Reviewer’s report
Title: 
Comparing Colon Capsule Endoscopy To Colonoscopy; A Symptomatic
Patient’s Perspective
Version: 
0 
Date: 
12 Jun 2021
Reviewer's report:
Dear Editor, 
Thank you for giving me the opportunity to review the manuscript by Dr. M.
Syafiq Ismail et al. entitled: "Comparing Colon Capsule Endoscopy to
Colonoscopy; A Symptomatic Patient's Perspective". Authors are to be
commended for putting together a concise and well-written manuscript on a very
interesting yet underrated topic. My major concerns with this study are the
following with some of them being already acknowledged by authors
themselves:
1. I query the implications of this study in real world clinical practice. Authors
showed that CCE achieves higher satisfaction rates compared to standard
colonoscopy along with equivalent diagnostic yield. This is somewhat
anticipated, given the procedure`s easiness to complete, along with the favorable
patient safety profile. Beyond the need for bowel preparation that can be even
more demanding for CCE compared to standard colonoscopy, it remains
questionable whether replacing standard colonoscopy with CCE would be indeed
a valuable alternative, given its inability to perform biopsy or remove neoplastic
lesions. This cardinal disadvantage has perhaps prevented CCE from integrating
into everyday clinical practice, since patients discovered with mucosal
abnormalities must once again receive bowel preparation and undergo
conventional colonoscopy. In view of this, CCE could be indeed advantageous in
certain group of patients i.e. young, female where colonoscopy can be rather
cumbersome; however, authors din not aim to investigate this since patients
enrolled were of a wide age range with final results of the study not supporting
such a hypothesis, perhaps due to a type II error. Moreover, assessment of both
diagnostic modalities by all patients is a major advantage indeed; however, does
not replicate real world conditions. 
2. Authors do not mention anything about the significant higher cost of CCE
compared to colonoscopy (or even higher costs when patients receive both
examinations). Apparently a financial cost analysis was beyond the scope of the
study; still, it should be taken into account that in several European countries
fiscal austerity measures still apply and CCE in most cases is not reimbursed.
CCE may be everyday routine for the particular medical center, however these
results clearly cannot be generalized. 
3. Studies investigating patient reported outcomes are per se prone to several
sources of bias. I understand that measuring satisfaction with an endoscopic
procedure cannot be done otherwise, but authors should acknowledge this as
study limitation. 
4. All colonoscopies were eventually performed exclusively with air insufflation,
since Carbon Dioxide (CO2) insufflation was unavailable, although authors state
in the Methods section that use of air or CO2 insufflation was noted. Besides
confusing, air insufflation is well-established factor associated with higher
patients` discomfort. In this sense, this could be a potential confounder for the
results and should be better highlighted. 
Below you may find my other comments:
Introduction
This section contains many redundant information (i.e. reference to exact
complications risk of colonoscopy or CCE complications risk). Patients were not
allowed to choose their diagnostic modality based on the potential risks, thus I
would suggest authors to omit them. 
Method
Please list all major indications for performing CCE in your facility ("we
perform about 250-300 CCEs per year"). 
Please clearly list all the indications for patients to be enrolled in this study
(inclusion criteria)? Similarly, please also state exclusion criteria. There is only a
reference regarding this in the Results section "Both CCE and colonoscopy tests
were performed as part of another prospective comparison study of CCE and
colonoscopy for the investigation of symptoms in an average risk cohort (1)".
However, it should all reasons for the examination should be included in the
Methods section. 
Please assign Tables 1 and 2 (and Table 3 according to my comment below) to
an Appendix or present them as Supplementary material according to Journal`s
policy. Other than presenting the questionnaires and scale used during the study,
they do not include any data regarding the study`s main outcomes of interest.
Results
Patient demographics: Please present all patients demographics (age, gender,
indication, medication etc.) within a Table. These data should be presented there.
Bowel preparation: this section should be moved to the "Methods" section.
Moreover, Table 3 should be presented only as a Supplementary material since it
does not add any information regarding study outcomes. See my comment
regarding all Tables above. 
CCE data: please include in Methods section how "positive findings" were
defined
Colonoscopy data: PDR is not listed among the principal quality indicators of
colonoscopy procedure (contrary to adenoma detection rate - ADR); thus, I
would suggest authors to omit this
Subgroup analysis: performing subgroup analyses when the sample of the study
is so small entails considerable risk for error and results may be particularly
susceptible to chance. Thus, I would suggest authors to omit this section,
especially when no significant findings are produced.
Table 4 is not listed the first time it appears within the manuscript text. Please
correct. 
Discussion
I disagree with authors about the potentially unknown impact of diagnosis on the
overall satisfaction and thus use of this as argument to avoid reporting on any
patient diagnosis. The risk for major large bowel pathology is age-related. CCE
could be used for younger patients but results do not support such a notion.
Publons Reviewer Recognition
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find the details of processing in Publons’ privacy policy
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Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
None
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Comparing Colon Capsule Endoscopy To Colonoscopy; A Symptomatic
Patient’s Perspective
Version: 
0 
Date: 
12 Jun 2021
Reviewer's report:
Dear Editor, 
Thank you for giving me the opportunity to review the manuscript by Dr. M.
Syafiq Ismail et al. entitled: "Comparing Colon Capsule Endoscopy to
Colonoscopy; A Symptomatic Patient's Perspective". Authors are to be
commended for putting together a concise and well-written manuscript on a very
interesting yet underrated topic. My major concerns with this study are the
following with some of them being already acknowledged by authors
themselves:
1. I query the implications of this study in real world clinical practice. Authors
showed that CCE achieves higher satisfaction rates compared to standard
colonoscopy along with equivalent diagnostic yield. This is somewhat
anticipated, given the procedure`s easiness to complete, along with the favorable
patient safety profile. Beyond the need for bowel preparation that can be even
more demanding for CCE compared to standard colonoscopy, it remains
questionable whether replacing standard colonoscopy with CCE would be indeed
a valuable alternative, given its inability to perform biopsy or remove neoplastic
lesions. This cardinal disadvantage has perhaps prevented CCE from integrating
into everyday clinical practice, since patients discovered with mucosal
abnormalities must once again receive bowel preparation and undergo
conventional colonoscopy. In view of this, CCE could be indeed advantageous in
certain group of patients i.e. young, female where colonoscopy can be rather
cumbersome; however, authors din not aim to investigate this since patients
enrolled were of a wide age range with final results of the study not supporting
such a hypothesis, perhaps due to a type II error. Moreover, assessment of both
diagnostic modalities by all patients is a major advantage indeed; however, does
not replicate real world conditions. 
2. Authors do not mention anything about the significant higher cost of CCE
compared to colonoscopy (or even higher costs when patients receive both
examinations). Apparently a financial cost analysis was beyond the scope of the
study; still, it should be taken into account that in several European countries
fiscal austerity measures still apply and CCE in most cases is not reimbursed.
CCE may be everyday routine for the particular medical center, however these
results clearly cannot be generalized. 
3. Studies investigating patient reported outcomes are per se prone to several
sources of bias. I understand that measuring satisfaction with an endoscopic
procedure cannot be done otherwise, but authors should acknowledge this as
study limitation. 
4. All colonoscopies were eventually performed exclusively with air insufflation,
since Carbon Dioxide (CO2) insufflation was unavailable, although authors state
in the Methods section that use of air or CO2 insufflation was noted. Besides
confusing, air insufflation is well-established factor associated with higher
patients` discomfort. In this sense, this could be a potential confounder for the
results and should be better highlighted. 
Below you may find my other comments:
Introduction
This section contains many redundant information (i.e. reference to exact
complications risk of colonoscopy or CCE complications risk). Patients were not
allowed to choose their diagnostic modality based on the potential risks, thus I
would suggest authors to omit them. 
Method
Please list all major indications for performing CCE in your facility ("we
perform about 250-300 CCEs per year"). 
Please clearly list all the indications for patients to be enrolled in this study
(inclusion criteria)? Similarly, please also state exclusion criteria. There is only a
reference regarding this in the Results section "Both CCE and colonoscopy tests
were performed as part of another prospective comparison study of CCE and
colonoscopy for the investigation of symptoms in an average risk cohort (1)".
However, it should all reasons for the examination should be included in the
Methods section. 
Please assign Tables 1 and 2 (and Table 3 according to my comment below) to
an Appendix or present them as Supplementary material according to Journal`s
policy. Other than presenting the questionnaires and scale used during the study,
they do not include any data regarding the study`s main outcomes of interest.
Results
Patient demographics: Please present all patients demographics (age, gender,
indication, medication etc.) within a Table. These data should be presented there.
Bowel preparation: this section should be moved to the "Methods" section.
Moreover, Table 3 should be presented only as a Supplementary material since it
does not add any information regarding study outcomes. See my comment
regarding all Tables above. 
CCE data: please include in Methods section how "positive findings" were
defined
Colonoscopy data: PDR is not listed among the principal quality indicators of
colonoscopy procedure (contrary to adenoma detection rate - ADR); thus, I
would suggest authors to omit this
Subgroup analysis: performing subgroup analyses when the sample of the study
is so small entails considerable risk for error and results may be particularly
susceptible to chance. Thus, I would suggest authors to omit this section,
especially when no significant findings are produced.
Table 4 is not listed the first time it appears within the manuscript text. Please
correct. 
Discussion
I disagree with authors about the potentially unknown impact of diagnosis on the
overall satisfaction and thus use of this as argument to avoid reporting on any
patient diagnosis. The risk for major large bowel pathology is age-related. CCE
could be used for younger patients but results do not support such a notion.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
None
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Comparing Colon Capsule Endoscopy To Colonoscopy; A Symptomatic
Patient’s Perspective
Version: 
0 
Date: 
12 Jun 2021
Reviewer's report:
Dear Editor, 
Thank you for giving me the opportunity to review the manuscript by Dr. M.
Syafiq Ismail et al. entitled: "Comparing Colon Capsule Endoscopy to
Colonoscopy; A Symptomatic Patient's Perspective". Authors are to be
commended for putting together a concise and well-written manuscript on a very
interesting yet underrated topic. My major concerns with this study are the
following with some of them being already acknowledged by authors
themselves:
1. I query the implications of this study in real world clinical practice. Authors
showed that CCE achieves higher satisfaction rates compared to standard
colonoscopy along with equivalent diagnostic yield. This is somewhat
anticipated, given the procedure`s easiness to complete, along with the favorable
patient safety profile. Beyond the need for bowel preparation that can be even
more demanding for CCE compared to standard colonoscopy, it remains
questionable whether replacing standard colonoscopy with CCE would be indeed
a valuable alternative, given its inability to perform biopsy or remove neoplastic
lesions. This cardinal disadvantage has perhaps prevented CCE from integrating
into everyday clinical practice, since patients discovered with mucosal
abnormalities must once again receive bowel preparation and undergo
conventional colonoscopy. In view of this, CCE could be indeed advantageous in
certain group of patients i.e. young, female where colonoscopy can be rather
cumbersome; however, authors din not aim to investigate this since patients
enrolled were of a wide age range with final results of the study not supporting
such a hypothesis, perhaps due to a type II error. Moreover, assessment of both
diagnostic modalities by all patients is a major advantage indeed; however, does
not replicate real world conditions. 
2. Authors do not mention anything about the significant higher cost of CCE
compared to colonoscopy (or even higher costs when patients receive both
examinations). Apparently a financial cost analysis was beyond the scope of the
study; still, it should be taken into account that in several European countries
fiscal austerity measures still apply and CCE in most cases is not reimbursed.
CCE may be everyday routine for the particular medical center, however these
results clearly cannot be generalized. 
3. Studies investigating patient reported outcomes are per se prone to several
sources of bias. I understand that measuring satisfaction with an endoscopic
procedure cannot be done otherwise, but authors should acknowledge this as
study limitation. 
4. All colonoscopies were eventually performed exclusively with air insufflation,
since Carbon Dioxide (CO2) insufflation was unavailable, although authors state
in the Methods section that use of air or CO2 insufflation was noted. Besides
confusing, air insufflation is well-established factor associated with higher
patients` discomfort. In this sense, this could be a potential confounder for the
results and should be better highlighted. 
Below you may find my other comments:
Introduction
This section contains many redundant information (i.e. reference to exact
complications risk of colonoscopy or CCE complications risk). Patients were not
allowed to choose their diagnostic modality based on the potential risks, thus I
would suggest authors to omit them. 
Method
Please list all major indications for performing CCE in your facility ("we
perform about 250-300 CCEs per year"). 
Please clearly list all the indications for patients to be enrolled in this study
(inclusion criteria)? Similarly, please also state exclusion criteria. There is only a
reference regarding this in the Results section "Both CCE and colonoscopy tests
were performed as part of another prospective comparison study of CCE and
colonoscopy for the investigation of symptoms in an average risk cohort (1)".
However, it should all reasons for the examination should be included in the
Methods section. 
Please assign Tables 1 and 2 (and Table 3 according to my comment below) to
an Appendix or present them as Supplementary material according to Journal`s
policy. Other than presenting the questionnaires and scale used during the study,
they do not include any data regarding the study`s main outcomes of interest.
Results
Patient demographics: Please present all patients demographics (age, gender,
indication, medication etc.) within a Table. These data should be presented there.
Bowel preparation: this section should be moved to the "Methods" section.
Moreover, Table 3 should be presented only as a Supplementary material since it
does not add any information regarding study outcomes. See my comment
regarding all Tables above. 
CCE data: please include in Methods section how "positive findings" were
defined
Colonoscopy data: PDR is not listed among the principal quality indicators of
colonoscopy procedure (contrary to adenoma detection rate - ADR); thus, I
would suggest authors to omit this
Subgroup analysis: performing subgroup analyses when the sample of the study
is so small entails considerable risk for error and results may be particularly
susceptible to chance. Thus, I would suggest authors to omit this section,
especially when no significant findings are produced.
Table 4 is not listed the first time it appears within the manuscript text. Please
correct. 
Discussion
I disagree with authors about the potentially unknown impact of diagnosis on the
overall satisfaction and thus use of this as argument to avoid reporting on any
patient diagnosis. The risk for major large bowel pathology is age-related. CCE
could be used for younger patients but results do not support such a notion.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
None
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant