Aanesthetic Agents for Day Surgery - NIHR Health Technology ...

agent used (see appendix 18). It was expected that
the Dion formula would over- or underestimate the
actual amount of agent used, due to differences in
temperature, adsorption of the volatile, and so on,
and this effect was in fact observed. It was not
possible to estimate formally a ‘correction factor’
for the Dion formula because of the small sample
size in this substudy. However, at this stage it is
possible to calculate the mean difference between
the Dion estimate and the true weight of volatile
anaesthetic used. The actual correction of the
amount of anaesthetic used ranged from 49% to
81%. The percentage mean difference was used to
indicate the average magnitude of the difference
between the Dion estimate and the actual weight
of true anaesthetic. It is clear that the use of the
Dion formula underestimates the use of volatile
anaesthetic agents.
Sensitivity analysis was used to explore the
impact of this imprecision on the results of
the CESA RCT. Overall, the sensitivity analysis
confirmed that anaesthetic regimens that used
propofol for induction of anaesthesia were more
cost-effective than those using sevoflurane for
induction of anaesthesia. Furthermore, the slight
advantage seen for propofol/isoflurane was
increased when the costs of the volatile agents
were inflated. This alternative was associated
with net savings and a lower incidence of PONV
when compared to sevoflurane/sevoflurane.
Staff resource use
The staff resource use study confirmed the stages
and tasks that comprise a day-surgery episode,
identified the type and grade of NHS staff present
at each stage, and quantified the length of time
that each grade of staff took to complete each
task (see appendix 19). Differences in working
practices in terms of skill mix were observed
between the three hospital sites, but this did not
translate into notable differences in the average
semi-fixed cost. The study reported that the staff
resource use of paediatric and adult patients
differed, particularly on the ward postoperatively,
where patient monitoring was much more intensive
for children than for adults. These differences
may affect the external rather than the internal
validity of the results.
The assessment and recording of outcomes
by the research nurses and project coordinator
were subject to quality-control measures (see
appendix 22). The quality-control procedures
indicated a high level of consistency and reliability.
These factors, taken together with the statistical
and sensitivity analyses, suggest that the potential
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Health Technology Assessment 2002; Vol. 6: No. 30
for bias or imprecision in the clinical cost and
CV data recorded for the trial is low.
Precision of statistical analysis
As noted above, problems with the recruitment
of anaesthetists and patients meant that the target
sample size was not met. This meant that the
power to detect statistically significant differences
in the primary outcome may not have been
sufficient. In addition, the trial was powered
to test for differences in the incidence of PONV
between treatment groups rather than for equivalence.
These factors may mean that the absence
of statistically significant differences between
the three regimens that used propofol for induction
of anaesthesia could be due to insufficient
observations rather than to equivalence between
the regimens. The published literature indicates
that TIVA is associated with a lower risk of PONV
than is propofol followed by a volatile anaesthetic
agent. However, post hoc power calculations indicate
that the study had 70% power to detect a
difference in PONV from 20% to 10% at
1% significance.
It was not possible to control for all the factors
that may affect the incidence of PONV. This,
combined with the lower than optimum sample
size, may have further reduced the power of the
trial to detect statistically significant differences.
The potential confounding variables were evenly
distributed between the groups. Regression
analysis was conducted to explore the impact
of factors that were a priori thought to influence
the incidence of PONV. The analysis indicated
that the main determinant of PONV was
anaesthetic regimen.
The CESA RCT was not powered to detect differences
in the secondary outcomes of patient preferences
and CV or costs. However, the analysis did
indicate some statistically significant differences.
Importantly, sensitivity and statistical analyses
of the ICERs and net benefits confirmed the
differences in PONV, costs and willingness-to-pay
values between the different anaesthetic regimens.
Multiple outcomes were tested in the CESA RCT,
which increases the probability that a difference
will be found and shown to be statistically significant
when it has in fact occurred by chance.
For this reason the analysis used a low level of
statistical significance (1%) to reduce the impact
of multiple testing. The statistical differences
found were mostly significant at less than the 1%
level of significance. In addition, the key variables
to be tested were defined a priori in a detailed
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