Review for 10.1186/s12876-022-02462-z (2022)

Reviewer’s report
Title: 
Effect of ice water injection toward the duodenal papilla for preventing
post-ERCP pancreatitis: study protocol for 
a multicenter, single-blinded,
randomized controlled trial (EUTOPIA study)
Version: 
0 
Date: 
28 Jun 2022
Reviewer's report:
I compliment the authors with a well-designed and original multicenter RCT
comparing placebo with cold water spraying of the papilla. 
I was a little bit
puzzled about the title: Effect of ice water injection toward the duodenal papilla
for preventing post-ERCP 2 pancreatitis: Study protocol for a multicenter, single-
blinded, randomized controlled trial. Perhaps injection should be replaced by
spraying
MAJOR remarks
1. In modern PEP research a placebo group is not ethical, I suggest the standard
of care in the control group (according to the Japanese guideline)
2. There is no clear statement about the use of PD-stents, this can potentially
confound your primary outcome
MINOR remarks
- Line 109-110: (2) age younger than 20 110 years; (3) non-native papilla;
already mentioned in the inclusion criteria, I recommend to remove this from the
exclusion
- PEP definition and severity according to the Cotton criteria seems logical,
however the severity should also be scored according to the revised Atlanta
criteria.
- Line 74-76 is not completely true for single use of a rectal NSAID, only
allergies are a contraindication in our unit (and country)
- Is the doctor who assesses PEP blinded for the treatment (ward or emergency
doctor)?
- Line 146: secondary outcomes: should include potential side effects of the
intervention, such as: aspiration, perhaps vagal stimmulation(?), ect
- Power calculation should explicitly show a lost to follow up percentage,
usually 10-15% By including 10% drop-out and a 50% reduction of PEP (alpha
of 0.05 and beta of 80%) our power calculation reveals 954 patients. 50%
reduction is quite impressive for a PEP-prophylactic therapy. For instance
NSAIDs and PD stents have a reported 32-42 % PEP reduction (meta-analyses).
Perhaps a more realistic approach 12% in the placebo (see latest NMA) and 7%
in the control group (40% reduction): leads to 1074 patients drop out of 10%
must be added
- Adjucation committee? 
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