BACKGROUND: Although cholinesterase inhibitors have produced statistically significant treatment effects, their clinical meaningfulness in Alzheimer's disease is disputed. An important aspect of clinical meaningfulness is the extent to which an intervention meets the goals of treatment. METHODS: In this randomized controlled trial, patients with mild to moderate Alzheimer's disease were treated with either galantamine or placebo for 4 months, followed by a 4-month open-label extension during which all patients received galantamine. The primary outcome measures were Goal Attainment Scaling (GAS) scores from assessments by clinicians and by patients or caregivers of treatment goals set before treatment and evaluated every 2 months. Secondary outcome measures included the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), the Clinician's Interview-based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia (DAD) and the Caregiving Burden Scale (CBS). To evaluate treatment effect, we calculated effect sizes (as standardized response means [SRMs]) and p values. RESULTS: Of 159 patients screened, 130 (mean age 77 [standard deviation (SD) 7.7]; 63% women) were enrolled in the study (64 in the galantamine group and 66 in the placebo group); 128 were included in the analysis because they had at least one post-baseline evaluation. In the intention-to-treat analysis, the clinician-rated GAS scores showed a significantly greater improvement in goal attainment among patients in the galantamine group than among those in the placebo group (change from baseline score 4.8 [SD 9.6]) v. 0.9 [SD 9.5] respectively; SRM = 0.41, p = 0.02). The patient- caregiver-rated GAS scores showed a similar improvement in the galantamine group (change from baseline score 4.2 [SD 10.6]); however, because of the improvement also seen in the placebo group (2.3 [SD 9.0]), the difference between groups was not statistically significant (SRM = 0.20, p = 0.27). Of the secondary outcome measures, the ADAS-cog scores differed significantly between groups (SRM = -0.36, p = 0.04), as did the CIBIC-plus scores (SRM = -0.40, p = 0.03); no significant differences were in either the DAD scores (SRM = 0.28, p = 0.13) or the CBS scores (SRM = -0.17, p = 0.38). INTERPRETATION: Clinicians, but not patients and caregivers, observed a significantly greater improvement in goal attainment among patients with mild to moderate Alzheimer's disease who were takinggalantamine than among those who were taking placebo.
RCT Entities:
BACKGROUND: Although cholinesterase inhibitors have produced statistically significant treatment effects, their clinical meaningfulness in Alzheimer's disease is disputed. An important aspect of clinical meaningfulness is the extent to which an intervention meets the goals of treatment. METHODS: In this randomized controlled trial, patients with mild to moderate Alzheimer's disease were treated with either galantamine or placebo for 4 months, followed by a 4-month open-label extension during which all patients received galantamine. The primary outcome measures were Goal Attainment Scaling (GAS) scores from assessments by clinicians and by patients or caregivers of treatment goals set before treatment and evaluated every 2 months. Secondary outcome measures included the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), the Clinician's Interview-based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia (DAD) and the Caregiving Burden Scale (CBS). To evaluate treatment effect, we calculated effect sizes (as standardized response means [SRMs]) and p values. RESULTS: Of 159 patients screened, 130 (mean age 77 [standard deviation (SD) 7.7]; 63% women) were enrolled in the study (64 in the galantamine group and 66 in the placebo group); 128 were included in the analysis because they had at least one post-baseline evaluation. In the intention-to-treat analysis, the clinician-rated GAS scores showed a significantly greater improvement in goal attainment among patients in the galantamine group than among those in the placebo group (change from baseline score 4.8 [SD 9.6]) v. 0.9 [SD 9.5] respectively; SRM = 0.41, p = 0.02). The patient- caregiver-rated GAS scores showed a similar improvement in the galantamine group (change from baseline score 4.2 [SD 10.6]); however, because of the improvement also seen in the placebo group (2.3 [SD 9.0]), the difference between groups was not statistically significant (SRM = 0.20, p = 0.27). Of the secondary outcome measures, the ADAS-cog scores differed significantly between groups (SRM = -0.36, p = 0.04), as did the CIBIC-plus scores (SRM = -0.40, p = 0.03); no significant differences were in either the DAD scores (SRM = 0.28, p = 0.13) or the CBS scores (SRM = -0.17, p = 0.38). INTERPRETATION: Clinicians, but not patients and caregivers, observed a significantly greater improvement in goal attainment among patients with mild to moderate Alzheimer's disease who were taking galantamine than among those who were taking placebo.
Authors: C Courtney; D Farrell; R Gray; R Hills; L Lynch; E Sellwood; S Edwards; W Hardyman; J Raftery; P Crome; C Lendon; H Shaw; P Bentham Journal: Lancet Date: 2004-06-26 Impact factor: 79.321
Authors: Lee A Jennings; Alina Palimaru; Maria G Corona; Xavier E Cagigas; Karina D Ramirez; Tracy Zhao; Ron D Hays; Neil S Wenger; David B Reuben Journal: Qual Life Res Date: 2016-12-20 Impact factor: 4.147
Authors: David B Hogan; Peter Bailey; Sandra Black; Anne Carswell; Howard Chertkow; Barry Clarke; Carole Cohen; John D Fisk; Dorothy Forbes; Malcolm Man-Son-Hing; Krista Lanctôt; Debra Morgan; Lilian Thorpe Journal: CMAJ Date: 2008-11-04 Impact factor: 8.262