Butler 2007

Methods	Randomised controlled trial, parallel arm, double‐blind, stratification by tumour type, treatment and KPS.
Participants	Inclusion criteria: Aged 18 years or over; histologically confirmed metastatic or primary brain tumour; KPS > 70; life expectancy > 3months; haemoglobin > 10.0, white blood cell count > 1,500, platelets > 75,000, planned partial or WBRT at a total dose of > 25 Gy via > 10 fractions of 180‐300 c Gy. Exclusion criteria: Serious medical or psychiatric illness that would prevent informed consent; completion of protocol therapy or QoL questionnaires; history of hypersensitivity to d,l‐MPH; history of steroid psychosis; history of/currently taking medication for ADD, anxiety disorder, schizophrenia or substance abuse; currently taking antidepressants; family history or active Tourette's Syndrome; history or active glaucoma; history of RT; undergoing craniospinal axis irradiation; hypertension or other CV disease requiring antihypertensives or other CV medications; pregnant of breast‐feeding. No. randomised: d,l‐MPH: 34; placebo: 34. Follow‐up: end of RT and at 4, 8 and 12 weeks. Setting: four centres in the United states.
Interventions	Treatment arm schedule: Day 1: 10 mg oral d,l‐MPH taken in divided doses (5 mg before breakfast, 5 mg before 6 pm) Day 5‐7 to Day 10: 20 mg oral d,l‐MPH taken in divided doses (10 mg before breakfast, 10 mg before 6pm) Day 10‐14 to Week 8: 30 mg to oral d‐threo‐methylphenidate taken in divided doses (15 mg before breakfast, 15 mg before 6pm) Control Arm: Matched placebo
Outcomes	Cognitive function (MMSE) Fatigue (FACIT‐Fatigue sub‐scale) QoL (FACT, FACT‐Br, FACIT‐Fatigue) Depression (CESDS)
Notes	Study funded by pharmaceutical company and closed prematurely due to withdrawal of funding and low accrual.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patients were stratified by tumour type, treatment and KPS and randomized within strata to one of the two treatment arms with equal probability." "Randomised by computer program" (obtained via correspondence).
Allocation concealment (selection bias)	Low risk	"Used a 3rd party research pharmacy that knew which group patient was assigned to and mailed drug or placebo in containers that were labelled to include instructions for use." (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	"We did do intent to treat analysis. The dropouts were due to disease progression either in the brain or systemically ... not due to toxicity of intervention" (obtained via correspondence).
Selective reporting (reporting bias)	Low risk	All outcomes reported.
Other bias	Low risk	None.