Docetaxel with prednisone or prednisolone for the treatment of ...

Economic evaluation
Only one published study met the inclusion criteria
for the cost-effectiveness review. In addition, a
separate submission was received from Sanofi-
Aventis. Both of these studies were based on costeffectiveness
analyses undertaken alongside
separate RCTs. Hence the range of comparators
included in both was constrained to those evaluated
in each of these trials. The published study and
manufacturer’s submission were assessed, and a new
model was developed to address the limitations
identified in these sources and to provide a direct
comparison of the full range of possible strategies
that are potentially relevant to the NHS. The model
explored a range of uncertainties and sources of
variability that were not fully addressed in existing
data sources. In particular, the lack of quality
adjustment in the outcome measure used in the
submission by Sanofi-Aventis was addressed using a
separate systematic review of external evidence
reporting on the QoL in patients with mHRPC in
order to estimate QALYs.
The analyses presented here indicate that
mitoxantrone plus prednisone/prednisolone
dominates the use of prednisone/prednisolone
alone. For the purposes of assessing the
incremental cost-effectiveness of docetaxel (3weekly)
plus prednisone/prednisolone, the
appropriate comparator for these estimates is
therefore mitoxantrone plus
prednisone/prednisolone. The economic model
presented in this report demonstrates that
docetaxel (3-weekly) plus prednisone/prednisolone
appears cost-effective, in patients with mHRPC,
provided that the NHS is willing to pay £32,706
per QALY. A series of sensitivity analyses were
undertaken to determine the robustness of this
result to alternative assumptions related to
discount rates and the estimates of QoL applied in
the model. The ICER associated with docetaxel
(3-weekly) plus prednisone/prednisolone remained
fairly robust to these variations, with estimates
ranging from £28,019 to £33,298 per QALY.
Central to the development of the economic
model was the need to consider the full range of
comparators that are likely to be relevant from an
NHS perspective. Hence it was necessary to
consider a broader range of comparators than
considered in either of the two studies considered
in the review of cost-effectiveness evidence. In the
absence of direct (‘head-to-head’) comparisons for
the full range of comparators considered, it was
necessary to synthesise effectiveness data using
indirect treatment comparisons. The strength of
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Health Technology Assessment 2007; Vol. 11: No. 2
this approach is that it allows consideration of the
complete evidence base and facilitates a valid
comparison of the full range of treatment
strategies. However, it must also be recognised
that when indirect evidence is used as the basis for
the assessment of relative treatment effects, it is
not possible to rule out the introduction of bias,
hence the results should be interpreted
accordingly. Although concerns are often raised
regarding the use of indirect approaches in
establishing the cost-effectiveness of particular
interventions, it is important to recognise that
these approaches are necessary in order to provide
a simultaneous assessment of the full range of
potential comparators. It is only through such
approaches that the potential inconsistencies that
could be introduced by a series of separate
comparisons (i.e. assessing the cost-effectiveness of
those interventions considered in individual RCTs)
can be avoided. As a result, this avoids the
inevitable difficulties faced by a decision-maker in
making a single recommendation based on
multiple sources of evidence. Furthermore, the
analytic approach used to estimate the indirect
estimates for the treatment effects considered are
based on similar assumptions as applied in
standard meta-analysis.
While the cost-effectiveness model addressed a
number of the major limitations considered in the
review of the submission by Sanofi-Aventis, this
model also has several potential limitations that
need to be considered in conjunction with the
main results. First, it should be recognised that the
model did not attempt to quantify any additional
palliative benefits conferred by any of the
chemotherapeutic regimens (over and above the
increased benefits derived from gains in survival).
By not considering these benefits the costeffectiveness
estimate from the model should be
taken to be conservative. It is difficult to assess the
size of these potential palliative benefits due to the
limitations noted in the effectiveness review of
existing QoL studies and whether these would be
sufficient to offset any potential decrements
associated with the emergence of major sideeffects.
The problems encountered in this part of
the analysis emphasise the importance of assessing
QoL, using a generic measure which can be
applied in cost-effectiveness analyses, as part of
any future study in this area.
In the absence of patient-level data, it was not
possible to conduct a detailed analysis of the
resource use and costs associated with the
component parts of the follow-up costs considered
(i.e. the management of adverse events,
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