Page 9 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

The first key question addresses the issue of effectiveness: do drugs used to treat AD differ in their effects
under real-life circumstances? This report addresses both efficacy (i.e., do AD drugs differ in their effects

under ideal or highly controlled circumstances) and effectiveness. We distinguish between efficacy
(explanatory) studies and effectiveness (pragmatic) studies; studies conducted in primary care or office-
based settings that use less stringent eligibility criteria (i.e., broad range of population characteristics and

disease severity) have long follow-up periods (i.e., greater than one year), and assess health outcomes are
characterized as effectiveness studies. Studies conducted in more highly selected populations over shorter

periods of time are characterized as efficacy studies. We summarize the results of efficacy and
effectiveness studies separately as the results of effectiveness studies are more generalizable than results
from highly selected populations (i.e., efficacy studies).

For assessing efficacy and effectiveness, our review includes methodologically valid comparative

evidence from controlled clinical trials and fair- or good-quality systematic reviews. For evaluating
safety we include controlled clinical trials, systematic reviews, and observational studies. A summary of
outcome measures and study eligibility criteria can be found in Table 2; a more complete description of

commonly used scales and outcome measures can be found in Appendix B.

The second key question specifically addresses the time to achieve statistical and clinical differences

between available drugs. Although we searched for direct and indirect evidence addressing time to
statistical and clinical differences, several points should be considered. In general, determining time to
effect and time required to assess clinical response are both difficult tasks given the progressive nature of

AD, the design of most trials, and the nature of measurement scales. Because limited evidence compares
one AD drug to another and because placebo-controlled trials are too heterogeneous with respect to study

design, outcomes assessment, and populations to allow any inferences about the comparative time to
effect, drawing conclusions about one drug compared to another is similarly difficult. Furthermore, given
the fact that changes in cognition and global assessment can be reached only with sustained treatment

with ChEIs and memantine, the clinical significance of time to effect is likely to be of minimal
importance to physicians and patients. We review the available evidence below, but we caution readers

about interpretation given the nature of the evidence and questionable significance of any differences
reported across trials.

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