Review for 10.1186/s12876-023-02946-6 (2023)

Title: Multicentre prospective study to evaluate effectiveness and safety of gel-forming
and hyaluronic-acid containing chewable tablets as add-on treatment in patients with
gastroesophageal reflux disease (GERD) symptoms and unsatisfying proton pump inhibitor
therapy.
Version: 0 Date: 20 Jan 2023
Reviewer's report:
Gross et al reported a multiple centre prospective study on effectiveness and safety of gel-
forming and hyaluronic-acid containing chewable tablets as add-on to proton pump inhibitor
therapy in the treatment of refractory gastroesophageal reflux disease (GERD) symptoms in an
industrial sponsored trial.
I have several comments:
Title/ Introduction:
1. Refractory GERD is most commonly defined as GERD is not responsive to BD dose of PPI.
In this study, this does not seem to be the situation. I would suggest to change 'refractory GERD'
to a more suitable term throughout this paper.
2. Mentioned the trial product  as medical devices may cause confusion as devices is often
referred as machine or instruments.
3. Can you find any other reference on this medicine Sobrade? any animal study or any in vivo
study?
4. Sobrade® chewable tablet is a preparation with a solely physical mode of action and classified
as a medical device of lowest risk (Class 1). Can you please cite this reference?
Method:
1. Are the patients recruited in a consecutive manner? or random? 2 GP sites and 2
gastroenterology specialist sites were included. Is the patients from specialist sites more severe
or truly refractory? What are the proportion of the patients?
2.  The patients recruited had exposure to PPI in the past 1 year. Were they on regular PPI? OD
or BD dose of PPI or PRN?
3. Did the patients had endoscopy before recruitment?
4. I can see patients with Barrett's oesophagus were excluded. Were patients with GI malignancy
or red flag symptoms excluded?  Were patients with overlap functional dyspepsia included?
as FD and GERD often overlap and they usually had a more severe form n less responsive to
management.
5. After patients were started on the IP, how about the PPI? Did they continue the same PPI?
Were they more compliant to PPI than before the trial? generally they may be more compliant
during trial.
6. On visit 2, can please specify clearer? seen patient immediately after completed the
medications +/- 2 days? or 14 days +/- 2 days after completed 2 weeks of medications
7. Are the questionnaire validated?
Results:
1. Table 2 & Figure 1&2; Table 3 & figure 3&4 have similar data. May consider to remove
either some of the overlap info
2. '73.8 % of investigator ratings on the treatment effectiveness were positive which was
confirmed by the ratings by patients (71.4 %).' How the Investigators and patients ratings were
not described in the methodology.
3. Will be better to explain more on the method of MID analyses either in the result or method
section.
Discussion:
1. 'Thus, a protective coat not only covering the oesophagus but the laryngeal epithelium as
well, as formed the IMD, can be a valuable contribution to treatment of refractory reflux and
prevention of its potential detrimental long-term effects.'
Can you cite the evidence to show that laryngeal epithelium can be covered by the IMD?
2. Limitations
-Long term AE and efficacy is not evaluated in this study.
-GERD related QOL except sleep were not evaluated