Reviewer's report
Title:Nitroglycerin 0.4% ointment vs placebo in the treatment of pain resulting
from chronic anal fissure: a phase 3, randomized, double-blind,
placebo-controlled study
Version: 2Date:6 September 2012
Reviewer: Yinghong Wang
Reviewer's report:
Major compulsory revisions
Reviewer #1: This is a randomized, double-blind, placebo-controlled trial
comparing nitroglycerin 0.4% ointment with placebo for pain associated with
chronic anal fissure. It is a large series of 247 patients enrolled. The data show
that nitroglycerin 0.4% ointment effectively reduced chronic anal fissure pain
compared with placebo in patients with moderate-to-severe CAF pain.
1. The analgesic effect on the anal fissure pain from nitroglycerin 0.4% ointment
has been well known and studied previously, this study is not adding any new
findings to the existed evidence.
2. How would the finding of this study change the clinical practice? As
nitroglycerin 0.4% ointment has already been approved by FDA to use for anal
fissure pain regardless of its severity. Especially the healing of the fissure was
not included in this study which is one of the most important therapeutic aspects
of the treatment.
3. Not sure how authors decided on the duration of 21 days, given majority of the
studies used 8 weeks of treatment, especially there is high recurrence rate.
4. The placebo effect is almost comparable to the nitroglycerin group including
the primary and secondary end points, with the small (<10mm) but significant
difference between the two groups in the VAS score change on post-hoc
analysis, I don’t see the clinical significance.
5. Authors reported that the VAS pain score is recorded as 24 hours average
during days 14-18, however, no details about how the patients were supposed to
record their VAS score during 24 hours period. The timing of the recording and
its association with defecation is critical to change the overall analysis.
6. Authors used days 14-18 as the evaluation time point, which covered only ¼ of
the overall study period. This is quite different from other similar studies, which
compared several times point from each week on the treatment to minimize the
biase.
7. In Table 2, authors used both SD and SE, why there is an inconsistency?
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
Reviewer's report
Title:Nitroglycerin 0.4% ointment vs placebo in the treatment of pain resulting
from chronic anal fissure: a phase 3, randomized, double-blind,
placebo-controlled study
Version: 2Date:6 September 2012
Reviewer: Yinghong Wang
Reviewer's report:
Major compulsory revisions
Reviewer #1: This is a randomized, double-blind, placebo-controlled trial
comparing nitroglycerin 0.4% ointment with placebo for pain associated with
chronic anal fissure. It is a large series of 247 patients enrolled. The data show
that nitroglycerin 0.4% ointment effectively reduced chronic anal fissure pain
compared with placebo in patients with moderate-to-severe CAF pain.
1. The analgesic effect on the anal fissure pain from nitroglycerin 0.4% ointment
has been well known and studied previously, this study is not adding any new
findings to the existed evidence.
2. How would the finding of this study change the clinical practice? As
nitroglycerin 0.4% ointment has already been approved by FDA to use for anal
fissure pain regardless of its severity. Especially the healing of the fissure was
not included in this study which is one of the most important therapeutic aspects
of the treatment.
3. Not sure how authors decided on the duration of 21 days, given majority of the
studies used 8 weeks of treatment, especially there is high recurrence rate.
4. The placebo effect is almost comparable to the nitroglycerin group including
the primary and secondary end points, with the small (<10mm) but significant
difference between the two groups in the VAS score change on post-hoc
analysis, I don’t see the clinical significance.
5. Authors reported that the VAS pain score is recorded as 24 hours average
during days 14-18, however, no details about how the patients were supposed to
record their VAS score during 24 hours period. The timing of the recording and
its association with defecation is critical to change the overall analysis.
6. Authors used days 14-18 as the evaluation time point, which covered only ¼ of
the overall study period. This is quite different from other similar studies, which
compared several times point from each week on the treatment to minimize the
biase.
7. In Table 2, authors used both SD and SE, why there is an inconsistency?
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
Please review this paper.
user
Reviewer's report
Title:Nitroglycerin 0.4% ointment vs placebo in the treatment of pain resulting
from chronic anal fissure: a phase 3, randomized, double-blind,
placebo-controlled study
Version: 2Date:6 September 2012
Reviewer: Yinghong Wang
Reviewer's report:
Major compulsory revisions
Reviewer #1: This is a randomized, double-blind, placebo-controlled trial
comparing nitroglycerin 0.4% ointment with placebo for pain associated with
chronic anal fissure. It is a large series of 247 patients enrolled. The data show
that nitroglycerin 0.4% ointment effectively reduced chronic anal fissure pain
compared with placebo in patients with moderate-to-severe CAF pain.
1. The analgesic effect on the anal fissure pain from nitroglycerin 0.4% ointment
has been well known and studied previously, this study is not adding any new
findings to the existed evidence.
2. How would the finding of this study change the clinical practice? As
nitroglycerin 0.4% ointment has already been approved by FDA to use for anal
fissure pain regardless of its severity. Especially the healing of the fissure was
not included in this study which is one of the most important therapeutic aspects
of the treatment.
3. Not sure how authors decided on the duration of 21 days, given majority of the
studies used 8 weeks of treatment, especially there is high recurrence rate.
4. The placebo effect is almost comparable to the nitroglycerin group including
the primary and secondary end points, with the small (<10mm) but significant
difference between the two groups in the VAS score change on post-hoc
analysis, I don’t see the clinical significance.
5. Authors reported that the VAS pain score is recorded as 24 hours average
during days 14-18, however, no details about how the patients were supposed to
record their VAS score during 24 hours period. The timing of the recording and
its association with defecation is critical to change the overall analysis.
6. Authors used days 14-18 as the evaluation time point, which covered only ¼ of
the overall study period. This is quite different from other similar studies, which
compared several times point from each week on the treatment to minimize the
biase.
7. In Table 2, authors used both SD and SE, why there is an inconsistency?
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
assistant