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

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Results
mitoxantrone plus a corticosteroid versus a
corticosteroid’ (p. 34). Therefore, patients in all of
the trials are receiving the ‘common comparator’
similarly. However, it still must be assumed that
prednisone is equivalent to hydrocortisone in
these circumstances.
Differences in populations
The trials used to obtain a pooled estimate in the
section ‘Pooled estimate of effectiveness of
mitoxantrone plus a corticosteroid versus a
corticosteroid’ (p. 34) had varying inclusion
criteria and therefore included patient populations
with varying degrees of disease severity, from
asymptomatic patients to patients experiencing
pain with analgesic requirements. The inclusion
criteria for TAX 327 restricted eligibility to those
with progressive mHRPC. This means that this
trial was conducted with a varied patient
population which included both asymptomatic and
symptomatic patients.
However, all patients included in the indirect
comparison had to have progressive mHRPC to be
eligible for inclusion. Hence the patient
populations between trials can be regarded as a
relatively homogeneous subset of patients healthy
enough to receive chemotherapy. Also, the
adjusted indirect comparisons approach aims to
obtain an unbiased estimate of treatment effect
even if there are different prognostic
characteristics between study participants in the
trials included in the comparison. 62
Results of the indirect comparison
Using the method proposed by Bucher and
colleagues 63 and considering carefully the
various restrictions and assumptions for
performing adjusted indirect comparisons, an
indirect comparison was undertaken for overall
survival only for the comparison of docetaxel
plus prednisone versus corticosteroids. Using
the random effects pooled estimate for
mitoxantrone plus corticosteroids versus
corticosteroids derived in the section ‘Pooled
estimate of effectiveness of mitoxantrone plus a
corticosteroid versus a corticosteroid’ (p. 34), the
estimated HR for death is 0.75 (95% CI: 0.57 to
0.99). Full details of the calculations are presented
in Appendix 8.
The results of this adjusted indirect comparison
suggest that docetaxel plus prednisone is superior
to corticosteroids alone in improving overall
survival. However, as the upper 95% CI is very
close to unity, this finding is of borderline
statistical significance.
As detailed in the previous section, CCI-NOV22 is
perhaps the trial most comparable to TAX 327 in
terms of treatment and the fact that crossovers
were allowed in both, although the baseline
prognostic factors of the patients in CCI-NOV22
were generally worse than those in TAX 327.
However, one of the aims of using an adjusted
indirect comparison approach is to reduce the
possibility of bias introduced by any differences in
prognostic characteristics between the populations
included in the comparison. 62 This means that it is
possible that the CCI-NOV22 is the most relevant
and comparable trial within this adjusted indirect
comparison.
Performing the indirect comparison again, using
only the result from CCI-NOV22, we obtain an
estimated HR for death of 0.69 (95% CI: 0.49 to
0.97). This clearly shows that the initial estimated
HR using the pooled treatment effect is more
conservative.
For the adjusted indirect comparison to give an
accurate estimate of the difference in treatment
effect between competing interventions, a number
of assumptions have to be made, especially with
regard to the similarities of the trials involved in
the indirect comparisons and in particular the
patients included in the trials and the doses and
schedules of interventions used. Because of these
assumptions, the findings of the adjusted indirect
comparisons should be interpreted with due
caution.
Indirect comparisons that do not include a
comparison with docetaxel plus prednisone should
not be undertaken, because the search strategy did
not include searches for all available evidence that
could inform such comparisons. Trials assessing
the efficacy of other chemotherapies or docetaxel
in combination with any other treatment were not
searched for, so there may be trials that could
provide additional information if any further
indirect comparisons were made. For the indirect
comparison of docetaxel plus prednisone versus
corticosteroids, all available evidence that could
inform the comparison has been included.
Summary of clinical effectiveness
One trial was found that assessed the intervention
under consideration: docetaxel plus prednisone;
this was in comparison with mitoxantrone plus
prednisone (TAX 327). No other trials were found
that assessed the clinical effectiveness of docetaxel
plus prednisone. The results of this trial showed