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

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Economic evaluation methods
similar to the bootstrap. Briggs and Gray 255
offer specific guidance for judging whether skew
in the data will have important implications for
the sampling distribution of the mean. They
suggest that the skew in the sampling distribution
of the mean (S m) will be a factor: S m = S S – √n S,
where S S is the skewness of the original sample
and n S is the number of observations in the
original sample. When this rule was applied,
the skewness in the samples was found to be
sufficiently low to indicate normality for the
sampling distribution of the mean. 255
Therefore, the t-test was employed in this study.
The t-test (and analysis of variance (ANOVA) for
multiple group comparisons) was used for length
of stay, cost, CV and net benefit variables.
Sensitivity analysis
Uncertainty: CESA RCT data
Sensitivity analysis was required to supplement the
statistical analysis, in order to assess the level of
uncertainty in the data collected within the CESA
RCT and the subsequent internal robustness of the
results. Sensitivity analysis was used to evaluate
uncertainty for two cases, as described below.
Incremental cost-effectiveness ratios
Statistical analysis is not appropriate for testing
the robustness of ICERs. It is not possible to
generate 95% CIs around ICERs because the
ratio of two distributions does not necessarily
have a finite mean or, therefore, a finite variance.
256 The 95% CIs of the principal clinical
outcome (PONV) were used to recalculate
ICERs in order to assess the impact of uncertainty
regarding clinical outcomes on ICERs. A simple
deterministic sensitivity analysis was used to
explore the impact of varying the incidence of
PONV. The values for PONV incidence were
varied between the limits of the 95% CIs. The
low rate of PONV incidence for each arm was
used simultaneously in the calculation of each
ICER in the sensitivity analysis.
This was followed by the generation of a
bootstrap estimate of the ICER sampling
distribution to identify the magnitude of
uncertainty around the ICERs. This method
allowed uncertainty around both the costs and
effects to be taken into account. Bootstrapping
with replacement was employed, utilising
Microsoft’s Excel ® , using 1000 iterations.
The 2.5% and 97.5% percentiles of the
ICER distribution were obtained.
Validity of the use of the Dion approximation
of volatile consumption
A substudy showed that the Dion algebraic
approximation consistently underestimated
the amount of volatile anaesthetic used (see
appendix 18). Results from this study suggested
that the actual amounts of isoflurane and sevoflurane
were 6% and 27% higher, respectively,
than estimated. There was a wide variation
in these inflation factors. One-way sensitivity
analysis was used was to recalculate the
variable costs using inflation factors. The
total variable cost for each group was calculated
for each inflation level. ICERs were
recalculated for the range of inflation
factors, if appropriate.
Uncertainty: differences between the
CESA RCT and routine practice
The trial protocol and comparators were defined
to reflect routine practice as far as possible.
However, it was recognised that anaesthesia
practice was changing. Additional analyses were
planned to combine the CESA RCT data with
published evidence to explore the relative costs
and effects of anaesthesia practice not included
in the trial. The literature review (see chapter 2)
and the national survey (see chapter 3) indicated
that some anaesthetic agents and practices
now in use were not measured in the trial.
Decision analysis and probabilistic sensitivity
analysis were used to assess the impact of
the following on patient outcomes and
total costs:
• differences between the trial and routine
practice in the use of prophylactic anti-emetics
in adults (CESA MODEL)
• differences between the trial and routine
practice in the inhalational anaesthetics
used in children (CESA MODEL).
Additional data for these analyses were obtained
from the literature review (see chapter 2) and
national survey (see chapter 3). The literature
review extracted and evaluated the clinical and
economic evidence for the sensitivity analysis and
modelling section. The data obtained from the
survey are summarised in chapter 3.
The analysis of uncertainty used the mean
costs and variance calculated for the trial-based
analysis above. To extrapolate the results of the
trial to alternative anaesthetic agents and PONV
prophylaxis practices, the results of the trial were
synthesised with the data from the literature
reviews and national survey.