Reviewer ’s report  
 
Title: Micro -costing analysis of guideline -based treatment by direct -acting agents: the real -life 
case of hepatitis C management in Brazil  
 
Version: 0 Date: 14 May 2017  
 
Reviewer: Antonio Ciaccio  
 
Reviewer's report:  
 
The Authors propose a cost -analysis of new DAAs treatment for genotype 1 chronic hepatitis C, 
compared to two different schedules of IFN -based approach (without and with first generation 
PI).  
The study clearly shows a net cost reduction produced by selected IFN -free treatment regi mens 
(i.e. DCV plus SOF and SIM plus SOF, both for 12 weeks), that have been recently 
recommended by the Brazilian Ministry of Health for patients with advanced fibrosis and 
cirrhosis, following a negotiation with pharmaceutical companies. Results are pres ented also 
with an adjustment for purchasing power parity. A cost analysis of three different strategies to 
assess disease stage is also included.  
 
Major comments.  
1. the analysis is set on the basis of the current guidelines of the BMoH (2015A and 2015B ) 
that recommend to treat patients with a liver stiffness equal to or higher than 9.6 KPa, 
(advanced fibrosis or cirrhosis) with a DAAs regimen that is deemed suboptimal for patients 
with these characteristics, as patients with more advanced fibrosis stage  should be treated for 
24 weeks, in some cases also adding ribavirin to the schedule. The extensive implementation 
of this guideline will produce a large proportion (up to 15%) of treatment failure, that means 
individuals that will need to be re -treated in  the future, using higher cost drugs combinations 
and also facing drug resistance problems. Although the analysis reported in this paper is 
coherent with MoH current guidelines, a comment about this issue should be reported in the 
discussion. A separate st udy reporting a cost -effective analysis that compares 12 -weeks to 
24-weeks regimens of the approved drugs combinations is highly advised, taking into 
account future retreatment of patients who fail the first course of DAAs.   
2. In the section "Literature overview for efficacy…" it is necessary to report separately the 
results for cirrhotics and non -cirrhotics patients, avoiding overall results that may be 
misleading. Subanalysis that considers subtype (i.e. genotype 1a and 1b) should also be 
reported in th e same section.  
3. A mention should be done about the prevalence and distribution of genotype 1a and 1b in 
the Brazilian HCV -infected population.  
 
Minor comments.  
1. the abbreviation in brackets is lacking in the abstracts when you first mention telaprevi r.  
2. Line 7: fibroscan is not strictly an imaging method. Review.  
3. Line 13: as above.  
4. Line 129 - 132: it does not appear clear that a stiffness cutoff exists to consider treatment. 
Write it in a different way.  
5. Line 169: DAAs instead of DDAs.  
6. Line 181: PEG instead of PEF.  
7. Line 214: "where nurses" instead of "that nurses".  
8. Line 221: an analysis "of for a": correct this form.  
9. Line 251: filgrastim instead of filgastrim.  
10. Line 267: hypothesize instead of hypothesis.  
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 the autho rs. 
 
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 statistical revi ew? 
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manusc ript: 
 
Acceptable  
 
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 ma y in any way gain 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 future?  
 
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 have received fees from Gilead Sciences for occasional activity in advisory board (Hepatitis C).  
 
I agree to the open peer review policy of the jou rnal. 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 Creative 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: Micro -costing analysis of guideline -based treatment by direct -acting agents: the real -life 
case of hepatitis C management in Brazil  
 
Version: 0 Date: 14 May 2017  
 
Reviewer: Antonio Ciaccio  
 
Reviewer's report:  
 
The Authors propose a cost -analysis of new DAAs treatment for genotype 1 chronic hepatitis C, 
compared to two different schedules of IFN -based approach (without and with first generation 
PI).  
The study clearly shows a net cost reduction produced by selected IFN -free treatment regi mens 
(i.e. DCV plus SOF and SIM plus SOF, both for 12 weeks), that have been recently 
recommended by the Brazilian Ministry of Health for patients with advanced fibrosis and 
cirrhosis, following a negotiation with pharmaceutical companies. Results are pres ented also 
with an adjustment for purchasing power parity. A cost analysis of three different strategies to 
assess disease stage is also included.  
 
Major comments.  
1. the analysis is set on the basis of the current guidelines of the BMoH (2015A and 2015B ) 
that recommend to treat patients with a liver stiffness equal to or higher than 9.6 KPa, 
(advanced fibrosis or cirrhosis) with a DAAs regimen that is deemed suboptimal for patients 
with these characteristics, as patients with more advanced fibrosis stage  should be treated for 
24 weeks, in some cases also adding ribavirin to the schedule. The extensive implementation 
of this guideline will produce a large proportion (up to 15%) of treatment failure, that means 
individuals that will need to be re -treated in  the future, using higher cost drugs combinations 
and also facing drug resistance problems. Although the analysis reported in this paper is 
coherent with MoH current guidelines, a comment about this issue should be reported in the 
discussion. A separate st udy reporting a cost -effective analysis that compares 12 -weeks to 
24-weeks regimens of the approved drugs combinations is highly advised, taking into 
account future retreatment of patients who fail the first course of DAAs.   
2. In the section "Literature overview for efficacy…" it is necessary to report separately the 
results for cirrhotics and non -cirrhotics patients, avoiding overall results that may be 
misleading. Subanalysis that considers subtype (i.e. genotype 1a and 1b) should also be 
reported in th e same section.  
3. A mention should be done about the prevalence and distribution of genotype 1a and 1b in 
the Brazilian HCV -infected population.  
 
Minor comments.  
1. the abbreviation in brackets is lacking in the abstracts when you first mention telaprevi r.  
2. Line 7: fibroscan is not strictly an imaging method. Review.  
3. Line 13: as above.  
4. Line 129 - 132: it does not appear clear that a stiffness cutoff exists to consider treatment. 
Write it in a different way.  
5. Line 169: DAAs instead of DDAs.  
6. Line 181: PEG instead of PEF.  
7. Line 214: "where nurses" instead of "that nurses".  
8. Line 221: an analysis "of for a": correct this form.  
9. Line 251: filgrastim instead of filgastrim.  
10. Line 267: hypothesize instead of hypothesis.  
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 the autho rs. 
 
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 statistical revi ew? 
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manusc ript: 
 
Acceptable  
 
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 ma y in any way gain 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 future?  
 
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 have received fees from Gilead Sciences for occasional activity in advisory board (Hepatitis C).  
 
I agree to the open peer review policy of the jou rnal. 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 Creative 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: Micro -costing analysis of guideline -based treatment by direct -acting agents: the real -life 
case of hepatitis C management in Brazil  
 
Version: 0 Date: 14 May 2017  
 
Reviewer: Antonio Ciaccio  
 
Reviewer's report:  
 
The Authors propose a cost -analysis of new DAAs treatment for genotype 1 chronic hepatitis C, 
compared to two different schedules of IFN -based approach (without and with first generation 
PI).  
The study clearly shows a net cost reduction produced by selected IFN -free treatment regi mens 
(i.e. DCV plus SOF and SIM plus SOF, both for 12 weeks), that have been recently 
recommended by the Brazilian Ministry of Health for patients with advanced fibrosis and 
cirrhosis, following a negotiation with pharmaceutical companies. Results are pres ented also 
with an adjustment for purchasing power parity. A cost analysis of three different strategies to 
assess disease stage is also included.  
 
Major comments.  
1. the analysis is set on the basis of the current guidelines of the BMoH (2015A and 2015B ) 
that recommend to treat patients with a liver stiffness equal to or higher than 9.6 KPa, 
(advanced fibrosis or cirrhosis) with a DAAs regimen that is deemed suboptimal for patients 
with these characteristics, as patients with more advanced fibrosis stage  should be treated for 
24 weeks, in some cases also adding ribavirin to the schedule. The extensive implementation 
of this guideline will produce a large proportion (up to 15%) of treatment failure, that means 
individuals that will need to be re -treated in  the future, using higher cost drugs combinations 
and also facing drug resistance problems. Although the analysis reported in this paper is 
coherent with MoH current guidelines, a comment about this issue should be reported in the 
discussion. A separate st udy reporting a cost -effective analysis that compares 12 -weeks to 
24-weeks regimens of the approved drugs combinations is highly advised, taking into 
account future retreatment of patients who fail the first course of DAAs.   
2. In the section "Literature overview for efficacy…" it is necessary to report separately the 
results for cirrhotics and non -cirrhotics patients, avoiding overall results that may be 
misleading. Subanalysis that considers subtype (i.e. genotype 1a and 1b) should also be 
reported in th e same section.  
3. A mention should be done about the prevalence and distribution of genotype 1a and 1b in 
the Brazilian HCV -infected population.  
 
Minor comments.  
1. the abbreviation in brackets is lacking in the abstracts when you first mention telaprevi r.  
2. Line 7: fibroscan is not strictly an imaging method. Review.  
3. Line 13: as above.  
4. Line 129 - 132: it does not appear clear that a stiffness cutoff exists to consider treatment. 
Write it in a different way.  
5. Line 169: DAAs instead of DDAs.  
6. Line 181: PEG instead of PEF.  
7. Line 214: "where nurses" instead of "that nurses".  
8. Line 221: an analysis "of for a": correct this form.  
9. Line 251: filgrastim instead of filgastrim.  
10. Line 267: hypothesize instead of hypothesis.  
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 the autho rs. 
 
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 statistical revi ew? 
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manusc ript: 
 
Acceptable  
 
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 ma y in any way gain 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 future?  
 
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 have received fees from Gilead Sciences for occasional activity in advisory board (Hepatitis C).  
 
I agree to the open peer review policy of the jou rnal. 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 Creative 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