Introduction
Colonoscopy is considered the gold standard for the detection and removal of premalignant
colorectal lesions. Despite its effectiveness, a notable number of lesions are still
missed during colonoscopy [1], increasing the risk of post-colonoscopy colorectal cancer (CRC) [2]. This risk is inversely correlated with the adenoma detection rate (ADR), which
is widely considered the main quality parameter in colonoscopy [3]
[4].
Recently, artificial intelligence systems, such as computer-aided detection (CADe)
systems, have emerged to assist in the detection of colorectal polyps during colonoscopy.
A recent systematic review of 21 randomized controlled trials (RCTs) assessing CADe
vs. conventional colonoscopy in over 18 000 patients demonstrated an approximate 24 %
relative increase in ADR due to CADe [5]. Despite this significant benefit in overall ADR, there were no significant differences
between CADe and conventional colonoscopy in the detection of advanced adenomas or
sessile serrated lesions (SSLs) [5], raising concerns regarding the efficacy of CADe in these lesions with a higher
risk of CRC. Furthermore, despite reports of high efficacy in RCTs, there has been
an increasing recognition of the variability in the performance of CADe systems across
different colonoscopy indications and pragmatic trials [6]
[7].
The aim of this study was to compare ADR and other quality indicators in CADe-assisted
colonoscopy vs. conventional colonoscopy in patients with diagnostic, non-immunochemical
fecal occult blood test (iFOBT) screening, or surveillance indications for colonoscopy.
Methods
Study design and participants
This multicenter RCT, involving seven hospitals in Canada (n = 1), France (n = 1),
Germany (n = 2), Italy (n = 1), The Netherlands (n = 1), and Russia (n = 1), was conducted
by 14 endoscopists. Eligible participants, aged 18 years or older, were scheduled
for non-iFOBT screening, surveillance, or diagnostic (excluding iFOBT-positive referrals)
colonoscopy. Exclusion criteria included known colorectal tumors or polyps upon referral,
referral for therapeutic procedures, inadequately corrected coagulation disorder,
inadequately continued use of anticoagulation medication, American Society of Anesthesiologists
score of ≥ 3, or known or suspected inflammatory bowel disease. Participants with
insufficient bowel preparation (Boston Bowel Preparation Scale score < 6), active
colitis, polyposis syndrome, colonic stricture, or obstructing CRC impeding complete
colonoscopy were excluded from the final analysis. Participants in the Yaroslavl,
Russia, study site enrolled after 24 February 2022, were excluded from the final analysis
following a directive from the Dutch Federation of University Hospitals, mandating
the temporary suspension of all collaborations with Russian study sites.
The study received approval from independent institutional review boards at each site,
adhered to the Declaration of Helsinki, and followed applicable Good Clinical Practice
guidelines. Data verification and monitoring complied with national and local guidelines
where appropriate. The study was reported in accordance with CONSORT-AI guidelines
for RCTs, and all participants provided written informed consent. All authors had
access to the study data and reviewed and approved the final manuscript.
Randomization
Participants were randomized after eligibility was assessed and informed consent was
obtained. Participants were randomized in a 1:1 ratio to either CADe-assisted colonoscopy
or conventional colonoscopy. Randomization employed varying block sizes of 4, 6, and
8. Stratification for randomization was based on whether the subject was undergoing
an index colonoscopy, defined as the first lifetime colonoscopy of a participant.
Randomization was performed on-site, within 24 hours before the scheduled colonoscopy,
by a central, cloud-based randomization service (CastorEDC; Ciwit B.V., Amsterdam,
The Netherlands). Endoscopists, participants, and the data analyst were not blinded
to the study allocation.
Artificial intelligence system
The CADe DISCOVERY system (PENTAX Medical, Tokyo, Japan) used for the CADe-assisted
colonoscopies is a real-time computing device that acquires the video output from
the processor during colonoscopy. The CADe system uses a deep neural network to generate
a bounding box around a suspected polyp as an output on the monitor screen in real
time ([Fig. 1]). The system is used as an auxiliary device and aims to improve the detection rate
by highlighting potential lesions. Final assessment of the highlighted region was
the responsibility of the endoscopist. The endoscopist could choose to be acoustically
notified of detections. During the study, CADe software versions 1.0.3.1 and 1.0.4
were used.
Fig. 1 The computer-aided detection system generates an overlay during real-time colonoscopy,
with a blue bounding box to highlight a lesion.
Study investigators
All endoscopists underwent training in CADe-assisted colonoscopy, completing a minimum
of five CADe procedures to confirm their familiarity with the system. The study was
conducted at sites with an annual performance exceeding 5000 colonoscopies. Participation
was limited to experienced endoscopists to mitigate potential improvements in ADR
due to training throughout the study. Endoscopists were eligible if they had independently
performed over 500 colonoscopies, reflecting procedural experience rather than a specific
minimum ADR. This approach aimed to approach the real-world variability in ADR among
endoscopists. Notably, all endoscopists had completed over 2000 independent colonoscopies
prior to the start of the study.
Study procedures
In the CADe arm, the device was switched on at the beginning of the CADe colonoscopy,
and the use of CADe was mandatory during the withdrawal phase. Endoscopists were advised
to primarily use the CADe monitor; however, the use of a dual monitor setup, with
separate displays for the conventional image and the CADe overlay, was not explicitly
prohibited.
Each study site used local bowel preparation protocols and sedation administration.
All participants randomized to conventional colonoscopy underwent colonoscopy as per
standard of care. During the study, conventional PENTAX high-definition colonoscopes
were used for both arms. To ensure adequate bowel inspection, all participating endoscopists
were instructed to aim for a minimum withdrawal time of 6 minutes (excluding time
spent on polypectomies or other interventions) following societal guidelines [3]. In addition, an upper withdrawal time of 10 minutes was recommended to reflect
everyday procedural scheduling and reduce observation-related bias.
All lesions were collected for histopathologic examination in separate containers
for each polyp. Diminutive (1–5 mm) polyps located in the rectum and considered to
be hyperplastic by the performing endoscopist could be left in place according to
endoscopists’ individual judgment and standard of care. Experienced pathologists,
who were blinded to the endoscopic diagnosis, determined the histopathologic diagnosis
according to the Vienna classification [8].
Study outcomes
The primary outcome was ADR, calculated as the proportion of colonoscopies with at
least one histologically confirmed detected adenoma. Additionally, ADR was evaluated
across various variables, including colonoscopy indication and in a per-endoscopist
analysis. Secondary outcomes were mean number of adenomas per colonoscopy (APC; total
number of histologically confirmed adenomas divided by the total number of colonoscopies),
polyp detection rate (proportion of colonoscopies with at least one histologically
confirmed detected polyp), sessile serrated lesions (SSLs) per colonoscopy (total
number of histologically confirmed SSLs divided by the total number of colonoscopies),
and SSL detection rate (proportion of colonoscopies with at least one histologically
confirmed detected SSL). Other secondary outcomes included withdrawal time without
interventions and the number of false positives during CADe-assisted colonoscopy (defined
as a non-neoplastic, non-hyperplastic area highlighted by CADe for > 3 consecutive
seconds). The reasons for false positives were reported and were calculated as the
number of CADe colonoscopies with at least one subcategory of the reason for false
positives.
Sample size calculation
This study was powered to detect a significant difference in ADR. The sample size
calculation was performed using G*Power, version 3.1.9.7 (Heinrich-Heine-Universität,
Düsseldorf, Germany). During the design of the study protocol, only one RCT had been
published regarding the effect of CADe on ADR, reporting an increase in ADR from 20.3 %
to 29.1 % [9]. With this limited prior data, we set the baseline ADR at 18 % for conventional
colonoscopy, expecting a 50 % relative increase with CADe to 27 %. Furthermore, we
expected no decrease in detection given the working mechanism of CADe, as it is used
as an auxiliary device to conventional colonoscopy, enhancing the displayed image
output without directly interfering with colonoscope handling. Consequently, we assumed
a one-directional effect and used a one-sided test for sample size calculations. Using
a one-sided Z test for independent proportions (5 % alpha, 80 % power), the sample size was 532
participants. To account for a dropout rate of 5 %, the final sample size was set
at 560, evenly distributed between the two study arms (280 each).
Statistical analysis
Analyses of the primary and secondary outcomes followed a modified intention-to-treat
approach, excluding participants with an inadequate Boston Bowel Preparation Scale
score or for whom a quality colonoscopy could not be performed. Analysis of the primary
outcome was performed using the chi-squared test, dividing the two-sided P value by two to calculate the one-sided P value. Statistical analyses were performed using SPSS 27 (IBM Corp., Armonk, New York,
USA) or R Studio 4.1.3 (R Foundation for Statistical Computing, Vienna, Austria).
Continuous variables were presented as means (SD) or medians (interquartile range
[IQR]), and categorical data as numbers/percentages. Differences between study arms
for secondary outcomes were assessed using t tests, Mann–Whitney U tests, or chi-squared tests, as appropriate. Two-sided P values were reported for the secondary outcomes. Wilson Score Method was used to calculate
95 %CIs where applicable. A logistic regression model evaluated ADR. Predetermined
potential confounding factors, including sex, age, body mass index, smoking status,
reason for colonoscopy, and study site, were excluded from the model following study
protocol, as these variables appeared evenly distributed across study arms. Sensitivity
analysis compared APC and SSLs per colonoscopy using Poisson regression. Post hoc
analysis explored the effect of CADe among low, medium, and high detectors, categorizing
endoscopists based on ADR tertiles. Additionally, to address our relatively high dropout
rate, a post hoc analysis of the primary outcome was conducted on an intention-to-treat
cohort. Statistical significance was set at P < 0.05, unless otherwise specified.
Results
The study was performed from 9 March 2021 to 6 February 2023. The relatively long
inclusion period was partly related to the COVID-19 pandemic in the initial period
of the study. A total of 581 participants were enrolled and randomized (1:1) to either
CADe (n = 288) or conventional colonoscopy (n = 293). A total of 84 participants were
excluded, leaving 497 participants in the final analysis (modified intention-to-treat):
250 participants in the CADe arm and 247 in the conventional colonoscopy arm ([Fig. 2]). While the dropout rate of our modified intention-to-treat analysis (14.5 %; 497/581)
exceeded our expected dropout rate, we were unable to replace these participants due
to institutional review board guidelines. Baseline characteristics were similar between
the study arms ([Table 1]). No missing values were observed for the calculation of the primary and secondary
outcomes. All procedures in the CADe arm were performed with the CADe modality activated.
Fig. 2 Study flow chart. CADe, computer-aided detection; BBPS, Boston Bowel Preparation
Scale; mITT, modified intention-to-treat. 1Other exclusions: Russian site enrollment after 24 February 2022 (n = 12), new polyposis
diagnosis (n = 2), American Society of Anesthesiologists score of 3 (n = 1), or new
diagnosis of inflammatory bowel disease (n = 1).
Table 1
Baseline characteristics in the modified intention-to-treat population.
|
CADe (n = 250)
|
Conventional colonoscopy (n = 247)
|
|
Age, median (IQR), years
|
61.0 (52–69)
|
61.0 (52–69)
|
|
Sex, n (%)
|
|
|
141 (56.4)
|
136 (55.1)
|
|
|
109 (43.6)
|
111 (44.9)
|
|
Colonoscopy indication, n (%)
|
|
|
50 (20.0)
|
46 (18.6)
|
|
|
98 (39.2)
|
104 (42.1)
|
|
|
102 (40.8)
|
97 (39.3)
|
|
Index colonoscopy, n (%)
|
112 (44.8)
|
108 (43.7)
|
|
Smoking, n (%)
|
26 (10.4)
|
32 (13.0)
|
|
Family history of CRC, n (%)
|
60 (24.0)
|
45 (18.2)
|
|
BMI2, kg/m2
|
25.5 (23.1–28.3)
|
25.0 (22.5–28.8)
|
|
BBPS score, n (%)
|
|
|
61 (24.4)
|
65 (26.3)
|
|
|
27 (10.8)
|
27 (10.9)
|
|
|
29 (11.6)
|
34 (13.8)
|
|
|
133 (53.2)
|
121 (49.0)
|
CADe, computer-aided detection; IQR, interquartile range; iFOBT, immunochemical fecal
occult blood test; CRC, colorectal cancer; BMI, body mass index; BBPS, Boston Bowel
Preparation Scale.
1Diagnostic indications did not include iFOBT-positive referrals.
2Weight was missing for one patient.
Overall findings
ADR was similar between the CADe arm and the conventional colonoscopy arm (38.4 %
vs. 37.7 %, P = 0.43; total colonoscopies with at least one adenoma, 96 vs. 93) ([Table 2]). Logistic regression analysis calculated an odds ratio (OR) of 1.032 (95 %CI 0.719–1.483)
for CADe relative to conventional colonoscopy ([Table 3]). Similarly, APC was comparable between the CADe arm and the conventional colonoscopy
arm (0.66 vs. 0.66, P = 0.97; total detected adenomas 165 vs. 163). While polyp detection rate was numerically
increased in the CADe arm compared with the conventional colonoscopy arm, the difference
was not significant (55.2 % vs. 51.4 %, P = 0.40; total colonoscopies with at least one polyp, 138 vs. 127). Furthermore, SSLs
per colonoscopy was significantly higher in the CADe arm compared with the conventional
colonoscopy arm (0.30 vs. 0.19, P = 0.049; total detected SSLs, 76 vs. 46) and SSL detection rate was increased in
the CADe arm compared with the conventional colonoscopy arm (18.4 % vs. 12.1 %; P = 0.053, total colonoscopies with at least one SSL, 46 vs. 30, respectively). Median
withdrawal time was similar between study arms (withdrawal time without interventions
[IQR] 9.2 [8.0–11.0] vs. 9.0 [8.0–11.0] minutes, P = 0.05, for CADe and conventional colonoscopy, respectively).
Table 2
Primary and secondary outcomes in the modified intention-to-treat population.
|
CADe (n = 250)
|
Conventional colonoscopy (n = 247)
|
Difference (treatment – control) [95 %CI]1
|
P value
|
|
Adenoma detection rate2, % (n)
|
38.4 (96)
|
37.7 (93)
|
0.7 [–7.8 to 9.3]
|
0.43
|
|
Adenoma per colonoscopy, n (n/N)
|
0.66 (165 /250)
|
0.66 (163 /247)
|
0.00 [–0.19 to 0.19]
|
0.97
|
|
Polyp detection rate, % (n)
|
55.2 (138)
|
51.4 (127)
|
3.8 [–5.0 to 12.5]
|
0.40
|
|
SSLs per colonoscopy, n (n/N)
|
0.30 (76 /250)
|
0.19 (46 /247)
|
0.11 [0.00 to 0.24]
|
0.049
|
|
SSL detection rate, % (n)
|
18.4 (46)
|
12.1 (30)
|
6.3 [–0.04 to 12.5]
|
0.05
|
|
Mean polyps per colonoscopy, n (n/N)
|
1.20 (299 /250)
|
1.09 (270 /247)
|
0.11 [–0.15 to 0.36]
|
0.52
|
|
Withdrawal time without interventions, median (IQR), minutes
|
9.2 (8.0–11.0)
|
9.0 (8.0–11.0)
|
0.2
|
0.05
|
|
Total procedure time, median (IQR), minutes
|
20.0 (15.0–27.6)
|
20.0 (15.0–24.7)
|
0.0
|
0.43
|
CADe, computer-aided detection; SSL, sessile serrated lesion; IQR, interquartile range.
195 %CI calculated using Wilson score interval for proportions.
2Statistical analysis of the primary outcome was performed using a one-sided approach
to the chi-squared test. Other P values represent two-sided analyses.
Table 3
Additional analysis of primary and secondary outcomes in the modified intention-to-treat
population.
|
CADe (n = 250)
|
Conventional colonoscopy (n = 247)
|
OR/effect ratio CADe to conventional colonoscopy [95 %CI]
|
P value
|
|
Adenoma detection rate1, %, (n)
|
38.4 (96)
|
37.7 (93)
|
1.032 [0.719 to 1.483]
|
0.86
|
|
Mean number of adenomas per colonoscopy2, n (n/N)
|
0.66 (165 /250)
|
0.66 (163 /247)
|
1.006 [0.811 to 1.249]
|
0.96
|
|
SSLs per colonoscopy3, n (n/N)
|
0.30 (76 /250)
|
0.19 (46 /247)
|
1.632 [1.132 to 2.354]
|
0.01
|
|
Mean number of polyps per colonoscopy3, n (n/N
|
1.20 (299 /250)
|
1.09 (270 /247)
|
1.098 [0.863 to 1.397]
|
0.45
|
CADe, computer-aided detection; OR, odds ratio; SSL, sessile serrated lesion.
1OR from logistic binary regression with treatment arm and adenoma detection rate.
2Effect ratio from Poisson regression with log-link function.
3Effect ratio from Poisson regression with negative binomial function.
When stratified by colonoscopy indication the results were similar. For diagnostic
colonoscopies (n = 199), ADR was increased by 5.5 percentage points in the CADe arm
compared with the conventional colonoscopy arm (33.3 % vs. 27.8 %, P = 0.40; total colonoscopies with at least one adenoma, 34 vs. 27), and for SSLs per
colonoscopy the increase was 0.09 in the CADe arm compared with the conventional colonoscopy
arm (0.25 vs. 0.16, P = 0.15; total detected SSLs, 26 vs. 16). For surveillance colonoscopies (n = 202),
ADR in the CADe arm was equal to that in the conventional colonoscopy arm (43.9 %
vs. 43.9 %, P = 0.93; total colonoscopies with at least one adenoma, 43 vs. 45), and for SSLs per
colonoscopy the increase was 0.15 in the CADe arm compared with the conventional colonoscopy
arm (0.36 vs. 0.21, P = 0.41; total detected SSLs, 35 vs. 22). For non-iFOBT screening colonoscopies (n = 96),
ADR was decreased by 7.7 percentage points in the CADe arm compared with the conventional
colonoscopy arm (38.0 % vs. 45.7 %, P = 0.45; total colonoscopies with at least one adenoma, 19 vs. 21), and for SSLs per
colonoscopy the increase was 0.13 in the CADe arm compared with the conventional colonoscopy
arm (0.30 vs. 0.17, P = 0.23; total detected SSLs, 15 vs. 8). Additional outcomes are reported in [Table 2] and [Table 3] (see also Tables 1s–4 s in the online-only Supplementary material).
During the withdrawal phase of the CADe-assisted colonoscopy, the median number of
false positives was 2.0 (IQR 0.0–5.0; mean 4.1 [SD 6.1]). Colonic haustral folds were
the most frequently reported reason for false positives during CADe-assisted colonoscopy
(40.8 %) (Table 5 s).
Discussion
In this multicenter RCT involving experienced endoscopists from both university and
non-university hospitals, the use of CADe did not significantly increase ADR or APC
in diagnostic, non-iFOBT screening, or surveillance colonoscopies. However, despite
the non-significant increase in adenoma detection, use of the CADe system resulted
in an absolute increase of 0.11 (relative increase 58 %) of SSLs per colonoscopy compared
with conventional colonoscopy.
Our study did not find a significant increase in ADR or APC with CADe, which contrasts
with previously published Western RCTs, as well as a recent meta-analysis of 21 RCTs
including over 18 000 patients, which reported an absolute ADR difference of 8.1 %
(44.0 % vs. 35.9 %) with CADe compared with conventional colonoscopy [5]
[10]
[11]
[12]
[13]
[14]
[15]. Moreover, one of the earliest RCTs on CADe, by Repici et al., reported an absolute
increase of 14.4 % in ADR among expert endoscopists [16]. However, a recent non-university, single-center study by Karsenti et al., with
over 2000 participants, reported an ADR of 37.5 % with CADe, which was similar to
that found in our study. In their conventional colonoscopy arm, the baseline ADR was
33.7 %, resulting in an absolute difference of only 3.8 % with the use of CADe. Their
study had a similar proportion of diagnostic and screening colonoscopies as reported
in our study [15].
Our non-significant increase in adenoma detection is consistent with recently published
controlled and real-world studies. An RCT conducted in a screening and surveillance
population at four US community hospitals reported a non-significant increase in APC
from 0.67 to 0.73, comparable to our study [17]. A pragmatic implementation trial performed by Ladabaum et al., which employed CADe
during all colonoscopies without specific instructions, reported no significant differences
in detection rates [6]. Notably, their baseline ADR was comparable to that in our study. Moreover, their
study did not identify differences in the efficacy of CADe between low detectors and
high detectors. Similarly, Levy et al. integrated CADe into all colonoscopies at their
high-volume tertiary referral center. Their study also did not find a significant
increase in adenoma detection compared with a retrospective cohort [7]. While our study employed an RCT design, the study period extended over nearly 2
years, which may have resulted in a reduced level of constant scrutiny and observation.
This intermittent exposure to the CADe device could have reduced the Hawthorne effect
while using CADe, which is a potential source of bias in controlled studies [18]. The extended duration of our study, combined with the variable colonoscopy indications,
may reflect a more real-world clinical setting compared with previous positive RCTs
on CADe that had substantially shorter study durations [9]
[12]
[16].
On the other hand, our non-significant results may be attributed to the relatively
high baseline ADR in the conventional colonoscopy arm, approaching 38 %. As a result,
this may have limited the potential beneficial effect of CADe, as endoscopists with
a higher ADR might derive less benefit from CADe compared with their peers with a
lower ADR [5]
[15]
[19]. We also observed this trend in our post hoc analysis comparing low, medium, and
high detectors based on their baseline ADR, although no statistically significant
difference was observed (Table 6 s, Fig. 1 s); however, owing to the post hoc nature of this analysis, findings should be interpreted
with caution. Moreover, the median withdrawal time in our study significantly exceeded
the recommended 6 minutes and approached the upper-end target of 10 minutes [3]
[20]. Our relatively long withdrawal times may have contributed to the high baseline
ADR of our conventional colonoscopy arm, as each additional minute has been shown
to be associated with an increase in ADR; however, this effect seems to diminish after
10 minutes [21]
[22]. Finally, while our study is the first RCT evaluating this CADe system, we are cautious
about attributing the non-significant results to the potential lack of stand-alone
efficacy of the system. While most CADe RCTs have reported an increase in ADR with
CADe use, some RCTs did not find an increase [23]
[24], despite previous positive results using the same CADe system [10]. This suggests that factors beyond the CADe system are important when interpreting
these results. Nonetheless, our findings suggest a potential increase in detection,
as indicated by the significant increase in SSLs per colonoscopy and a trend toward
increased polyp detection rates. However, additional studies are required to provide
a more comprehensive understanding of the performance of this CADe system.
The clinical relevance of our study is supported by the increased detection of SSLs,
as reflected by the significant relative 58 % increase of SSLs per colonoscopy and
a borderline significant but absolute increase of 6.3 % in the SSL detection rate
in the CADe arm. Although our overall SSL detection rate of 12.1 % in the conventional
colonoscopy arm might appear relatively high, it is comparable to previously published
CADe studies with variable indications [6]
[12]
[23]. This relatively high SSL detection rate is not unexpected, given the increasing
awareness and recognition of SSLs, as demonstrated by the steady increase in SSL detection
rates since 2008 [25]. Furthermore, in a retrospective analysis of the training and evaluation sets of
this CADe system (unpublished results), we found that 11 % of the used lesions were
diagnosed as SSLs. This relatively large proportion of SSLs in the training set may
have contributed to our significant increase in the detection of these lesions, which
are notably hard to detect. Our study is, to the best of our knowledge, the first
to demonstrate a significant increase in the detection of SSLs with the use of CADe.
These SSLs are nowadays recognized for their clinical importance in the CRC pathway,
and the SSL detection rate is increasingly recognized as a potential quality parameter
in colonoscopy [26]. Furthermore, a recent study has shown that endoscopists with an increased SSL detection
rate have a lower risk of post-colonoscopy CRC, even when corrected for ADR [27]. However, we acknowledge that the detection of SSLs was a secondary outcome in our
study.
The strengths of this study include the balanced distribution of participants across
six countries, in both Europe and Canada, among both university and non-university
hospitals. This approach reduced the potential risk of bias associated with endoscopists
who conduct a substantial number of procedures and show significantly improved detection
with CADe. In addition, the inclusion criteria reflect everyday colonoscopy populations
by incorporating varied colonoscopy indications. Furthermore, distal attachments were
not used. Finally, the validation of the CADe system was not performed on the included
study populations of participating study sites, reducing the risk of potential overfitting,
which is a well-known risk of artificial intelligence systems.
However, our study has some limitations. First, in hindsight, our assumptions for
the sample size calculation were rather conservative. Initially, we assumed a baseline
ADR of only 18 % in the conventional colonoscopy arm, influenced by limited data,
notably a single Chinese CADe RCT [9]. Despite our initial assumptions proving to be underestimated, particularly with
the inclusion of experienced endoscopists, our total calculated sample size did not
significantly differ from early Western CADe studies [10]
[16]
[28]. Additionally, detecting a significant result with our modest difference in ADR
would require a substantially larger sample size, as exemplified by a recent RCT with
over 2000 participants, where use of CADe resulted in a borderline significant absolute
increase in ADR of only 3.8 % (P = 0.05) [15]. Nevertheless, we acknowledge the potential increased risk of a type II statistical
error resulting from our sample size calculation. Second, pathology slides were not
evaluated by a second, independent, expert pathologist. This could have introduced
some bias in the diagnosis of SSLs in our study, considering that even expert pathologists
have only a moderate interobserver agreement when diagnosing SSLs [29]. Nonetheless, this risk is likely to be limited because the pathologists in our
study demonstrated proficiency in recognizing SSLs, as indicated by our relatively
high detection rates of SSLs compared with previous CADe RCTs [9]
[10]
[11]
[16]. Third, the modified intention-to-treat analysis included 497 (85.5 %) of the 581
colonoscopies, reflecting a higher than anticipated exclusion rate due to insufficient
or missing Boston Bowel Preparation Scale scores. This could be attributed to the
varied colonoscopy indications and non-standardized bowel preparation. While our dropout
rate was higher than expected, the subsequent potential risk of further underpowering
in the study appears to be limited, as supported by the similar results of the intention-to-treat
analysis (Table 7 s). To mitigate the risk of exclusion due to insufficient bowel preparation in future
studies, randomizing after reaching the cecum could be considered. Fourth, although
training recommended primarily using the CADe monitor in a single-monitor setup, a
dual-monitor setup displaying both the conventional image and CADe output side by
side was not prohibited, potentially influencing gaze patterns in the selected cases
where such a setup was used [30].
In conclusion, use of CADe by experienced endoscopists did not result in an increased
ADR and APC in everyday diagnostic, non-iFOBT screening, and surveillance colonoscopies
in our study. CADe increased the detection of SSLs, which are notoriously hard to
detect and are increasingly recognized for their clinical relevance; however, SSLs
per colonoscopy was not a primary outcome in our study.
