Reviewer ’s report  
 
Title:  Efficacy, safety and pharmacokinetics of simeprevir and TMC647055/ritonavir with or 
without ribavirin and JNJ -56914845 in HCV genotype 1 infection  
 
Version: 0 Date: 11 Nov 2016 
 
Reviewer:  Lindsey  Childs -Kean  
 
Reviewer’s report:  
 
Overall, this study looking at simeprevir with 1 -2 more DAA's, ritonavir, with/without ribavirin 
adds to the literature.  The face that 2 DAA -combos with just an NS3/4A PI and NNI NS5B did 
not give h igh SVRs is important.   
 
 
Suggested minor revisions:  
 
* QD is not an acceptable medical abbreviation.  Recommend change to "daily" throughout 
paper.  
 
* Lines 96 -97: The ABT -### does not add anything to the paper.  Recommend removing.  
 
* Lines 104 -109: These s tatements need to be referenced.  
 
* Line 110: Remove "of the same enzyme"  
 
* Lines 118 -119: The statement is that ritonavir "was expected" to increase exposure.  Has 
this been studied before this current study?  If so, it should be referenced.  
 
* Lines 144 -148: An explanation of why patients with cirrhosis (particularly compensated 
cirrhosis) and prior DAA therapy were excluded would be helpful.  
 
* Line 163: It's also the approved dose in the US.  
 
* Lines 165 -167: An explanation of why there was a PEG -RBV "tail"  would be helpful.  
 
* Lines 175 -179: Why the need for stopping rules?  
 
* Line 333: Did the influenza -like illness reports occur before or during the PEG -RBV part 
of treatment?  
 
* Lines 405 -411: Recommend making a statement that other combinations of drugs did  not 
perform as well in the Conclusion section.  
 
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 authors.  
 
Yes 
 
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 stat istical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
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 may 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 thi s 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 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 unde r 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:  Efficacy, safety and pharmacokinetics of simeprevir and TMC647055/ritonavir with or 
without ribavirin and JNJ -56914845 in HCV genotype 1 infection  
 
Version: 0 Date: 11 Nov 2016 
 
Reviewer:  Lindsey  Childs -Kean  
 
Reviewer’s report:  
 
Overall, this study looking at simeprevir with 1 -2 more DAA's, ritonavir, with/without ribavirin 
adds to the literature.  The face that 2 DAA -combos with just an NS3/4A PI and NNI NS5B did 
not give h igh SVRs is important.   
 
 
Suggested minor revisions:  
 
* QD is not an acceptable medical abbreviation.  Recommend change to "daily" throughout 
paper.  
 
* Lines 96 -97: The ABT -### does not add anything to the paper.  Recommend removing.  
 
* Lines 104 -109: These s tatements need to be referenced.  
 
* Line 110: Remove "of the same enzyme"  
 
* Lines 118 -119: The statement is that ritonavir "was expected" to increase exposure.  Has 
this been studied before this current study?  If so, it should be referenced.  
 
* Lines 144 -148: An explanation of why patients with cirrhosis (particularly compensated 
cirrhosis) and prior DAA therapy were excluded would be helpful.  
 
* Line 163: It's also the approved dose in the US.  
 
* Lines 165 -167: An explanation of why there was a PEG -RBV "tail"  would be helpful.  
 
* Lines 175 -179: Why the need for stopping rules?  
 
* Line 333: Did the influenza -like illness reports occur before or during the PEG -RBV part 
of treatment?  
 
* Lines 405 -411: Recommend making a statement that other combinations of drugs did  not 
perform as well in the Conclusion section.  
 
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 authors.  
 
Yes 
 
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 stat istical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
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 may 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 thi s 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 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 unde r 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:  Efficacy, safety and pharmacokinetics of simeprevir and TMC647055/ritonavir with or 
without ribavirin and JNJ -56914845 in HCV genotype 1 infection  
 
Version: 0 Date: 11 Nov 2016 
 
Reviewer:  Lindsey  Childs -Kean  
 
Reviewer’s report:  
 
Overall, this study looking at simeprevir with 1 -2 more DAA's, ritonavir, with/without ribavirin 
adds to the literature.  The face that 2 DAA -combos with just an NS3/4A PI and NNI NS5B did 
not give h igh SVRs is important.   
 
 
Suggested minor revisions:  
 
* QD is not an acceptable medical abbreviation.  Recommend change to "daily" throughout 
paper.  
 
* Lines 96 -97: The ABT -### does not add anything to the paper.  Recommend removing.  
 
* Lines 104 -109: These s tatements need to be referenced.  
 
* Line 110: Remove "of the same enzyme"  
 
* Lines 118 -119: The statement is that ritonavir "was expected" to increase exposure.  Has 
this been studied before this current study?  If so, it should be referenced.  
 
* Lines 144 -148: An explanation of why patients with cirrhosis (particularly compensated 
cirrhosis) and prior DAA therapy were excluded would be helpful.  
 
* Line 163: It's also the approved dose in the US.  
 
* Lines 165 -167: An explanation of why there was a PEG -RBV "tail"  would be helpful.  
 
* Lines 175 -179: Why the need for stopping rules?  
 
* Line 333: Did the influenza -like illness reports occur before or during the PEG -RBV part 
of treatment?  
 
* Lines 405 -411: Recommend making a statement that other combinations of drugs did  not 
perform as well in the Conclusion section.  
 
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 authors.  
 
Yes 
 
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 stat istical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
I recommend additional statistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
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 may 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 thi s 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 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 unde r 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