Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Round 1

Reviewer 1 Report

It is a very interesting and relevant manuscript updating ADRs pharmacogenomics literature. It contains very important and complete information on this subject that is worth reading for physicians, pharmacists and scientists in order to improve the use of PGx to avoid ADRs.

Minor notes are highlighted in the file enclosed. 

Comments for author File: Comments.pdf

Author Response

Dear Editor and Referees,

Thank you very much for your kind recommendations.

We have taken into account all the suggestions proposed by the referees and we are very grateful to them for their kindness and intelligent comments. All the appropriate corrections have been made, following the criteria of the referees, as you can see in the attached document (with all the changes introduced, indicated in the Track Changes of Word.

Table 5 has been deleted. We fully agree with the referee's suggestion. This table does not bring novelty in the general context of the review and therefore it makes sense to delete it.

In relation to comment-2, we agree with the referee's point of view that part of the problem in the introduction of PGx into the medical routine is due to the absence of conclusive studies that give confidence to the physician when he/she comes to following PGx criteria for prescribing drugs.

With reference to comment-3 on the possibility of converting Tables 1-4 into an Appendix or a Data Supplement, we believe that such a decision would weaken the strength of the content of the review, so we suggest that Tables 1-4 be retained as an integral part of the review.

All Tables are original and have been designed specifically for this work; their contents are unique, providing key pharmacogenetic information, available to date, on the drugs of greatest use in prevalent pathologies. This originality makes them unique and therefore we consider that they are a fundamental part in the body of the review.

I reiterate my thanks to you for your kindness.

With all my appreciation

               Ramón Cacabelos, M.D., Ph.D., D.M.Sci.

                              Professor & Chairman of Genomic Medicine

Reviewer 2 Report

Drs. Cacabelos R. and others have reviewed “GenoPhenotypic factors and pharmacogenomics in adverse drug reactions”. Reading through the manuscript, this referee considers that this is one of the most updated, extensive and thorough review of the topics. He also considers that Tables 1 through 4 are interesting. He would like to give comments and suggestions shown below.

1. This referee recommends that Table 5 be removed. It seems to convey no additional information than those written in the prescribing information of the respective vaccines.
2. The authors have searched for a large volume of information that apparently indicates a possible link between genomic variants and clinical outcomes as ADRs. Nevertheless, most of them have been suggested, but not been proved, to have a robust contribution to clinical outcomes by RCTs. For instance, the pre-emptive genotyping of CYP2C9 and VCORC1 has not been shown to be superior to the traditional clinical care with measurements of INR-PT in terms of the quality of anticoagulation assessed by the time within therapeutic range of INR-PT. From a point of view of researchers, they attribute the slow implementation of PGx to the clinical practice to a lack of education/knowledge of PGXs in general practitioners. However, they also should keep a balanced view about a relative lack of robust evidence that the genomic information critically influences on the patients’ clinical outcomes.
3. Tables 1 through 4 may be moved to Appendix or Supplementary data, if the editor-in-chief considers for the sake of saving space for the Journal.

Author Response

Dear Editor and Referees,

Thank you very much for your kind recommendations.

We have taken into account all the suggestions proposed by the referees and we are very grateful to them for their kindness and intelligent comments. All the appropriate corrections have been made, following the criteria of the referees, as you can see in the attached document (with all the changes introduced, indicated in the Track Changes of Word.

Table 5 has been deleted. We fully agree with the referee's suggestion. This table does not bring novelty in the general context of the review and therefore it makes sense to delete it.

In relation to comment-2, we agree with the referee's point of view that part of the problem in the introduction of PGx into the medical routine is due to the absence of conclusive studies that give confidence to the physician when he/she comes to following PGx criteria for prescribing drugs.

With reference to comment-3 on the possibility of converting Tables 1-4 into an Appendix or a Data Supplement, we believe that such a decision would weaken the strength of the content of the review, so we suggest that Tables 1-4 be retained as an integral part of the review.

All Tables are original and have been designed specifically for this work; their contents are unique, providing key pharmacogenetic information, available to date, on the drugs of greatest use in prevalent pathologies. This originality makes them unique and therefore we consider that they are a fundamental part in the body of the review.

I reiterate my thanks to you for your kindness.

With all my appreciation

               Ramón Cacabelos, M.D., Ph.D., D.M.Sci.

                              Professor & Chairman of Genomic Medicine