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Tacrine for Alzheimer's Disease-Reply

David S. Knopman, MD; Paul R. Solomon, PhD; William W. Pendlebury, MD; Charles S. Davis, PhD; Margaret J. Knapp, PharmD; Stephen I. Gracon, DVM
JAMA. 1994;272(24):1897. doi:10.1001/jama.1994.03520240024023.
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In Reply.  —We would like to address several points raised by Dr Luqman. First, in our report of the 30-week high-dose study of tacrine, we acknowledged both differential dropout rates between treatment groups and difficulties in interpreting study results. The large number of withdrawals included placebo-treated patients (32%) and tacrine-treated patients (68%). Nonetheless, the most conservative intent-to-treat analysis showed significant treatment differences in favor of tacrine vs placebo on the primary outcome measures.Second, the conclusion that patients with a shorter duration of Alzheimer's disease tolerated the higher tacrine dose for a longer period of time is incorrect. In the week 30 intent-to-treat group, only seven patients had disease durations exceeding the maximum duration of 5.2 years reported for the week 30 evaluable patients, and only four had disease durations exceeding 6 years (6.4,6.8,7.4, and 12.7 years). The median disease duration in the evaluable patient population of 64 (treated with

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