Data synthesis and analysis
The main results of the SR are described narratively and tabulated as
summary of findings. Data were pooled and meta-analysed using Review
Manager (Review Manager V.5.3, Cochrane Collaboration, Oxford, UK) using
the random effects model approach. For binary outcomes pooled relative
risk ratios and rate ratios (RRs) were calculated. For continuous
outcomes mean differences (MDs) with 95% confidence intervals (CI),
were used. If mean or standard deviations (SD), or changes of mean and
SDs from baseline were not reported, standard errors (SE), CI, or the
correlation coefficient were used. Where multiple arms were compared to
a common placebo arm, SE were adjusted to avoid the unit of analysis
error (22).
The magnitude of heterogeneity between the included studies was
calculated using the Higgings’ I2 statistic interpreted according to the
Cochrane Handbook guidelines (23). To account for clinical
heterogeneity, subgroup analysis was predefined if possible by different
doses of dupilumab, age and ROB. The median estimate reported in the
control arms was used as baseline risk to estimate absolute effects. For
the economic evidence, results are summarized narratively and tabulated,
including the cost, incremental effectiveness, ICERs and the degree of
uncertainty.