Title: Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation:
A systematic literature review with meta-analysis and number needed to treat/harm
Version: 1 Date: 23 Jul 2023
Reviewer:  Kok-Ann Gwee
Reviewer's report:
General comments
This study is of clinical relevance and interest given the prevalence of constipation, plethora of
treatments and high patient dissatisfaction. The 3 selected agents have in common a relatively
new approach that involves inducing intestinal secretion. In essence this is a comparative review
that serves to provide clinical guidance in the selection of 3 treatments with overlapping modes
of action. The key findings are: all have similar efficacy, but differing side effect profile.
Overall the paper is very lengthy. In the Introduction, the paragraph detailing the various
treatment approaches: “Several treatment approaches have been defined for constipation” can
be removed as this is not a review paper on the general management of constipation. In its place,
a bit more details can be provided on the mechanisms of actions for the 3 agents under review.
This will allow for the details about mechanisms to be removed from the Discussion, so that
there is more space to discuss the findings of the study. As the title of the paper is after all
“Comparative profiles …” the authors should provide more critical evaluation of the similarities
and the differences among the 3 agents, based on their study findings.
Methods
The methodology is clearly defined, appropriate and relevant. Except, why was a large sample
size study (linaclotide) excluded? Is this appropriate?
Results
This is a very lengthy paper. There are enough data for 3 standalone papers; ie, one for each drug.
Essentially the authors are iterating a parallel list of findings for each drug.
I believe the paper will be more reader friendly if the bulk of the data are presented in table
format with brief explanatory notes. For example, the repetitive declaration that this study was
based in the US and this study was in Japan, become tedious reading.
All the key and relevant information is provided in the supplementary tables S2 to S6, while the
meta-analyses are contained in the supplementary figures S1-S5. These tables and figures are
useful and could be placed in the main paper.
Discussion
To report that “SBM frequency was a common primary outcome measure” is a self-fulfilling
prophecy as this is the outcome dictated by the Rome committee during the period when these
clinical trials were conducted, and as the authors ‘selected’ this as the primary outcome because
this was an endpoint used by studies for the 3 agents.
The following statement is speculative and not relevant to the objective of this paper.
“Linaclotide … at different doses … It is probably due to lifestyle and racial differences such
as diet, gut microbiota, genetic polymorphism.”
Another self-fulfilling assertion is to suggest as limitations of the study that “the evaluation for
traditional laxatives, topical agents, and other new agents is not conducted”.
Title: Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation:
A systematic literature review with meta-analysis and number needed to treat/harm
Version: 1 Date: 23 Jul 2023
Reviewer:  Kok-Ann Gwee
Reviewer's report:
General comments
This study is of clinical relevance and interest given the prevalence of constipation, plethora of
treatments and high patient dissatisfaction. The 3 selected agents have in common a relatively
new approach that involves inducing intestinal secretion. In essence this is a comparative review
that serves to provide clinical guidance in the selection of 3 treatments with overlapping modes
of action. The key findings are: all have similar efficacy, but differing side effect profile.
Overall the paper is very lengthy. In the Introduction, the paragraph detailing the various
treatment approaches: “Several treatment approaches have been defined for constipation” can
be removed as this is not a review paper on the general management of constipation. In its place,
a bit more details can be provided on the mechanisms of actions for the 3 agents under review.
This will allow for the details about mechanisms to be removed from the Discussion, so that
there is more space to discuss the findings of the study. As the title of the paper is after all
“Comparative profiles …” the authors should provide more critical evaluation of the similarities
and the differences among the 3 agents, based on their study findings.
Methods
The methodology is clearly defined, appropriate and relevant. Except, why was a large sample
size study (linaclotide) excluded? Is this appropriate?
Results
This is a very lengthy paper. There are enough data for 3 standalone papers; ie, one for each drug.
Essentially the authors are iterating a parallel list of findings for each drug.
I believe the paper will be more reader friendly if the bulk of the data are presented in table
format with brief explanatory notes. For example, the repetitive declaration that this study was
based in the US and this study was in Japan, become tedious reading.
All the key and relevant information is provided in the supplementary tables S2 to S6, while the
meta-analyses are contained in the supplementary figures S1-S5. These tables and figures are
useful and could be placed in the main paper.
Discussion
To report that “SBM frequency was a common primary outcome measure” is a self-fulfilling
prophecy as this is the outcome dictated by the Rome committee during the period when these
clinical trials were conducted, and as the authors ‘selected’ this as the primary outcome because
this was an endpoint used by studies for the 3 agents.
The following statement is speculative and not relevant to the objective of this paper.
“Linaclotide … at different doses … It is probably due to lifestyle and racial differences such
as diet, gut microbiota, genetic polymorphism.”
Another self-fulfilling assertion is to suggest as limitations of the study that “the evaluation for
traditional laxatives, topical agents, and other new agents is not conducted”.
Please review this paper.
user
Title: Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation:
A systematic literature review with meta-analysis and number needed to treat/harm
Version: 1 Date: 23 Jul 2023
Reviewer:  Kok-Ann Gwee
Reviewer's report:
General comments
This study is of clinical relevance and interest given the prevalence of constipation, plethora of
treatments and high patient dissatisfaction. The 3 selected agents have in common a relatively
new approach that involves inducing intestinal secretion. In essence this is a comparative review
that serves to provide clinical guidance in the selection of 3 treatments with overlapping modes
of action. The key findings are: all have similar efficacy, but differing side effect profile.
Overall the paper is very lengthy. In the Introduction, the paragraph detailing the various
treatment approaches: “Several treatment approaches have been defined for constipation” can
be removed as this is not a review paper on the general management of constipation. In its place,
a bit more details can be provided on the mechanisms of actions for the 3 agents under review.
This will allow for the details about mechanisms to be removed from the Discussion, so that
there is more space to discuss the findings of the study. As the title of the paper is after all
“Comparative profiles …” the authors should provide more critical evaluation of the similarities
and the differences among the 3 agents, based on their study findings.
Methods
The methodology is clearly defined, appropriate and relevant. Except, why was a large sample
size study (linaclotide) excluded? Is this appropriate?
Results
This is a very lengthy paper. There are enough data for 3 standalone papers; ie, one for each drug.
Essentially the authors are iterating a parallel list of findings for each drug.
I believe the paper will be more reader friendly if the bulk of the data are presented in table
format with brief explanatory notes. For example, the repetitive declaration that this study was
based in the US and this study was in Japan, become tedious reading.
All the key and relevant information is provided in the supplementary tables S2 to S6, while the
meta-analyses are contained in the supplementary figures S1-S5. These tables and figures are
useful and could be placed in the main paper.
Discussion
To report that “SBM frequency was a common primary outcome measure” is a self-fulfilling
prophecy as this is the outcome dictated by the Rome committee during the period when these
clinical trials were conducted, and as the authors ‘selected’ this as the primary outcome because
this was an endpoint used by studies for the 3 agents.
The following statement is speculative and not relevant to the objective of this paper.
“Linaclotide … at different doses … It is probably due to lifestyle and racial differences such
as diet, gut microbiota, genetic polymorphism.”
Another self-fulfilling assertion is to suggest as limitations of the study that “the evaluation for
traditional laxatives, topical agents, and other new agents is not conducted”.
assistant