Fact-Finding Survey and Exploration of Preventive Drugs for Antineoplastic Drug-Induced Oral Mucositis Using the Japanese Adverse Drug Event Report Database

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This work is focussed in the oral mucositis induced by antineoplasic drugs.

This adverse effect is well know, but improvements can be detected in the prevention and treatment.

The work has an important number of data and are well exploited. However, there are some aspects that could be improved.

Figure 3 and 4 are could be improved in the way that some of the data are difficult to read, as they are too small.

Some other considerations:

As the authors say in the limitations, the data do not take into account the association of drugs. As these drugs are alway used in combination this is an important limitations. Because, how people that made the adverse reaction report could attribute the mucositis to only one of the drugs of the treatment? Or did they report all the drugs as possible cause?

Another aspect that I would like to point out is the fact that some of the patients could be receiving treatment for the mucositis. Some are reported in the work, but I think that there could be more. For instance, is habitual to use plant preparations for the prevention and treatment of mucositis (thyme infusions is one of this).

 

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

I read with interest the paper titled "Fact-finding survey and exploration of preventive drugs for antineoplastic drug-induced oral mucositis using the Japanese Adverse Drug Event Report database"

 

Introduction

 

First lines of introduction requires several references to report each AE,

 

The definition of oral mucositis requires one or several references found.

 

Line 51 - Please clarify this: "The primary sources of information for managing OM are package inserts and clinical trials" - what you mean by package inserts? The sentense should be referenced as well. 

 

Line 52 - Recent reports - please add reference

 

Line 53 - based on meta-analysis - please add reference

 

Line 58 - recent studies - please add reference

 

Line 94 - The sex distribution was as follows: 40.3% were females, 54.6% were males, and 5.1% were others or unknown. - There are no other sexes, maybe all of them are unknown? Or the data were already delivered to you this way?

 

Figure 2 is great to compare risk of the OM within drugs. My suggestion is to give more enphasis on this (bigger image, more relevant data highlighted). This is good for clarifying the drugs that have highest risk, but also the ones with lower (or protective effect, if any), so this is a great add for clinicians in drug shifting. 

 

My suggestion in that the most important data on Table S3 could come to the main manuscript. Your work is based on that data, it makes sense to me to present that in the main manuscript and maybe it's more relevant clinically than the Table 2. Suggest to add or swap. 

 

So, you analysed 20 AEs but only 11AEs entered in the cluster analysis? Please clarify if with 11 you already have the clusters made, or if the other were previously excluded. It was because the others have less than 20 cases? Please clarify. 

 

Have you tested iteration with less AEs? It leads to similar results or different? 

 

Methods: How do you defined the MedDRA PTs related with Oral Mucositis. Oral Mucositis is a LLT indeed, so how do you found those related PTs and not others?

 

Reference 17 have incorrect link

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 3 Report

Comments and Suggestions for Authors

Title: Fact-finding survey and exploration of preventive drugs for antineoplastic drug-induced oral mucositis using the Japanese Adverse Drug Event Report database

 

 COMMENTS TO THE AUTHORS

General comments

The authors conducted a disproportionality analysis of antineoplastic drug-induced OM and explored candidate preventive drugs for OM using the Japanese Adverse Drug Event Report (JADER) database. This is a well-done study and an important one since it can help in drugs prioritization to validate their effect against antineoplastic-induced OM. This study can also be replicated to assess other drugs for other diseases.

Specific comments for revision:

a)      Major

• I am not sure how the manuscripts should be formatted for this journal. However, I had to read the material and methods section first before reviewing the results. I suggest moving the material/methods section to before the results section.

b)      Minor

• Figure 1: spell out ATC and JADER in the figure’s footnote.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have made improvements and have answered the questions that I included in my report.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors incorporated the requested changes in the manuscript. Accept in the current form. 

Reviewer 3 Report

Comments and Suggestions for Authors

The authors have addressed my comments! Congrats! However, I have noticed now that some editing needs to be done for the highlighted added sentences. For instance: 

Lines: 64-66

Lines: 264-266

 

Comments on the Quality of English Language

The authors have addressed my comments! Congrats! However, I have noticed now that some editing needs to be done for the highlighted added sentences. For instance: 

Lines: 64-66

Lines: 264-266