Effectiveness of rivastigmine in Alzheimer's diseaseBMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7210.640a (Published 04 September 1999) Cite this as: BMJ 1999;319:640
Improvements in functional ability remain unestablished
- Peter Bentham, consultant in old age psychiatry,
- Richard Gray, professor of medical statistics,
- Elizabeth Sellwood, AD2000 trial coordinator,
- James Raftery, professor of health economics
- Mental Health Services for the Older Adult, Queen Elizabeth Psychiatric Hospital, Birmingham B15 2QZ
- University of Birmingham Clinical Trials Unit, Institute of Clinical Research, Medical School, Birmingham B15 2TH
- University of Birmingham Health Economics Facility, Park House, Birmingham B15 2RT on behalf of the AD2000 Trial Steering Committee
- Sektion Gerontopsychiatric, Psychiatrische Universitätsklinik, D 97089 Würzburg, Germany On behalf of the B303 Exelon Study Group
- Raymond Way Neuropsychiatry Research Group, National Hospital For Neurology and Neurosurgery, London WC1N 3BG
- Dementia Research Group, National Hospital For Neurology and Neurosurgery, London WC1N 3BG
- Medicine Evaluation Board of the Netherlands, Kalvermarkt 53, PO 16229, 2500 BE Den Haag, Netherlands
EDITOR—Two recent reports on rivastigmine in Alzheimer's disease 1 2 provide further proof that cholinesterase inhibitors produce modest improvements in cognitive testing and in clinical impression of change. The new claim is of improved functionality with rivastigmine, which, if true, would be an important advance in the management of Alzheimer's disease.
Unfortunately, however, these studies do not establish that functional ability is improved. Both studies rated functionality using the progressive deterioration scale, which was developed to assess quality of life not activities of daily living.3 It contains considerable duplication (for example, four questions on handling finances), and only two items relate peripherally to the basic activities of dressing and eating. It cannot be concluded, therefore, that improved scores equate to improved functionality.
Moreover, Rösler et al misrepresent the small improvement in progressive deterioration score seen with rivastigmine (2.8 on a 100 point scale) by citing in the discussion that one third of patients taking higher dose rivastigmine attained at least a 10% improvement in score without noting that 20% of placebo patients also improved to this extent. The benefit was actually only 13% (33% v 20%), which is reduced to 10% (29% v 19%) on more appropriate intention to treat analysis.
The intention to treat analyses are also potentially biased because of non-random drop outs: 77 (32%) of 243 higher dose rivastigmine patients did not have a 26 week assessment compared with 31 (13%) of the 239 placebo patients. Alzheimer's disease is progressive and so replacing missing data by carrying forward values obtained earlier in the trial underestimates natural deterioration. No improvements in progressive deterioration score were seen in the lower dose rivastigmine group, which …