A systematic review and economic model of the effectiveness and ...

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Economic model
TABLE 86 Response rates used in the base case analysis: response defined as score of 1 or 2 on CGI-I
Trial Treatment Responders (%) No. in group
Sharp, 1999 149a
Greenhill, 2002 59
Kemner, 2004 99
Steele, 2004 90
Pliszka, 2000 83
Klein, 1997 65
a Not currently reviewed in Chapter 4.
defined as a score of ≤1 on the SNAP-IV scale
were used in the MTA trial. The problems with
interpreting the results of this trial have been
described in more detail in Chapter 4, but
nevertheless it is an important trial in this disease
area. As such, it was felt appropriate to include a
scenario using response rates defined according to
the definition used in the MTA trial.
The base case analysis uses a consistent definition
of response to compare all relevant options.
Because this excluded a number of trials, and
hence reduced the amount of available data,
sensitivity analyses were conducted by relaxing the
definition of response to include more trials and
to assess the impact of different definitions of
response on the estimates of cost-effectiveness.
Table 86 displays the source trials used to estimate
response rate in the base case analysis. Further
detail about each trial has been provided in
Chapter 3, where the trial concerned was included
in the effectiveness review. A number of studies
excluded from the effectiveness review, for reasons
of data presentation, were nevertheless found to
provide information on response rate. These
studies were therefore included in the calculation
of response rate for the cost-effectiveness analysis.
Further details of these excluded studies are given
in Appendix 3. All of the trials were set in North
America (five in the USA and one in Canada 90 ),
and most recruited children aged between 6 and
12 years (one study recruited from age 6 to
16 years 59 ). Four used the DSM-IV diagnostic
IR-MPH 26 (81) 32
DEX 27 (84) 32
Placebo 5 (16) 32
ER-MPH8 125 (81) 154
Placebo 78 (50) 156
ER-MPH12 583 (69) 850
ATX 250 (53) 473
ER-MPH12 58 (83) 70
IR-MPH 45 (62) 73
IR-MPH 13 (65) 20
Adderall 18 (90) 20
Placebo 5 (28) 18
IR-MPH + BT 28 (97) 29
IR-MPH 23 (79) 29
Placebo + BT 14 (50) 28
criteria, and the remaining two used other
diagnostic interviews. 65,83 The average daily dose
of IR-MPH and ER-MPH12 varied between the
trials, and this is not reflected in the calculation of
response rates. It is important to note that in the
clinical trials, patients were titrated to the ‘best’
dose, which reflects our model structure, but does
allow average dose to differ between trials. Three
of the trials excluded subjects who were known
non-responders to stimulant therapy, 59,90,99 and
this is also not reflected in the calculation of
response rates. This heterogeneity between trials
must be borne in mind when interpreting the
results of the model.
Table 86 excludes one trial 84 [Confidential
information removed]. An important assumption
in the base case model is that the treatment effects
are independent of treatments previously received.
In other words, the response rate to IR-MPH is
the same if it is received as first-line therapy as
when it is received following failure on DEX or
ATX. This assumption was necessary as data were
not available to calculate response rates
conditional on specified previous treatments.
Ideally, the relative treatment effects of no
treatment, IR-MPH, ER-MPH8, ER-MPH12, ATX
and DEX would be estimated in a single, direct
head-to-head RCT. However, such a trial does not
exist, and instead we have a number of trials
assessing the treatment effects of different subsets
of the full set of relevant comparators. Clearly, the
absolute response rates differ by trial, but the