Data synthesis
Studies were grouped according to the data they contained relevant to
this systematic review’s three co-primary objectives. Group 1 studies
reported the proportion of hospital admissions attributed to ADRs, group
2 studies reported the proportion of hospital admissions prolonged by
ADRs, and group 3 studies reported the proportion of in-hospital deaths
attributable to ADRs; a study could be included in more than one group.
Since findings could be reported on the level of the patient or on the
level of the admission (i.e., allowing for re-admissions), we decided to
use admission-level data if reported, and patient-level data if no
admission-level data were reported.
In the primary analysis, we pooled data from all studies in each group,
regardless of study quality, study setting, methodological
considerations, or study populations. We tested for heterogeneity using
I2 statistics to decide whether to conduct
meta-analysis: in the presence of heterogeneity, we would summarise the
proportions mentioned above as medians and interquartile ranges; in the
absence of heterogeneity, we would conduct random-effects meta-analysis,
calculating the pooled estimate proportion after Freeman-Tukey double
arcsine transformation to stabilise the variances.
We explored the proportions mentioned above by subgroups relating to
study quality, study setting, methodological considerations, and study
populations. Depending on heterogeneity within each subgroup (using
I2 statistics) we would proceed to synthesise the data
as above.
A similar approach was followed for the secondary objectives, where we
summarised serious preventable ADRs. For the remainder of the secondary
and explorative objectives, we narratively summarised clinical
presentations commonly reported, drugs commonly implicated, and the
contribution of HIV, ART, and methodological and quality issues.