Reviewer ’s report  
 
Title: Economic Evaluation of Pegylated Interferon p lus Ribavirin for Treatment of Chronic 
Hepatitis C in Thailand: Genotype 1 and 6  
 
 
Version: 0 Date: 27 Apr 2016  
 
 
Reviewer: Mendel  Singer  
 
 
Reviewer's report:  
 
This cost -utility modeling study is generally well done and conforms with usual standards for 
these types of studies. The strategies compared were of recent interest in Thaila nd, and changes 
in approved regimen were based on these results. It is likely there are other developing nations 
where these are still appropriate strategies to compare.  
 
Comments:  
1. The paper should state explicitly that there are no previously approved t reatments for 
these genotypes, so it is perfectly clear that palliative care is the appropriate comparator.  
2. It would be helpful to note countries similar to Thailand which have still not approved 
this treatment, demonstrating that the strategies compare d are here are still relevant 
somewhere.  
3. The methods should state the time horizon for the analysis (lifetime?).  
4. 18 years old is remarkably young for a reference case and leads to the most favorable 
results for treatment due to the longer life years saved from preventing deaths. Most 
models in this area consider reference cases much older (e.g. 45). Data on the distribution 
of age of people with HCV in Thailand would be helpful. Perhaps the median age would 
be a better reference case. The paper says i n the methods this is taken from THASL 
guidelines - but this seems rather odd. Do the guidelines say age at least 18? A more 
reasonable age for the reference case should be adopted, AND sensitivity analysis should 
be done on age to consider ages as young a s 18 but also older ages. This paper is being 
submitted now after changes in coverage for this treatment, so the paper should focus on 
the range of cases regardless of what the policy currently is.  
5. One-way sensitivity analysis needs to be conducted. It accomplishes a different goal than 
the probabilistic sensitivity analysis, namely the possibility of single parameters being 
mis-specified.  
6. It would be better if there was some allowance for poor adherence. Trials have 
unrealistically high adherence ra tes and therefore have inflated success rates. The issue 
isn't someone refusing to undergo treatment entirely, but the people who take the drugs - 
but miss many doses. At the absolute minimum, it should be addressed in the discussion 
section and cite data on adherence from other countries, if not form Thailand for 
Genotypes 2 -3 where this treatment was already being used.  
7. Probability of death from other causes is listed as .0025 per year. This may be true at age 
18, but is certainly not true forever! Lon g-term models like this one must take into 
account death from other causes at plausible values. This will grossly overestimate the 
benefit of treatment. What is the mean life expectancy in Thailand? Perhaps this was not 
the rate used throughout the time ho rizon (what was the time horizon??) - if so, the 
authors need to explain.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to th e authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistic al review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the  manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from 
an organisation that may in any way ga in or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the f uture?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I  declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my  report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access C reative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Economic Evaluation of Pegylated Interferon p lus Ribavirin for Treatment of Chronic 
Hepatitis C in Thailand: Genotype 1 and 6  
 
 
Version: 0 Date: 27 Apr 2016  
 
 
Reviewer: Mendel  Singer  
 
 
Reviewer's report:  
 
This cost -utility modeling study is generally well done and conforms with usual standards for 
these types of studies. The strategies compared were of recent interest in Thaila nd, and changes 
in approved regimen were based on these results. It is likely there are other developing nations 
where these are still appropriate strategies to compare.  
 
Comments:  
1. The paper should state explicitly that there are no previously approved t reatments for 
these genotypes, so it is perfectly clear that palliative care is the appropriate comparator.  
2. It would be helpful to note countries similar to Thailand which have still not approved 
this treatment, demonstrating that the strategies compare d are here are still relevant 
somewhere.  
3. The methods should state the time horizon for the analysis (lifetime?).  
4. 18 years old is remarkably young for a reference case and leads to the most favorable 
results for treatment due to the longer life years saved from preventing deaths. Most 
models in this area consider reference cases much older (e.g. 45). Data on the distribution 
of age of people with HCV in Thailand would be helpful. Perhaps the median age would 
be a better reference case. The paper says i n the methods this is taken from THASL 
guidelines - but this seems rather odd. Do the guidelines say age at least 18? A more 
reasonable age for the reference case should be adopted, AND sensitivity analysis should 
be done on age to consider ages as young a s 18 but also older ages. This paper is being 
submitted now after changes in coverage for this treatment, so the paper should focus on 
the range of cases regardless of what the policy currently is.  
5. One-way sensitivity analysis needs to be conducted. It accomplishes a different goal than 
the probabilistic sensitivity analysis, namely the possibility of single parameters being 
mis-specified.  
6. It would be better if there was some allowance for poor adherence. Trials have 
unrealistically high adherence ra tes and therefore have inflated success rates. The issue 
isn't someone refusing to undergo treatment entirely, but the people who take the drugs - 
but miss many doses. At the absolute minimum, it should be addressed in the discussion 
section and cite data on adherence from other countries, if not form Thailand for 
Genotypes 2 -3 where this treatment was already being used.  
7. Probability of death from other causes is listed as .0025 per year. This may be true at age 
18, but is certainly not true forever! Lon g-term models like this one must take into 
account death from other causes at plausible values. This will grossly overestimate the 
benefit of treatment. What is the mean life expectancy in Thailand? Perhaps this was not 
the rate used throughout the time ho rizon (what was the time horizon??) - if so, the 
authors need to explain.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to th e authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistic al review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the  manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from 
an organisation that may in any way ga in or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the f uture?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I  declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my  report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access C reative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Economic Evaluation of Pegylated Interferon p lus Ribavirin for Treatment of Chronic 
Hepatitis C in Thailand: Genotype 1 and 6  
 
 
Version: 0 Date: 27 Apr 2016  
 
 
Reviewer: Mendel  Singer  
 
 
Reviewer's report:  
 
This cost -utility modeling study is generally well done and conforms with usual standards for 
these types of studies. The strategies compared were of recent interest in Thaila nd, and changes 
in approved regimen were based on these results. It is likely there are other developing nations 
where these are still appropriate strategies to compare.  
 
Comments:  
1. The paper should state explicitly that there are no previously approved t reatments for 
these genotypes, so it is perfectly clear that palliative care is the appropriate comparator.  
2. It would be helpful to note countries similar to Thailand which have still not approved 
this treatment, demonstrating that the strategies compare d are here are still relevant 
somewhere.  
3. The methods should state the time horizon for the analysis (lifetime?).  
4. 18 years old is remarkably young for a reference case and leads to the most favorable 
results for treatment due to the longer life years saved from preventing deaths. Most 
models in this area consider reference cases much older (e.g. 45). Data on the distribution 
of age of people with HCV in Thailand would be helpful. Perhaps the median age would 
be a better reference case. The paper says i n the methods this is taken from THASL 
guidelines - but this seems rather odd. Do the guidelines say age at least 18? A more 
reasonable age for the reference case should be adopted, AND sensitivity analysis should 
be done on age to consider ages as young a s 18 but also older ages. This paper is being 
submitted now after changes in coverage for this treatment, so the paper should focus on 
the range of cases regardless of what the policy currently is.  
5. One-way sensitivity analysis needs to be conducted. It accomplishes a different goal than 
the probabilistic sensitivity analysis, namely the possibility of single parameters being 
mis-specified.  
6. It would be better if there was some allowance for poor adherence. Trials have 
unrealistically high adherence ra tes and therefore have inflated success rates. The issue 
isn't someone refusing to undergo treatment entirely, but the people who take the drugs - 
but miss many doses. At the absolute minimum, it should be addressed in the discussion 
section and cite data on adherence from other countries, if not form Thailand for 
Genotypes 2 -3 where this treatment was already being used.  
7. Probability of death from other causes is listed as .0025 per year. This may be true at age 
18, but is certainly not true forever! Lon g-term models like this one must take into 
account death from other causes at plausible values. This will grossly overestimate the 
benefit of treatment. What is the mean life expectancy in Thailand? Perhaps this was not 
the rate used throughout the time ho rizon (what was the time horizon??) - if so, the 
authors need to explain.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to th e authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistic al review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the  manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from 
an organisation that may in any way ga in or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the f uture?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I  declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my  report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access C reative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant