Flaws revealed in Alzheimer’s disease trials
Recommendations on the use of cholinesterase inhibitors in dementia have a questionable scientific basis, according to a review in last week’s BMJ (2005;331:321).
The authors assessed the methodology of 22 double blind, randomised controlled
trials examining the efficacy of donepezil (Aricept), rivastigmine (Exelon)
and galantamine (Reminyl). They discovered considerable flaws, including
incomplete data, use of several primary end points without correction
for multiple comparisons, and missing intention-to-treat analyses in
studies in which patients were excluded after randomisation. In addition,
although 19 of the 22 trials found benefits of cholinesterase inhibitors
over placebo, the differences were “rather moderate”, the
authors say.
They add: “Owing to several methodological shortcomings, the validity
of the reported small findings seems to be limited. Missing rigour might
have led to an overestimation of beneficial effects.”
The National Institute for Health and Clinical Excellence is reviewing
use of donepezil, rivastigmine and galantamine, as well as memantine,
in Alzheimer’s disease. Last month, it requested
more evidence from manufacturers and will consider their responses in October (PJ,
23 July, p107). |
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