Title: Predictive modeling to evaluate long-term treatment effectiveness of darvadstrocel in
patients with complex perianal fistulas in Crohn’s disease
Version: 5 Date: 19 Jul 2024
Reviewer:  Claire Liefferinckx
Reviewer's report:
Abstract:
About method part:
• More details should be given about the approach of predictive models instead of developing
which countries were involved in the three studies.
About result part:
• p-value should be added for proportions
About the conclusion:
• this conclusion is not useful and should be rephrased to capture the key results of the study
instead of rephrasing the aim of the study.
Background
• There is no “.” to separate the sentences. Syntax should be improved
• The reason for using such predictive models should be mentioned since introduction to help
the reader to understand the added value of this methodology.
Methods
• Patients from the three studies (ADMIRE-CD, INSPECT, and PREFACE) are different or
some patients could be present in the studies? If risk of duplicated data, how it was managed?
• Clinical validation of the model: this is a good idea to have an external validation of the model
before implementing. Nevertheless, I’m not convinced that clinical experts are the best experts
to properly evaluate the structure, assumptions, and inputs of the semi-Markov model
Results/ Discussion
• Table 3 should include comparative analyses (with p-val) between ADMIRE-CD and
PREFACE
• Regarding the following sentence: “The best-fitting location- and shape-adjusted models
decreased the differential treatment effect for all definitions of relapse when compared with the
Gompertz curve, which was chosen as the base-case model because its estimates were considered
appropriate and clinically plausible by the panel of clinical experts”. Authors should develop
what means “clinically plausible”
• It appears unclear how authors managed the differences between cohorts (specially between
ADMIRE-CD and PREFACE) before pooling them together.
• There is no external validation of the predictive model. This might be explained, as mentioned
by the authors, be the low number of events (particularly relapses) which limits the ability to
split the dataset for external validation. Nevertheless, this should be mentioned in the limits.
Title: Predictive modeling to evaluate long-term treatment effectiveness of darvadstrocel in
patients with complex perianal fistulas in Crohn’s disease
Version: 5 Date: 19 Jul 2024
Reviewer:  Claire Liefferinckx
Reviewer's report:
Abstract:
About method part:
• More details should be given about the approach of predictive models instead of developing
which countries were involved in the three studies.
About result part:
• p-value should be added for proportions
About the conclusion:
• this conclusion is not useful and should be rephrased to capture the key results of the study
instead of rephrasing the aim of the study.
Background
• There is no “.” to separate the sentences. Syntax should be improved
• The reason for using such predictive models should be mentioned since introduction to help
the reader to understand the added value of this methodology.
Methods
• Patients from the three studies (ADMIRE-CD, INSPECT, and PREFACE) are different or
some patients could be present in the studies? If risk of duplicated data, how it was managed?
• Clinical validation of the model: this is a good idea to have an external validation of the model
before implementing. Nevertheless, I’m not convinced that clinical experts are the best experts
to properly evaluate the structure, assumptions, and inputs of the semi-Markov model
Results/ Discussion
• Table 3 should include comparative analyses (with p-val) between ADMIRE-CD and
PREFACE
• Regarding the following sentence: “The best-fitting location- and shape-adjusted models
decreased the differential treatment effect for all definitions of relapse when compared with the
Gompertz curve, which was chosen as the base-case model because its estimates were considered
appropriate and clinically plausible by the panel of clinical experts”. Authors should develop
what means “clinically plausible”
• It appears unclear how authors managed the differences between cohorts (specially between
ADMIRE-CD and PREFACE) before pooling them together.
• There is no external validation of the predictive model. This might be explained, as mentioned
by the authors, be the low number of events (particularly relapses) which limits the ability to
split the dataset for external validation. Nevertheless, this should be mentioned in the limits.
Please review this paper.
user
Title: Predictive modeling to evaluate long-term treatment effectiveness of darvadstrocel in
patients with complex perianal fistulas in Crohn’s disease
Version: 5 Date: 19 Jul 2024
Reviewer:  Claire Liefferinckx
Reviewer's report:
Abstract:
About method part:
• More details should be given about the approach of predictive models instead of developing
which countries were involved in the three studies.
About result part:
• p-value should be added for proportions
About the conclusion:
• this conclusion is not useful and should be rephrased to capture the key results of the study
instead of rephrasing the aim of the study.
Background
• There is no “.” to separate the sentences. Syntax should be improved
• The reason for using such predictive models should be mentioned since introduction to help
the reader to understand the added value of this methodology.
Methods
• Patients from the three studies (ADMIRE-CD, INSPECT, and PREFACE) are different or
some patients could be present in the studies? If risk of duplicated data, how it was managed?
• Clinical validation of the model: this is a good idea to have an external validation of the model
before implementing. Nevertheless, I’m not convinced that clinical experts are the best experts
to properly evaluate the structure, assumptions, and inputs of the semi-Markov model
Results/ Discussion
• Table 3 should include comparative analyses (with p-val) between ADMIRE-CD and
PREFACE
• Regarding the following sentence: “The best-fitting location- and shape-adjusted models
decreased the differential treatment effect for all definitions of relapse when compared with the
Gompertz curve, which was chosen as the base-case model because its estimates were considered
appropriate and clinically plausible by the panel of clinical experts”. Authors should develop
what means “clinically plausible”
• It appears unclear how authors managed the differences between cohorts (specially between
ADMIRE-CD and PREFACE) before pooling them together.
• There is no external validation of the predictive model. This might be explained, as mentioned
by the authors, be the low number of events (particularly relapses) which limits the ability to
split the dataset for external validation. Nevertheless, this should be mentioned in the limits.
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