A Real-Life Evaluation of the Best Bowel Preparation Regimen Identified in the PrepRICE Trial for Capsule Endoscopies

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

Congratulations on the manuscript. I believe the topic is highly relevant. Nevertheless, I have a few suggestions and certain points have to be addressed in order to make the manuscript publishable.

• Please consider moving Section 4. Materials and Methods before the Results (standard IMRaD structure), and expand it to improve reproducibility. This also improves readability, given the fact that, in the abstract, this section is placed second
• Preparation protocol needs more detail- While you state that patients ingested 1 L after the capsule reached the duodenum and you report the main preparation solutions used (mostly 1 L PEG + ascorbate), the protocol remains difficult to replicate in other centers. Please clarify: diet on the day before (low-residue vs clear liquids) and fasting instructions (solids/fluids, hours), whether simethicone (or other antifoaming agents) and/or prokinetics were used (guidelines are mentioned in the Discussion but not in Methods), and how “capsule reached the duodenum” was operationalized: real-time viewer used? Who confirmed? What was the time window, and what happened if gastric transit was prolonged? Post-ingestion instructions (allowed liquids, ambulation, timing of meals).
  A short “protocol box/table” would be very helpful.
• Please provide explicit inclusion and exclusion criteria (e.g., pregnancy, suspected obstruction, swallowing disorders, prior surgery/strictures, etc.). At present, the cohort is described as “all consecutive adult patients”, but the eligibility framework is not fully specified.
• You report an adequate visualization rate (~91%), but the manuscript does not clearly define what threshold on the Brotz scale constitutes “adequate” (global? Specific cut-off?). Please provide the operational definition and cite the source/justification.
• Please clarify how the p-values were derived for comparisons with PrepRICE (did you use aggregated published statistics only, or did you have access to individual-level data?). If individual-level data were not available, inferential testing may not be appropriate; a descriptive comparison may be more transparent.
• The Introduction and Discussion emphasize improved diagnostic yield (DY) in PrepRICE, yet your Results focus mainly on technical metrics (QSBV, completion, transit times). To support clinical relevance, please add diagnostic yield in your cohort (overall and ideally by indication: IDA, suspected/known Crohn’s disease, diarrhea, etc.). If available, downstream consequences (e.g., changes in management, need for device-assisted enteroscopy, therapeutic decisions).

Author Response

Comment 1: Please consider moving Section 4. Materials and Methods before the Results (standard IMRaD structure), and expand it to improve reproducibility. This also improves readability, given the fact that, in the abstract, this section is placed second.

Author’s response 1: The authors agree and accept your suggestion. Materials and Methods are now section 2 and was expanded.

 

Comment 2:  Preparation protocol needs more detail- While you state that patients ingested 1 L after the capsule reached the duodenum and you report the main preparation solutions used (mostly 1 L PEG + ascorbate), the protocol remains difficult to replicate in other centers. Please clarify: diet on the day before (low-residue vs clear liquids) and fasting instructions (solids/fluids, hours), whether simethicone (or other antifoaming agents) and/or prokinetics were used (guidelines are mentioned in the Discussion but not in Methods), and how “capsule reached the duodenum” was operationalized: real-time viewer used? Who confirmed? What was the time window, and what happened if gastric transit was prolonged? Post-ingestion instructions (allowed liquids, ambulation, timing of meals). A short “protocol box/table” would be very helpful.

Author’s response 2: The authors thank you for your suggestion. We added a table explaining in detail our protocol (Table 1 in section 2.2. SBCE procedure). 

Comment 3: Please provide explicit inclusion and exclusion criteria (e.g., pregnancy, suspected obstruction, swallowing disorders, prior surgery/strictures, etc.). At present, the cohort is described as “all consecutive adult patients”, but the eligibility framework is not fully specified.

Author’s response 3: The authors thank you for this suggestion. The requested information was added on the new Section 2.1. (“Study design and patient selection”).

 

Comment 4: You report an adequate visualization rate (~91%), but the manuscript does not clearly define what threshold on the Brotz scale constitutes “adequate” (global? Specific cut-off?). Please provide the operational definition and cite the source/justification.

Author’s response 4: The authors thank you for this suggestion. The requested information was added on the manuscript (quantitative index of at least 7 points).

 

Comment 5: Please clarify how the p-values were derived for comparisons with PrepRICE (did you use aggregated published statistics only, or did you have access to individual-level data?). If individual-level data were not available, inferential testing may not be appropriate; a descriptive comparison may be more transparent.

Author’s response 5: Thank you for this important clarification request. The p-values for comparisons with the PrepRICE cohort were derived using individual-level data. We had direct access to the original patient dataset and performed the statistical analyses de novo, applying the same methodology described in the Methods section (ANOVA F test for normally distributed variables and Mann–Whitney U test for nonnormally distributed variables). We have now clarified this in the Methods section to avoid ambiguity.

 

Comment 6: The Introduction and Discussion emphasize improved diagnostic yield (DY) in PrepRICE, yet your Results focus mainly on technical metrics (QSBV, completion, transit times). To support clinical relevance, please add diagnostic yield in your cohort (overall and ideally by indication: IDA, suspected/known Crohn’s disease, diarrhea, etc.). If available, downstream consequences (e.g., changes in management, need for device-assisted enteroscopy, therapeutic decisions).

Author’s response 6: The authors thank the reviewer for this important suggestion. Data on DY was collected and analyzed according to clinical indication in our cohort and has now been added to the Results section. A direct comparison with the PrepRICE study was performed in patients with suspected small-bowel bleeding (anemia), as this was the only indication shared between both cohorts, allowing a meaningful comparison. DY for other indications, including suspected/confirmed Crohn’s disease, chronic diarrhea, and other clinical scenarios, is now also reported descriptively. Unfortunately, assessment of downstream clinical consequences was not feasible due to the relatively short follow-up period of our cohort and the lack of access to comparable outcome data from the PrepRICE study.

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript entitled “Real life evaluation of the best bowel preparation regimen identified in the PrepRICE trial for capsule endoscopy” aims to assess the implementation of a previously validated bowel preparation protocol in a real life setting. While the topic is clinically relevant, the present work offers limited novelty and lacks sufficient scientific depth to justify publication as a full original article.

First, the study is essentially a short observational report confirming previously published findings from the PrepRICE trial. The primary outcomes, including quality of small bowel visualization, adequate visualization rate, transit times, and complete examination rate, show results largely comparable to the original trial. The only statistically significant difference reported is a slightly lower Brotz score, which does not meaningfully alter clinical interpretation. As such, the study does not provide new mechanistic insights, methodological innovation, or clinically impactful data beyond confirming feasibility in routine practice.

Second, the scientific contribution is modest. The manuscript does not explore predictive factors for visualization quality, does not perform subgroup analyses, and does not provide additional diagnostic yield or outcome correlations that would deepen understanding of the preparation strategy. The analysis remains descriptive and limited in scope.

Third, the structure and presentation are minimal. The work includes only two tables and lacks figures or additional analytical components. This level of presentation is not sufficient for a full original article. The manuscript reads more as a brief communication or single center audit rather than a comprehensive scientific study.

Moreover, the comparison with the PrepRICE trial is relatively superficial. Differences in patient characteristics, indications, procedural timing, or protocol adherence are not explored in detail. The real life cohort is heterogeneous, but this heterogeneity is not analyzed or discussed as a potential strength or limitation.

In summary, although the study confirms that implementation of the protocol is feasible in daily clinical practice, it does not substantially advance the field of small bowel capsule endoscopy or bowel preparation strategies. The scientific novelty, analytical depth, and overall impact are limited.

I therefore cannot recommend acceptance as a full original article in its current form. At most, the work might be considered as a brief report, provided the scope and format are adjusted accordingly.

Comments on the Quality of English Language

English needs refinement.

Author Response

Comment 1: First, the study is essentially a short observational report confirming previously published findings from the PrepRICE trial. The primary outcomes, including quality of small bowel visualization, adequate visualization rate, transit times, and complete examination rate, show results largely comparable to the original trial. The only statistically significant difference reported is a slightly lower Brotz score, which does not meaningfully alter clinical interpretation. As such, the study does not provide new mechanistic insights, methodological innovation, or clinically impactful data beyond confirming feasibility in routine practice.

Author’s response 1: The authors thank the reviewer for this thoughtful comment. We acknowledge that our study is observational and primarily aimed at confirming the findings of the PrepRICE trial. However, we believe its value lies in providing real-world evidence on the feasibility and reproducibility of the PrepRICE protocol outside a controlled trial setting. Demonstrating comparable visualization quality, cleansing adequacy, transit times, and completion rates in routine clinical practice supports the external validity and generalizability of the original results. These data help bridge the gap between clinical trial efficacy and everyday practice implementation.

 

Comment 2: Second, the scientific contribution is modest. The manuscript does not explore predictive factors for visualization quality, does not perform subgroup analyses, and does not provide additional diagnostic yield or outcome correlations that would deepen understanding of the preparation strategy. The analysis remains descriptive and limited in scope.

Author’s response 2: The authors thank the reviewer for this comment and agree with it. The primary objective of this study was to report real-world results obtained outside the controlled setting of a RCT and to assess the external validity and applicability of this preparation strategy in routine clinical practice. To strengthen the clinical relevance of the manuscript, we have now added DY data, analyzed according to indication, and performed a comparison with the PrepRICE study in patients with suspected small-bowel bleeding (section 3.4. Diagnostic Yield). Notably, similar DY results were observed between cohorts, further supporting the effectiveness of this preparation approach in a real-world setting.

 

Comment 3: Third, the structure and presentation are minimal. The work includes only two tables and lacks figures or additional analytical components. This level of presentation is not sufficient for a full original article. The manuscript reads more as a brief communication or single center audit rather than a comprehensive scientific study.

Author’s response 3: We thank the reviewer for this valuable comment and agree with this observation. Accordingly, we have expanded the analytical component of the study (such as differences in patient characteristics and added a whole new section about DY, including differences in in DY in suspicion of SB bleeding) and added new tables (“Table 1. SBCE preparation protocol”; “Table 4. Summary of the lesions detected in the SB in patients with anemia: DY (percentage of patients with lesions classified as having high bleeding potential [P2]); Table 5. Summary of lesions detected in the SB in patients with suspicion/confirmed CD: DY (percentage of patients with inflammatory/fibrotic lesions)”) to provide a more comprehensive evaluation of the data.

 

Comment 4: Moreover, the comparison with the PrepRICE trial is relatively superficial. Differences in patient characteristics, indications, procedural timing, or protocol adherence are not explored in detail. The real life cohort is heterogeneous, but this heterogeneity is not analyzed or discussed as a potential strength or limitation.

Author’s response 4: We thank the reviewer for this comment. A statistical comparison of baseline patient characteristics between cohorts has now been added. The difference in indications was already inherent to the study design, as our cohort included all SBCE indications, whereas PrepRICE enrolled only patients with suspected small-bowel bleeding; this has now been further clarified. Detailed comparisons regarding procedural timing and protocol adherence were not possible due to lack of available data from the PrepRICE study. Additionally, the Discussion has been expanded to address cohort heterogeneity as a strength, highlighting its reflection of real-world clinical practice and supporting the external validity of our findings – “Notably, these findings reflect real-world clinical practice, encompassing a heterogeneous patient population with diverse comorbidities, including inpatients that were bedbound and with a tendency toward a higher prevalence of diabetes mellitus, which have been associated with incomplete capsule endoscopy and inadequate cleanliness[20]. Additionally, it included a wide range of indications for SBCE, in contrast to more selective study populations such as PrepRICE, in which the only SBCE indication was suspected SB bleeding. Additionally, patients in our cohort used different types of bowel preparation solutions, as the choice of preparation was left to individual preference. This heterogeneity strengthens the clinical relevance of our results, as adequate SB visualization and comparable DY was achieved despite some unfavorable conditions. Additionally, it supports the external validity of our findings and indicates that the timing of bowel preparation may be a more critical determinant of adequate SB visualization than the specific purgative agent, as evidenced by higher SBVQ compared with preprocedural regimens.”

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you for taking my suggestions into consideration. I believe the manuscript looks better now and fits the publishing criteria.

I wish you all the best in all your future scientific endeavors.

Author Response

Comment 1: 

" Dear Authors,

Thank you for taking my suggestions into consideration. I believe the manuscript looks better now and fits the publishing criteria.

I wish you all the best in all your future scientific endeavors."

 

Response: Thank you for your kind feedback and for your valuable suggestions throughout the review process. 

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have made several improvements to the manuscript, which are appreciated. However, the main concern remains unresolved, namely the limited scientific soundness and the relatively modest scientific contribution. Although the authors emphasize the “real-world” context of the study, this aspect alone does not sufficiently strengthen the methodological rigor or the scientific impact of the work.

In its current form, the study appears to provide only a limited advancement of knowledge, and several aspects of the analysis and interpretation remain insufficiently developed to support a full research article. For this reason, the manuscript may be more suitable for consideration as a Short Communication, where the scope and expectations regarding depth of analysis and contribution are more aligned with the present content and limitations of the study.

Best regards.

Comments on the Quality of English Language

English needs refinement.

Author Response

Comment 1: "

The authors have made several improvements to the manuscript, which are appreciated. However, the main concern remains unresolved, namely the limited scientific soundness and the relatively modest scientific contribution. Although the authors emphasize the “real-world” context of the study, this aspect alone does not sufficiently strengthen the methodological rigor or the scientific impact of the work.

In its current form, the study appears to provide only a limited advancement of knowledge, and several aspects of the analysis and interpretation remain insufficiently developed to support a full research article. For this reason, the manuscript may be more suitable for consideration as a Short Communication, where the scope and expectations regarding depth of analysis and contribution are more aligned with the present content and limitations of the study.

Best regards."

Response: 

Dear Reviewer,

Thank you for your thoughtful and constructive comments, as well as for acknowledging the improvements made to the manuscript.

We have further strengthened the Discussion to better highlight the scientific contribution of our study. In particular, our results demonstrate that the PrepRICE-based protocol remains effective in a real-world setting, achieving comparable completion rates, visualization quality, and diagnostic yield despite a more heterogeneous population. Additionally, we show that this approach provides superior small-bowel visualization compared with pre-procedural regimens, underscoring the importance of purgative timing. Furthermore, the study also demonstrates the usefulness of this preparation regiment in other indications for small bowel capsule endoscopy, as the PrepRICE study only evaluated patients with suspected small bowel bleeding.

We have considered your suggestion regarding a Short Communication; however, we believe that the scope and depth of our data support its suitability as a full research article.

We sincerely thank you for your valuable feedback, which has helped us improve the clarity and scientific impact of our work.

Best regards.

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors, thank you for your answer. The primary concerns remain unresolved. The manuscript demonstrates limited scientific contribution, and the study design does not sufficiently support strong conclusions. Additionally, the level of novelty and overall scientific impact is modest. In its current form, the work may be more suitable for consideration as a short note or preliminary communication rather than a full research article. best regards!

Comments on the Quality of English Language

English needs refinement.