Reviewer's report
Title:Factors influencing treatment outcome in patients with gastroesophageal
reflux disease: outcome of a prospective pragmatic trial in Asian patients
Version:2Date:6 December 2013
Reviewer: David Peura
Reviewer's report:
The manuscript by professor K L Goh and colleagues reports a subgroup
analysis of a larger prospective worldwide pantoprazole treatment trial of GERD
patients. The Asian specific results suggest that response to PPI especially in
NERD patients may be less in Asia than in the rest of the world and as such is an
important original contribution. I would make the following general comments and
suggestions.
1. It would be useful to include possibly in table 1 demographics of rest of the
world group for comparison or at least add a statement in the results whether or
not they were different.
2. Western studies and physicians identify GERD based on heartburn which may
not be the case in Asia where regurgitation and chest pain are more common.
ReQuest may emphasize heartburn rather than regurgitation- I was unable to fine
the actual questions to verify. A reference to the actual questionnaire if published
would be helpful. Could the differences in response be explained on different
symptoms predominance? This should be mentioned in the discussion since the
authors do not provide any explanation for the difference between Asia and the
rest of the world. I suspect grades of esophagitis may have been lower in Asia
than in the rest of the world. Also in the whole study (ref 4) BMI, female gender,
anxiety and IBS were factors predicting response but not in the Asian subgroup.
This is worth mentioning in the discussion.
3. It is unclear how ReQuest was validated related to normal subjects. Reference
18 is a 7 year old abstract. If a subject had a ReQuest score of < 1.6 on study
days 3, 4 and 5 (3 consecutive days) and then for the remainder of the 8 weeks
they had much higher scores were they still considered as responders?
Sustained response or days of response would be important variables to report
and I note they were also absent in the full report (ref. 4). Unless this can be
reconciled it is a major weakness in this as well as the full report and should be
noted in the discussion.
4. The discussion should include speculation on why PPI response in Asia is
different. Also a 40 mg dose of pantoprazole was used even in NERDs. Is this an
approved dose and might response have even been less if 20 mg was used?
There was no placebo group so true response in the more subjective
psychological measures may have been overestimated and may invalidate the
last sentence of the discussion.
5. Figure 4 is confusing for example in Asia ~ 45%, 20% and 0% of responders
were very, fairly or not satisfied respectively. What about the other 35% of
responders? Or do the total % of all bars in both responders and non responders
add up to 100%?
Discretionary comments:
Were there any country specific differences noted?
Were any specific ReQuest questions predictors by themselves of response or
non response – that data may not be available?
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I have served as a consultant and as a speaker for Takeda pharmaceuticals
Reviewer's report
Title:Factors influencing treatment outcome in patients with gastroesophageal
reflux disease: outcome of a prospective pragmatic trial in Asian patients
Version:2Date:6 December 2013
Reviewer: David Peura
Reviewer's report:
The manuscript by professor K L Goh and colleagues reports a subgroup
analysis of a larger prospective worldwide pantoprazole treatment trial of GERD
patients. The Asian specific results suggest that response to PPI especially in
NERD patients may be less in Asia than in the rest of the world and as such is an
important original contribution. I would make the following general comments and
suggestions.
1. It would be useful to include possibly in table 1 demographics of rest of the
world group for comparison or at least add a statement in the results whether or
not they were different.
2. Western studies and physicians identify GERD based on heartburn which may
not be the case in Asia where regurgitation and chest pain are more common.
ReQuest may emphasize heartburn rather than regurgitation- I was unable to fine
the actual questions to verify. A reference to the actual questionnaire if published
would be helpful. Could the differences in response be explained on different
symptoms predominance? This should be mentioned in the discussion since the
authors do not provide any explanation for the difference between Asia and the
rest of the world. I suspect grades of esophagitis may have been lower in Asia
than in the rest of the world. Also in the whole study (ref 4) BMI, female gender,
anxiety and IBS were factors predicting response but not in the Asian subgroup.
This is worth mentioning in the discussion.
3. It is unclear how ReQuest was validated related to normal subjects. Reference
18 is a 7 year old abstract. If a subject had a ReQuest score of < 1.6 on study
days 3, 4 and 5 (3 consecutive days) and then for the remainder of the 8 weeks
they had much higher scores were they still considered as responders?
Sustained response or days of response would be important variables to report
and I note they were also absent in the full report (ref. 4). Unless this can be
reconciled it is a major weakness in this as well as the full report and should be
noted in the discussion.
4. The discussion should include speculation on why PPI response in Asia is
different. Also a 40 mg dose of pantoprazole was used even in NERDs. Is this an
approved dose and might response have even been less if 20 mg was used?
There was no placebo group so true response in the more subjective
psychological measures may have been overestimated and may invalidate the
last sentence of the discussion.
5. Figure 4 is confusing for example in Asia ~ 45%, 20% and 0% of responders
were very, fairly or not satisfied respectively. What about the other 35% of
responders? Or do the total % of all bars in both responders and non responders
add up to 100%?
Discretionary comments:
Were there any country specific differences noted?
Were any specific ReQuest questions predictors by themselves of response or
non response – that data may not be available?
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I have served as a consultant and as a speaker for Takeda pharmaceuticals
Please review this paper.
user
Reviewer's report
Title:Factors influencing treatment outcome in patients with gastroesophageal
reflux disease: outcome of a prospective pragmatic trial in Asian patients
Version:2Date:6 December 2013
Reviewer: David Peura
Reviewer's report:
The manuscript by professor K L Goh and colleagues reports a subgroup
analysis of a larger prospective worldwide pantoprazole treatment trial of GERD
patients. The Asian specific results suggest that response to PPI especially in
NERD patients may be less in Asia than in the rest of the world and as such is an
important original contribution. I would make the following general comments and
suggestions.
1. It would be useful to include possibly in table 1 demographics of rest of the
world group for comparison or at least add a statement in the results whether or
not they were different.
2. Western studies and physicians identify GERD based on heartburn which may
not be the case in Asia where regurgitation and chest pain are more common.
ReQuest may emphasize heartburn rather than regurgitation- I was unable to fine
the actual questions to verify. A reference to the actual questionnaire if published
would be helpful. Could the differences in response be explained on different
symptoms predominance? This should be mentioned in the discussion since the
authors do not provide any explanation for the difference between Asia and the
rest of the world. I suspect grades of esophagitis may have been lower in Asia
than in the rest of the world. Also in the whole study (ref 4) BMI, female gender,
anxiety and IBS were factors predicting response but not in the Asian subgroup.
This is worth mentioning in the discussion.
3. It is unclear how ReQuest was validated related to normal subjects. Reference
18 is a 7 year old abstract. If a subject had a ReQuest score of < 1.6 on study
days 3, 4 and 5 (3 consecutive days) and then for the remainder of the 8 weeks
they had much higher scores were they still considered as responders?
Sustained response or days of response would be important variables to report
and I note they were also absent in the full report (ref. 4). Unless this can be
reconciled it is a major weakness in this as well as the full report and should be
noted in the discussion.
4. The discussion should include speculation on why PPI response in Asia is
different. Also a 40 mg dose of pantoprazole was used even in NERDs. Is this an
approved dose and might response have even been less if 20 mg was used?
There was no placebo group so true response in the more subjective
psychological measures may have been overestimated and may invalidate the
last sentence of the discussion.
5. Figure 4 is confusing for example in Asia ~ 45%, 20% and 0% of responders
were very, fairly or not satisfied respectively. What about the other 35% of
responders? Or do the total % of all bars in both responders and non responders
add up to 100%?
Discretionary comments:
Were there any country specific differences noted?
Were any specific ReQuest questions predictors by themselves of response or
non response – that data may not be available?
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I have served as a consultant and as a speaker for Takeda pharmaceuticals
assistant