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

Quantity and quality of research
available
Number of studies identified, included
and excluded
In the previous systematic reviews (NICE, AHRQ
and CCOHTA), 70 papers were identified that
appeared relevant to the current systematic review,
and full paper copies were ordered. Of these, 42
papers (describing 40 studies) met the inclusion
criteria.
In the updated search, 2515 references were
identified (following de-duplication) and screened
for relevance. A total of 423 full papers were
ordered for more detailed examination, some of
which were obtained by checking references of
relevant studies (see Figure 3). Of these, 20 RCTs
and one SR met the inclusion criteria. In
addition, four commercial-in-confidence (CIC)
papers were included and the Multimodal
Treatment Study of ADHD (MTA) trial was
assessed. Overall, this gives a total of 66 studies
(40 studies from previous SRs, 21 papers from the
updated search, four CIC papers and the MTA
trial). An additional 52 papers/abstracts related to
the trials described in the 66 papers. These were
not considered to be fully included, but are
referenced in the data extraction tables with the
studies to which they relate. Reasons for
exclusions are presented for each of the 115
papers from the updated search in Appendix 3
and for each of the 28 papers from the previous
reviews in Appendix 4.
Quality of studies
The quality of reporting for each of the included
studies is presented in Table 1. A key to how poor
and good were defined for each question is
presented in Appendix 5. No summary score
could be tabulated; however, the first two columns
of the table can be used to identify immediately
studies that reported their study methodology
well. It is acknowledged that the quality
assessments presented here reflect only the quality
of reporting of trials.
The majority of included studies poorly reported
on study methodology. Only five out of the 60
non-confidential RCTs adequately reported the
Chapter 4
Clinical effectiveness
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Health Technology Assessment 2006; Vol. 10: No. 23
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 nonconfidential
studies reported to have used an
intention-to-treat (ITT) analysis, and 18 out of the
60 non-confidential studies provided a complete
description of withdrawals. Of 64 RCTs, 35 were
crossover trials and 29 were parallel trials. 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. [Confidential information
removed from this paragraph].
Trials included in the review
An overview of comparisons made in each of the
trials is presented in Table 2 (information from
four trials reported as CIC is omitted).
Assessment of effectiveness
As noted above, the clinical effectiveness data are
reported separately for each drug (by dose) and by
the type of comparison. This was done in order to
reproduce accurately the data/results as reported
in the original papers. 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 MPH were also analysed
separately based on immediate-release or
extended-release formulation.
Where possible, data on hyperactivity specifically
are presented in separate tables. The scales used
to measure this core symptom are as reported in
the trials, hence the level of detail regarding what
scale was used may vary.
MPH versus placebo
MPH low dose (≤ 15 mg/day) versus placebo
Twelve studies examined low-dose (≤15 mg/day)
immediate-release MPH compared with placebo
(Table 3, with additional information presented in
Appendix 12). Of these, three examined MPH
administered once daily and nine examined MPH
administered twice or three times daily.
13