Reviewer's report
Title:Albumin treatment regimen for type 1 hepatorenal syndrome: a
dose-response meta-analysis
Version:3Date:19 May 2015
Reviewer: Aleksander Krag
Reviewer's report:
The authors present a meta-analysis of the dose-response relationship of
albumin and survival in HRS type 1.
The topic is relevant and the manuscipt adresses an unmet need: dose
optimization studies regardin albumin in HRS. As the authors point out, the
optimal dose of albumin for HRS has never been estimated in a randomized
setting. The meta-analysis is sound and done in accordance with MOOSE
guidelines. I have only a few major concerns:
- Bias assessment. Bias assessment in observational study meta-analyses is
difficult, as there is no commonly agreed upon tool. However, the MOOSE group
still recommends to assess bias in the included studies. I suggest that authors
choose a previously published checklist or scoring system. Or simply evaluate
the following points recommended by the Oxford Center for Evidence Based
Medicine: whether patients are assembled at a common point in the course of
their disease, whether the follow up data are complete, how likely the outcomes
are over time and how precise the prognostic estimates are.
- Primary outcome. The authors focus on cumulative albumine dose, whereas
average daily dose is less thoroughly described in the manuscript. The reason for
this is unclear. 1) As the authors point out in their discussion, the association
between survival and high cumulative doses of albumin could be due to the fact
that patients surviving receive albumin for a longer time than patients that die.
This is somewhat accounted for by using the 30-day mortality rate as cut-point
and creating survival curves, but it would still seem more appropriate to use daily
albumin dose for their primary outcome report. 2) In a clinical context,
recommendations on the optimal daily albumin dose is more relevant than
cumulative albumin dose. The reason for focusing on cumulative albumin should
at least be clearly stated in the text.
- Adverse events. It is a major drawback of this analysis, that the authors have no
information on adverse events. For example, it remains unknown whether a
cumulative albumin dose of 600 g will result in an increased rate of pulmonary
oedema? From the text, I get the impression that adverse events was not
extracted from the data. If so, the reason for this needs to be stated. If the
opposite is true: that the authors could simply not extract sufficient AE data for
analysis, this fact needs to be stated.
- Text revision. Some lengthy paragraphs in the manuscript could be removed to
increase readability of the text. For example the reasoning for choosing to
include observational studies (“study selection” in the Patients & Methods
section); the “ethical approval and consent” paragraph; and much of the
discussion concerning possible mechanisms of albumin.
Minor concerns:
- In one analysis, increments of 100 g of cumulative albumin are accompanied by
increased OR for survival. But in the analysis of 30-day survival rates, the
authors use increments of 200 g cumulative albumin. The reason for this
discrepancy should be explained.
- The survival and HRS outcomes should also be referred in absolute numbers,
not only survival rates and ratios - i.e.: how many at-risk patients, and of these,
how many experienced the outcome.
- It is contra-intuitive to use hazard ratio >1.00 to denote increasing survival with
increasing albumin.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Albumin treatment regimen for type 1 hepatorenal syndrome: a
dose-response meta-analysis
Version:3Date:19 May 2015
Reviewer: Aleksander Krag
Reviewer's report:
The authors present a meta-analysis of the dose-response relationship of
albumin and survival in HRS type 1.
The topic is relevant and the manuscipt adresses an unmet need: dose
optimization studies regardin albumin in HRS. As the authors point out, the
optimal dose of albumin for HRS has never been estimated in a randomized
setting. The meta-analysis is sound and done in accordance with MOOSE
guidelines. I have only a few major concerns:
- Bias assessment. Bias assessment in observational study meta-analyses is
difficult, as there is no commonly agreed upon tool. However, the MOOSE group
still recommends to assess bias in the included studies. I suggest that authors
choose a previously published checklist or scoring system. Or simply evaluate
the following points recommended by the Oxford Center for Evidence Based
Medicine: whether patients are assembled at a common point in the course of
their disease, whether the follow up data are complete, how likely the outcomes
are over time and how precise the prognostic estimates are.
- Primary outcome. The authors focus on cumulative albumine dose, whereas
average daily dose is less thoroughly described in the manuscript. The reason for
this is unclear. 1) As the authors point out in their discussion, the association
between survival and high cumulative doses of albumin could be due to the fact
that patients surviving receive albumin for a longer time than patients that die.
This is somewhat accounted for by using the 30-day mortality rate as cut-point
and creating survival curves, but it would still seem more appropriate to use daily
albumin dose for their primary outcome report. 2) In a clinical context,
recommendations on the optimal daily albumin dose is more relevant than
cumulative albumin dose. The reason for focusing on cumulative albumin should
at least be clearly stated in the text.
- Adverse events. It is a major drawback of this analysis, that the authors have no
information on adverse events. For example, it remains unknown whether a
cumulative albumin dose of 600 g will result in an increased rate of pulmonary
oedema? From the text, I get the impression that adverse events was not
extracted from the data. If so, the reason for this needs to be stated. If the
opposite is true: that the authors could simply not extract sufficient AE data for
analysis, this fact needs to be stated.
- Text revision. Some lengthy paragraphs in the manuscript could be removed to
increase readability of the text. For example the reasoning for choosing to
include observational studies (“study selection” in the Patients & Methods
section); the “ethical approval and consent” paragraph; and much of the
discussion concerning possible mechanisms of albumin.
Minor concerns:
- In one analysis, increments of 100 g of cumulative albumin are accompanied by
increased OR for survival. But in the analysis of 30-day survival rates, the
authors use increments of 200 g cumulative albumin. The reason for this
discrepancy should be explained.
- The survival and HRS outcomes should also be referred in absolute numbers,
not only survival rates and ratios - i.e.: how many at-risk patients, and of these,
how many experienced the outcome.
- It is contra-intuitive to use hazard ratio >1.00 to denote increasing survival with
increasing albumin.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Albumin treatment regimen for type 1 hepatorenal syndrome: a
dose-response meta-analysis
Version:3Date:19 May 2015
Reviewer: Aleksander Krag
Reviewer's report:
The authors present a meta-analysis of the dose-response relationship of
albumin and survival in HRS type 1.
The topic is relevant and the manuscipt adresses an unmet need: dose
optimization studies regardin albumin in HRS. As the authors point out, the
optimal dose of albumin for HRS has never been estimated in a randomized
setting. The meta-analysis is sound and done in accordance with MOOSE
guidelines. I have only a few major concerns:
- Bias assessment. Bias assessment in observational study meta-analyses is
difficult, as there is no commonly agreed upon tool. However, the MOOSE group
still recommends to assess bias in the included studies. I suggest that authors
choose a previously published checklist or scoring system. Or simply evaluate
the following points recommended by the Oxford Center for Evidence Based
Medicine: whether patients are assembled at a common point in the course of
their disease, whether the follow up data are complete, how likely the outcomes
are over time and how precise the prognostic estimates are.
- Primary outcome. The authors focus on cumulative albumine dose, whereas
average daily dose is less thoroughly described in the manuscript. The reason for
this is unclear. 1) As the authors point out in their discussion, the association
between survival and high cumulative doses of albumin could be due to the fact
that patients surviving receive albumin for a longer time than patients that die.
This is somewhat accounted for by using the 30-day mortality rate as cut-point
and creating survival curves, but it would still seem more appropriate to use daily
albumin dose for their primary outcome report. 2) In a clinical context,
recommendations on the optimal daily albumin dose is more relevant than
cumulative albumin dose. The reason for focusing on cumulative albumin should
at least be clearly stated in the text.
- Adverse events. It is a major drawback of this analysis, that the authors have no
information on adverse events. For example, it remains unknown whether a
cumulative albumin dose of 600 g will result in an increased rate of pulmonary
oedema? From the text, I get the impression that adverse events was not
extracted from the data. If so, the reason for this needs to be stated. If the
opposite is true: that the authors could simply not extract sufficient AE data for
analysis, this fact needs to be stated.
- Text revision. Some lengthy paragraphs in the manuscript could be removed to
increase readability of the text. For example the reasoning for choosing to
include observational studies (“study selection” in the Patients & Methods
section); the “ethical approval and consent” paragraph; and much of the
discussion concerning possible mechanisms of albumin.
Minor concerns:
- In one analysis, increments of 100 g of cumulative albumin are accompanied by
increased OR for survival. But in the analysis of 30-day survival rates, the
authors use increments of 200 g cumulative albumin. The reason for this
discrepancy should be explained.
- The survival and HRS outcomes should also be referred in absolute numbers,
not only survival rates and ratios - i.e.: how many at-risk patients, and of these,
how many experienced the outcome.
- It is contra-intuitive to use hazard ratio >1.00 to denote increasing survival with
increasing albumin.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
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