Reviewer ’s report  
Title: Sustained Efficacy Following Resolution of Frequent Hea rtburn With an Over -the-
Counter Regimen of Esomeprazole 20 mg or Placebo for 14 Days: Two Randomized Trials  
 
Version: 2 Date: 14 Feb 2018  
 
Reviewer: Amy Tyberg  
 
Reviewer's report:  
This is an interesting study evaluating factors predictive of sustained heartburn relief after self -
treatment with short -term PPI use.  
 
A few comments:  
1. The objective stated at the end of the introduction is a bit confusing. I believe the authors 
intende d for the main objective to be determining factors predictive of sustained response 
after self -treatment with short -term PPI? And what is listed as the objective is more consistent 
with a secondary objective? Which could be stated a little bit more concise ly, for example: a 
secondary objective was to determine whether resolution of heartburn symptoms during the 
treatment period was associated with durability of response in the follow -up period.  
2. Please define "long -term prescription therapy" under exclus ion criteria - does this mean more 
than 2 weeks? Or 1 month? What about patients that had tried 14 days of PPI in the past? 
These patients might be less likely to respond if they had unsuccessful PPI trial previously...  
3. What kind of questionnaire did p atients use to report their symptoms? Did all patients have 
classic heartburn symptoms? Or atypical symptoms were included as well?  
4. It seems that the authors grouped placebo and PPI patients into one group when looking at 
predictors of heartburn resolu tion during follow -up period. Although more PPI patients had 
resolution of symptoms and therefore more sustained response, it would be important to 
compare the two groups.  
5. I think the conclusions stated are justified by the data, but it would be helpfu l to have a 
sentence in the conclusion as to why these findings are important. Since sustained response is 
seen with PPI use, the guidelines are justified in recommending a 14 day trial prior to seeking 
care with a physician? Or physicians can move more qu ickly to other treatment options in 
patients who have not responded to PPIs within the first 2 weeks as they are less likely to have 
a sustained response?  
 
Are the methods approp riate 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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review i s recommended, please speci fy 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 fi ve years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
2. Do you hold any stocks or shares in an organisation that m ay 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 com peting interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare th at 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 Creative Com mons 
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: Sustained Efficacy Following Resolution of Frequent Hea rtburn With an Over -the-
Counter Regimen of Esomeprazole 20 mg or Placebo for 14 Days: Two Randomized Trials  
 
Version: 2 Date: 14 Feb 2018  
 
Reviewer: Amy Tyberg  
 
Reviewer's report:  
This is an interesting study evaluating factors predictive of sustained heartburn relief after self -
treatment with short -term PPI use.  
 
A few comments:  
1. The objective stated at the end of the introduction is a bit confusing. I believe the authors 
intende d for the main objective to be determining factors predictive of sustained response 
after self -treatment with short -term PPI? And what is listed as the objective is more consistent 
with a secondary objective? Which could be stated a little bit more concise ly, for example: a 
secondary objective was to determine whether resolution of heartburn symptoms during the 
treatment period was associated with durability of response in the follow -up period.  
2. Please define "long -term prescription therapy" under exclus ion criteria - does this mean more 
than 2 weeks? Or 1 month? What about patients that had tried 14 days of PPI in the past? 
These patients might be less likely to respond if they had unsuccessful PPI trial previously...  
3. What kind of questionnaire did p atients use to report their symptoms? Did all patients have 
classic heartburn symptoms? Or atypical symptoms were included as well?  
4. It seems that the authors grouped placebo and PPI patients into one group when looking at 
predictors of heartburn resolu tion during follow -up period. Although more PPI patients had 
resolution of symptoms and therefore more sustained response, it would be important to 
compare the two groups.  
5. I think the conclusions stated are justified by the data, but it would be helpfu l to have a 
sentence in the conclusion as to why these findings are important. Since sustained response is 
seen with PPI use, the guidelines are justified in recommending a 14 day trial prior to seeking 
care with a physician? Or physicians can move more qu ickly to other treatment options in 
patients who have not responded to PPIs within the first 2 weeks as they are less likely to have 
a sustained response?  
 
Are the methods approp riate 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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review i s recommended, please speci fy 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 fi ve years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
2. Do you hold any stocks or shares in an organisation that m ay 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 com peting interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare th at 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 Creative Com mons 
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: Sustained Efficacy Following Resolution of Frequent Hea rtburn With an Over -the-
Counter Regimen of Esomeprazole 20 mg or Placebo for 14 Days: Two Randomized Trials  
 
Version: 2 Date: 14 Feb 2018  
 
Reviewer: Amy Tyberg  
 
Reviewer's report:  
This is an interesting study evaluating factors predictive of sustained heartburn relief after self -
treatment with short -term PPI use.  
 
A few comments:  
1. The objective stated at the end of the introduction is a bit confusing. I believe the authors 
intende d for the main objective to be determining factors predictive of sustained response 
after self -treatment with short -term PPI? And what is listed as the objective is more consistent 
with a secondary objective? Which could be stated a little bit more concise ly, for example: a 
secondary objective was to determine whether resolution of heartburn symptoms during the 
treatment period was associated with durability of response in the follow -up period.  
2. Please define "long -term prescription therapy" under exclus ion criteria - does this mean more 
than 2 weeks? Or 1 month? What about patients that had tried 14 days of PPI in the past? 
These patients might be less likely to respond if they had unsuccessful PPI trial previously...  
3. What kind of questionnaire did p atients use to report their symptoms? Did all patients have 
classic heartburn symptoms? Or atypical symptoms were included as well?  
4. It seems that the authors grouped placebo and PPI patients into one group when looking at 
predictors of heartburn resolu tion during follow -up period. Although more PPI patients had 
resolution of symptoms and therefore more sustained response, it would be important to 
compare the two groups.  
5. I think the conclusions stated are justified by the data, but it would be helpfu l to have a 
sentence in the conclusion as to why these findings are important. Since sustained response is 
seen with PPI use, the guidelines are justified in recommending a 14 day trial prior to seeking 
care with a physician? Or physicians can move more qu ickly to other treatment options in 
patients who have not responded to PPIs within the first 2 weeks as they are less likely to have 
a sustained response?  
 
Are the methods approp riate 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 manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review i s recommended, please speci fy 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 fi ve years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
2. Do you hold any stocks or shares in an organisation that m ay 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 com peting interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare th at 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 Creative Com mons 
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