Review for 10.1186/s12876-021-01740-6 (2021)

Title: Distinct clinical phenotypes for Crohn’s disease derived from patient surveys
Version: 2 Date: 14 Feb 2021
Reviewer's report:
Summary:
Based on a questionnaire designed for other research purposes the authors investigated the
degree to which IBD patient-reported survey health and medical data suggests disease sub-
phenotypes that are useful for prognosis and therapy selection. As a secondary aim, the authors
reported challenges of questionnaire design. The authors included questionnaire answers from
1961 IBD patients (1118 CD and 843 UC patients) who had flares in the last 12 months
and identified two subpopulations of CD termed CD-like CD and UC-like CD. The two CD
populations differed in disease severity, associations with smoking, and genetic transmission
patterns. The study deals with an interesting topic but the reporting could be improved and
the authors need to add a description of the IBD cohort of investigation (i.e. the initial 5355
respondents).
Please find my comments to consider below:
Comments:
1. My main concern is the missing information on the initial 5355 respondents. The authors
need to add a description including information on recruitment (from which hospital, country, or
region?), number of patients invited to respond, number of patients that actually responded etc.
2. The IBD cohort under investigation includes a higher proportion of CD than UC patients.
Usually, it would be the other way around suggesting that the cohort may represent a selected
group of IBD patients. The proportion of CD patients is higher than UC also before excluding
patients without flares within the last 12 months. Can the authors elaborate on that point?
3. Is the questionnaire validated? The manuscript lacks information on questionnaire validation
(i.e. prior validation according to content, criterion, and construct validity). If no prior validation
exists this should be stated in the manuscript.
4. As far as I understand, the authors removed questions from the original questionnaire after
patient responding; however, this specific detail is not described and I suggest the authors to
include further clarification.
5. The manuscript would benefit from a more systematically reporting approach, preferably
in accordance with the IMRAD structure. The following paragraphs could be moved to other
sections or deleted:
a) Page 5, “Specifically, we identify novel subtypes…” I would argue that this is a finding of
the study. As such, it belongs to the results section.
b) Page 8-9, “Our initial PCA analysis…resulting in 3576 patients (2140 CD ad 1436 UC)”
could be moved to the methods section.
c) Page 10-11, “Cigarette smoking is a confirmed risk factor… more likely to develop fistulae”
could be moved to the discussion as it represents an interpretation of results.
d) Page 11, “Previous studies suggest a greater rate… family-specific risk of severe CD” could
be moved to the discussion.
e) Page 12, “ASH1L has been previously shown… classified with UC-like phenotypes” could
be moved to the discussion.
f) Page 12, “RAB1A is an oncogene that has implications… signal differentiating the two CD
subtypes” could be moved to the discussion.
g) Page 15-16, “(1) When answering to the question… phenotype of skin conditions”. This
paragraph is already mentioned in the methods section and could be deleted.
6. The background part is well-written and interesting but quite extensive. The authors should
consider to shorten this part.
7. The authors should consider to include information on number of respondents in the abstract.
8. Table 2: The authors should consider to include percentages.
9. Table 3A: Please insert percentages for CD total.
10. Table 3B: The authors should consider to include percentages.
11. Table 2-5: I would recommend that the table legends only describe the content of the tables
and not the interpretation of findings.