Pandina 2011.

Methods	Allocation: random. Blinding: double. Duration: 13 weeks. Design: parallel, double dummy, non‐inferiority comparative study. Setting: international multi‐centre, 89 centres from 14 countries (Bulgaria; Czech Republic; Estonia; Hungary; Lithuania; Poland; Russia; Ukraine; USA; Austria; France; Germany; Spain; India).
Participants	Diagnosis: schizophrenia (DSM‐IV). N = 1220. Age: ≥18 years of age. Sex: 701 M, 513 F. History: 65% PP and 69% RIS‐LAI participants were receiving atypical antipsychotics prior to study, with oral risperidone used by similar percentage of participants in each group; Included: PANSS total score between 60 and 120, BMI ≥17 kg/m2 and <40 kg/m2; schizophrenia DSM‐IV criteria for >1 year. Excluded: DSM‐IV Axis I diagnoses other than schizophrenia; decrease in at least 25% in PANSS total from screening to baseline; substance dependence within 3 months before screening; history of treatment resistance; significant unstable systemic disease; suicidal or violent behaviour; previously received injections of PP and treatment with any other 'disallowed' medications (including mood stabilisers, lithium and anticonvulsants); exposure to an experimental drug, biologic or medical device within past 6 months pre‐screening; pregnancy/ planning or currently nursing. Consent: Independent Ethics Committee or Institutional Review Board at each study site approved protocol and amended protocol. Study conducted in accordance with Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent required.
Interventions	1. Risperidone depot: bi‐weekly, oral supplementation (1 mg; mean final dose 3.3 ± 1.59 mg) and placebo injections (matched to PP); 25, 37.5 and 50 mg; mean final dose 31.7 ± 9.28 mg, n = 613. 2. Paliperidone palmitate (PP): initiation regimen*, monthly PP injections, placebo injections (matched to RIS) and placebo oral supplementation; 50, 100 and 150 mg equivalents; mean final dose 104.5 ±3 0.51 mg, n = 607.
Outcomes	Global state: CGI‐ S score change; Shedule for Deficit Syndrome. Mental state: PANSS total score change; responder rate with more than 30% reduction in PANSS. Adverse events: treatment‐emergent adverse events; EPS rating scales; Simpson and Angus Rating scale; BARS; AIMS. General functioning: Personal and Social Performance (PSP).
Notes	*PP deltoid injections day 1, 150 mg eq, day 8, 100 mg eq and subsequent flexible dosing (50, 100 or 150 mg eq) once a month
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised: 1:1, computer‐generated randomisation scheme, stratified by centre, implemented by an interactive voice response system.
Allocation concealment (selection bias)	Low risk	Interactive voice response system used.
Blinding (performance bias and detection bias) All outcomes	Low risk	Study drug administrator was the only person to contact IVRS to receive medication number and was not allowed to communicate patient‐related information to study site personal or to perform any efficacy and safety assessment. Patient and staff performing study‐related procedures were to be precluded from seeing the contents of syringe or observing the injection.
Incomplete outcome data (attrition bias) All outcomes	Low risk	N = 927 (76%) completed the study (n = 456 in PP; n = 471 in RIS‐LAI); n = 151 withdrawn from PP group (n = 55 withdrawn consent, n = 40 lack of efficacy, n = 20 adverse events, n = 11 lost to follow‐up, n = 2 death, n = 1 pregnancy, n = 22 'other'); n = 142 withdrawn from RIS‐LAI group (n = 52 withdrawn consent, n = 43 lack of efficacy, n = 10 adverse event, n = 18, lost to follow‐up, n = 19 'other'). 'Safety analysis' conducted (n = 1214), which included all participants that had received at least one dose of the study drug.
Selective reporting (reporting bias)	Unclear risk	Unclear.
Other bias	High risk	Funding: "Johnson & Johnson Pharmaceutical Research and Development, L.L.C. funded this study and was responsible for study design and data collection, analysis and its interpretation..." (p225). Many of the authors are employees of Johnson & Johnson Pharmaceutical Research and Development, L.L.C.