Title: A PHASE 2 EVALUATION OF A NEW FLAVORED PEG AND SULFATE
SOLUTION FOR Colonoscopy
Version: 1 Date: 16 Oct 2023
Reviewer's report:
Reviewer Comments:
DiPalma and colleagues report their pilot study, “A Phase 2 Evaluation of a New Flavored PEG
and Sulfate Solution Compared to an Over-the-Counter Laxative, PEG and Sports Drink Bowel
Preparation Combination” designed to compare preliminary safety, efficacy, and tolerability
data between their novel FPSS solution and off-label PEG-Sports Drink bowel cleanser.  This
is a clinically relevant question, as off-label PEG-Sports Drink bowel cleanser is prescribed for
millions of patients each year, yet this off-label solution had not had the rigorous safety testing
of FDA-approved bowel cleansers. There may be well-designed products that balance the triad
of safety, efficacy, and tolerability more favorably.
Their paper is a useful addition to this area of gastroenterology, but there are some questions
and some opportunities for improvement in the manuscript. I suggest that this paper be accepted
for publication after revision. My comments are as follows:
Clinical relevance:  Good.
Patient population:  Adequate. As the authors note, it is unfortunate that there is such an age
discrepancy between the FPSS and PEG-SD treatment groups. Further, the patients were not
randomized to treatment. There is a discrepancy between the number of patients reported in
this manuscript and the number of patients studied as reported in the submitted protocol and
ClinicalTrials.gov. Perhaps the authors can shed some light on this?
Study design:  Adequate. The authors should be more explicit in stating their primary endpoint.
Further, central readers blinded to treatment were used although this process is not described in
their FDA protocol. The local endoscopists were not blinded to treatment, which is suboptimal.
Tolerability is a key secondary outcome in this study. It would be very useful to include validated
tolerability instruments (validated,  meaning tolerability questionnaires that have been tested and
confirmed to show the feature that they purport to measure). As this is a safety study, it would
be appropriate to have ECG data and follow-up on all subjects beyond the day of colonoscopy.
Power:  Appropriate for parameters selected in a Phase 2 study.
Results:  It would be desirable to have statistical review as the authors claim a significant
difference in efficacy with the comparator having an n of just 20.
The authors collapse the questionnaire responses to “Ease of consuming prep” by combining
“very easy,” “easy,” and “tolerable” into one category and claim the responses were comparable
between the two treatment arms. Are there significant differences for any of the individual
responses between the two treatment arms?  The authors should report and discuss the analysis
at the individual response level.
Discussion:  I think the discussion is valid for the most part but should be expanded to include
a more detailed discussion of the tolerability data. Curiously, patients treated with PEG-SD
responded that consuming their prep was “very easy” at a rate almost twice that of FPSS
(27.5% for FPSS vs. 47.4% for PEG-SD) yet they responded that their “Overall Experience”
was “excellent” at a rate much lower than that for FPSS patients (21.1% for PEG-SD vs. 32.5%
for FPSS). Were these differences significant and why the discordant response trend between
ease of consumption and overall experience?
Title: A PHASE 2 EVALUATION OF A NEW FLAVORED PEG AND SULFATE
SOLUTION FOR Colonoscopy
Version: 1 Date: 16 Oct 2023
Reviewer's report:
Reviewer Comments:
DiPalma and colleagues report their pilot study, “A Phase 2 Evaluation of a New Flavored PEG
and Sulfate Solution Compared to an Over-the-Counter Laxative, PEG and Sports Drink Bowel
Preparation Combination” designed to compare preliminary safety, efficacy, and tolerability
data between their novel FPSS solution and off-label PEG-Sports Drink bowel cleanser.  This
is a clinically relevant question, as off-label PEG-Sports Drink bowel cleanser is prescribed for
millions of patients each year, yet this off-label solution had not had the rigorous safety testing
of FDA-approved bowel cleansers. There may be well-designed products that balance the triad
of safety, efficacy, and tolerability more favorably.
Their paper is a useful addition to this area of gastroenterology, but there are some questions
and some opportunities for improvement in the manuscript. I suggest that this paper be accepted
for publication after revision. My comments are as follows:
Clinical relevance:  Good.
Patient population:  Adequate. As the authors note, it is unfortunate that there is such an age
discrepancy between the FPSS and PEG-SD treatment groups. Further, the patients were not
randomized to treatment. There is a discrepancy between the number of patients reported in
this manuscript and the number of patients studied as reported in the submitted protocol and
ClinicalTrials.gov. Perhaps the authors can shed some light on this?
Study design:  Adequate. The authors should be more explicit in stating their primary endpoint.
Further, central readers blinded to treatment were used although this process is not described in
their FDA protocol. The local endoscopists were not blinded to treatment, which is suboptimal.
Tolerability is a key secondary outcome in this study. It would be very useful to include validated
tolerability instruments (validated,  meaning tolerability questionnaires that have been tested and
confirmed to show the feature that they purport to measure). As this is a safety study, it would
be appropriate to have ECG data and follow-up on all subjects beyond the day of colonoscopy.
Power:  Appropriate for parameters selected in a Phase 2 study.
Results:  It would be desirable to have statistical review as the authors claim a significant
difference in efficacy with the comparator having an n of just 20.
The authors collapse the questionnaire responses to “Ease of consuming prep” by combining
“very easy,” “easy,” and “tolerable” into one category and claim the responses were comparable
between the two treatment arms. Are there significant differences for any of the individual
responses between the two treatment arms?  The authors should report and discuss the analysis
at the individual response level.
Discussion:  I think the discussion is valid for the most part but should be expanded to include
a more detailed discussion of the tolerability data. Curiously, patients treated with PEG-SD
responded that consuming their prep was “very easy” at a rate almost twice that of FPSS
(27.5% for FPSS vs. 47.4% for PEG-SD) yet they responded that their “Overall Experience”
was “excellent” at a rate much lower than that for FPSS patients (21.1% for PEG-SD vs. 32.5%
for FPSS). Were these differences significant and why the discordant response trend between
ease of consumption and overall experience?
Please review this paper.
user
Title: A PHASE 2 EVALUATION OF A NEW FLAVORED PEG AND SULFATE
SOLUTION FOR Colonoscopy
Version: 1 Date: 16 Oct 2023
Reviewer's report:
Reviewer Comments:
DiPalma and colleagues report their pilot study, “A Phase 2 Evaluation of a New Flavored PEG
and Sulfate Solution Compared to an Over-the-Counter Laxative, PEG and Sports Drink Bowel
Preparation Combination” designed to compare preliminary safety, efficacy, and tolerability
data between their novel FPSS solution and off-label PEG-Sports Drink bowel cleanser.  This
is a clinically relevant question, as off-label PEG-Sports Drink bowel cleanser is prescribed for
millions of patients each year, yet this off-label solution had not had the rigorous safety testing
of FDA-approved bowel cleansers. There may be well-designed products that balance the triad
of safety, efficacy, and tolerability more favorably.
Their paper is a useful addition to this area of gastroenterology, but there are some questions
and some opportunities for improvement in the manuscript. I suggest that this paper be accepted
for publication after revision. My comments are as follows:
Clinical relevance:  Good.
Patient population:  Adequate. As the authors note, it is unfortunate that there is such an age
discrepancy between the FPSS and PEG-SD treatment groups. Further, the patients were not
randomized to treatment. There is a discrepancy between the number of patients reported in
this manuscript and the number of patients studied as reported in the submitted protocol and
ClinicalTrials.gov. Perhaps the authors can shed some light on this?
Study design:  Adequate. The authors should be more explicit in stating their primary endpoint.
Further, central readers blinded to treatment were used although this process is not described in
their FDA protocol. The local endoscopists were not blinded to treatment, which is suboptimal.
Tolerability is a key secondary outcome in this study. It would be very useful to include validated
tolerability instruments (validated,  meaning tolerability questionnaires that have been tested and
confirmed to show the feature that they purport to measure). As this is a safety study, it would
be appropriate to have ECG data and follow-up on all subjects beyond the day of colonoscopy.
Power:  Appropriate for parameters selected in a Phase 2 study.
Results:  It would be desirable to have statistical review as the authors claim a significant
difference in efficacy with the comparator having an n of just 20.
The authors collapse the questionnaire responses to “Ease of consuming prep” by combining
“very easy,” “easy,” and “tolerable” into one category and claim the responses were comparable
between the two treatment arms. Are there significant differences for any of the individual
responses between the two treatment arms?  The authors should report and discuss the analysis
at the individual response level.
Discussion:  I think the discussion is valid for the most part but should be expanded to include
a more detailed discussion of the tolerability data. Curiously, patients treated with PEG-SD
responded that consuming their prep was “very easy” at a rate almost twice that of FPSS
(27.5% for FPSS vs. 47.4% for PEG-SD) yet they responded that their “Overall Experience”
was “excellent” at a rate much lower than that for FPSS patients (21.1% for PEG-SD vs. 32.5%
for FPSS). Were these differences significant and why the discordant response trend between
ease of consumption and overall experience?
assistant