Efficacy of donepezil in Alzheimer's disease: fact or artifact?
| Autor: | W. A. van Gool, S. L. Rogers, L. T. Friedhoff, M. R. Farlow, R. S. Doody, R. Mohs |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Clinical Trials as Topic Experimental drug business.industry Disease medicine.disease Placebo Placebo group Piperidines Alzheimer Disease Internal medicine Indans Muscle strength Medicine Humans In patient Donepezil Neurology (clinical) Amyotrophic lateral sclerosis business Artifacts Nootropic Agents medicine.drug |
| Zdroj: | Neurology. 52(1) |
| ISSN: | 0028-3878 |
| Popis: | To the Editor: From their study of donepezil, Rogers et al. conclude that this drug is “efficacious in treating symptoms of memory and cognitive loss in patients with mild to moderately severe AD.”1 The following characteristics of their methodology make this general conclusion premature: 1) Patients who withdrew were encouraged to return for assessment at the study endpoint. However, if patients were lost to follow-up, the last assessment available was defined as the study endpoint. The investigators do not report the number of patients in which this technique of last observation carried forward (LOCF) was used. In the donezepil 10 mg/d group, 32% of patients withdrew. The study results may be biased if in a significant number of these patients the investigators used scores from assessment at week 6 or 12 as if they were at week 24. LOCF is only acceptable in research on neurodegenerative diseases if there is a balance between placebo and treatment groups with respect to the number of patients in whom LOCF is used, as well as to the distribution of points in time being carried forward. Here is a simple, but admittedly unrealistic, example: an experimental drug with severe side effects studied in a poorly organized trial may result in a loss to follow-up of 80% of patients with amyotrophic lateral sclerosis after a first assessment of muscle strength at 1 month. If these values are “carried forward” and compared with those of a complete placebo group at an endpoint after 12 months, no one would consider the observed difference in favor of the treatment group significant. LOCF should be used with the utmost caution only in studies of progressive diseases such as most neurodegenerative disorders. 2) The … |
| Databáze: | OpenAIRE |
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