Page 19 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

conducted in patients with moderate to severe AD. Most trials specifically excluded patients with
vascular dementia and clinically significant neurologic disease other than AD. Some trials did not specify

such exclusion criteria or report the proportion of patients with such comorbid disease. Most studies
allowed patients to use other medications except for drugs with cholinomimetic effects or anticholinergic
medications.

C. Outcome measures

Studies commonly included measures to assess symptom stabilization (e.g., cognition, global assessment
of change) and behavioral disturbances. Most studies included a measure of cognition (e.g., ADAS-cog)
as the primary outcome; other commonly included measures of cognition were the MMSE and SIB.

Global change often was measured using scales such as the CGI-C, CIBIC-plus, or GDS; functional status
was commonly assessed using measures such as the ADCS-ADL, DAD, Bristol ADL, and PDS. Changes

in mood, behavior, and personality were assessed with measures such as the NPI or BEHAVE-AD. Some
studies included other instruments that assessed quality of life or caregiver burden.

D. Head-to-head comparisons

We did not identify any randomized, double-blind, comparative trials. We did identify three open-label

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head-to-head trials. 27-29 One trial compared donepezil to galantamine over 52 weeks, one compared
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donepezil to galantamine over 12 weeks, and one compared donepezil to rivastigmine over 12 weeks.
These trials blinded only the rater to treatment allocation. Although open-label trials are subject to “fatal
flaws” for internal validity, we review their results because they provide the only comparative evidence.
We do not provide quality ratings for these trials.

We included two meta-analysis 30, 31 that evaluated evidence comparing donepezil, galantamine, and
rivastigmine with placebo. Although these reviews do not make indirect comparisons among included

ChEIs, the quantitative summary of placebo-controlled trials is useful for summarizing evidence for
ChEIs in general.

Donepezil vs. Galantamine

One 52-week open-label trial compared donepezil 10 mg/day to galantamine 24 mg/day in 182 patients
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with probable AD and MMSE scores between 9 and 18 at screening. Although raters were blinded to
treatment allocation, patients, caregivers, and physicians were not blinded because of differences between

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