Review for 10.1186/s12876-021-01759-9 (2021)

Reviewer’s report
Title: 
Colorectal cancer screening using a stool DNA-based SDC2 methylation
test: a multicenter, prospective trial
Version: 
0 
Date: 
03 Feb 2021
Reviewer's report:
As the authors mentioned in this manuscript and their previous reports, I also
think that evaluation of a stool DNA methylation is an attractive target for early
CRC screening and EarlyTect-Colon Cancer is an interesting product. If this
strategy proves to be useful, it will be beneficial to many people. This study
protocol is generally fine. However, I think that some additional information
require to make it more meaningful.
(1) Could SCD2 methylation status and accuracy of this product be affected by
age, gender, or race? If these factors have been known to affect the methylation
in previous analyses, please state in discussion.
(2) The authors include patients with IBD. Could fecal methylated SDC2 be
influenced by IBD not CRC? Please comment.
(3) How many times do participants collect stool samples? Once or more? If the
sample is collected only once despite being asymptomatic, I am concerned that
the accuracy may not guaranteed like fecal occult blood test. On the other hand,
the amount to be provided 20g seems to be higher than other similar test. Is this
because of the product? Please indicate evidences that the authors decided this
protocol of collecting stool.
(4) If the aim of this trial is to validate in asymptomatic population, please also
state it in participant selection criteria.
(5) Niu F et al reported berberine affected fecal detection of methylated SDC2
(Cancer Epidemiol Biomarkers Prev, 2017). Is there any daily medication that
interferes the methylation? If some kind of the drug exists, I think its history is
also better to be considered in criteria and recorded as clinical background.
(6) As the above report, some similar clinical trials of fecal methylated SDC2
have been reported. What are the strengths of this study and product compared
with others? How do you suggest this study protocol will help to improve the
standard of medical research?
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Is the study design appropriate to answer the research question (including the use
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