Page 28 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

in the quantity of evidence, design of available trials (i.e., open-label), use of outcome measures not
previously validated in AD populations (e.g., caregiver satisfaction), suspicious directionality of findings

favoring the funding drug company, and the minimal differences observed between compared drugs (i.e.,
clinical significance of differences is inconclusive), we conclude that the evidence is inadequate to draw
conclusions about the effectiveness of one AD drug compared to another.

Evidence from placebo-controlled trials and systematic reviews of placebo-controlled trials provide

general evidence of the efficacy and effectiveness of these drugs. Overall, the ChEIs as a class are
modestly effective in reducing the rate of decline in cognition. 30, 31 The NNT to yield one additional ChEI
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(excluding tacrine) global responder is 12; the NNT to yield one additional cognitive responder is 10.
Evidence from placebo-controlled trials and a systematic review of placebo-controlled trials provide
general evidence of the efficacy of memantine.

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Evidence from one placebo-controlled effectiveness trial and 22 efficacy trials 39-60, 64, 65 supports modest
effects on symptom stabilization, behavior, and functional status as measured by various scales.

Although some trials did not support statistically significant differences between active treatment and
placebo on all outcome measures, 38, 39, 42, 45, 48-51, 54, 58, 59 most trials yielded data supporting a slower rate of
decline or modest improvement in measures of cognition and global assessment. Fewer trials supported

differences in measures of behavior or functioning. Caregiver burden was infrequently assessed or
reported, although 4 trials found significantly greater improvement for active treatment compared to
placebo. 52, 59, 60, 64, 65 Only one study assessed nursing home placement as a function of medication

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treatment. This trial did not detect significant differences in institutionisations between donepezil and
placebo after 1 and 3 years.

The clinical significance of some statistical differences is controversial. Although some trials defined
clinical and global responders a priori, inconsistencies in trial design and reporting make it difficult to

assess the clinical relevance of differences across trials.

Overall, the quality of evidence of general efficacy of ChEIs and memantine is fair; the quality of
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evidence of effectiveness of ChEIs and memantine is limited to one study on donepezil and therefore
poor. On the basis of current evidence, we cannot demonstrate substantial differences in efficacy between

one AD drug and another.

Alzheimer's Drugs Page 28 of 205