Review for 10.1186/s12876-023-03100-y (2023)

Title: Efficacy comparison of 7- and 14-day P-CAB based bismuth-containing quadruple
regimen with PPI based bismuth-containing quadruple regimen for Helicobacter pylori
infection: rationale and design of an open-label, multicenter, randomized controlled trial
Version: 1 Date: 31 Oct 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
No - manuscript has some fundamental flaw(s)
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: I appreciate the effort in the point-to-point response, but I believe
this important trial deserves a more comprehensive protocol. Some answers to my queries lack
direct engagement with the core issues. Let me highlight three examples where I feel there is
room for improvement, starting with the statistical plan, which does not convince me entirely .
1. I asked for a strategy what to do with missing data for the antibiotic resistance tests?
Answer  Thank you for your valuable comment. We completely agree with your opinion.
To solve this problem, we will collect samples through sufficient explanation to patients and
conduct antibiotic resistance tests as quickly as possible to minimize the possibility of missing
data.
Comment: I still fail to see a contingency plan for missing data. The answer by the author to my
query is (free translation) ‘rest assured we will not going to have missing data”.  The basis of my
question is to have a plan in place, because you will have missing data despite all your efforts.
2. I asked to see a list of number of limitations in the discussion (apart from the strengths that
the authors highlight).
Answer; not provided
Comments Unfortunately the authors do not address this point and I challenge them to think
hard. The discussion remained unchanged
3. I urged the authors to use a validated questionnaire on adverse events
Answer: there are no validated adverse events questionnaire in Korean
Comments:  The authors did not dig very deep. A brief pubmed search revealed at least 1
validated questionnaire in Korean language https://e-jhis.org/journal/view.php?number=527  I
cite The findings show that the Korean version of the BMQ-specific was reliable and valid
in measuring the patients’ beliefs about medication in Korean. The K-BMQ-specific enables
healthcare providers to effectively measure the necessity beliefs and concern beliefs of patients
regarding medication so they can provide appropriate and adequate management and strategies
for medication adherence.
I asked the authors for a appropriate sample size calculation. The answer provided “with a
statistical power of 85%, a non-inferiority limit 8%, and a one-sided # = 0.025.”
If I use these data (90% instead of 85%) to calculate the sample size I see the following
result.  If there is a true difference in favour of the standard treatment of 6.8% (89.6% vs
82.8%), then 20240 patients are required to be 80% sure that the upper limit of a one-sided
95% confidence interval (or equivalently a 90% two-sided confidence interval) will exclude
a difference in favour of the standard group of more than 8% Sealed Envelope Ltd. 2012.
Power calculator for binary outcome non-inferiority trial. [Online] Available from: https://
www.sealedenvelope.com/power/binary-noninferior/ [Accessed Tue Oct 31 2023].
I think that the author should provide us with more data to explain why the choose 85% as
powercalculation and why the go for 1 one-sided confidence interval.
REQUESTED REVISIONS:
My version of the manuscript does not contain a consort statement which I think should be part
of a protocol paper.