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

Effectiveness evidence
This review presents a comprehensive overview of
studies (that meet our inclusion criteria) on MPH,
DEX and ATX published up to July/August 2004.
Overall, the systematic review of effectiveness
studies represents an archive of data for reference.
The results are presented separately for low,
medium and high doses. Although we
acknowledge that this may be less relevant for
clinical practice, because the dose will be
established by titration for individual patients, this
approach was chosen for the SR because most of
the evidence was presented by dose.
The majority of included studies were of poor
quality. Only five out of the 60 non-confidential
studies properly reported the method used to
assign participants to patient groups. Nine out of
the 60 non-confidential studies reported that the
sequence of allocation was truly random. Most
studies were blinded, but none of the included
studies reported whether blinding was successful.
Eleven out of the 60 non-confidential studies
reported to have used an ITT analysis and 18 out
of the 60 non-confidential studies provided a
complete description of withdrawals. For most of
the crossover trials the statistical analysis was
either not clearly reported or not appropriate; for
parallel trials the quality of the analysis was better
reported.
It should be noted that some of the quality items
reflect the quality of reporting and not necessarily
the quality of the actual trial. However, given the
poor scores on these quality items, the reliability
of the study results is unknown.
As reported in the previous NICE report 4 and the
AHRQ 28 and CCOHTA 30 reviews, the plethora of
MPH studies suggest that MPH (both immediateand
extended-release) is effective at reducing
hyperactivity, and improving QoL (as determined
by CGI – either the Improvement or Severity
subscale) in children. It was noted, however, that
the majority of studies that evaluated the
effectiveness of MPH did not adequately report
their study methodology. There appears to be
little evidence of a statistically significant difference
in the effectiveness of IR-MPH and ER-MPH.
Chapter 7
Discussion
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Health Technology Assessment 2006; Vol. 10: No. 23
Similarly, DEX also appears to be effective at
reducing hyperactivity and improving QoL.
However, there were generally very few high-quality
studies that evaluated the effectiveness of DEX. As
with MPH, some of the results were variable.
There was consistent evidence that ATX was
superior to placebo for hyperactivity and CGI.
These more recent studies on ATX had wellreported
study methodologies and the results are
likely to be reliable.
Very few studies made head-to-head comparisons
between the drugs. The previous NICE report 4
stated that there appeared to be little difference in
the effectiveness of MPH and DEX. No recent
studies were found in our updated search. While
the studies reported variable results, the one study
that reported no statistically significant differences
between drugs was deemed to be of good quality,
whereas the quality of the others was uncertain,
given the poor reporting of study methodologies.
One study that compared MPH and ATX reported
no statistically significant difference between the
drugs for hyperactivity or CGI. However, this
study did not adequately report on their study
methodology. Hence there is insufficient evidence
to judge the relative effectiveness of these drugs.
Few studies were included in the review that
examined a non-drug intervention in combination
with MPH, DEX or ATX. Generally, the results
were variable. The studies were, however,
heterogeneous regarding the type of non-drug
interventions examined and the scales used to
measure outcomes.
Adverse events
Upon examination of the evidence, it is clear that
adequate and informative data regarding the
potential adverse effects of MPH, DEX and ATX
are lacking. Of the 64 studies included in the
clinical effectiveness section of this review, 38
contributed some data to the analysis of adverse
events. However, this contribution was minimal in
the majority of cases: only eight studies, for
example, provided usable data regarding the
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