Antiamoebic drugs for treating amoebic colitis - The Cochrane Library

trial authors for clarification. We noted the reasons for excluding
studies.
Data extraction and management
Two authors (MLM Gonzales and EG Martinez) independently
extracted data from the trials using pre-tested data extraction
forms. We collected details regarding the inclusion and exclusion
criteria for the participants, treatment intervention given, total
number randomized, number of participants in each group for all
outcomes, drop outs and withdrawals, and numbers experiencing
each outcome. For dichotomous data, we extracted the number of
participants who experienced the event of interest and the number
of participants randomized and analysed in each treatment group.
We resolved any disagreements by referring to the trial report and
through discussion. Where data were insufficient or missing, we
made attempts to contact the trial authors. MLM Gonzales entered
data for analysis using double data entry.
Assessment of risk of bias in included studies
Two authors (MLM Gonzales and LF Dans) independently assessed
the risk of bias in each trial using a prepared form. We assessed
the generation of allocation sequence and allocation concealment
as adequate, inadequate, or unclear according to Jüni
2001. We noted who was blinded, such as the trial participants,
care providers, or outcome assessors, and assessed the inclusion
of randomized participants in the analysis as adequate if 90% or
greater, and inadequate if not.
Assessment of reporting biases
We determined publication bias by looking for asymmetry in a
funnel plot. The presence of asymmetry in the funnel plot suggests
possible publication bias, although it may also indicate heterogeneity
or poor methodological quality of the trials.
Data synthesis
We analysed data collected using Review Manager 5. For dichotomous
outcomes, we calculated risk ratios (RR) with 95% confidence
intervals (CI).
Stratification of results
The main comparisons were between any single antiamoebic drug
and metronidazole (current standard therapy), any antiamoebic
drug and placebo, combination regimens and monotherapy, and
any single-dose regimen and longer regimens. We included but
did not pool data from other trials that compared any antiamoebic
drug with another antiamoebic drug and did not address any particular
pharmacological or clinical question relevant to this review.
For trials reporting results at multiple or varying time points, we
performed separate analyses for outcomes measured from the end
of treatment to 14 days and from 15 to 60 days after the end of
treatment. In trials comparing drugs with different treatment durations,
we measured the time point in relation to the last day of
the longest treatment period. We did not consider outcomes that
were measured during treatment or before completion of treatment.
Likewise, we did not include outcomes measured beyond
two months because this could be a reinfection rather than true
failure or relapse.
Heterogeneity
We calculated summary RR from meta-analysis using both a fixedeffect
model (Mantel-Haenszel method), which assumes trial homogeneity,
and a random-effects model (DerSimonian and Laird
method), which accounts for trial heterogeneity.
We reported results using the random-effects model when there
were differences between trials that may potentially influence the
size of the treatment effect or when significant statistical heterogeneity
was detected. We determined the presence of statistical
heterogeneity among the same interventions by inspecting the forest
plots for overlapping confidence intervals and by applying the
Chi 2 test for heterogeneity (P value < 0.10 considered statistically
significant) and the I 2 statistic to quantify inconsistency across trials
(I 2 value of greater than 50% used to denote substantial heterogeneity).
If heterogeneity was detected, but it was still considered
clinically meaningful to combine trial data, we explored potential
sources of heterogeneity using subgroup analysis. Only subtotals
for each subgroup were presented if the pooled results showed significant
heterogeneity. We determined clinical categories (amoebic
dysentery, nondysenteric amoebic colitis, or unspecified amoebic
colitis) and participant age (adults were those aged 15 years or
more, and children were those aged less than 15 years) to be important
subgroups even before data collection although we failed
to specify this in the protocol. Subgroup analysis could not be
undertaken as planned based on diagnostic tests because only one
trial used a stool E. histolytica ELISA test. The post hoc sources of
heterogeneity considered were types of intestinal infection (E. histolytica
infection alone or mixed intestinal infection), criteria for
determining outcome (based on WHO 1969 criteria or another
criteria), and regimens used.
Sensitivity analysis
Antiamoebic drugs for treating amoebic colitis (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
We performed sensitivity analyses to assess the robustness of the
overall estimates by calculating the results using all trials and then
excluding trials of a lower methodological quality (ie trials with
inadequate generation of allocation sequence, allocation concealment,
or blinding, or trials where less than 90% of randomized
participants were analysed), and excluding trials that were sponsored
by pharmaceutical companies. Although pharmaceuticalsponsored
trials may publish only where demonstrating positive
treatment effects, it may also be possible that pharmaceutical-
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