% (95% CI, 44.1-
51.6) (Supplementary Fig. 5, available online at www.
giejournal.org). All pooled results are summarized in
Table 3.
Pooled ADR by subgroup analyses. Subgroup ana-
lyses were performed as follows: based on the number of
stool samples (1, 2, or 3 samples); FIT cutoff threshold
(100, <100, or >100 ng hemoglobin/mL); FIT kit type
(OC-Sensor [Eiken Chemical Co, Tokyo, Japan], Mag-
stream [Fujirebio, Tokyo, Japan], or HemeSelect [SmithK-
line Diagnostics, San Jose, Calif, USA]); quantitative,
qualitative, or either type of FIT analysis; study characteris-
tics (population based or prospectively done); and geogra-
phy (Americas, Asia, or Europe). The results are
summarized in Table 4 and forest plots for ADR by stool
sample, test type, test kit, and test cutoff threshold are
provided in Supplementary Figures 6 through 9, respec-
tively (available online at www.giejournal.org).
Validation of meta-analysis results
Sensitivity analysis. To assess whether any 1 study
had a dominant effect on the meta-analysis, we excluded
1 study at a time and analyzed its effect on the main sum-
mary estimate. In this analysis, no single study significantly
affected the outcome or the heterogeneity.
Heterogeneity. Considerable heterogeneity was ex-
pected because of the presence of multiple test–related
variabilities. The calculated I2 and 95% prediction interval

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ADR in FIT-positive colonoscopy Mohan et al

TABLE 1. Study and population characteristics

Total Individuals with adenomas
Test positivity population
Details of threshold cohort FIT-positive Individuals
First FIT kit and (100 ng Hb/ (intention- Total Total FIT- individuals Individuals with
author, Male/ positivity mL [ 20 mg to-screen FIT test screened positive undergoing with any colorectal
year Study details Age (y) female threshold Hb/g feces) analysis) details by FIT individuals colonoscopy polyp Any >10 mm Advanced cancer

Akram, Retrospective 50- 75 M93.6% Polymedco 100 ng Hb/mL 4662 1 kit, 1 1985 185 101 NR NR 34 37 3
201722 analysis, Mar OC auto 80, (manufacturer sample, NR
2014 to Jan Cortland, NY cutoff) qualitative
2015, USA or
quantitative
test
Allison, Population- 50 M40.7% HemeSelect, 10 mg Hb/g 10702 1 kit, 1 7493 440 355 134 NR NR NR 32
199624 based, SmithKline feces (50 ng sample, NR
prospective Diagnostics, Hb/mL) qualitative
cohort study, Oct San Jose, or
1990 to Oct Calif, USA quantitative
1991, USA test
Allison, Population- 50 M47.5% FlexSure 30 mg Hb/g 11,564 3 samples 5932 181 172 NR NR 128 NR 14
200723 based, OBT, feces (150 ng (study not in
prospective Beckman Hb/mL) folder)
cohort study, Apr Coulter Inc,
1997 to Oct Brea, Calif,
1999, USA USA
Castiglione, Population- 40-70 NR HemeSelect, NR 14,682 1 kit, 1 8008 245 203 NR 62 NR NR 17
199625 based, (mean, SmithKline sample, NR
prospective 54.1) Diagnostics qualitative
cohort study, or
Mar 1992 to Jul quantitative
1995, Italy test
Chen, RCT, multicenter 50-74 3335/ Pupu Tube, 100 ng Hb/mL 7854 1 kit, 1 7386 1084 827 500 397 NR 82 7
202026 (6 centers), May 4519 New Horizon (manufacturer sample,
2018 to Apr Health cutoff) both
2019, China Technology, qualitative
China test (current
study) and
quantitative
test (pilot
study)
Chiu, 201527 Population- 50-69 NR OC-Sensor 100 ng Hb/mL 5,417,699 Biennial FIT, 1,160,895 46,963 37,585 21,386 14,834 NR 4248 2304
based, (Eiken (Eiken); 8 ng 1 kit, 1
prospective Chemical Co, hemoglobin/ sample,
cohort study of Tokyo, mL (Kyowa) quantitative
national Japan) or (both are test
database, 2004- Kyowa HM- manufacturer
2009, Taiwan Jack cutoff)
Crotta, Population- 50-74 NR OC-Sensor 100 ng Hb/mL 2959 Biennial FIT, 2161 92 87 NR NR NR 35 5
201228 based, (manufacturer 1 kit, 1
prospective cutoff) sample,
cohort study, quantitative
2001-2010, Italy test
(cohort with 1
FIT)
Crotta, First round 2001 2959 1660 72 67 NR NR NR 25 NR
201228
Second round 2566 1600 67 60 NR NR NR 21 NR
2003
Third round 2006 2056 1179 43 39 NR NR NR 15 NR
Fourth round 1862 1165 51 48 NR NR NR 15 NR
2008
Dancourt, Population- 50-74 M45.7% Instant-view, 50 mg Hb/g NR 1 kit, 1 17,215 1188 932 NR 364 NR 251 55
200829 based, Alpha feces sample, NR
prospective Scientific (manufacturer qualitative
cohort study, Designs, cutoff) or
2005, France Poway, Calif, quantitative
USA test
Denis, Population- 62.4 8019/ OC-Sensor 30 mg Hb/g NR 1 kit, 1 44.40% 3.80% 14,228 9082 7602 NR 4736 773
202030 based, (7.0) 5436 feces sample, NR
retrospective qualitative
data analysis, or
2007-2019, quantitative
France test

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Mohan et al ADR in FIT-positive colonoscopy

TABLE 1. Continued

Total Individuals with adenomas

Test positivity population
Details of threshold cohort FIT-positive Individuals
First FIT kit and (100 ng Hb/ (intention- Total Total FIT- individuals Individuals with
author, Male/ positivity mL [ 20 mg to-screen FIT test screened positive undergoing with any colorectal
year Study details Age (y) female threshold Hb/g feces) analysis) details by FIT individuals colonoscopy polyp Any >10 mm Advanced cancer

Denters, Population- 60 (7) M45% OC-Sensor 50 ng Hb/mL 5039 1 kit, 1 2871 233 186 143 130 66 88 12
201231 based, sample, nr
(first prospective qualitative
round) cohort analysis, or
Jun 2006 to Feb quantitative
2007, test
Netherlands
Denters, 61 (6) M44% 2348 1 kit, 1 2022 284 252 192 169 NR 103 9
201231 sample, NR
(second qualitative
round) or
quantitative
test
Faivre, 2012 Population- 50-74 NR FOB-Gold, 176 ng Hb/mL NR 1 kit, 1 32,215 1665 1527 NR 608 NR 316 91
(1)32 based, cross- Beckman sample, NR
sectional analysis Coulter qualitative
of database, or
2008, France quantitative
test
Faivre, 2012 Magstream, 20 ng Hb/mL 1 kit, 1 19,244 892 828 NR 367 NR 211 65
(2)32 Fujirebio, sample, NR
Tokyo, Japan qualitative
or
quantitative
test
Faivre, 2012 OC-Sensor 150 ng Hb/mL 1 kit, 1 33,690 1260 1181 NR 550 NR 403 92
(3)32 sample, NR
qualitative
or
quantitative
test
Guittet, Population- 50-74 M42.7% Magstream 20-50 ng Hb/ 10,804 2 samples, 10,673 733 644 NR 115 NR 48 2
2007 based, mL quantitative
(1)33 prospective test
cohort study, Jun
2004 to Jun
2005, France
Guittet, 50-75 ng Hb/ NR 32 NR 17 3
2007 mL
(2)33
Guittet, >75 ng Hb/mL NR 95 NR 74 16
2007
(3)33
Hilsden, Population- 50-74 2864/ OC-Sensor 75 ng Hb/mL NR 1 kit, 1 NR NR 4574 3443 2673 NR 1174 NR
201634 based 1710 sample, NR
retrospective qualitative
analysis, Jan or
2014 to Jun quantitative
2015, single test
center, Canada
Hol, 201035 Population- 50-74 NR OC-Sensor 100 ng Hb/mL 5007 1 kit, 1 2975 143 137 89 82 NR 59 14
based RCT, Nov (manufacturer sample,
2006 to Nov cutoff) quantitative
2007, test
Netherlands
Itoh, 199636 Population- 40 NR OC-Hemodia 50 ng 33,049 1 kit, 1 27,860 1490 1207 NR NR NR NR 77
based, (no longer in hemoglobin/ sample,
prospective production mL biennial,
cohort study, in USA) quantitative
1991-1992, test
Japan
Jensen, Population- 50-70 M46.4% OC FIT-CHEK, 20 mg Hb/g 670,841 1 kit, 1 323,349 16,037 12,113 NR 3297/ NR 895/6396 545
201637 based, Polymedco, feces sample, NR 6396
(round retrospective Cortland, NY (manufacturer qualitative
1) analysis of health cutoff) or
plan database, quantitative
2007-2008, USA test

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ADR in FIT-positive colonoscopy Mohan et al

TABLE 1. Continued

Total Individuals with adenomas

Test positivity population
Details of threshold cohort FIT-positive Individuals
First FIT kit and (100 ng Hb/ (intention- Total Total FIT- individuals Individuals with
author, Male/ positivity mL [ 20 mg to-screen FIT test screened positive undergoing with any colorectal
year Study details Age (y) female threshold Hb/g feces) analysis) details by FIT individuals colonoscopy polyp Any >10 mm Advanced cancer

Jensen, 1 kit, 1 183,988 7143 5747 NR 1403/ NR 295/2962 147

201637 sample, NR 2962
(round qualitative
2) or
quantitative
test
Jensen, 1 kit, 1 163,281 6102 4912 NR 1288/ NR 265/2657 138
201637 sample, NR 2657
(round qualitative
3) or
quantitative
test
Jensen, 1 kit, 1 145,452 6211 5039 NR 1380/ NR 243/2880 128
201637 sample, NR 2880
(round qualitative
4) or
quantitative
test
Kligman, Retrospective, 63.4 NR Polymedco 20 mg Hb/g NR 1 kit, 1 NR NR 207 NR 151 NR 67 2
201838 Jan 2013 to Jul (6.3) Inc feces sample,
2014, single (manufacturer qualitative
center, USA cutoff) test
Launoy, Population- 50-74 NR Magstream 20 ng Hb/mL NR 2 kit, 2 7421 434 366 NR 181 102 102 22
200539 based cancer (manufacturer sample,
registry, Jan cutoff) quantitative
2001 to Dec test
2003, France
Leen, Prospective, 50-74 NR OC-Sensor 100 ng Hb/mL 10,000 2 kit, 2 978 56 51 NR 26 NR 11 0
201440 population- (manufacturer sample,
based, 2011- cutoff) quantitative
2013, Ireland test
Levi, 201141 Prospective, 50-75 M45.4% OC-MICRO, 70 ng Hb/mL 4657 3 1224 153 108 72 66 NR 29 6
population- Eiken consecutive
based, Israel Chemical Co daily
samples, NR
qualitative
or
quantitative
test
Levin, Population- 45-56 47.50% OC-Sensor 20 mg Hb/g 13,835 1 kit, 1 4195 173 146 NR 84 32 45 4
202042 based, Diana, feces sample, NR
(AA) retrospective Polymedco qualitative
data analysis, Inc or
2018, USA (data quantitative
for African test
Americans)
Levin, American whites 51-56 53.20% 22,832 6772 309 245 NR 162 44 70 10
202042
(AW)
Levin, Hispanics 51-56 58.50% 10,930 2905 116 92 NR 65 15 24 0
202042
(H)
Levin, Asia-Pacific 51-56 50.70% 8893 2960 113 84 NR 54 14 19 6
202042 Islanders
(AP)
Miutescu, Prospective, 61.2 M40.7% Hem Check NR NR 1 kit, 1 1389 87 57 NR 44 32 29 10
201343 single center, (12.8) 1, Veda Lab, sample,
Romania France qualitative
test
Nakama, Population- 40 NR Monohaem, 20 mg Hb/g 3982 1 kit, 1 3365 157 157 43 NR NR NR 10
199644 based, Nihon feces sample, NR
prospective Pharma, (manufacturer qualitative
cohort study, Japan cutoff) or
1991, Japan quantitative
test

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Mohan et al ADR in FIT-positive colonoscopy

TABLE 1. Continued

Total Individuals with adenomas

Test positivity population
Details of threshold cohort FIT-positive Individuals
First FIT kit and (100 ng Hb/ (intention- Total Total FIT- individuals Individuals with
author, Male/ positivity mL [ 20 mg to-screen FIT test screened positive undergoing with any colorectal
year Study details Age (y) female threshold Hb/g feces) analysis) details by FIT individuals colonoscopy polyp Any >10 mm Advanced cancer

Parra- Population- 50-79 M32.8% OC-Light 50 ng Hb/mL 3092 1 kit, 1 1756 174 163 104 85 NR 42 14
Blanco, based, years (Eiken sample,
201045 prospective Chemical Co) qualitative
cohort study, Jan test
2004 to Aug
2006, Spain
Quintero, RCT, multicenter 59.3 F54.3% OC-Sensor 75 ng Hb/mL 26,599 1 kit, 1 10,611 767 663 NR 350 NR 231 36
201246 (15 centers), Jun (5.6) sample,
2009 to Jun semi-
2011, Spain quantitative
test
Raginel, Population- 50-74 M44% Magstream 55 ng Hb/mL 19,797 1 kit, 1 NR 390 344 NR NR NR 146 28
201347 based, sample,
(1) prospective quantitative
cohort, Jun 2009 test
to May 2011,
France
Raginel, Magstream 55 ng Hb/mL 19,797 2 19,797 632 554 NR NR NR 210 36
201347 consecutive
(2) stool
samples,
quantitative
test
Raginel, Magstream 20 ng Hb/mL 19,797 1 kit, 1 19,797 548 484 NR NR NR 209 37
201347 (manufacturer sample,
(3) cutoff) quantitative
test
Raginel, OC-Sensor 150 ng Hb/mL 19,797 1 kit, 1 19,797 551 488 NR NR NR 225 37
201347 sample,
(4) quantitative
test
Raginel, OC-Sensor 150 ng Hb/mL 19,797 2 19,797 801 712 NR NR NR 290 44
201347 consecutive
(5) stool
samples,
quantitative
test
Raginel, OC-Sensor 100 ng Hb/mL 19,797 1 kit, 1 19,797 694 615 NR NR NR 275 44
201347 (manufacturer sample,
(6) cutoff) quantitative
test
Robinson, Population- 50-75 M40.4% HemeSelect 20-30 mg Hb/g 4018 3 samples 1489 145 138 NR 48 31 29 9
200548 based, feces (study not in
prospective folder)
cohort, Feb 1991
to Jul 1992,
United Kingdom
Segnan, Population- 55-64 NR Immudia- NR 6075 1 kit, 1 1965 92 81 NR 39 NR 21 2
200749 based RCT, Oct HemSp, sample, NR
2002 to Jan Fujirebio Inc qualitative
2004, Italy or
quantitative
test
Shahidi, Population- 50-74 M48.5% NS-Plus, 50 ng Hb/mL 168,599 1 kit, 1 168,599 32,152 20,322 NR 10,663 NR 4012 449
201650 based, Alfresa sample,
(cutoff prospective Pharma quantitative
50) cohort, Nov 2013 Corporation, test
to Dec 2014, Osaka, Japan
Canada
Shahidi, 100 ng Hb/mL 168,599 32,152 20,322 NR 6043 NR 2712 388
201650
(cutoff
100)

(continued on the next page)

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ADR in FIT-positive colonoscopy Mohan et al

TABLE 1. Continued

Total Individuals with adenomas

Test positivity population
Details of threshold cohort FIT-positive Individuals
First FIT kit and (100 ng Hb/ (intention- Total Total FIT- individuals Individuals with
author, Male/ positivity mL [ 20 mg to-screen FIT test screened positive undergoing with any colorectal
year Study details Age (y) female threshold Hb/g feces) analysis) details by FIT individuals colonoscopy polyp Any >10 mm Advanced cancer

Singal, Population- 53-60 F62% OC-Auto FIT 100 ng Hb/mL 2400 1 kit, 1 1676 NR 671 NR 128 NR 42 7
201751 based, CHEK, (manufacturer sample, NR
prospective Polymedco cutoff) qualitative
cohort, Mar 2013 or
to Jul 2016, USA quantitative
test
Smith, Population- 50-75 M47.8% InSure test NR 2351 2 NR NR 131 NR 41 NR 20 14
200652 based, kit consecutive
retrospective stool
database samples, NR
analysis of 2 qualitative
centers, Jun or
2000 to Sep quantitative
2004, Australia test
Sultanian, Population- 50-75 M59% OC FIT-CHEK, 75 mg Hb/g NR 1 kit, 1 NR NR 2167 NR 1575 NR 770 67
202053 based, Polymedco feces sample, NR
retrospective qualitative
analysis, Jan 1 or
2014 to Dec 31 quantitative
2014, Canada test
Van Population- 50-75 163/ OC-Sensor 100 ng Hb/mL 10322 1 kit, 1 6157 339 280 218 201 106 145 24
Rossum, based, (60.7 117 (manufacturer sample,
200854 prospective [7.1]) cutoff) semi-
cohort study, Jun quantitative
2006 to Feb test
2007,
Netherlands
Wong, Multicenter (8 62.8 1404/ OC-Sensor 100 ng Hb/mL NR 1 kit, 1 NR NR 2485 NR 1332 NR 743 102
201955 centers) (7.4) 1081 (manufacturer sample, NR
retrospective cutoff) qualitative
cohort study, or
2009-2016, Hong quantitative
Kong (1), Japan test
(2), Korea (2),
Singapore (1),
and Taiwan (2)

FIT, Fecal immunochemical test; Hb, hemoglobin; NR, not reported; RCT, randomized controlled trial.

TABLE 2. Adenomas detected by gender

People with fecal

immunochemical
test positive who
underwent
colonoscopy Men Women
Any Advanced Colorectal Any Advanced Colorectal
First author, year Men Women adenoma adenoma cancer adenoma adenoma cancer

Miutescu, 201343 40 47 26 18 6 18 11 4
27
Chiu, 2015 (first) 17874 19438 8645 2718 1262 6189 1530 1042
Chiu, 201527 (second) 4623 6392 2348 656 253 2216 561 248
30
Denis, 2020 8019 5436 5092 3288 NR 2522 1446 NR
Jensen, 201637 8117 6778 4506 1027 508 2862 671 450
Segnan, 200749 56 36 27 16 0 12 5 2
Van Rossum, 200854 163 117 123 93 16 78 52 8
Wong, 201955 1404 1081 865 NR NR 467 NR NR
NR, Not reported.

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Mohan et al ADR in FIT-positive colonoscopy

Figure 2. Forest plot, adenoma detection rate. CI, Confidence interval.

values are summarized in Tables 3 and 4. Although
subgroup analysis did not reveal many changes to the
calculated heterogeneity, the dispersion was noted to be
the least with the OC-Sensor FIT kit and 1 stool sample
for the FIT.
Publication bias. Publication bias assessment was per-
formed based on the ADR and aADR data points. Visual in-
spection of the funnel plot and quantitative Egger’s
measurement demonstrated no evidence of publication
bias (Egger’s 2-tailed P Z .4 based on ADR data and Egger’s
2-tailed P Z .2 based on aADR data) (Supplementary Fig. 10,
available online at www.giejournal.org).
DISCUSSION
Based on this meta-analysis of 34 high-quality studies
that intended to screen over 6 million asymptomatic
average-risk individuals, we report a pooled FIT comple-
tion rate of 69.8%, with a pooled FIT positivity rate of
5.4%. The pooled colonoscopy completion rate was
85%. Because of the extensive literature search and care-
ful selection of studies, we were able to include
2,655,345 individuals screened by FIT and 163,839 FIT-
positive individuals, making this the largest study on this
topic.
Moreover, this is the first meta-analysis to report on the
pooled ADR parameters of colonoscopy in FIT-positive
asymptomatic average-risk individuals. The pooled ADR
in this analysis was 47.8%. In the setting of FIT-positive in-
dividuals, the number of adenomas detected is expected to
be higher. The multicenter Italian EQuIPE study (Evalu-
ating Quality Indicators of the Performance of Endoscopy),
a population-based screening program, where 50- to 69-
year-old residents are invited via mail every 2 years to
perform a single FIT, reported a mean ADR of 44.8%,56
and the National Health System Bowel Cancer Screening
Program in the United Kingdom reported a 46.5% ADR.57

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ADR in FIT-positive colonoscopy Mohan et al

TABLE 3. Summary of pooled rates detection because of a lack of historical data to compare.
Additionally, no data were available to study a possible
Quality metrics of Heterogeneity decrease in interval CRC. We hope our results can help
colonoscopy in Pooled rate
guide future additional benchmarks in FIT-positive individ-
FIT-positive % (95% confidence 95% Prediction I2
individuals interval) interval (%) uals undergoing colonoscopy. Such benchmarks are
important, because ADR per endoscopist is the most
FIT screening rate 69.8 (62.8-76.1) 26-94 99
important quality indicator of screening colonoscopy. It
37 cohorts;
6,624,020 individuals is directly related to key outcome measures, such as inter-
val cancer incidence, mortality, quality of preparation,
FIT positivity rate 5.4 (4.3-6.9) 1-26 99
46 cohorts completeness of colonoscopy, and withdrawal time.
With increasing acceptability of ADR as a quality metric
Colonoscopy 85 (82.8-86.9) 65-93 99
completion rate 46 cohorts across the globe, endoscopists continue to monitor their
in FIT-positive personal performance and achieve these quality metric
individuals goals. A recent study based on the data from GI Quality
ADR 47.8 (44.1-51.6) 26-70 99 Improvement Consortium Ltd that analyzed a large na-
39 cohorts tional U.S. sample standardized to the U.S. population
Men 58.3 (52.8-63.6) 41-75 99 demonstrated an average ADR of 39.05% that increased
8 cohorts over 4 years of study time from 33.93% to 38.12%.59 The
Women 41.9 (36.4-47.6) 26-62 98 GiQuIC experience of 10 million colonoscopies in their
8 cohorts online database reflect an increase of ADR from 25% to
Advanced ADR 25.3 (22-29) 8-56 99 45% from year 2011 to 2019.60 Our time-period cumulative
50 cohorts analysis demonstrated increased ADRs from 30.5% to
Men 27.5 (16.9-41.4) 5-78 99 47.8% over the span of more than 20 years of data included
7 cohorts in this study.
Womne 16.5 (9.9-26.2) 3-63 99 Additional key findings of this study include the pooled
7 cohorts gender-based ADR data in asymptomatic average-risk FIT-
>10-mm ADR 33.2 (24-43.8) 7-75 96 positive individuals undergoing colonoscopy. In men, we
12 cohorts reported a pooled ADR of 58.3%, aADR of 27.5%, and
Colorectal cancer 5.1 (4.4-5.9) 2-13 95 CRCDR of 6.6%. The corresponding pooled values in
detection rate 50 cohorts women were 41.9%, 16.5%, and 5.4%, respectively.
Men 6.6 (5.7-7.7) 5-10 77 Furthermore, based on our subgroup analyses, this study
6 cohorts reported novel findings in terms of the number of stool
Women 5.4 (4.3-6.8) 3-10 88 samples tested. The number of stool samples required
6 cohorts for the FIT differ based on the screening programs prac-
Polyp detection 63.1 (58-67.9) 42-79 98 ticed. Our data suggest an acceptable ADR of 52.8% with
rate 12 cohorts just 1 stool sample.
Publication bias The FIT kit hemoglobin cutoff threshold to report a pos-
Based on ADR Egger’s 2-tailed P Z .4 itive or negative result can differ based on the manufac-
data turer. Additionally, multiple manufacturers make FIT kits.
Based on Egger’s 2-tailed P Z .2 In this study, the OC-Sensor kit (Eiken Chemical Co) was
advanced the most used (14 study cohorts). The most often used
ADR data
cutoff was a hemoglobin of 100 ng/mL that corresponds
FIT, Fecal immunochemical test; ADR, adenoma detection rate. to a 20 mg hemoglobin/g of feces. Based on our subgroup
analysis, the pooled ADR with the OC-Sensor test kit was
Likewise, the results from the largest COLONPREV dataset 59.5% and the pooled rate at a test cutoff of 100 ng hemo-
that aimed at evaluating the efficacy of once-only colonos- globin/mL was 52.1%. Although the FIT uses a specific
copy and biennial FIT from 15 tertiary centers in Spain immunoglobulin-based assessment, the test can report a
showed that the ADR in FIT-positive colonoscopy was qualitative (positive or negative) or a quantitative assess-
55%.58 Based on our study results, we add quality ment of the hemoglobin in feces. The pooled ADR based
evidence that the current benchmarks set by professional on qualitative assessment was 67.7%.
societies are acceptable. One of the limitations of this study was the considerable
Robust data on aADR, CRCDR, and PDR in FIT-positive heterogeneity with wide prediction intervals. Understand-
individuals are particularly limited in the current literature. ably, a high heterogeneity is unavoidable given the pres-
In this study we report pooled aADR of 25.3%, pooled ence of variables that could not be controlled for in 1
CRCDR of 5.1%, and pooled PDR of 63.1%. We were not specific subgroup analyzed. The pooled ADR data were
able to assess if these rates reflected an improved CRC based on population and/or person cohorts and were not

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Mohan et al ADR in FIT-positive colonoscopy

TABLE 4. Pooled results of subgroup analyses

Pooled rate
% (95% confidence interval)
No. of cohorts
I2
% (95% prediction interval)
Subgroup analyses ADR aADR CRCDR

No. of stool samples

1 sample 52.8 (48.8-56.8) 27.9 (24-32.1) 5.3 (4.5-6.2)
31 cohorts 42 cohorts 41 cohorts
99 (31-74) 99 (9-59) 96 (2-14)
2 samples 23.6 (11.9-41.5) 11.7 (6.1-21.4) 2.1 (.8-5.4)
6 cohorts 6 cohorts 6 cohorts
98 (1-87) 96 (1-64) 90 (1-92)
3 samples NA NA 7 (4.9-9.9)
3 cohorts
0 (1-46)
Test cutoff threshold
100 ng Hb/mL 52.1 (47-57.1) 23.1 (19.3-27.4) 4.4 (3.4-5.7)
17 cohorts 24 cohorts 22 cohorts
99 (31-73) 98 (8-48) 96 (2-12)
<100 ng Hb/mL 44.7 (37-52.7) 25.6 (21-30.8) 4.3 (3.1-6.1)
13 cohorts 16 cohorts 16 cohorts
99 (18-75) 98 (10-51) 94 (1-16)
>100 ng Hb/mL 44.7 (37-52.7) 33 (27.6-38.9) 6.4 (5.6-7.3)
4 cohorts 6 cohorts 7 cohorts
98 (14-80) 97 (16-55) 64 (4-9)
Test kit type
OC-Sensor 59.5 (56.4-62.4) 35.9 (32.9-39) 6 (5.2-6.9)
14 cohorts 22 cohorts 17 cohorts
91 (48-70) 93 (23-50) 67 (3-9)
Magstream 21.6 (10.1-40.4) 20 (12.1-31.1) 4.2 (2.7-6.4)
5 cohorts 8 cohorts 8 cohorts
98 (1-90) 98 (3-69) 88 (1-17)
HemeSelect NA NA 8.4 (6.5-10.7)
3 cohorts
0 (NA)
Fecal immunochemical test type
Quantitative 31.4 (25-38.7) 26.3 (21.4-31.9) 4.4 (3.1-6.1)
9 cohorts 20 cohorts 17 cohorts
99 (12-60) 99 (9-56) 98 (1-17)
Qualitative 67.7 (50.7-81) 34.9 (24.1-47.6) 6.4 (1.9-19.6)
3 cohorts 3 cohorts 3 cohorts
90 (1-99) 82 (1-99) 87 (NA)
Either (quantitative/qualitative) 51.4 (48.1-54.8) 23.7 (19.7-28.3) 5.4 (4.7-6.2)
27 cohorts 27 cohorts 30 cohorts
97 (34-68) 98 (8-53) 87 (3-10)
Study characteristics
Population based Yes: 46 (42-50.1) Yes: 24.7 (21.2-28.6) Yes: 5.2 (4.5-6.2)
34 cohorts 44 cohorts 44 cohorts
99 (24-69) 99 (8-55) 96 (2-13)
No: 58.9 (52.2-65.3) No: 30 (21.1-40.7) No: 3.6 (1.9-6.7)
5 cohorts 6 cohorts 6 cohorts
92 (35-79) 96 (7-70) 89 (1-25)
(continued on the next page)

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ADR in FIT-positive colonoscopy Mohan et al

TABLE 4. Continued

Pooled rate
% (95% confidence interval)
No. of cohorts
I2
% (95% prediction interval)
Subgroup analyses ADR aADR CRCDR

Prospective Yes: 42.1 (37-47.5) Yes: 26.9 (22.5-31.7) Yes: 4.9 (3.8-6.2)
21 cohorts 31 cohorts 32 cohorts
99 (20-67) 99 (8-58) 96 (1-16)
No: 53.9 (50.5-57.3) No: 23.1 (18.5-28.3) No: 5.4 (4.5-6.3)
18 cohorts 19 cohorts 18 cohorts
97 (39-68) 99 (7-52) 90 (3-10)
Americas 53.8 (46.3-61.1) 18.9 (15.4-23.1) 3.7 (2.6-5.4)
14 cohorts 15 cohorts 16 cohorts
99 (25-81) 99 (7-40) 98 (1-15)
Asia 46.9 (36.8-57.3) 15.4 (6.8-31.2) 4.5 (3.2-6.2)
3 cohorts 3 cohorts 5 cohorts
99 (1-99) 99 (1-99) 91 (1-13)
Europe 44.8 (38.5-51.3) 30.8 (27.3-34.6) 6.3 (5.5-7.1)
21 cohorts 31 cohorts 28 cohorts
98 (19-74) 96 (14-53) 75 (3-10)
NA, Not applicable; ADR, adenoma detection rate; aADR, advanced ADR; CRCDR, colorectal cancer detection rate.

particularly endoscopist specific. We were not able to
analyze the pooled histology of detected polyps, especially
sessile serrated lesions, because of a lack of data. More-
over, patient characteristics including age, diabetes,
obesity, smoking status, and procedure characteristics
like bowel preparation quality and withdrawal times were
unaccounted for. Data were not available for adenomas de-
tected per colonoscopy, and therefore the pooled out-
comes per colonoscopy were not feasible.
Nevertheless, this study is the best available in the liter-
ature thus far on pooled ADR parameters in FIT-positive
asymptomatic average-risk population. The strengths of
this study primarily reside in the thorough literature search
to include only screening-based studies that “longitudi-
nally” evaluated FIT-positive individuals who underwent
colonoscopy and the inclusion of a large number of asymp-
tomatic individuals, with subgroup analyses yielding multi-
ple novel findings. Although GI physicians strive to achieve
ADR as benchmarked by society recommendations, it is to
the patients’ benefit for physician endoscopists to strive to-
ward achieving an ADR as reported in this study. To this
end, the use of water exchange, cuff, and cap colonoscopy
can help maximize detection rates.61,62
In conclusion, based on this meta-analysis, the pooled
FIT screening rate for CRC in the asymptomatic average-
risk population was 69.8%. The pooled ADR (47.8% overall,
58.3% in men, and 41.9% in women) supports the current
ADR benchmarks put forth by GI professional societies.
Excellent pooled ADR parameters were demonstrated
with qualitative assessment of 1 stool sample at a test cut-
off value of 100 ng hemoglobin/mL. The pooled aADR,
CRCDR, and PDR values reported in this study are novel
quality benchmarks. Future studies should explore ADR
outcomes with respect to polyp histology and procedure
factors like bowel preparation quality and scope with-
drawal time in FIT-positive asymptomatic average-risk indi-
viduals undergoing colonoscopy.
ACKNOWLEDGMENT
We thank Cynthia Beeler, MLIS, AHIP, medical librarian,
Mayo Clinic Libraries (Mayo Clinic, Rochester, Minn, USA)
for the database literature search.
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rectal cancer. Eur J Cancer 2012;48:2969-76.
33. Guittet L, Bouvier V, Mariotte N, et al. Comparison of a guaiac based
and an immunochemical faecal occult blood test in screening for
colorectal cancer in a general average risk population. Gut 2007;56:
210-4.
34. Hilsden RJ, Bridges R, Dube C, et al. Defining benchmarks for adenoma
detection rate and adenomas per colonoscopy in patients undergoing
colonoscopy due to a positive fecal immunochemical test. Am J Gas-
troenterol 2016;111:1743-9.
35. Hol L, van Leerdam ME, van Ballegooijen M, et al. Screening for colo-
rectal cancer: randomised trial comparing guaiac-based and immuno-
chemical faecal occult blood testing and flexible sigmoidoscopy. Gut
2010;59:62.
36. Itoh M, Takahashi K, Nishida H, et al. Estimation of the optimal cut off
point in a new immunological faecal occult blood test in a corporate
colorectal cancer screening programme. J Med Screen 1996;3:66-71.
37. Jensen CD, Corley DA, Quinn VP, et al. Fecal immunochemical test pro-
gram performance over 4 rounds of annual screening: a retrospective
cohort study. Ann Intern Med 2016;164:456-63.
38. Kligman E, Li W, Eckert GJ, et al. Adenoma detection rate in asymptom-
atic patients with positive fecal immunochemical tests. Dig Dis Sci
2018;63:1167-72.
39. Launoy GD, Bertrand HJ, Berchi C, et al. Evaluation of an immunochem-
ical fecal occult blood test with automated reading in screening for
colorectal cancer in a general average-risk population. Int J Cancer
2005;115:493-6.
40. Leen R, Seng-Lee C, Holleran G, et al. Comparison of faecal M2-PK and
FIT in a population-based bowel cancer screening cohort. Eur J Gastro-
enterol Hepatol 2014;26:514-8.
41. Levi Z, Birkenfeld S, Vilkin A, et al. A higher detection rate for colorectal
cancer and advanced adenomatous polyp for screening with immuno-
chemical fecal occult blood test than guaiac fecal occult blood test,
despite lower compliance rate. A prospective, controlled, feasibility
study. Int J Cancer 2011;128:2415-24.
42. Levin TR, Jensen CD, Chawla NM, et al. Early screening of African Amer-
icans (45-50 years old) in a fecal immunochemical test-based colo-
rectal cancer screening program. Gastroenterology 2020;159:1695-704.
43. Miuţescu B, Sporea I, Popescu A, et al. Results of faecal immunochem-
ical test for colorectal cancer screening, in average risk population, in a
cohort of 1389 subjects. Clujul Med 2013;86:102.
44. Nakama H, Kamijo N, Fattah AA, et al. Validity of immunological faecal
occult blood screening for colorectal cancer: a follow up study. J Med
Screen 1996;3:63-5.
45. Parra-Blanco A, Gimeno-García AZ, Quintero E, et al. Diagnostic accu-
racy of immunochemical versus guaiac faecal occult blood tests for
colorectal cancer screening. J Gastroenterol 2010;45:703-12.
46. Quintero E, Castells A, Bujanda L, et al. Colonoscopy versus fecal immu-
nochemical testing in colorectal-cancer screening. N Engl J Med
2012;366:697-706.
47. Raginel T, Puvinel J, Ferrand O, et al. A population-based comparison
of immunochemical fecal occult blood tests for colorectal cancer
screening. Gastroenterology 2013;144:918-25.
48. Robinson MHE, Marks CG, Farrands PA, et al. Population screening for
colorectal cancer: comparison between guaiac and immunological
faecal occult blood tests. Br J Surg 2005;81:448-51.
49. Segnan N, Senore C, Andreoni B, et al. Comparing attendance and
detection rate of colonoscopy with sigmoidoscopy and FIT for colo-
rectal cancer screening. Gastroenterology 2007;132:2304-12.
50. Shahidi N, Gentile L, Gondara L, et al. Correlating quantitative fecal
immunochemical test results with neoplastic findings on colonoscopy
in a population-based colorectal cancer screening program: a prospec-
tive study. Can J Gastroenterol Hepatol 2016;2016:4650471.
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51. Singal AG, Gupta S, Skinner CS, et al. Effect of colonoscopy outreach
vs fecal immunochemical test outreach on colorectal cancer
screening completion: a randomized clinical trial. JAMA 2017;318:
806-15.
52. Smith A, Young GP, Cole SR, et al. Comparison of a brush-sampling
fecal immunochemical test for hemoglobin with a sensitive guaiac-
based fecal occult blood test in detection of colorectal neoplasia. Can-
cer 2006;107:2152-9.
53. Sultanian R, Du L, Moysey B, et al. The impact of transitioning from
guaiac-fecal occult blood testing to fecal immunochemical testing in
a Canadian colon cancer screening program. J Can Assoc Gastroenter-
ol 2020;3:177-84.
54. Van Rossum LG, Van Rijn AF, Laheij RJ, et al. Random comparison of
guaiac and immunochemical fecal occult blood tests for colorectal
cancer in a screening population. Gastroenterology 2008;135:82-90.
55. Wong JC, Chiu H-M, Kim H-S, et al. Adenoma detection rates in colo-
noscopies for positive fecal immunochemical tests versus direct
screening colonoscopies. Gastrointest Endosc 2019;89:607-13.
56. Zorzi M, Senore C, Da Re F, et al. Quality of colonoscopy in an organ-
ised colorectal cancer screening programme with immunochemical
faecal occult blood test: the EQuIPE study (Evaluating Quality Indica-
tors of the Performance of Endoscopy). Gut 2015;64:1389.
57. Lee TJ, Rutter MD, Blanks RG, et al. Colonoscopy quality measures:
experience from the NHS Bowel Cancer Screening Programme. Gut
2012;61:1050-7.
58. Castells A, Quintero E. Programmatic screening for colorectal cancer:
the COLONPREV study. Dig Dis Sci 2015;60:672-80.
59. Shaukat A, Holub J, Pike IM, et al. Benchmarking adenoma detection
rates for colonoscopy: results from a US-based registry. Am J Gastroen-
terol 2021;116:1946-9.
60. GI Quality Improvement Consortium Ltd. Available at: https://GiQuIC.
org/docs/20GiQuIC-10mil-adenoma-3.17.20.pdf. Accessed March 25,
2022.
61. Shao PP, Bui A, Romero T, et al. Adenoma and advanced adenoma detec-
tion rate of water exchange, endocuff and cap colonoscopyda network
meta-analysis with pooled data of randomized controlled trials. Dig Dis
Sci 2021;66:1175-88.
Audio and Podcasts of article abstracts published in Gastrointestinal Endoscopy are now
available online. Recordings are performed by Deborah Bowman, MFA, ELS, Senior Managing
Editor of Clinical Publications.
Scan the QR code or log on to www.giejournal.org to listen to recordings from the
current issue.
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Mohan et al
62. Shao PP, Shao CR, Romero T, et al. Sessile serrated adenoma/po-
lyp detection rate of water exchange, endocuff and cap colonos-
copy: a network meta-analysis. J Gastroenterol Hepatol 2021;36:
3268-77.
Abbreviations: aADR, advanced adenoma detection rate; ADR, ade-
noma detection rate; CI, confidence interval; CRC, colorectal cancer;
CRCDR, colorectal cancer detection rate; FIT, fecal immunochemical
test; PDR, polyp detection rate.
DISCLOSURE: The following author disclosed financial relationships: D.
G. Adler: Consultant for Boston Scientific. All other authors disclosed no
financial relationships. No funding was received for this study.
Copyright ª 2022 by the American Society for Gastrointestinal Endoscopy
0016-5107/$36.00
https://doi.org/10.1016/j.gie.2022.04.004
Received March 6, 2022. Accepted April 4, 2022.
Current affiliations: Department of Gastroenterology & Hepatology (1),
Department of Internal Medicine (3), Department of Medicine, University
of Utah Health, Salt Lake City, Utah, USA; Department of Medicine,
Brigham and Women’s Hospital, Harvard Medical School, Boston,
Massachusetts, USA (2), Department of Gastroenterology, Creighton
University School of Medicine, Omaha, Nebraska, USA (4), Department of
Internal Medicine, Roanoke Carilion Memorial Hospital, Roanoke, Virginia,
USA (5), Gastroenterology Unit, University of Foggia, Foggia, Italy (6),
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota,
USA (7), Department of Gastroenterology, Singapore General Hospital,
Singapore (8), Department of Gastroenterology, Center for Advanced
Therapeutic Endoscopy, Denver, Colorado, USA (9).
Reprint requests: Douglas G. Adler, MD, Centura Health, Gastroenterology
& Hepatology, 2525 South Downing St, Porter Adventist Hospital, Denver,
CO 80210.
If you would like to chat with an author of this article, you may contact Dr
Adler at dougraham2001@gmail.com.
www.giejournal.org
Mohan et al
APPENDIX 1
Literature search strategy
Searches run on October 14, 2021
OVID
Database(s): Ovid MEDLINE(R) ALL (1946 to October
13, 2021), EBM Reviews-Cochrane Central Register of
Controlled Trials August 2021, EBM Reviews-Cochrane
Database of Systematic Reviews 2005 to October 9, 2021,
Embase 1974 to 2021 October 14
No. Searches
1 *occult blood test/or *occult blood/or fecal
immunochemical test.mp. or *guaiac/or guaiac.mp. or
guaiac based.mp.
2 *mass screening/or *cancer diagnosis/or *early detection 411,292
of cancer/or cancer detection.mp. or cancer
screening.mp. or cancer diagnosis.mp.
3 *colorectal cancer/or *colorectal neoplasms/or colon 773,957
cancer.mp. or colorectal cancer.mp. or *adenoma/or
adenoma.mp. or advanced adenoma.mp. or *polyps/or
*colonic polyps/or *polyp/or polyp.mp. or polyps.mp.
4 *colonoscopy/or colonoscopy.mp.
5 1 and 2 and 3 and 4
6 limit 5 to english language (Limit not valid in CDSR;
records were retained]
7 remove duplicates from 6
PubMed, 1816 results (English only)
((Feces [majr] AND immunochemistry [majr]) OR
“Feces/chemistry”[majr] OR “occult blood”[majr] OR
occult blood [tiab] OR Fecal Immunochemical Test [tiab]
OR guaiac [majr] OR guaiac [tiab] OR guaiac-based
[tiab]) AND
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ADR in FIT-positive colonoscopy
(“mass screening”[majr] OR “Early Detection of Can-
cer”[majr] OR cancer detection [tiab] OR cancer screening
[tiab] OR cancer diagnosis [tiab]) AND
(“Colorectal Neoplasms”[majr] OR colon cancer [tiab]
OR colorectal cancer [tiab] OR adenoma [majr] OR ade-
noma [tiab] OR advanced adenoma [tiab] OR polyps
[majr] OR colonic polyps [mesh] OR polyp [tiab] OR
polyps [tiab]) AND
(“Colonoscopy”[majr] OR colonoscopy [tiab])
19671542, 28167157, 29487413, 19671542 (PMIDs used
for search terms)
Scopus
Results
9941
1 TITLE-ABS-KEY ( ( “fecal immunochemical test” OR “occult 4363
blood” OR guaiac OR “guaiac based” ) AND ( “mass screening”
OR “cancer diagnosis” OR “cancer detection” OR “cancer
screening” ) AND ( “colon cancer” OR “colorectal cancer” OR
adenoma OR polyps OR polyp OR “advanced adenoma” ) AND (
colonoscopy ) )
2 ( LIMIT-TO ( LANGUAGE , “English” ) ) 3969
Web of Science
144,472
3221
1 (“fecal immunochemical test” OR “occult blood” OR guaiac OR 1758
3029
“guaiac based”) AND (“mass screening” OR “cancer diagnosis”
OR “cancer detection” OR “cancer screening”) AND (“colon
2152 cancer” OR “colorectal cancer” OR adenoma OR polyps OR
polyp OR “advanced adenoma”) AND (colonoscopy)
2 Limit to English 1711
9648 total article references
3964 duplicates found in EndNote
546 conference abstracts found in EndNote
5138 total references in EndNote
Volume 96, No. 2 : 2022 GASTROINTESTINAL ENDOSCOPY 222.e1
ADR in FIT-positive colonoscopy Mohan et al

APPENDIX 2. Meta-analysis Of Observational Studies in Epidemiology checklist

Item no. Recommendation Reported on page no.

Reporting of background should include

1 Problem definition 6
2 Hypothesis statement NA
3 Description of study outcome(s) 6, 7
4 Type of exposure or intervention used 67
5 Type of study designs used 6-8
6 Study population 6-8
Reporting of search strategy should include
7 Qualifications of searchers (eg, librarians and investigators) 7, Appendix 1
8 Search strategy, including time period included in the synthesis and key 7, Appendix 1
words
9 Effort to include all available studies, including contact with authors 8
10 Databases and registries searched 7, Appendix 1
11 Search software used, name and version, including special features used NA
(eg, explosion)
12 Use of hand searching (eg, reference lists of obtained articles) 7
13 List of citations located and those excluded, including justification Figure 1
14 Method of addressing articles published in languages other than English 7
15 Method of handling abstracts and unpublished studies 7, 8
16 Description of any contact with authors 8
Reporting of methods should include
17 Description of relevance or appropriateness of studies assembled for 8
assessing the hypothesis to be tested
18 Rationale for the selection and coding of data (eg, sound clinical 8
principles or convenience)
19 Documentation of how data were classified and coded (eg, multiple NA
raters, blinding, and inter-rater reliability)
20 Assessment of confounding (eg, comparability of cases and controls in NA
studies where appropriate)
21 Assessment of study quality, including blinding of quality assessors, 8, Supplementary Table 1
stratification, or regression on possible predictors of study results
22 Assessment of heterogeneity 9
23 Description of statistical methods (eg, complete description of fixed- or 9
random-effects models, justification of whether the chosen models
account for predictors of study results, dose-response models, or
cumulative meta-analysis) in sufficient detail to be replicated
24 Provision of appropriate tables and graphics Provided
Reporting of results should include
25 Graphic summarizing individual study estimates and overall estimate Forest plots, Table 2
26 Table giving descriptive information for each study included Table 1
27 Results of sensitivity testing (eg, subgroup analysis) Table 2
28 Indication of statistical uncertainty of findings 11
Reporting of discussion should include
29 Quantitative assessment of bias (eg, publication bias) 11
30 Justification for exclusion (eg, exclusion of non–English language NA
citations)
31 Assessment of quality of included studies Supplementary Table 2
(continued on the next page)

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APPENDIX 2. Continued

Item no. Recommendation Reported on page no.

Reporting of conclusions should include

32 Consideration of alternative explanations for observed results 12, 13
33 Generalization of the conclusions (ie, appropriate for the data presented 12, 13
and within the domain of the literature review)
34 Guidelines for future research 13, 14
35 Disclosure of funding source 13, 14
NA, Not applicable.

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ADR in FIT-positive colonoscopy Mohan et al

APPENDIX 3. Preferred Reporting items for Systematic Reviews and Meta-Analyses checklist

Section/topic No. Checklist item Reported on page no.

TITLE
Title 1 Identify the report as a systematic review, meta-analysis, or both. 1
ABSTRACT
Structured summary 2 Provide a structured summary including, as applicable: background; 4
objectives; data sources; study eligibility criteria, participants, and
interventions; study appraisal and synthesis methods; results;
limitations; conclusions and implications of key findings; systematic
review registration number.
INTRODUCTION
Rationale 3 Describe the rationale for the review in the context of what is already 6
known.
Objectives 4 Provide an explicit statement of questions being addressed with 6
reference to participants, interventions, comparisons, outcomes, and
study design (PICOS).
METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (eg, NA
web address), and, if available, provide registration information
including registration number.
Eligibility criteria 6 Specify study characteristics (eg, PICOS, length of follow-up) and report 7
characteristics (eg, years considered, language, publication status) used
as criteria for eligibility, giving rationale.
Information sources 7 Describe all information sources (eg, databases with dates of coverage, 7
contact with study authors to identify additional studies) in the search
and date last searched.
Search 8 Present full electronic search strategy for at least one database, 7, Appendix 1
including any limits used, such that it could be repeated.
Study selection 9 State the process for selecting studies (ie, screening, eligibility, included 7
in systematic review, and, if applicable, included in the meta-analysis).
Data collection process 10 Describe method of data extraction from reports (eg, piloted forms, 7, 8
independently, in duplicate) and any processes for obtaining and
confirming data from investigators.
Data items 11 List and define all variables for which data were sought (eg, PICOS, 7, 8, 9
funding sources) and any assumptions and simplifications made.
Risk of bias in individual studies 12 Describe methods used for assessing risk of bias of individual studies 8
(including specification of whether this was done at the study or
outcome level), and how this information is to be used in any data
synthesis.
Summary measures 13 State the principal summary measures (eg, risk ratio, difference in 9
means).
Synthesis of results 14 Describe the methods of handling data and combining results of 9
studies, if done, including measures of consistency (eg, I2) for each
meta-analysis.
Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative 9
evidence (eg, publication bias, selective reporting within studies).
Additional analyses 16 Describe methods of additional analyses (eg, sensitivity or subgroup 9
analyses, meta-regression), if done, indicating which were prespecified.
RESULTS
Study selection 17 Give numbers of studies screened, assessed for eligibility, and included 10
in the review, with reasons for exclusions at each stage, ideally with a
flow diagram.
Study characteristics 18 For each study, present characteristics for which data were extracted 10, Table 1
(eg, study size, PICOS, follow-up period) and provide the citations.
(continued on the next page)

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Mohan et al ADR in FIT-positive colonoscopy

APPENDIX 3. Continued

Section/topic No. Checklist item Reported on page no.

Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome 10, Supplementary Table 1
level assessment (see item 12).
Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: 10
(a) simple summary data for each intervention group and (b) effect
estimates and confidence intervals, ideally with a forest plot.
Synthesis of results 21 Present the main results of the review. If meta-analyses are done, 10
include for each confidence intervals and measures of consistency
Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see item Supplementary Table 1
15).
Additional analysis 23 Give results of additional analyses, if done (eg, sensitivity or subgroup 11, Table 2
analyses, meta-regression [see item 16]).
DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for 12-14
each main outcome; consider their relevance to key groups (eg,
healthcare providers, users, and policymakers).
Limitations 25 Discuss limitations at study and outcome level (eg, risk of bias) and at 13, 14
review level (eg, incomplete retrieval of identified research, reporting
bias).
Conclusions 26 Provide a general interpretation of the results in the context of other 14
evidence, and implications for future research.
FUNDING
Funding 27 Describe sources of funding for the systematic review and other support 14
(eg, supply of data); role of funders for the systematic review.
NA, Not applicable.

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ADR in FIT-positive colonoscopy Mohan et al

Supplementary Figure 1. Forest plot,* 10-mm adenoma detection rate. CI, Confidence interval.

Supplementary Figure 2. Forest plot,* polyp detection rate. CI, Confidence interval.

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Mohan et al ADR in FIT-positive colonoscopy

Supplementary Figure 3. Forest plot,* adenoma detection rate in men. CI, Confidence interval.

Supplementary Figure 4. Forest plot,* adenoma detection rate in women. CI, Confidence interval.

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ADR in FIT-positive colonoscopy Mohan et al

Supplementary Figure 5. Forest plot,* time-period cumulative analysis of adenoma detection rate. CI, Confidence interval.

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Mohan et al ADR in FIT-positive colonoscopy

Supplementary Figure 6. Forest plot,* adenoma detection rate by stool sample. CI, Confidence interval.

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ADR in FIT-positive colonoscopy Mohan et al

Supplementary Figure 7. Forest plot,* adenoma detection rate by test type. CI, Confidence interval.

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Mohan et al ADR in FIT-positive colonoscopy

Supplementary Figure 8. Forest plot,* adenoma detection rate by test kit. CI, Confidence interval.

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ADR in FIT-positive colonoscopy Mohan et al

Supplementary Figure 9. Forest plot,* adenoma detection rate by test cutoff threshold. CI, Confidence interval.

Supplementary Figure 10. Funnel plot by adenoma detection rate data.

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Mohan et al ADR in FIT-positive colonoscopy

SUPPLEMENTARY TABLE 1. Study quality assessment

Selection Comparability Outcome Score

Outcome
Representativeness Information not Adequate
of the average adult Cohort on present colonoscopic Follow-up Adequacy of
in community size outcomes at start NA assessment time follow-up
All patients
followed up,
1; >50%
followed up, Max [
Information Not .5; <50% 7, high
>40 with clarity, present, followed up >5,
Population based, patients, 1; 1; Yes, 1; not or not medium
1; multicenter, .5; 1; 39-20, information present, mentioned, mentioned, 3-5,
Study single center, 0 .5; <20, 0 derived, .5 0 NA Yes, 1; no, 0 0 0 low <3 Quality

Akram, 1 1 1 1 0 1 1 .5 6.5 High

201722
Allison, 0 1 1 1 0 1 1 .5 5.5 High
199624
Allison, .5 1 1 1 0 1 1 .5 6 High
200723
Castiglione, 1 1 1 1 0 1 1 .5 6.5 High
199625
Chen, 1 1 1 1 0 1 1 .5 6.5 High
202026
Chiu, 201527 1 1 .5 1 0 1 1 .5 6 High
Crotta, 1 1 1 1 0 1 1 .5 6.5 High
201228
Dancourt, 1 1 1 1 0 1 1 .5 6.5 High
200829
Denis, 0 1 1 1 0 1 1 .5 5.5 High
202030
Denters, 1 1 1 1 0 1 1 .5 6.5 High
201231
Faivre, 1 1 1 1 0 1 1 .5 6.5 High
201232
Guittet, 1 1 1 1 0 1 1 .5 6.5 High
2007
Hilsden, 1 1 1 1 0 1 1 .5 6.5 High
201634
Hol, 201035 1 1 1 1 0 1 1 .5 6.5 High
36
Itoh, 1996 .5 1 1 1 0 1 1 .5 6 High
Jensen, 1 1 1 1 0 1 1 1 7 High
201637
Kligman, 0 1 1 1 0 1 1 .5 5.5 High
201838
Launoy, .5 1 .5 1 0 1 1 .5 5.5 High
200539
Leen, 1 1 1 1 0 1 1 .5 6.5 High
201440
Levi, 201141 1 1 1 1 0 1 1 .5 6.5 High
Levin, 1 1 1 1 0 1 1 .5 6.5 High
202042
Miutescu, 0 1 1 1 0 1 1 .5 5.5 High
201343
(continued on the next page)

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ADR in FIT-positive colonoscopy Mohan et al

SUPPLEMENTARY TABLE 1. Continued

Selection Comparability Outcome Score

Outcome
Representativeness Information not Adequate
of the average adult Cohort on present colonoscopic Follow-up Adequacy of
in community size outcomes at start NA assessment time follow-up
All patients
followed up,
1; >50%
followed up, Max [
Information Not .5; <50% 7, high
>40 with clarity, present, followed up >5,
Population based, patients, 1; 1; Yes, 1; not or not medium
1; multicenter, .5; 1; 39-20, information present, mentioned, mentioned, 3-5,
Study single center, 0 .5; <20, 0 derived, .5 0 NA Yes, 1; no, 0 0 0 low <3 Quality

Nakama, 1 1 1 1 0 1 1 .5 6.5 High

199644
Parra- 1 1 1 1 0 1 1 .5 6.5 High
Blanco,
201045
Quintero, .5 1 1 1 0 1 1 .5 6 High
201246
Raginel, 1 1 1 1 0 1 1 .5 6.5 High
201347
Robinson, 1 1 1 1 0 1 1 .5 6.5 High
200548
Segnan, 1 1 1 1 0 1 1 .5 6.5 High
200749
Shahidi, 1 1 1 1 0 1 1 .5 6.5 High
201650
Singal, 1 1 1 1 0 1 1 .5 6.5 High
201751
Smith, 1 1 1 1 0 1 1 .5 6.5 High
200652
Sultanian, 1 1 1 1 0 1 1 .5 6.5 High
202053
Van 1 1 1 1 0 1 1 .5 6.5 High
Rossum,
200854
Wong, .5 1 1 1 0 1 1 .5 6 High
201955

222.e14 GASTROINTESTINAL ENDOSCOPY Volume 96, No. 2 : 2022 www.giejournal.org

Descargado para Maria Andrea Lerda (malerda@garrahan.gov.ar) en Paediatric Hospital Dr Juan Garrahan de ClinicalKey.es por Elsevier en febrero 15,
2023. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2023. Elsevier Inc. Todos los derechos reservados.