Donepezil, rivastigmine, galantamine and memantine for ...

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Clinical effectiveness
by the patient’s physician for the duration of the
study. Participants from the study by Reisberg and
colleagues 72 were not receiving any ongoing
cholinesterase inhibitor therapy.
The main primary outcome measure used in the
two studies is the ADCS/ADLsev. Other outcomes
common to both studies are the CIBIC-plus, the
SIB and the NPI. The Reisberg study also used the
MMSE, the GDS and the Functioning Assessment
Staging Scale (FAST). Tariot and colleagues also
included the Behavioural Rating Scale for
Geriatric Patients (BGP). Adverse events were also
recorded in both studies.
The quality of reporting and methodology of the
two included RCTs was generally good (see
Table 39). The method of randomisation was
adequate in both studies, as was the concealment
of allocation. Likewise, both studies reported on
whether or not the comparison groups were
similar at baseline, and also reported eligibility
criteria. These factors should limit the possibility
of selection bias. Blinding was adequate in both
studies with regard to the assessors, the care
provider and the patient, therefore reducing the
risk of measurement bias. In both cases, the drug
and placebo tablets were described as being
identical. The studies adequately reported the
TABLE 39 Quality assessment table for memantine
Study
Randomisation
Concealment of
allocation
Baseline
characteristics
point estimates and measures of variability for the
primary outcomes. However, although the studies
reported that they undertook an ITT analysis,
neither study was rated as demonstrating an
adequate ITT. One study, for example, defined the
ITT as participants in the safety population who
completed at least one postbaseline efficacy
assessment. 71 Both studies did, however,
adequately explain any patient withdrawals.
Assessment of clinical effectiveness
Functional outcome measurements
ADCS/ADL
The primary outcome used in both studies was the
ADCS/ADLsev (also known as ADCS/ADL 19). This
is a 19-item subset of the original 42-item
inventory focusing on items appropriate for the
assessment of the later stages of dementia. Results
are given in Table 40. It has a range of possible
scores from 0 to 54, with a higher score indicating
a better function.
Both trials reported statistically significant
improvements. In the study by Reisberg and
colleagues, 72 the total ADCS/ADLsev scores at
baseline were similar in the two groups (26.8 in
the memantine group and 27.4 in the placebo
group). The mean change from baseline was –3.1
in the memantine group and –5.2 in the placebo
Reisberg et al. 72 Ad Un Rep Ad Par Ad Ad Ad In Ad
Tariot et al. 71 Ad Ad Rep Ad Un Ad Ad Ad In Ad
Ad, adequate; In, inadequate; Par, partial; Rep, reported; Un, unknown.
TABLE 40 ADCS/ADL for memantine
Eligibility
Blinding of assessors
Care provider
blinding
Reisberg et al. 72 ADCS/ADLsev: mean (± SD) change from baseline
Memantine 20 mg/day (n = 124) Placebo (n = 123) p-Value vs placebo
–3.1 ± 6.79 –5.2 ± 6.33 0.02
Tariot et al. 71 ADCS/ADL19: least-squares mean score (SE) change from baseline
Memantine 20 mg/day (n = 198) Placebo (n = 197) p-Value vs placebo
–2.0 (0.50) –3.4 (0.51) 0.03
Patient blinding
Reporting outcomes
ITT analysis
Withdrawals
explained