Evaluating the Use of Dalbavancin for Off-Label Indications

Round 1

Reviewer 1 Report

Dear Authors,

it is a very interesting research work. As a general remark, please format the tables according to the journal's requirements. Additionally, I suggest choosing a different way of presenting data in the case of Figure 2. 
Please standardize the method of citation in the text.

I would complete the discussion on whether, in the case of patients in whom dalbavancin did not help, whether, for example, there was bacterial resistance to a given antibiotic, or whether there were complications after administration of the drug.

Author Response

Response to reviewer #1

Thank you for your comments and suggestions on how to improve our manuscript.  They are appreciated.  Here is our response:

As a general remark, please format the tables according to the journal's requirements.

Tables reformatted

Additionally, I suggest choosing a different way of presenting data in the case of Figure 2.

Figure 2 modified

Please standardize the method of citation in the text.

Citations modified to MDPI style

I would complete the discussion on whether, in the case of patients in whom dalbavancin did not help, whether, for example, there was bacterial resistance to a given antibiotic, or whether there were complications after administration of the drug.

We added a comment to the results section (old line 161) to state that neither of these occurred in any of the patients

Reviewer 2 Report

This is primarily a pharmacoeconomic study using a cost minimization technique to determine the relative safety and efficacy of dalbavancin used off-label in an adult infectious diseases cohort within a 4-unit health system. The analysis is based solely on the cost difference between dalbavancin and institutional days avoided (IDA) without the additional costs associated with other antibiotics or lab tests. Generally, the manuscript is well written. The following comments and suggestions are offered in order to strengthen an already robust presentation.

Title: "Evaluating" is too non-specific. Consider "The pharmacoeconomics of off-label dalbavancin in a real-world cohort"

Abstract: line 17: Change 'financial analysis' to 'pharmacoeconomic analysis'. What was the percentage of off-label use? Line 26-27: consider changing the last sentence to 'Dalbavancin use was associated with a comparable clinical outcome based on prior studies, and ....'

Key words: All are MeSh terms. However, to increase the searchability of the manuscript, consider adding the following terms: pharmacoeconomics; cohort studies, historical 

Introduction:  citation #8 is not in mdpi style in the text. Please correct. Also at line 227.

Literature review and health system description are appropriate. 

Line 56: insert USD with $.

Methods: should state that the analysis was undertaken from the perspective of the health-system. Why wasn't reimbursement data included? This often drives 'real-world' agent selection.

Line 81: Was a culture-confirmed infection part of the inclusion criteria? If not, how much was empiric? Does your strict use criteria allow for empiric use? You elude to it.

Lines 84-90: a citation is needed for appropriate monitoring of toxicity biomarkers. I would suggest the package insert.

Results: How many patients needed diose adjustments based on renal function as per literature ?

Discussion:  Appropriate literature is summarized and contextualized. Limitations are well explained.

Conclusion: Follows from their results.

References: not in mdpi style.

Thank you for the opportunity to reviedw this interesting and important manuscript.

Author Response

Response to reviewer #2

Thank you for your comments and suggestions on how to improve our manuscript.  They are appreciated.  Here is our response:

Title: "Evaluating" is too non-specific. Consider "The pharmacoeconomics of off-label dalbavancin in a real-world cohort"

We respectfully disagree with this suggestion.  The major outcome of our study is clinical success and not just economic difference.  Therefore, we think the term “evaluating” is appropriate since we are looking at clinical response, safety, and potential cost avoidance.

Abstract: line 17: Change 'financial analysis' to 'pharmacoeconomic analysis'.

Term changed

What was the percentage of off-label use?

It was 100%.  It was an inclusion criteria for the study

Line 26-27: consider changing the last sentence to 'Dalbavancin use was associated with a comparable clinical outcome based on prior studies, and ....'

Again, we respectfully disagree with this suggestion.  Our study evaluated clinical outcomes, so the statement is appropriate as written.

Key words: All are MeSh terms. However, to increase the searchability of the manuscript, consider adding the following terms: pharmacoeconomics; cohort studies, historical

Terms added.

Introduction:  citation #8 is not in mdpi style in the text. Please correct. Also at line 227.

These have been changed to mdpi style.

Line 56: insert USD with $.

US$ inserted

Methods: should state that the analysis was undertaken from the perspective of the health-system.

This was added to line 85.

Why wasn't reimbursement data included? This often drives 'real-world' agent selection.

We agree that reimbursement often drives real world decisions.  However, reimbursement is very complicated for dalbavancin.  It is dependent on many variables including place of infusion, patient mix, type of insurance, and potential drug replacement by the company.  We also were not be able to include the reimbursement of the potential alternative antibiotics, so we were not able to accurately include reimbursement in our analysis.

Line 81: Was a culture-confirmed infection part of the inclusion criteria? If not, how much was empiric? Does your strict use criteria allow for empiric use? You elude to it.

Table 2 lists the pathogens isolated.  There were no positive cultures for 8 patients (ie, empiric use).

Lines 84-90: a citation is needed for appropriate monitoring of toxicity biomarkers. I would suggest the package insert.

These toxicity biomarkers are not specific for any drugs.  The list includes various things that we monitored including how we defined nephrotoxicy and hepatotoxicity.

Results: How many patients needed diose adjustments based on renal function as per literature ?

None.  (1 pt received 1 gram; the rest received 1500mg)

References: not in mdpi style.

References modified to mdpi style.