Critical Appraisal for Therapy Articles

Therapy Study

“The role of Bifidobacterium lactis B94 plus inulin in the treatment of acute infectious diarrhea in
children”

What question did the study ask?

Patients : Children with acute diarrhea
Intervention : Bifidobacterium lactis + inulin (symbiotic)
Comparison : Maltodextrin (placebo)
Outcome(s) : Duration of diarrhea, number of diarrheal stools on 3rd day, percentage of patients with
diarrhea on 5th day

Are the results of the trial valid? (Internal Validity)

1a. R- Was the assignment of patients to treatments randomised?

What is best? Where do I find the information?
Centralised computer randomisation is ideal and often The Methods should tell you how patients were allocated
used in multi-centred trials. Smaller trials may use an to groups and whether or not randomisation was
independent person (e.g, the hospital pharmacy) to concealed.
“police” the randomization.
This paper: Yes  No  Unclear x
Comment:

“The patients were randomized and assigned to the synbiotic and placebo groups in a double-blind manner using a
preformed randomization list. Each patient was given a code.” [Materials and Methods / 2nd Paragraph]

Randomized with preformed list, but who make the list? Code for identification or intervention?

1b. R- Were the groups similar at the start of the trial?

What is best?
If the randomisation process worked (that is, achieved
comparable groups) the groups should be similar. The
more similar the groups the better it is.
There should be some indication of whether differences
between groups are statistically significant (ie. p values).
This paper: Yes x No  Unclear 
Comment:
Where do I find the information?
The Results should have a table of "Baseline
Characteristics" comparing the randomized groups on a
number of variables that could affect the outcome (ie. age,
risk factors etc). If not, there may be a description of group
similarity in the first paragraphs of the Results section.

“Before the treatment, there was no difference between the groups in terms of age, gender, degree of dehydration,
number of vomiting episodes, fever, frequency of stools, or initial period of diarrhea.” [Results / 1 st Paragraph]

“There was no difference between the groups in terms of identified etiological factors.” [Results / 2nd Paragraph]

Table 1 & 2  p > 0.5 for demographic characteristics and microorganisms detected in stool

2a. A – Aside from the allocated treatment, were groups treated equally?
What is best? Where do I find the information?
Apart from the intervention the patients in the different Look in the Methods section for the follow-up schedule,
groups should be treated the same, eg., additional and permitted additional treatments, etc and in Results for
treatments or tests. actual use.

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Critical Appraisal for Therapy Articles

This paper: Yes x No  Unclear 

Comment:

“All the patients received routine treatment such as oral and/or intravenous fluid therapy, and nutritional support, and
breastfeeding was promoted. The patients who required intravenous fluids were treated in the emergency rooms or
outpatient treatment rooms and were then discharged.” [Materials and Methods / 2nd Paragraph]

“The parents were phoned every day for 10 days and were asked if their child took the preparations […] The parents
were also asked whether they needed any medical support.” [Materials and Methods / 4 th Paragraph]

In Methods sections, it was mentioned how groups were planned to be treated equally. No info in the Results section.

2b. A – Were all patients who entered the trial accounted for? – and were they analysed in the
groups to which they were randomised?
What is best?
Losses to follow-up should be minimal – preferably less
than 20%. However, if few patients have the outcome of
interest, then even small losses to follow-up can bias the
results. Patients should also be analysed in the groups to
which they were randomised – ‘intention-to-treat analysis’.
This paper: Yes  No x Unclear 
Comment:
Where do I find the information?
The Results section should say how many patients were
randomised (eg., Baseline Characteristics table) and how
many patients were actually included in the analysis. You
will need to read the results section to clarify the number
and reason for losses to follow-up.

“[…] 179 patients were included in the study. The patients were divided into two groups in a double-blind manner; 90
patients were assigned to the synbiotic group and 89 to the placebo group. During the study period, 11 patients in the
synbiotic group and 12 patients in the placebo group were excluded from the study as they used antibiotics, did not take
the required preparations, or did not communicate.” [Results / 1st Paragraph]

Excluded patients were not accounted in the analysis, as demographic characteristics (based on dehydration status)
only accounted for 79 patients in symbiotic group and 77 patients in placebo group. Moreover, patients who did not the
medications were considered dropout. Thus, this study used as treated analysis.

Nevertheless, the count for lost to follow up was < 20%, thus, the analysis can be considered valid

3. M - Were measures objective or were the patients and clinicians kept “blind” to which
treatment was being received?
What is best?
It is ideal if the study is ‘double-blinded’ – that is, both
patients and investigators are unaware of treatment
allocation. If the outcome is objective (eg., death) then
blinding is less critical. If the outcome is subjective (eg.,
symptoms or function) then blinding of the outcome
assessor is critical.
This paper: Yes  No  Unclear x
Comment:
Where do I find the information?
First, look in the Methods section to see if there is some
mention of masking of treatments, eg., placebos with the
same appearance or sham therapy. Second, the Methods
section should describe how the outcome was assessed
and whether the assessor/s were aware of the patients'
treatment.

“The patients in the placebo group received a maltodextrin-containing placebo with the same appearance as the
synbiotic once a day for five days […] The parents were phoned every day for 10 days and were asked if their child took
the preparations. They answered questions about stool frequency, vomiting frequency (if any), stool consistency, fever,
and any dietary problems […] Statistical analyses were performed by a gastroenterologist using patient codes only and
who was unaware of the treatment administered.” [Materials and Methods / 4th Paragraph]

Patient reported outcome measures, but no mention of the person that contacted and recorded the data, or whether the
person was blinded or not. The statistical analyses were done blindly.

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Critical Appraisal for Therapy Articles

What were the results?

1. How large was the treatment effect?

The paper used mean difference and percentages to describe the results using Mann Whitney U test and Chi Square
test, respectively. However, the paper provided the mean of individual groups instead of exact mean difference.

The most notable mean difference was the stool frequency in 3rd day, which was about 3. Another notable finding was
mean difference of 2 days for duration of diarrhea caused by rotavirus The other 2 significant findings might not be
clinically significant considering the mean difference were approximately 1 day.

Unfortunately, the paper didn’t provide the RR for number of patients with diarrhea in 5th day.
EER = 14/79 = 0.18
CER = 30/77 = 0.39
RR = 0.18/0.39 = 0.45, thus synbiotic decreases the risk of diarrhea up to 5 days
ARR = 0.39 – 0.18 = 0.21, thus symbiotic decrease 21% in rate of diarrhea up to 5 days
RRR = 1 – 0.45 = 0.55
NNT = 1/0.21 = 4.7

2. How precise was the estimate of the treatment effect?

Confidence interval was not provided in all of the results. Moreover, instead of writing down the range or IQR range,
considering it was implied that the data was not normally distributed, the authors presented the point estimate with
standard deviation.

CI for ARR = 7.47 to 35.00

CI for NNT = 2.85 to 13.38

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Critical Appraisal for Therapy Articles

Will the results help me in caring for my patient? (ExternalValidity/Applicability)

The questions that you should ask before you decide to apply the results of the study to your patient are:
 Is my patient so different to those in the study that the results cannot apply?
 Is the treatment feasible in my setting?
 Will the potential benefits of treatment outweigh the potential harms of treatment for my patient?

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