Reviewer's report
Title:A candidate probiotic with unfavorable effects in subjects with irritable
bowel syndrome: a randomized controlled trial
Version: 1Date:15 June 2009
Reviewer: Filippo Cremonini
Reviewer's report:
Comment to Authors
Ligaarden and colleagues report on the lack of efficacy and comment on
potential unfavorable effects of L.plantarum MF1298 in a randomized,
double-blind, placebo crossover trial of 16 IBS patients. The methods are
rigorous and the study is performed in an evolving area of experimental
treatment. My concerns are as follows:
1. The Authors report on “aggravation” of symptoms. While one hand I feel it
would be more cautious to report on the lack of benefit, assuming this study is
appropriately powered, I believe that, when comparing the results to the baseline,
there is no actual “aggravation” or significant negative change that can justify the
hype put on the “potential unfavorable effects” of a this probiotic species
2. When found, the significant differences are quite small, and I question what
the clinical relevance of these would be, when we have a 2-pts. Difference in a
scale with a range of 14.
3. The differences in composite scores are not mirrored by clear, understandable
effects on individual symptoms/bowel habit changes. This is possibly due, as in
part the Authors acknowledge, to the heterogeneity of the sample in terms of
bowel habit predominance. This lack of a specific symptom to point to weakens
the argument of the “toxicity” of the probiotic in question, as one would have to
understand first what would specifically define such toxicity.
4. The length of treatment is too short to overcome the fluctuations in symptoms
which are typical in IBS patients, thus limiting the internal validity of the trial itself
5. Which one of the “ideal" characteristics of a probiotic is more useful to target
putative pathophysiological determinants of IBS? The superficial reader might be
“tricked” into believing that “The Best Probiotic” we have actually worsens IBS,
which is a risky argument. All I see here is that a probiotic that showed promise
in the lab failed to improve IBS in a small, crossover trial. Considering the size
needed in IBS clinical trials to show significant effects on symptoms, global relief
(see classical studies on tegaserod, alosetron, etc) this way of interpreting results
poses the risk of throwing away the baby with the water.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:A candidate probiotic with unfavorable effects in subjects with irritable
bowel syndrome: a randomized controlled trial
Version: 1Date:15 June 2009
Reviewer: Filippo Cremonini
Reviewer's report:
Comment to Authors
Ligaarden and colleagues report on the lack of efficacy and comment on
potential unfavorable effects of L.plantarum MF1298 in a randomized,
double-blind, placebo crossover trial of 16 IBS patients. The methods are
rigorous and the study is performed in an evolving area of experimental
treatment. My concerns are as follows:
1. The Authors report on “aggravation” of symptoms. While one hand I feel it
would be more cautious to report on the lack of benefit, assuming this study is
appropriately powered, I believe that, when comparing the results to the baseline,
there is no actual “aggravation” or significant negative change that can justify the
hype put on the “potential unfavorable effects” of a this probiotic species
2. When found, the significant differences are quite small, and I question what
the clinical relevance of these would be, when we have a 2-pts. Difference in a
scale with a range of 14.
3. The differences in composite scores are not mirrored by clear, understandable
effects on individual symptoms/bowel habit changes. This is possibly due, as in
part the Authors acknowledge, to the heterogeneity of the sample in terms of
bowel habit predominance. This lack of a specific symptom to point to weakens
the argument of the “toxicity” of the probiotic in question, as one would have to
understand first what would specifically define such toxicity.
4. The length of treatment is too short to overcome the fluctuations in symptoms
which are typical in IBS patients, thus limiting the internal validity of the trial itself
5. Which one of the “ideal" characteristics of a probiotic is more useful to target
putative pathophysiological determinants of IBS? The superficial reader might be
“tricked” into believing that “The Best Probiotic” we have actually worsens IBS,
which is a risky argument. All I see here is that a probiotic that showed promise
in the lab failed to improve IBS in a small, crossover trial. Considering the size
needed in IBS clinical trials to show significant effects on symptoms, global relief
(see classical studies on tegaserod, alosetron, etc) this way of interpreting results
poses the risk of throwing away the baby with the water.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:A candidate probiotic with unfavorable effects in subjects with irritable
bowel syndrome: a randomized controlled trial
Version: 1Date:15 June 2009
Reviewer: Filippo Cremonini
Reviewer's report:
Comment to Authors
Ligaarden and colleagues report on the lack of efficacy and comment on
potential unfavorable effects of L.plantarum MF1298 in a randomized,
double-blind, placebo crossover trial of 16 IBS patients. The methods are
rigorous and the study is performed in an evolving area of experimental
treatment. My concerns are as follows:
1. The Authors report on “aggravation” of symptoms. While one hand I feel it
would be more cautious to report on the lack of benefit, assuming this study is
appropriately powered, I believe that, when comparing the results to the baseline,
there is no actual “aggravation” or significant negative change that can justify the
hype put on the “potential unfavorable effects” of a this probiotic species
2. When found, the significant differences are quite small, and I question what
the clinical relevance of these would be, when we have a 2-pts. Difference in a
scale with a range of 14.
3. The differences in composite scores are not mirrored by clear, understandable
effects on individual symptoms/bowel habit changes. This is possibly due, as in
part the Authors acknowledge, to the heterogeneity of the sample in terms of
bowel habit predominance. This lack of a specific symptom to point to weakens
the argument of the “toxicity” of the probiotic in question, as one would have to
understand first what would specifically define such toxicity.
4. The length of treatment is too short to overcome the fluctuations in symptoms
which are typical in IBS patients, thus limiting the internal validity of the trial itself
5. Which one of the “ideal" characteristics of a probiotic is more useful to target
putative pathophysiological determinants of IBS? The superficial reader might be
“tricked” into believing that “The Best Probiotic” we have actually worsens IBS,
which is a risky argument. All I see here is that a probiotic that showed promise
in the lab failed to improve IBS in a small, crossover trial. Considering the size
needed in IBS clinical trials to show significant effects on symptoms, global relief
(see classical studies on tegaserod, alosetron, etc) this way of interpreting results
poses the risk of throwing away the baby with the water.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
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