Review for 10.1186/1471-230X-11-42 (2011)

Reviewer's report
Title:A prospective, double-blind, multi center, randomized clinical study to
compare the efficacy and safety of Ertapenem 3 days versus
Ampicillin-Sulbactam 3 days in the treatment of localized community acquired
intra-abdominal infections. (T.E.A. Study: Three days Ertapenem vs three days
Ampicillin-Sulbactam)
Version: 1Date:14 October 2010
Reviewer: Greger Lindberg
Reviewer's report:
This protocol describes a study aimed at comparing the failure rates of two
different antibiotics for acute intra-abdominal infections. Both antibiotics are
intended to be given for a shorter than normal period of 3 days. It is important to
search evidence in favour of reducing the use of antibiotics. However, it is difficult
to find sponsors for this type of studies, since they may contradict the aims of
pharmaceutical companies.
The authors wish to compare two 3-day regimens comprising in one arm
ertapenem and in the other arm the combination of ampicillin and sulbactam. The
study size builds on an assumed 3-fold better efficacy of ertapenem. Although
the appropriate research ethics body has already approved the study, the current
description raises a number of questions that need to be answered:
Major Compulsory Revisions
1. The title of the manuscript is misleading in two ways. Firstly, this is not a
blinded study at all and certainly not at double-blind study. Both the patient and
the doctor will know the type of treatment. Even though some of the evaluation
will be done by a third party presumably blinded for treatment allocation, I would
suspect that the case review will reveal also the treatment allocation. Secondly,
the title says that this is a multi-centre trial but although two of the authors come
from other hospitals (Riuniti Hospital, Bergamo and Maggiore Hospital, Bologna)
the protocol only mentions patients from St. Orsola-Malpighi University Hospital.
The latter indicates a single-centre study. Please change the title.
2. The primary endpoint is the failure rate. However, the protocol lacks a firm
description of "failure" as well as the timing of its evaluation. In the paragraph
Data Collection both "failure" and "late failure" are mentioned. The definition of
the primary endpoint is crucial to this study. Hence it needs a clear definition.
Please include a clear definition of the primary endpoint. Please also state the
secondary endpoints under a separate heading (Secondary endpoints).
3. The sample size was determined from the hypothesis that treatment with
ertapenem should give no more than 10% failures. This is reasonable given the
results from the study by Basoli et al. (ref #6). However, the basis for assuming
that ampicillin-sulbactam would lead to at least 30% failures is not stated. Please
clarify how the figure 30% was arrived at since this is crucial for the size (n=142)
of the study.
Minor Essential Revisions
4. There are some peculiarities regarding the order of events that either require
re-writing or explanation:
4.1 In Randomization the text reads "if the patient fulfils the inclusion criteria the
responsible surgeon will disclose the envelope and accordingly to the protocol
the patient will sign an informed consent". I don't understand what the authors
mean by "disclose the envelope" and in any case this should not be done before
obtaining informed consent. Hence, the order should be first to establish if a
patient fulfils inclusion criteria and no exclusion criteria, secondly to inform the
patient about the study, thirdly to obtain informed consent, and fourthly to
randomize.
4.2 In the paragraph Informed Consent or Informaion Sheet the text reads: "the
patient will receive all the information about the study protocol, the confidential
nature of personal data and will fill up a questionnaire before signing or refuse."
This is an incorrect order of events since the patient should not be asked to fill
out a questionnaire before having consented to participation. Hence the order
should be information – consent – questionnaire.
5. The manuscript needs a thorough linguistic revision. There are numerous
syntax errors, inappropriate use of definite article, and past tense when future
tense should be used.
Level of interest: An article of importance in its field
Quality of written English: Not suitable for publication unless extensively edited
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