Reviewer's report
Title:Gaviscon(R) vs. omeprazole in symptomatic treatment of moderate
gastroesophageal reflux. A direct comparative randomised trial
Version: 3Date:15 December 2011
Reviewer: Vicki Strugala
Reviewer's report:
Major Compulsory Revisions
1. Primary Endpoint. The description of this in the text and the presentation of
data in the tables (table 2) are confusing. I feel that it is not important to state that
this is taken on D7 (or D14). It is clearly the time to onset of the first 24 hour
period free from heartburn from initial dosing. (since you cite Miner et al 2002 as
your inspiration this does not note the date in which the data was calculated).
Also I am unsure of how this data was calculated for D14. Please clarify. This
should be thoroughly reviewed and improved since it makes the main content of
the paper.
Minor Essential Revisions
1. References: The in-text citation numbers for the references are incorrect from
ref [2] onwards. Please thoroughly review that the correct reference is cited at the
appropriate place. E.g Introduction paragraph 1 – PPI refs are [2,3] alginates refs
are [4-9] and [10] is a statistical method.
2. Details of the patient questionnaire used are lacking. Please provide full details
of this.
3. Secondary endpoint data missing. Mean number of days without heartburn by
D14 is missing but stated in the methods. Please add the data.
4. In paragraph 4 of the Background the authors state ‘ there have been no
studies with a modern scientific design directly comparing one alginate to a PPI’.
I feel that unless you are sure you must use caution with such definite
statements. I refer the authors to the following paper comparing Gaviscon, PPI,
H2RA and water using modern objective techniques (pHmetery) to assess
impact on reflux sufferers. (Please amend in first line of discussion also.)
Dettmar PW, Sykes J, Little SL, Bryan J. Rapid onset of effect of sodium alginate
on gastro-oesophageal reflux compared with ranitidine and omeprazole, and
relationship between symptoms and reflux episodes. International Journal of
Clinical Practise 2006;60(3):275-283.
Discretionary Revisions
1. Alginates – I would suggest that somewhere within the manuscript there is
mention of the fact that alginates are specifically ‘ raft forming oral
suspensions/formulations’. I would also suggest that further detail is added to the
methods regarding the Gaviscon product used. Since many variants exist (and
that historically French Gaviscon has been a different formulation to other
countries) that stating concentration of alginate and sodium bicarbonate used
would be helpful to the readers who have a particular interest in this field.
2. An additional reference will strengthen the statement that alginate formulae
differ.
Hampson FC, Farndale A, Strugala V, Sykes J, Jolliffe IG, Dettmar PW. Alginate
rafts and their characterisation. Int J Pharm 2005;294:137-147.
3. Double-placebo. This is a misleading term suggesting a placebo controlled
study. Please tone down this use throughout and keep to discussion in the
methods only.
4. Alginate placebo. I’d be interested to find more about the alginate placebo
used in this study as it is notoriously difficult to produce a realistic non-functioning
placebo of Gaviscon.
5. Table 1 data. Please indicate if the baseline demographic details differ
statistically between the 2 groups. Although it says they are comparable this is
not sufficiently explicit.
6. I would prefer to see the percentage values added for patient compliance
since the data almost reaches statistical significance. I suspect this is because
the compliance is poor for Gaviscon but this can be nicely discussed.
7. End statements (discussion and abstract). You can afford to be stronger here.
The use of ‘interesting’ is bland and irrelevant. Alginates are an established
treatment and you need to focus on the fact that there are ‘as good’ as PPI and
there use should be advocated more, especially as they are non-systemic and
safe.
8. I would like to see discussion on the large number of centres used (90
planned, 75 used) and thus the low numbers of patients from each centre. Could
this have an important impact on the patient population in the study.
9. I would like to see wider discussion regarding interpretation of the data
generated. In particular Why despite continuous PPI treatment does only half of
the time period see freedom from heartburn. Why is the time to onset of 24 hour
freedom from heartburn longer in the second 7 days (D7-D14) than the first (D0 –
D7) despite continuous treatment.
10. Perhaps it could be brought to the readers’ attention that PPI and alginates
can be used safely together. Suitable references:
Dettmar PW, Hampson FC, Jain A, Choubey S, Little SL, Baxter T.
Administration of an alginate based gastric reflux suppressant on the
bioavailability of omeprazole. Indian Journal of Medical Research
2006;123:517-524.
Dettmar PW, Little SL, Baxter T. The effect of omeprazole pre-treatment on rafts
formed by reflux suppressant tablets containing alginate. Journal of International
Medical Research 2005;33(3):301-308.
Connolly MP, Bhatt A, Simmonds R. Implementing UK national dyspepsia
guidelines for returning patients to self-care: findings from an educational
intervention and 12-month follow-up clinical re-audit. Gut 2009;58(Suppl
II):A128-9.
Inadomi JM, Jamal R, Murata GH, Hoffman RM, Lavezo LA, Vigil JM, Swanson
KM, Sonnenberg A. Step-down management of gastroesophageal reflux disease.
Gastroenterology 2001;121(5):1095-100.
11. I would suggest replacing ‘on D7’ to ‘by D7’ throughout as appropriate.
12. Language and grammar can be improved in the Conclusion.
13. Page 8 Statistical analysis. Note that it is a ‘Student t-test’ and not a ‘Student
test’.
14. Page 10 Primary outcome 2nd paragraph. Please add proportions to the
90.1% i.e (109/121) for consistency.
15. Competing Interests/Acknowledgements. Remove the hyphen from
Reckitt-Benckiser.
16. Competing interests. MC – study was ‘funded’ not ‘founded’.
17. References no9 Chatfield. Add last page (152-159).
18. References no 21. Check that this is the correct way to cite this guideline.
19. Statistics. I would suggest a more detailed statistical review of this
manuscript. I am not sure that mean time to heartburn free is correct as other
similar papers utilise median. perhaps both could be noted in the table.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I am an employee of Technostics Ltd which acts as a consultant and medical
writer for Reckitt Benckiser Healthcare (UK) Ltd.
Reviewer's report
Title:Gaviscon(R) vs. omeprazole in symptomatic treatment of moderate
gastroesophageal reflux. A direct comparative randomised trial
Version: 3Date:15 December 2011
Reviewer: Vicki Strugala
Reviewer's report:
Major Compulsory Revisions
1. Primary Endpoint. The description of this in the text and the presentation of
data in the tables (table 2) are confusing. I feel that it is not important to state that
this is taken on D7 (or D14). It is clearly the time to onset of the first 24 hour
period free from heartburn from initial dosing. (since you cite Miner et al 2002 as
your inspiration this does not note the date in which the data was calculated).
Also I am unsure of how this data was calculated for D14. Please clarify. This
should be thoroughly reviewed and improved since it makes the main content of
the paper.
Minor Essential Revisions
1. References: The in-text citation numbers for the references are incorrect from
ref [2] onwards. Please thoroughly review that the correct reference is cited at the
appropriate place. E.g Introduction paragraph 1 – PPI refs are [2,3] alginates refs
are [4-9] and [10] is a statistical method.
2. Details of the patient questionnaire used are lacking. Please provide full details
of this.
3. Secondary endpoint data missing. Mean number of days without heartburn by
D14 is missing but stated in the methods. Please add the data.
4. In paragraph 4 of the Background the authors state ‘ there have been no
studies with a modern scientific design directly comparing one alginate to a PPI’.
I feel that unless you are sure you must use caution with such definite
statements. I refer the authors to the following paper comparing Gaviscon, PPI,
H2RA and water using modern objective techniques (pHmetery) to assess
impact on reflux sufferers. (Please amend in first line of discussion also.)
Dettmar PW, Sykes J, Little SL, Bryan J. Rapid onset of effect of sodium alginate
on gastro-oesophageal reflux compared with ranitidine and omeprazole, and
relationship between symptoms and reflux episodes. International Journal of
Clinical Practise 2006;60(3):275-283.
Discretionary Revisions
1. Alginates – I would suggest that somewhere within the manuscript there is
mention of the fact that alginates are specifically ‘ raft forming oral
suspensions/formulations’. I would also suggest that further detail is added to the
methods regarding the Gaviscon product used. Since many variants exist (and
that historically French Gaviscon has been a different formulation to other
countries) that stating concentration of alginate and sodium bicarbonate used
would be helpful to the readers who have a particular interest in this field.
2. An additional reference will strengthen the statement that alginate formulae
differ.
Hampson FC, Farndale A, Strugala V, Sykes J, Jolliffe IG, Dettmar PW. Alginate
rafts and their characterisation. Int J Pharm 2005;294:137-147.
3. Double-placebo. This is a misleading term suggesting a placebo controlled
study. Please tone down this use throughout and keep to discussion in the
methods only.
4. Alginate placebo. I’d be interested to find more about the alginate placebo
used in this study as it is notoriously difficult to produce a realistic non-functioning
placebo of Gaviscon.
5. Table 1 data. Please indicate if the baseline demographic details differ
statistically between the 2 groups. Although it says they are comparable this is
not sufficiently explicit.
6. I would prefer to see the percentage values added for patient compliance
since the data almost reaches statistical significance. I suspect this is because
the compliance is poor for Gaviscon but this can be nicely discussed.
7. End statements (discussion and abstract). You can afford to be stronger here.
The use of ‘interesting’ is bland and irrelevant. Alginates are an established
treatment and you need to focus on the fact that there are ‘as good’ as PPI and
there use should be advocated more, especially as they are non-systemic and
safe.
8. I would like to see discussion on the large number of centres used (90
planned, 75 used) and thus the low numbers of patients from each centre. Could
this have an important impact on the patient population in the study.
9. I would like to see wider discussion regarding interpretation of the data
generated. In particular Why despite continuous PPI treatment does only half of
the time period see freedom from heartburn. Why is the time to onset of 24 hour
freedom from heartburn longer in the second 7 days (D7-D14) than the first (D0 –
D7) despite continuous treatment.
10. Perhaps it could be brought to the readers’ attention that PPI and alginates
can be used safely together. Suitable references:
Dettmar PW, Hampson FC, Jain A, Choubey S, Little SL, Baxter T.
Administration of an alginate based gastric reflux suppressant on the
bioavailability of omeprazole. Indian Journal of Medical Research
2006;123:517-524.
Dettmar PW, Little SL, Baxter T. The effect of omeprazole pre-treatment on rafts
formed by reflux suppressant tablets containing alginate. Journal of International
Medical Research 2005;33(3):301-308.
Connolly MP, Bhatt A, Simmonds R. Implementing UK national dyspepsia
guidelines for returning patients to self-care: findings from an educational
intervention and 12-month follow-up clinical re-audit. Gut 2009;58(Suppl
II):A128-9.
Inadomi JM, Jamal R, Murata GH, Hoffman RM, Lavezo LA, Vigil JM, Swanson
KM, Sonnenberg A. Step-down management of gastroesophageal reflux disease.
Gastroenterology 2001;121(5):1095-100.
11. I would suggest replacing ‘on D7’ to ‘by D7’ throughout as appropriate.
12. Language and grammar can be improved in the Conclusion.
13. Page 8 Statistical analysis. Note that it is a ‘Student t-test’ and not a ‘Student
test’.
14. Page 10 Primary outcome 2nd paragraph. Please add proportions to the
90.1% i.e (109/121) for consistency.
15. Competing Interests/Acknowledgements. Remove the hyphen from
Reckitt-Benckiser.
16. Competing interests. MC – study was ‘funded’ not ‘founded’.
17. References no9 Chatfield. Add last page (152-159).
18. References no 21. Check that this is the correct way to cite this guideline.
19. Statistics. I would suggest a more detailed statistical review of this
manuscript. I am not sure that mean time to heartburn free is correct as other
similar papers utilise median. perhaps both could be noted in the table.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I am an employee of Technostics Ltd which acts as a consultant and medical
writer for Reckitt Benckiser Healthcare (UK) Ltd.
Please review this paper.
user
Reviewer's report
Title:Gaviscon(R) vs. omeprazole in symptomatic treatment of moderate
gastroesophageal reflux. A direct comparative randomised trial
Version: 3Date:15 December 2011
Reviewer: Vicki Strugala
Reviewer's report:
Major Compulsory Revisions
1. Primary Endpoint. The description of this in the text and the presentation of
data in the tables (table 2) are confusing. I feel that it is not important to state that
this is taken on D7 (or D14). It is clearly the time to onset of the first 24 hour
period free from heartburn from initial dosing. (since you cite Miner et al 2002 as
your inspiration this does not note the date in which the data was calculated).
Also I am unsure of how this data was calculated for D14. Please clarify. This
should be thoroughly reviewed and improved since it makes the main content of
the paper.
Minor Essential Revisions
1. References: The in-text citation numbers for the references are incorrect from
ref [2] onwards. Please thoroughly review that the correct reference is cited at the
appropriate place. E.g Introduction paragraph 1 – PPI refs are [2,3] alginates refs
are [4-9] and [10] is a statistical method.
2. Details of the patient questionnaire used are lacking. Please provide full details
of this.
3. Secondary endpoint data missing. Mean number of days without heartburn by
D14 is missing but stated in the methods. Please add the data.
4. In paragraph 4 of the Background the authors state ‘ there have been no
studies with a modern scientific design directly comparing one alginate to a PPI’.
I feel that unless you are sure you must use caution with such definite
statements. I refer the authors to the following paper comparing Gaviscon, PPI,
H2RA and water using modern objective techniques (pHmetery) to assess
impact on reflux sufferers. (Please amend in first line of discussion also.)
Dettmar PW, Sykes J, Little SL, Bryan J. Rapid onset of effect of sodium alginate
on gastro-oesophageal reflux compared with ranitidine and omeprazole, and
relationship between symptoms and reflux episodes. International Journal of
Clinical Practise 2006;60(3):275-283.
Discretionary Revisions
1. Alginates – I would suggest that somewhere within the manuscript there is
mention of the fact that alginates are specifically ‘ raft forming oral
suspensions/formulations’. I would also suggest that further detail is added to the
methods regarding the Gaviscon product used. Since many variants exist (and
that historically French Gaviscon has been a different formulation to other
countries) that stating concentration of alginate and sodium bicarbonate used
would be helpful to the readers who have a particular interest in this field.
2. An additional reference will strengthen the statement that alginate formulae
differ.
Hampson FC, Farndale A, Strugala V, Sykes J, Jolliffe IG, Dettmar PW. Alginate
rafts and their characterisation. Int J Pharm 2005;294:137-147.
3. Double-placebo. This is a misleading term suggesting a placebo controlled
study. Please tone down this use throughout and keep to discussion in the
methods only.
4. Alginate placebo. I’d be interested to find more about the alginate placebo
used in this study as it is notoriously difficult to produce a realistic non-functioning
placebo of Gaviscon.
5. Table 1 data. Please indicate if the baseline demographic details differ
statistically between the 2 groups. Although it says they are comparable this is
not sufficiently explicit.
6. I would prefer to see the percentage values added for patient compliance
since the data almost reaches statistical significance. I suspect this is because
the compliance is poor for Gaviscon but this can be nicely discussed.
7. End statements (discussion and abstract). You can afford to be stronger here.
The use of ‘interesting’ is bland and irrelevant. Alginates are an established
treatment and you need to focus on the fact that there are ‘as good’ as PPI and
there use should be advocated more, especially as they are non-systemic and
safe.
8. I would like to see discussion on the large number of centres used (90
planned, 75 used) and thus the low numbers of patients from each centre. Could
this have an important impact on the patient population in the study.
9. I would like to see wider discussion regarding interpretation of the data
generated. In particular Why despite continuous PPI treatment does only half of
the time period see freedom from heartburn. Why is the time to onset of 24 hour
freedom from heartburn longer in the second 7 days (D7-D14) than the first (D0 –
D7) despite continuous treatment.
10. Perhaps it could be brought to the readers’ attention that PPI and alginates
can be used safely together. Suitable references:
Dettmar PW, Hampson FC, Jain A, Choubey S, Little SL, Baxter T.
Administration of an alginate based gastric reflux suppressant on the
bioavailability of omeprazole. Indian Journal of Medical Research
2006;123:517-524.
Dettmar PW, Little SL, Baxter T. The effect of omeprazole pre-treatment on rafts
formed by reflux suppressant tablets containing alginate. Journal of International
Medical Research 2005;33(3):301-308.
Connolly MP, Bhatt A, Simmonds R. Implementing UK national dyspepsia
guidelines for returning patients to self-care: findings from an educational
intervention and 12-month follow-up clinical re-audit. Gut 2009;58(Suppl
II):A128-9.
Inadomi JM, Jamal R, Murata GH, Hoffman RM, Lavezo LA, Vigil JM, Swanson
KM, Sonnenberg A. Step-down management of gastroesophageal reflux disease.
Gastroenterology 2001;121(5):1095-100.
11. I would suggest replacing ‘on D7’ to ‘by D7’ throughout as appropriate.
12. Language and grammar can be improved in the Conclusion.
13. Page 8 Statistical analysis. Note that it is a ‘Student t-test’ and not a ‘Student
test’.
14. Page 10 Primary outcome 2nd paragraph. Please add proportions to the
90.1% i.e (109/121) for consistency.
15. Competing Interests/Acknowledgements. Remove the hyphen from
Reckitt-Benckiser.
16. Competing interests. MC – study was ‘funded’ not ‘founded’.
17. References no9 Chatfield. Add last page (152-159).
18. References no 21. Check that this is the correct way to cite this guideline.
19. Statistics. I would suggest a more detailed statistical review of this
manuscript. I am not sure that mean time to heartburn free is correct as other
similar papers utilise median. perhaps both could be noted in the table.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I am an employee of Technostics Ltd which acts as a consultant and medical
writer for Reckitt Benckiser Healthcare (UK) Ltd.
assistant