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

Study
Parallel trials
Buitelaar 1996
Conners 1980
Crossover trials
Ahmann 1993
Barkley 1990
Klorman 1994
Stein 1996 (b.d.)
Stein 1996 (t.d.s.)
Stein 1996 (titrate)
MPH (medium dose)
n/N
4/10
13/20
121/206
51/82
41/114
15/25
15/25
14/25
immediate-release MPH compared with placebo
(Table 7; with additional information presented in
Appendix 12). All of these studies examined highdose
MPH administered more than once daily.
Of the studies that examined high-dose MPH and
placebo, two examined hyperactivity 43,67 and one
evaluated hyperactivity/impulsivity using the
SNAP-IV scale (a variation of the Conners’ scales).
These studies will be discussed separately below.
Three studies presented results for adverse events
only, 35,39,57 and these will also be presented below.
Two of the remaining studies examined
inattention/overactivity using an IOWA CTRS as
one of the main core outcomes: Kolko and
colleagues 69 observed that high-dose MPH was
better than placebo (p < 0.0001). Pelham and
colleagues 79 reported that behaviour improved
with treatment, but did not present direct
statistical comparisons (see Appendix 12).
[Confidential information removed].
Placebo
n/N
3/11
5/21
76/206
33/82
21/114
13/25
13/25
13/25
FIGURE 7 Relative risks of insomnia: MPH (medium dose) versus placebo
Hyperactivity
Of the three studies that examined hyperactivity,
one did not report enough data to be included in
Table 8. 67 One of the remaining studies used a
crossover design 43 and the other was a parallel
study. 97 The studies used different Conners’ scales,
but both reported results for parents and teachers.
The study by Brown and Sexson 43 also examined
hyperactivity using the ACTeRS. Given the
different outcome scales, study designs and age
groups, data from these two studies were not pooled.
Results from the two studies show some variability
(Table 8). Of the two results that were not found to
be significant, one used a scale that was assessed
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Health Technology Assessment 2006; Vol. 10: No. 23
RR (fixed)
95% CI
0.1 0.2 0.5 1 2 5 10
Favours MPH Favours placebo
1.47
2.73
1.59
1.55
1.95
1.15
1.15
1.08
by parents and the other used a scale assessed by
teachers.
Quality of life
Wolraich and colleagues 97 examined CGI and
reported that 47.2% of participants on immediaterelease
high-dose 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).
[Confidential information removed].
RR (fixed)
95% CI
(0.43 to 5.01)
(1.19 to 6.26)
(1.29 to 1.97)
(1.13 to 2.11)
(1.24 to 3.08)
(0.70 to 1.89)
(0.70 to 1.89)
(0.65 to 1.08)
It is noted that Klorman and colleagues 66,67 also
reported on ratings of global outcome (results
presented in Appendix 12) – data that could also
be used to assess QoL but were not considered to
be a primary outcome measure in this SR.
Adverse events
Of 10 trials comparing a high dose of MPH with
placebo, seven presented usable data on adverse
events (see Table 7). The occurrence of headache
was significantly higher in the treatment group
only in Ahmann and colleagues 35 (RR = 1.89, 95%
CI 1.34 to 2.68) (Figure 8).
One parallel trial found significantly higher
proportions of participants suffering from loss of
appetite in the treatment group, with an RR of
22.54 (95% CI 3.18 to 159.56). Three crossover
trials also detected higher proportions in the
treatment groups with RRs of between 2.44 and
4.67 (Figure 9).
Two crossover trials reporting occurrence of
stomach ache detected significant differences
between the treatment and placebo groups; RRs of
2.11 and 1.93 are reported (Figure 10). Both
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