Rapp 2013

Methods	Randomised controlled trial, parallel arm, double‐blind, stratification according to whole‐brain vs partial‐brain irradiation type and by study site.
Participants	Inclusion criteria: adults > 18 years; primary or metastatic brain tumour; completed a course of fractionated partial or whole brain irradiation of at least 30 Gy > 6 months prior to enrolment; no imaging evidence of disease progression within 6 months prior to enrolment; life expectancy > 6 months; ECOG score > 2; Exclusion criteria: currently taking cognition enhancing medications; planned treatment for the next 6 months; pregnant. No. randomised: donepezil: 99; placebo: 99. Follow‐up: 24 weeks Setting: two academic medical centres, 21 Community Clinical Oncology Programs (CCOPs), 3 Cancer Trial Support Unit sites (United States).
Interventions	Treatment arm schedule: Week 1‐6: 5 mg oral donepezil Week 7‐24: 10 mg oral donepezil if tolerated. Control arm: Matched oral placebo
Outcomes	Cognitive functioning (HVLT‐R, COWA, Digit Span, mROCF, TMT, grooved pegboard)
Notes	Conference abstract.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The randomization was generated using nQuery Advisor"... "Patients were stratified by accruing site (academic centers vs CCOP sites) and type of radiation (whole vs partial) and assigned within strata to receive donepezil or a placebo with equal probability using variably sized permuted block randomization." (obtained via correspondence).
Allocation concealment (selection bias)	Low risk	"Drug and placebo were over encapsulated and distributed to the study sites by Biologics Inc., Raleigh, NC" (obtained via correspondence).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding carried out.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding carried out.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Intention‐to‐treat analysis carried out.
Selective reporting (reporting bias)	Low risk	All outcomes reported.
Other bias	Low risk	None.

Scales MMSE Mini‐Mental State Examination; FACIT‐Fatigue sub‐scale The Functional Assessment of Chronic Illness Therapy ‐ Fatigue sub‐scale; FACT Functional Assessment of Cancer Therapy; FACT‐Br Functional Assessment of Cancer Therapy ‐ Brain; FACIT‐Fatigue Functional Assessment of Chronic Illness Therapy ‐ Fatigue; CESDS Center for Epidemiological Studies Depression Scale; WAIS‐III Digit Span and Digit Symbol Wechsler Adult Intelligence Scale III Digit Span and Digit Symbol sub‐tests; TMT Trail making test parts A and B; HVLT‐R Hopkin's Verbal Learning Test‐Revised;COWA Controlled Oral Word Association Test; BFI Brief Fatigue Inventory; POMS Profile of Mood States; POMS‐Fat POMS‐Fatigue sub‐sale; POMS‐Vig POMS‐Vigilance sub‐scale; BSDS Brief Sleep Disturbance Scale; BDI‐II Beck's Depression Inventory‐IIl; STAI State‐Trait Anxiety Inventory; FIM Functional Independence Measure; HDS Hamilton Depression Scale; RBANS Repeatable Battery of Assessment of Neuropsychological Status; CQOLC Caregiver Quality of Life Index‐Cancer; LASA Linear Analogue Self‐Assessment; MPAI‐4 Mayo‐Portland Adaptability Inventory‐4. Other ADD attention deficit disorder; CT computed tomography; CV cardiovascular; MRI magnetic resonance imaging; RT radiotherapy; WBRT whole brain radiotherapy.