Kane 2002*.

Methods	Allocation: random. Blinding: double. Duration: 12 weeks (preceded by up to 4 mg risperidone/day for 1 week). Design: parallel. Setting: inpatient and outpatient, multi‐centre (41 centres in the USA).
Participants	Diagnosis: schizophrenia (DSM‐IV). N = 400. Age: 18 to 55 years of age; mean˜37 ± 20 years. Sex: 301 M, 99 F. History: diagnosis of schizophrenia. Included: baselines PANSS of 60 to 120; good general health; standard laboratory test results 'within reference ranges or not clinically significant'. Excluded: received depot in past 120 days before start of trial; substance dependant diagnosis; tardive dyskinesia; history of neuroleptic malignant syndrome; clinically significant ECG abnormality; pregnant (or likely to become pregnant) or lactating; at risk of violent behaviour; current suicide ideation; history of severe drug sensitivity/ allergy (sensitivity to risperidone); people who were unresponsive to risperidone. Consent: trial conducted in accordance with 'current ICH‐Good Clinical Practice guidelines and the Declaration of Helsinki and its subsequent revisions'; written informed consent obtained from each participant or guardian/ legal representative.
Interventions	1. Risperidone depot: 25 mg 2 weekly + 2 mg/day oral risperidone for 3/52, n = 99. 2. Risperidone depot: 50 mg 2 weekly + 4 mg/day oral risperidone for 3/52, n = 100. 3. Risperidone depot: 75 mg 2 weekly + 6 mg/day oral risperidone for 3/52, n = 100. 4. Placebo injections: 2 weekly + placebo tablets for first 3/52, n = 100.
Outcomes	Adverse events: ESRS and others as reported by participants. Leaving the study early. Unable to use ‐ Global state: CGI. Mental state: 20% reduction PANSS. Body weight: change. Pain at injection site. Physiological tests: including ECG. Mental state: change PANSS (no SD).
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised: quote, "a dynamic method (22) was used to randomly assign patients to treatment groups. Stratification factors included investigator, inpatient/outpatient status, and Positive and Negative Syndrome Scale (23) total score at randomization."
Allocation concealment (selection bias)	Unclear risk	No details of allocation concealment.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	"Double blind study" but not clear who exactly was blinded, no indication given of whether the raters were blinded. Study controlled with "placebo injections that were identical in appearance [to the study drug injections]".
Incomplete outcome data (attrition bias) All outcomes	High risk	Greater than 50% attrition by study end.
Selective reporting (reporting bias)	Unclear risk	Unclear risk
Other bias	High risk	Funding: "supported by Johnson & Johnson Pharmaceutical Research and development, Titusville, N.J."