Title: Prolonged time to treatment of biologics in Inflammatory Bowel Disease: disparities from
a retrospective study in a tertiary referral centre in the UK
Version: 2 Date: 22 Mar 2025
Reviewer's report:
I commend the authors for a thorough and timely analysis of delays in biologic therapy initiation
among adult IBD patients. This is a well-executed retrospective cohort study from a tertiary UK
centre that adds meaningful data to the limited non-North American literature on IBD treatment
delays.
Below are comments for the authors to consider in strengthening the final version:
- Clarify the clinical definition of “Time to Treatment (TTT)” TTT is defined as the time from
referral to the Biologics Clinic (BC) to first dose of therapy. Given that pre-BC processes (e.g.,
funding forms, screening) were required prior to BC referral, please clarify whether these steps
are included in or precede the TTT interval. The flow diagrams in Figures 2 and 3 (supplement)
are helpful, but a more explicit description in the Methods section would improve transparency.
- The observation that South Asian patients had shorter TTT than White British and “other
minority groups” is important and somewhat counterintuitive given literature on healthcare
disparities. While you suggest possible reasons (e.g., local population demographics, more
severe presentations), this deserves further discussion. Could you provide stratified baseline
CRP, steroid use, or hospitalisation rates by ethnicity to explore whether disease severity may
explain this difference?
- Table 3 (supplement) shows no significant association between TTT and adverse outcomes.
However, it appears that the study may be underpowered to detect such associations (e.g.,
only 24 patients with primary non-response). Please clarify in the Discussion that the lack of
association may reflect sample size limitations or residual confounding. Consider presenting
subgroup analyses for biologic-naïve patients or those with elevated CRP, where treatment
timing may matter more.
- The detailed categorisation of delays (Table 4) is a key strength. However, pharmacy-related
and administrative delays — including those involving homecare providers — are under-
discussed in the main text. These insights are valuable and deserve greater attention, particularly
given your finding that Adalimumab was independently associated with delayed TTT (likely
due to SC delivery logistics). Consider highlighting this in the Results and Discussion more
explicitly.
- You included variables with p # 0.2 in the multivariate model (Table 1, supplement). This
is methodologically acceptable, but please justify this choice briefly in the Statistical Methods
section to clarify your rationale.
- Please avoid “other ethnic minority group” unless you can define this more clearly (e.g., Black
African, Arab, etc.). If grouping was necessary due to small cell sizes, please state this explicitly
and consider using “other non-White” or another term that more transparently reflects your data
structure.
- Correct typographical errors (e.g., “initiatiation” # “initiation”, “assocoiated” # “associated”)
and ensure consistent spacing in units (e.g., “10 mg/L”, not “10mg/L”).
Title: Prolonged time to treatment of biologics in Inflammatory Bowel Disease: disparities from
a retrospective study in a tertiary referral centre in the UK
Version: 2 Date: 22 Mar 2025
Reviewer's report:
I commend the authors for a thorough and timely analysis of delays in biologic therapy initiation
among adult IBD patients. This is a well-executed retrospective cohort study from a tertiary UK
centre that adds meaningful data to the limited non-North American literature on IBD treatment
delays.
Below are comments for the authors to consider in strengthening the final version:
- Clarify the clinical definition of “Time to Treatment (TTT)” TTT is defined as the time from
referral to the Biologics Clinic (BC) to first dose of therapy. Given that pre-BC processes (e.g.,
funding forms, screening) were required prior to BC referral, please clarify whether these steps
are included in or precede the TTT interval. The flow diagrams in Figures 2 and 3 (supplement)
are helpful, but a more explicit description in the Methods section would improve transparency.
- The observation that South Asian patients had shorter TTT than White British and “other
minority groups” is important and somewhat counterintuitive given literature on healthcare
disparities. While you suggest possible reasons (e.g., local population demographics, more
severe presentations), this deserves further discussion. Could you provide stratified baseline
CRP, steroid use, or hospitalisation rates by ethnicity to explore whether disease severity may
explain this difference?
- Table 3 (supplement) shows no significant association between TTT and adverse outcomes.
However, it appears that the study may be underpowered to detect such associations (e.g.,
only 24 patients with primary non-response). Please clarify in the Discussion that the lack of
association may reflect sample size limitations or residual confounding. Consider presenting
subgroup analyses for biologic-naïve patients or those with elevated CRP, where treatment
timing may matter more.
- The detailed categorisation of delays (Table 4) is a key strength. However, pharmacy-related
and administrative delays — including those involving homecare providers — are under-
discussed in the main text. These insights are valuable and deserve greater attention, particularly
given your finding that Adalimumab was independently associated with delayed TTT (likely
due to SC delivery logistics). Consider highlighting this in the Results and Discussion more
explicitly.
- You included variables with p # 0.2 in the multivariate model (Table 1, supplement). This
is methodologically acceptable, but please justify this choice briefly in the Statistical Methods
section to clarify your rationale.
- Please avoid “other ethnic minority group” unless you can define this more clearly (e.g., Black
African, Arab, etc.). If grouping was necessary due to small cell sizes, please state this explicitly
and consider using “other non-White” or another term that more transparently reflects your data
structure.
- Correct typographical errors (e.g., “initiatiation” # “initiation”, “assocoiated” # “associated”)
and ensure consistent spacing in units (e.g., “10 mg/L”, not “10mg/L”).
Please review this paper.
user
Title: Prolonged time to treatment of biologics in Inflammatory Bowel Disease: disparities from
a retrospective study in a tertiary referral centre in the UK
Version: 2 Date: 22 Mar 2025
Reviewer's report:
I commend the authors for a thorough and timely analysis of delays in biologic therapy initiation
among adult IBD patients. This is a well-executed retrospective cohort study from a tertiary UK
centre that adds meaningful data to the limited non-North American literature on IBD treatment
delays.
Below are comments for the authors to consider in strengthening the final version:
- Clarify the clinical definition of “Time to Treatment (TTT)” TTT is defined as the time from
referral to the Biologics Clinic (BC) to first dose of therapy. Given that pre-BC processes (e.g.,
funding forms, screening) were required prior to BC referral, please clarify whether these steps
are included in or precede the TTT interval. The flow diagrams in Figures 2 and 3 (supplement)
are helpful, but a more explicit description in the Methods section would improve transparency.
- The observation that South Asian patients had shorter TTT than White British and “other
minority groups” is important and somewhat counterintuitive given literature on healthcare
disparities. While you suggest possible reasons (e.g., local population demographics, more
severe presentations), this deserves further discussion. Could you provide stratified baseline
CRP, steroid use, or hospitalisation rates by ethnicity to explore whether disease severity may
explain this difference?
- Table 3 (supplement) shows no significant association between TTT and adverse outcomes.
However, it appears that the study may be underpowered to detect such associations (e.g.,
only 24 patients with primary non-response). Please clarify in the Discussion that the lack of
association may reflect sample size limitations or residual confounding. Consider presenting
subgroup analyses for biologic-naïve patients or those with elevated CRP, where treatment
timing may matter more.
- The detailed categorisation of delays (Table 4) is a key strength. However, pharmacy-related
and administrative delays — including those involving homecare providers — are under-
discussed in the main text. These insights are valuable and deserve greater attention, particularly
given your finding that Adalimumab was independently associated with delayed TTT (likely
due to SC delivery logistics). Consider highlighting this in the Results and Discussion more
explicitly.
- You included variables with p # 0.2 in the multivariate model (Table 1, supplement). This
is methodologically acceptable, but please justify this choice briefly in the Statistical Methods
section to clarify your rationale.
- Please avoid “other ethnic minority group” unless you can define this more clearly (e.g., Black
African, Arab, etc.). If grouping was necessary due to small cell sizes, please state this explicitly
and consider using “other non-White” or another term that more transparently reflects your data
structure.
- Correct typographical errors (e.g., “initiatiation” # “initiation”, “assocoiated” # “associated”)
and ensure consistent spacing in units (e.g., “10 mg/L”, not “10mg/L”).
assistant