Table 1.
Studies, interventions and patients’ characteristics, and risk of bias of included clinical trials
| Studies | |
|---|---|
| Number of studiesa | 18 |
| Number of drug-placebo comparisons | 19 |
| Number of patients/study (median) [range] | 287 [13–677] |
| Multi-site studies (%) | 77.8 |
| Lead-in period (%) | 33.3 |
| Placebo lead-in period (%) | 100 |
| AD severity (%) | |
| Mild | 0 |
| Mild-moderate | 33.3 |
| Moderate | 11.1 |
| Moderate-severe | 55.6 |
| Severe | 0 |
| Study funding (%) | |
| Independent | 16.7 |
| Industry | 83.3 |
| ITT statistical analysis (%) | |
| Discontinuation outcomes | 100 |
| Efficacy cognitive function | 56.2 |
| Efficacy global change | 70.0 |
| Efficacy neuropsychiatric symptoms | 14.3 |
| Efficacy functional ability | 60.0 |
| Safety outcomes | 100 |
| Interventionb | |
| Monotherapy (%) | 57.9 |
| Combination ChEI (%) | 42.1 |
| Dose (%) | |
| 20 mg | 94.4 |
| 28 mg | 5.6 |
| Dosage (%) | |
| Fixed | 94.4 |
| Flexible | 5.6 |
| Regimen (%) | |
| qd | 31.6 |
| bid | 68.4 |
| Length (mean) [range] | 39.1 [12–208] |
| 12–24weeks (%) | 15.8 |
| v≥24–36 weeks (%) | 52.6 |
| ≥36 weeks (%) | 31.6 |
| Patients | |
| Number of patients | 5004 |
| Age (mean) [range] | 75.8 [65.2–84.6] |
| <75 years (%) | 33.3 |
| ≥75–77 years (%) | 38.9 |
| ≥77–79 years (%) | 22.2 |
| ≥80 years (%) | 5.6 |
| Women (%) [range] | 59.5 [2.9–86.7] |
| Baseline cognitive function (mean) c[range] | 45.6 [24.3–72.4] |
| Baseline severity neuropsychiatric symptoms (mean) c[range] | 11.3 [4.4–25.4] |
| Baseline functional ability (mean) c[range] | 65.7 [50.2–79.6] |
| Scales of efficacy assessmenta | |
| Cognitive function | |
| ADAS-Cog (%) | 35.3 |
| MMSE (%) | 41.2 |
| SIB (%) | 23.5 |
| Global change | |
| CIBIC-Plus (%) | 80.0 |
| CGI (%) | 20.0 |
| Neuropsychiatric symptoms | |
| NPI (%) | 100 |
| Functional ability | |
| ADCS-ADL19 (%) | 60.0 |
| ADCS-ADL23 (%) | 40.0 |
| High risk of biasd | |
| Discontinuation outcomes | 0 |
| Efficacy cognitive function | 17.6 |
| Efficacy global change | 10.0 |
| Efficacy neuropsychiatric symptoms | 20.0 |
| Efficacy functional ability | 10.0 |
| Safety outcomes | 0 |
Abbreviations: AD Alzheimer’s disease, ADAS-Cog Alzheimer’s disease Assessment Scale-Cognitive subscale, ADCS-ADL Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory 19- or 23-item scale, bid twice a day, CGI Clinical Global Impression, CIBIC-Plus Clinician Interview-Based Impression on Change-Plus Caregiver Input, ITT intention to treat, MMSE Mini-Mental State Examination, NPI Neuropsychiatric Inventory, SIB Severe Impairment Battery, qd once a day
aOne RPCCT included with factorial design
bProportion of drug-placebo comparisons
cAs a percentage of scale maxima (0–100)
dProportion of comparisons with high risk of bias for each outcome