Page 13 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

For this review, results from well-conducted, head-to-head trials provide the strongest evidence to

compare drugs with respect to efficacy, effectiveness, and adverse events. We defined head-to-head trials
as those comparing one Alzheimer’s drug with another. Included studies were RCTs lasting at least 12
weeks that had an outpatient study population with a total sample size greater than 100 participants.

If we could not find sufficient evidence of efficacy or effectiveness from at least one randomized, double-

blinded, head-to-head trial, we reviewed randomized, controlled, open-label trials. For comparing
different drugs, however, the strength of evidence must be rated lower for these results than for results
from blinded trials.

If no head-to-head evidence was published, we reviewed placebo-controlled trials. We reviewed all

placebo-controlled trials to provide an overview of efficacy without taking drug equivalency into account.
Compared to placebo and all other things equal, higher dosages may yield greater treatment effects than
do low or medium dosages. For that reason, we did not evaluate the dosage of one drug relative to the

dosage of an alternative drug in a different trial. In addition, heterogeneity among study populations and
placebo groups demand caution in making comparative judgments about treatment effects across trials.

We examined adverse events in both experimental and observational studies. For observational studies
we included those with large sample sizes (> 100 patients) that lasted at least 1 year and reported an
outcome of interest.

We initially reviewed studies with health outcomes as the primary outcome measures. Outcomes were

institutionalizations, behavioral symptoms (e.g., aggression, agitation, mood disorders, psychosis),
discontinuation effects, mortality, and changes in the rate of decline in day-to-day functioning and
activities of daily living. Because health outcomes often were not reported, we also included intermediate

outcomes (e.g., cognition, global assessment). Safety parameters included overall and specific adverse
events (e.g., hepatotoxicity, weight loss, and gastrointestinal symptoms), withdrawals due to adverse

events, discontinuation effects, and drug interactions.

We included meta-analyses in our evidence report if we found them to be relevant for a key question and
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methodologically sound (based on the QUORUM statement); we did not review individual studies if
they had been included in a high-quality meta-analysis. We excluded meta-analyses that were not based
on a comprehensive systematic literature search or did not maintain the units of the studies in their

Alzheimer's Drugs Page 13 of 205