Strengths and limitations:
A strength of this secondary analysis
was the size of the original trial, which was considerably larger than
any previous trial investigating the efficacy of UDCA in this
population. The trial recruited women with a typical phenotype of ICP,
with 24% of women having a baseline bile acid concentration ≥40 µmol/L,
and the study findings are therefore likely to be generalisable to women
with a similar clinical phenotype. The subgroups of baseline bile acid
concentration analysed were based on clinically relevant thresholds that
had previously demonstrated an association with differences in perinatal
outcomes.2Interaction tests were used to test for differences in treatment effect,
which limited the possibility that the effect size seen in any
individual subgroup was over-interpreted. By understanding the size of a
clinically meaningful reduction in itch severity (judged by women and
clinicians), it was possible to consider whether or not any small
differences identified were clinically relevant.
The original trial was not designed with a view to undertaking the
present secondary analysis, and therefore no power calculation was
undertaken to ensure that the study was sufficiently powered to find
these effects. The study was limited by the size of certain subgroups,
particularly when investigating women with baseline bile acid
concentrations greater than 100 μmol/L (34 of 604 women). Although
multiple analyses were undertaken, increasing the risk of false positive
results, no significant differences were identified, mitigating the risk
of false discovery.