B351.

Methods	Double‐blinded, placebo controlled, parallel‐group randomised controlled trial 26 week treatment and follow up
Participants	Setting: USA, 14 centres between December 1994 to 22 March 1996 Sample size: 702 participants (393 female, 309 male) Age: range 45 to 89 years, mean 74.5 years Inclusion criteria: 50 years or older DSM‐IV, NINCDS‐ADRDA criteria for probable AD, MMSE range 10 to 26 inclusive head computed tomography or magnetic resonance imaging scan consistent with AD within 12 months most concomitant disease, most medications Exclusion criteria: severe and unstable medical illnesses anticholinergic drugs, acetylcholine precursor health food supplements, memory enhancers, insulin, psychotropic drugs (apart from occasional use of chloral hydrate for agitation or insomnia)
Interventions	1. Rivastigmine: 3 mg/day divided into 2 doses 2. Rivastigmine: 6 mg/day divided into 2 doses 3. Rivastigmine: 9 mg/day divided into 2 doses 4. Placebo Titration during weeks 1 to 12 to the fixed dose, fixed dose between week 13 and 26, no dose reductions allowed Patients who discontinued prematurely were asked to return at weeks 12, 18, and 26 for efficacy evaluation
Outcomes	1. Cognitive function Alzheimer's Disease Assessment Scale (ADAS‐Cog) Mini‐Mental State Examination (MMSE) ADAS‐Cog with the attention item from ADAS 2. Activities of daily living Progressive Deterioration Scale (PDS) Caregiver Activity Survey (CAS) ‐ listed in protocol but was not in study report 3. Physician rated global impression tests Clinician Interview‐Based Impression of Change‐Plus (CIBIC‐Plus) Global Deterioration Scale (GDS) 4. Adverse events
Source of funding	Novartis Pharma
Declaration of interest	Novartis Pharma
Notes	Main hypothesis: to evaluate the efficacy and safety of 3 fixed doses of rivastigmine (3, 6, 9 mg/day) and placebo for 26 weeks of treatment, and dose‐efficacy and dose‐safety relationships in patients with probable mild to moderate AD Assessments: baseline, 12,18, 26 weeks
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Not described, likely low risk
Allocation concealment (selection bias)	Low risk	Not described, likely low risk
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No information available
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information available
Incomplete outcome data (attrition bias) All outcomes	High risk	A 66% completion rate overall. Higher percentage in the 9 mg group (49%) and 6 mg (37%) group discontinued compared to the placebo group (25%)
Selective reporting (reporting bias)	Unclear risk	Study data were not published, obtained from the company. Only data pooled with other studies were published by the pharmaceutical company (pooled with B303 and B352)
Other bias	High risk