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

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Clinical effectiveness
medium-dose MPH administered once daily. Four
studies were parallel in design and two used a
crossover design. Although participants in
Swanson and colleagues’ trial 32 were assigned to
varying dosages of ER-MPH according to preexisting
requirements, data were presented by type
of treatment only (Metadate MPH, Concerta MPH
or placebo); hence it is included in the mediumdose
category. Similarly, data were presented
across varying dosages in the trials of Wolraich
and colleagues 97 and Quinn. 84
Most of the studies did not report results for
hyperactivity, but did measure other core
outcomes including [Confidential information
removed], the ADHD Rating Scale 92 and the
Swanson, Kotkin, Agler, M-Flynn and Pelham
(SKAMP Scale). 32 In addition, Dopfner and
colleagues 48 used the Peer Assessment for
Hyperkinetic Disorders as assessed by teachers,
and a five-point effectiveness scale as assessed by
parents, and also by physicians.
[Confidential information removed].
The statistical results from the other studies were
less clearly presented (see Appendix 12), although
Stein and colleagues 92 reported that as the ER-
MPH dose was increased from 0 to 54 mg, parentrated
ADHD symptoms decreased in a linear
manner (p < 0.001).
Hyperactivity
One study measured hyperactivity/impulsivity
using the Swanson, Nolan and Pelham (SNAP) IV
Scale (a variation of the Conners’ scales). 97
Wolraich and colleagues 97 observed significant
improvements in the ER-MPH group compared
with the placebo group (Table 15). This result was
consistent when rated by teachers and parents.
Quality of life
Four studies in this category reported on CGI.
Wolraich and colleagues 97 reported that 46.7% of
TABLE 15 Results for hyperactivity [ER-MPH medium dose (20–40 mg/day) versus placebo]
participants on medium-dose ER-MPH were
‘much or very much improved’ at the end of the
study compared with 16.7% of participants in the
placebo group (no significance value was
reported). Greenhill and colleagues 59 observed
that 81% assigned to active drug were significantly
improved compared with 50% in the placebo
group (p < 0.001).
[Confidential information removed].
Finally, Stein and colleagues 92 reported CGI
severity scores in children with ADHD inattentive
subtype and combined subtype. The results
increased with medication dose, and were better
than placebo; however, direct statistical
comparisons were not reported.
Adverse events
Five of the six studies reported usable data
regarding adverse events. Differences between
participants in the incidence of headache were not
detected in four of these trials. [Confidential
information removed].
Participants in the trials of Stein and colleagues 92
and Greenhill and colleagues 59 suffered from
significantly decreased appetite when assigned to
the extended-release form of MPH. Those
assigned to the Concerta form of MPH in Swanson
and colleagues’ trial 32 also suffered from
significantly decreased appetite (Figure 14).
One crossover trial 92 reported higher numbers of
participants suffering from stomach ache during
the ER-MPH phase compared with placebo
(RR = 2.09; 95% CI 1.15 to 3.79). The other three
non-confidential trials did not find significantly
different frequencies between treatment arms.
Of the three trials reporting incidence of
insomnia, 32,59,84,92 no trial detected significant
differences between participants assigned to ER-
MPH compared with placebo. No trial in this
comparison group reported data on weight.
Study Scale ER-MPH medium Placebo: Mean
dose: mean (SD) mean (SD) difference
6–12 years
Wolraich, 2001 97 SNAP-IV
(hyperactivity/impulsivity) MD (95%CI)
(teacher) 0.96 (0.79) 1.57 (0.89) –1.21 (–1.40 to –1.02)
(parent) 1.11 (0.65) 1.83 (0.89) –0.75 (–0.89 to –0.61)
Lower scores represent a better behavioural outcome.