Review for 10.1186/1471-230X-14-111 (2014)

Reviewer's report
Title:A randomised, controlled study of small intestinal motility in patients treated
with sacral nerve stimulation for irritable bowel syndrome.
Version:2Date:2 February 2014
Reviewer: Peter Bytzer
Reviewer's report:
This study evaluated the potential effects of sacral nerve stimulation (SNS) on
small intestinal motility in IBS patients. The 20 patients, who participated in a
clinical cross-over trial of symptomatic effects of SNS on IBS symptoms
(outcome of that study reported in a manuscript in print (ref. 7)), were all
investigated at the end of each treatment period (ON and OFF stimulation). The
authors used a novel non-invasive tool, based on continuous tracking of a small
magnet progressing though the digestive canal. The coordinates of the magnet
are calculated from sensors located over the abdomen. The parameters of GI
transit times are obtained from the magnet’s position and by estimating the
frequency of GI-tract contractions from changes in the magnet’s angles. The
main finding of the study is that SNS has no detectable effects on gastric
emptying or small intestinal transit in IBS-D or IBS-M patients.
Despite my overall impression of a good quality paper, applying a novel and
interesting technology to address an interesting hypothesis, which has been
central to understanding the pathophysiology of IBS for years, I have major
objections and some questions, mainly related to the reporting of the study.
Major compulsory revisions
1) Did the authors have an a priori hypothesis of specific effects of SNS, e.g.
prolonged or delayed gastric and small bowel transit times?
2) Considering the observed variability in the parameters related to intestinal
passage, as can be found in some of the studies referred to in the Reference list,
some form of power estimate would have added to the value of the study. Was it
realistic to expect a significant difference in e.g. gastric emptying or small
intestinal transit time in a study of 20 individuals?
3) The hypothesis underlying the study is based on the potential association
between symptoms of IBS, such as diarrhoea and urgency, and alterations in GI
motility. Only patients with diarrhoea-predominant IBS or mixed IBS were
included, but the authors provide no data on these symptoms at the time of the
measurements, but only at baseline. Symptoms in IBS wax and wane and even
the classification (IBS-C, IBS-D or IBS-M) changes over time for a considerable
proportion of the patients. The symptom data presented in the paragraph Bowel
Function on page 9 are very difficult to assess. The authors only report median
changes in the various parameters. Since symptom data are presented in
another paper by the group (ref 7), and since the aim of the study (page 5) was
to “…evaluate the effect of sacral nerve stimulation on small intestinal motility in
IBS patients of diarrhoea-predominant and mixed subgroups.”, I suggest that all
symptom data and mention of symptomatic effects of SNS be removed from this
paper (see below).
4) It is very surprising that the authors have chosen not to include a discussion of
the most important methodological drawback of their study: the unblinding of the
SNS activity. From discussions with the first author and from other manuscripts
from this group it is clear that patients were unblinded to the settings of the SNS
because almost all patients were able to distinguish between the ON and the
OFF position. It is clear that the authors are well aware of this potential bias
(quote from page 5: “Investigators were blinded to the setting of the stimulator
and patients were at no time informed about the setting”). This unmasking is
probably not very important when it comes to the physiological recordings but
has a substantial effect on the interpretation of the symptom data. The reader is
given the impression that it is an established fact (from the data presented in
reference no. 7, which is in press and thus unavailable to me at the time of
reviewing) that SNS has significant and clinically relevant effects on IBS
symptoms (quoting from the Conclusion: “SNS holds promise as an effective
treatment modality against severe diarrhoea predominant or mixed IBS. Even
though, SNS reduces the frequency of defecation, episodes of urgency, and time
spent on toilet….”). Furthermore, symptom data with p-values are quoted in a
paragraph in the Results section. However, all these effects are based on
symptom reporting done by patients, who were unblinded to the SNS settings. A
large placebo effect can thus be anticipated and needs to be discussed. I find it
surprising – and scientifically unsound – to withhold such an important
methodological information from the manuscript.
5) Apparently, according to the cover letter, this is a revised version of the
manuscript. Was the first version also sent to BMC?
Minor essential revisions:
1) Page 7: The GSRS is short for The Gastrointestinal Symptom Rating Scale
(GSRS) – not Syndrome
2) P-values with a precision of up to 4 digits are somewhat overdone. Should be
rounded to nearest integer; e.g. on page 9 p=0.0963 should be p=0.1 or p>0.09.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests