Review for 10.1186/s12876-021-02086-9 (2022)

Reviewer’s report
Title: 
Strategies for discontinuation of proton pump inhibitors (PPIs) in patients
with long-term PPI administration: a randomized controlled trial
Version: 
0 
Date: 
28 Jun 2021
Reviewer: 
Holmfridur Helgadottir
Reviewer's report:
This study protocol is for a randomized controlled trial designed to examine
strategies for discontinuation of PPIs in Japan. This is a very important topic and
we are in need for good evidence based methods on how best to advise patients
to deprescribe PPIs: is it more successful to taper the dose down before
discontinuation or to abruptly discontinue?
There are some concerns to be raised about this protocol:
The authors are including both PPIs and PCABs in the same study. Although
PCABs have been shown to be non-inferior to PPIs in the treatment of acid-
related disorders they lead to a significantly greater gastrin elevation compared
with PPIs. This is a major concern, and should be taken into consideration when
analyzing the data. Gastrin has been found to be an independent predictor of PPI
requirement in the Swedish study published in 2006 on the discontinuation of
PPIs after long-term treatment. I would have recommended to stratify the
randomization according to different acid suppressive agents included in the
study (PPIs vs. PCABs) to ensure equal ratio of different agents in group A and
group B. 
I agree with the authors that many patients/people on PPIs lack both explanation
that discontinuation is recommended in many cases and need for follow up. So
there is need to take into consideration, who are these patients included in the
study: reflux patients with symptom based diagnose or did they all have an
endoscopy verified diagnose of reflux oesophagitis, because there is difference in
comparison of GERD vs.NERD and one would believe that discontinuation
would be more successful in the NERD group. How will this be addressed and
accounted for. 
Do the participants get any information on lifestyle changes, that is self-
treatment of reflux disease (weight loss, stop smoking, no late night meals,
elevate the head of the bed…)
Gastrin levels, will there be taken blood test during the study process? Is this a
factor considered contributing to failure in additional analysis - what background
factors are there to be analyzed: BMI, hiatus hernia, diet habits, gender,
gastrin,dosage, 
agent ...
Why is the step down process only 2 weeks. The other group can take 7 tablets
of their previous medication as rescue medicine in the first two weeks (every
other day for the first two weeks) without that being an issue at follow up visit at
week 4. Then the to groups are not much different - PPIs tend to have effect up
to 48 hours because of their irreversible binding to the H,K-ATPase. 
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