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: 23 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The retrospective nature of the study is a significant limitation. This design inherently
introduces the risk of bias due to the reliance on existing medical records, and it is difficult
to control for unmeasured confounding factors that may influence treatment delays or adverse
outcomes.
-Although the study examines a wide range of clinical and demographic data, it lacks patient-
reported outcomes (e.g., quality of life, symptom severity from the patient's perspective) that
could provide more nuanced insights into the impact of prolonged TTT.
The study is conducted in a single tertiary referral center in the UK, which may limit the
generalizability of the findings to other settings, particularly in non-tertiary or resource-limited
environments. Variations in healthcare access, infrastructure, and treatment protocols may affect
the applicability of the results.
-While the study includes a range of variables, there may still be important confounding factors
that are not measured or captured in the electronic health records, such as psychological factors,
health literacy, or patient adherence to recommendations.
-The study focuses on short-term outcomes (within six months of biologic therapy), but long-
term outcomes of delayed biologic treatment (e.g., disease progression, long-term disability,
mortality) would provide a more complete understanding of the consequences of treatment
delays.
-While the study examines ethnicity and socio-economic status (via the IMDD score), the sample
population may not fully reflect the diversity of the general IBD population in terms of age, sex,
or ethnicity, particularly in countries with significant immigrant populations or those with high
levels of health disparities.
-Since the study uses retrospective data from electronic health records, there could be
inaccuracies or inconsistencies in how information was documented, such as the timing of
referrals, dates of biological therapy, and adverse outcomes. These could affect the accuracy of
the reported TTT and the association with adverse outcomes.
-The study doesn’t seem to compare outcomes for patients who did not experience delays in
biologic therapy, which would strengthen the understanding of the impact of timely treatment. It
would be useful to compare these groups directly to highlight the benefits of reducing treatment
delays.
-Although the study identifies delays in biological therapy, the discussion notes that the long-
term clinical outcomes associated with such delays are still uncertain. This gap in knowledge
is acknowledged, but it would have been valuable to more thoroughly address how treatment
delays might influence disease progression or long-term health outcomes, providing a clearer
rationale for timely biologic initiation.
-While ethnic disparities in care are a crucial topic, the discussion might have benefitted from a
more detailed analysis of how specific cultural, social, or economic factors influence access to
biologic therapy in different ethnic groups. The study mentions that South Asians in the local
population received treatment quicker, but more exploration of this subgroup’s specific needs,
and how they differ from other ethnicities, could provide deeper insights.
-The discussion could benefit from a more detailed exploration of the systemic barriers within the
healthcare system that contribute to delays in biological therapy. Issues such as administrative
inefficiencies, insurance or funding hurdles, or clinician variability in practice are briefly
mentioned, but a more thorough analysis of these barriers could help guide policy changes to
improve care access.
-The discussion briefly touches on the trend that older patients had longer TTT, but does not
provide in-depth exploration of why this may be the case. It could be valuable to delve deeper
into the clinical, social, or psychological factors that affect older adults’ treatment initiation.
Additionally, how can healthcare providers better support this patient group to ensure they
receive timely therapy?
-While clinician practice variability is mentioned, the discussion does not explore in detail how
different clinicians' decision-making and practices might contribute to delays. More emphasis
on how healthcare professionals’ practices or biases may affect timing could be important for
addressing the causes of delays.
-While the discussion acknowledges the pandemic as a factor that may have contributed to
delays, the exact role COVID-19 played in the delays could be further clarified. The mention of
COVID-19 seems more like a brief acknowledgment than a detailed exploration. Understanding
how the pandemic affected TTT in more detail could contribute to broader conclusions about
managing IBD during health crises.
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: 23 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The retrospective nature of the study is a significant limitation. This design inherently
introduces the risk of bias due to the reliance on existing medical records, and it is difficult
to control for unmeasured confounding factors that may influence treatment delays or adverse
outcomes.
-Although the study examines a wide range of clinical and demographic data, it lacks patient-
reported outcomes (e.g., quality of life, symptom severity from the patient's perspective) that
could provide more nuanced insights into the impact of prolonged TTT.
The study is conducted in a single tertiary referral center in the UK, which may limit the
generalizability of the findings to other settings, particularly in non-tertiary or resource-limited
environments. Variations in healthcare access, infrastructure, and treatment protocols may affect
the applicability of the results.
-While the study includes a range of variables, there may still be important confounding factors
that are not measured or captured in the electronic health records, such as psychological factors,
health literacy, or patient adherence to recommendations.
-The study focuses on short-term outcomes (within six months of biologic therapy), but long-
term outcomes of delayed biologic treatment (e.g., disease progression, long-term disability,
mortality) would provide a more complete understanding of the consequences of treatment
delays.
-While the study examines ethnicity and socio-economic status (via the IMDD score), the sample
population may not fully reflect the diversity of the general IBD population in terms of age, sex,
or ethnicity, particularly in countries with significant immigrant populations or those with high
levels of health disparities.
-Since the study uses retrospective data from electronic health records, there could be
inaccuracies or inconsistencies in how information was documented, such as the timing of
referrals, dates of biological therapy, and adverse outcomes. These could affect the accuracy of
the reported TTT and the association with adverse outcomes.
-The study doesn’t seem to compare outcomes for patients who did not experience delays in
biologic therapy, which would strengthen the understanding of the impact of timely treatment. It
would be useful to compare these groups directly to highlight the benefits of reducing treatment
delays.
-Although the study identifies delays in biological therapy, the discussion notes that the long-
term clinical outcomes associated with such delays are still uncertain. This gap in knowledge
is acknowledged, but it would have been valuable to more thoroughly address how treatment
delays might influence disease progression or long-term health outcomes, providing a clearer
rationale for timely biologic initiation.
-While ethnic disparities in care are a crucial topic, the discussion might have benefitted from a
more detailed analysis of how specific cultural, social, or economic factors influence access to
biologic therapy in different ethnic groups. The study mentions that South Asians in the local
population received treatment quicker, but more exploration of this subgroup’s specific needs,
and how they differ from other ethnicities, could provide deeper insights.
-The discussion could benefit from a more detailed exploration of the systemic barriers within the
healthcare system that contribute to delays in biological therapy. Issues such as administrative
inefficiencies, insurance or funding hurdles, or clinician variability in practice are briefly
mentioned, but a more thorough analysis of these barriers could help guide policy changes to
improve care access.
-The discussion briefly touches on the trend that older patients had longer TTT, but does not
provide in-depth exploration of why this may be the case. It could be valuable to delve deeper
into the clinical, social, or psychological factors that affect older adults’ treatment initiation.
Additionally, how can healthcare providers better support this patient group to ensure they
receive timely therapy?
-While clinician practice variability is mentioned, the discussion does not explore in detail how
different clinicians' decision-making and practices might contribute to delays. More emphasis
on how healthcare professionals’ practices or biases may affect timing could be important for
addressing the causes of delays.
-While the discussion acknowledges the pandemic as a factor that may have contributed to
delays, the exact role COVID-19 played in the delays could be further clarified. The mention of
COVID-19 seems more like a brief acknowledgment than a detailed exploration. Understanding
how the pandemic affected TTT in more detail could contribute to broader conclusions about
managing IBD during health crises.
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: 23 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The retrospective nature of the study is a significant limitation. This design inherently
introduces the risk of bias due to the reliance on existing medical records, and it is difficult
to control for unmeasured confounding factors that may influence treatment delays or adverse
outcomes.
-Although the study examines a wide range of clinical and demographic data, it lacks patient-
reported outcomes (e.g., quality of life, symptom severity from the patient's perspective) that
could provide more nuanced insights into the impact of prolonged TTT.
The study is conducted in a single tertiary referral center in the UK, which may limit the
generalizability of the findings to other settings, particularly in non-tertiary or resource-limited
environments. Variations in healthcare access, infrastructure, and treatment protocols may affect
the applicability of the results.
-While the study includes a range of variables, there may still be important confounding factors
that are not measured or captured in the electronic health records, such as psychological factors,
health literacy, or patient adherence to recommendations.
-The study focuses on short-term outcomes (within six months of biologic therapy), but long-
term outcomes of delayed biologic treatment (e.g., disease progression, long-term disability,
mortality) would provide a more complete understanding of the consequences of treatment
delays.
-While the study examines ethnicity and socio-economic status (via the IMDD score), the sample
population may not fully reflect the diversity of the general IBD population in terms of age, sex,
or ethnicity, particularly in countries with significant immigrant populations or those with high
levels of health disparities.
-Since the study uses retrospective data from electronic health records, there could be
inaccuracies or inconsistencies in how information was documented, such as the timing of
referrals, dates of biological therapy, and adverse outcomes. These could affect the accuracy of
the reported TTT and the association with adverse outcomes.
-The study doesn’t seem to compare outcomes for patients who did not experience delays in
biologic therapy, which would strengthen the understanding of the impact of timely treatment. It
would be useful to compare these groups directly to highlight the benefits of reducing treatment
delays.
-Although the study identifies delays in biological therapy, the discussion notes that the long-
term clinical outcomes associated with such delays are still uncertain. This gap in knowledge
is acknowledged, but it would have been valuable to more thoroughly address how treatment
delays might influence disease progression or long-term health outcomes, providing a clearer
rationale for timely biologic initiation.
-While ethnic disparities in care are a crucial topic, the discussion might have benefitted from a
more detailed analysis of how specific cultural, social, or economic factors influence access to
biologic therapy in different ethnic groups. The study mentions that South Asians in the local
population received treatment quicker, but more exploration of this subgroup’s specific needs,
and how they differ from other ethnicities, could provide deeper insights.
-The discussion could benefit from a more detailed exploration of the systemic barriers within the
healthcare system that contribute to delays in biological therapy. Issues such as administrative
inefficiencies, insurance or funding hurdles, or clinician variability in practice are briefly
mentioned, but a more thorough analysis of these barriers could help guide policy changes to
improve care access.
-The discussion briefly touches on the trend that older patients had longer TTT, but does not
provide in-depth exploration of why this may be the case. It could be valuable to delve deeper
into the clinical, social, or psychological factors that affect older adults’ treatment initiation.
Additionally, how can healthcare providers better support this patient group to ensure they
receive timely therapy?
-While clinician practice variability is mentioned, the discussion does not explore in detail how
different clinicians' decision-making and practices might contribute to delays. More emphasis
on how healthcare professionals’ practices or biases may affect timing could be important for
addressing the causes of delays.
-While the discussion acknowledges the pandemic as a factor that may have contributed to
delays, the exact role COVID-19 played in the delays could be further clarified. The mention of
COVID-19 seems more like a brief acknowledgment than a detailed exploration. Understanding
how the pandemic affected TTT in more detail could contribute to broader conclusions about
managing IBD during health crises.
assistant