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

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Methods for reviewing effectiveness and cost-effectiveness
● analyse safety and/or tolerability as a primary
objective
● examine children and/or adolescents with
ADHD
● present data by individual drug type: MPH,
DEX or ATX.
Of the studies that met our inclusion criteria, we
subsequently chose only to assess those with
primary studies not already included in our review.
The BNF 29 was used to provide information on
the side-effect profiles of MPH, DEX and ATX.
Data extraction strategy: clinical
effectiveness
Data relating to both study design and quality
were extracted by one reviewer into an Access
database and independently checked for accuracy
by a second reviewer. Any discrepancies were
resolved by consensus and, if necessary, a third
reviewer was consulted. Data from studies with
multiple publications were extracted and reported
as a single study.
Quality assessment strategy:
clinical effectiveness
The quality of the clinical effectiveness studies was
assessed using modified criteria based on CRD
Report No. 4 31 (see Appendix 5). Each study was
assessed by one reviewer and independently
checked for agreement with a second reviewer.
Disagreements were resolved by consensus and, if
necessary, a third reviewer was consulted.
Analysis strategy: clinical
effectiveness
Clinical effectiveness data were reported
separately for each drug and by the type of
comparison. Data for MPH were also analysed
separately based on immediate-release or
extended-release formulation. For all drugs, the
data were examined by dose. The cut-offs used for
defining low, medium and high for each type of
drug were those presented by Swanson and
colleagues. 32 Data for the outcomes of
hyperactivity (using any scale that measured
hyperactivity specifically), Clinical Global
Impression (CGI) (as a proxy of QoL) and adverse
events were analysed. Owing to time constraints,
information on other core outcomes and academic
performance were not analysed; however, this
information was extracted and is presented in the
data extraction tables (Appendix 12).
Any scale that appeared to have assessed pure
hyperactivity was included in the analysis. Results
from scales that may incorporate hyperactivity, but
also include other symptoms (for example, the
Conners’ Abbreviated Rating Scale) were not
analysed but are included in the data extraction
tables (Appendix 12). The type/version of the scale
used to assess hyperactivity has been reported as
presented in the original papers. Many different
scales and versions of the same scales (e.g. the
Conners’ scales) were used in the trials. Owing to
their complexity, no attempt was made to combine
results from data using different scales, different
versions of a scale or scales which may be the same
but have different names.
For crossover studies, the mean and standard
deviation (SD) for each outcome were data
extracted for end of trial data (i.e. baseline data
were not considered). Where possible, we aimed to
calculate mean difference and standard errors for
crossover studies in order to facilitate metaanalysis
where possible. 33 However, owing to the
lack of data information needed to calculate mean
differences in many of the studies, this was not
possible.
For parallel studies, change scores were reported
where given, otherwise means and SDs were
presented for end of trial data. In addition, mean
differences with 95% confidence intervals (CIs)
were calculated for each study.
For adverse events, self-ratings were reported
when used, otherwise parent reports were utilised.
Percentages of participants reporting adverse
events were used to calculate numbers of events in
each treatment arm. Where actual numbers of
participants included in safety analyses were
unclear, denominators were based on numbers of
participants originally randomised to each
treatment arm. Relative risks (RRs) were examined
within predefined subgroups (based on drug,
dosage and inclusion of a behavioural
intervention). Data on weight were also analysed
in view of recent concerns regarding the effects of
stimulants on growth in children. Mean
differences (with 95% CIs) were calculated for each
study. Where results were highly variable, possible
causes of this were explored in terms of
participant age, duration of intervention and
method of outcome measurement.