Maternal outcomes:
All analyses in this secondary analysis followed the intention-to-treat
principle: all randomly allocated women were analysed according to the
group they were allocated to, irrespective of the treatment they
received, if any. The analyses required data collected at
post-randomisation visits therefore women without post-randomisation
visit data were excluded.
For bile acid concentrations, subgroups were defined based on accepted
thresholds from the literature related to perinatal
risk.2For itch, subgroups were defined based on median itch at baseline in the
trial
participants.6The effect of baseline bile acid concentration (<40 μmol/L vs
≥40 μmol/L, <100 μmol/L vs ≥100 μmol/L) and baseline itch
score (<60 mm vs ≥60 mm) on two maternal outcomes were
analysed: i) serum bile acid concentration post-randomisation and ii)
itch score post-randomisation. Baseline bile acid trajectory was defined
as ‘increasing’ if the first bile acid concentration post-randomisation
was greater than or equal to the baseline bile acid concentration and
‘decreasing’ if the first bile acid concentration post-randomisation was
less than the baseline bile acid concentration. The effect of this
baseline itch trajectory on the two maternal outcomes was also analysed.
As bile acid concentrations demonstrate a lognormal distribution, the
geometric mean of all available post-randomisation bile acid
concentrations was used to calculate each participant’s mean
post-randomisation bile acid concentration, and the trial groups were
compared using a geometric mean ratio. An arithmetic mean of all
available itch scores post-randomisation was used to calculate each
participant’s mean post-randomisation itch score, and the trial groups
were compared using a mean difference. An interaction test (likelihood
ratio version) was used to test for a difference in treatment effect
between the individual subgroups.
The treatment effect in each group was visualised by plotting the
average itch score or geometric average bile acid concentration by
visit. Visits were seven days apart, plus or minus one day. Only visits
which had five or more women contributing results were included. Error
bars were added to represent the standard error of each group at each
visit. All available pairs of itch scores and bile acid concentrations
were plotted for all participants at all time points, and a correlation
coefficient between the two was calculated.