REFERENCE Study 2006.

Methods	Study design: parallel RCT Study duration: recruitment March 2000 to February 2002 Duration of follow‐up: 96 weeks
Participants	Setting: multicentre (12 centres) Country: France 1st or 2nd transplant cadaveric or live donor recipients aged 18 to 65 years who received CsA for at least 3 months before randomisation (1 to 10 years post‐transplant) Number: treatment group (77); control group (31) Mean age ± SD (years): treatment group (43.8 ± 10.6); control group (44.7 ± 11.1) Sex (M/F): treatment group (55/22); control group (27/4) Exclusion criteria: not reported
Interventions	Treatment group MMF: progressively increased to 2 g/d by the 4th week Half dose CsA: reduced every 2 weeks by 25% to reach half dose at 8 weeks Control group CsA: dose as per local practice (trough levels to be > 100 ng/mL)
Outcomes	Change in SCr Graft survival Patient survival BPAR and clinical rejection episodes CrCl Infections
Notes	Funding source: "The study sponsor, Roche (Neuilly sur Seine, France), identified the participating centers, funded the making of the central database, the external monitoring, and an independent design office which performed the statistical analysis, and participated to the writing of the manuscript."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was centralised and stratified
Allocation concealment (selection bias)	Low risk	"centralized randomization was ensured via Internet"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label study
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not performed
Incomplete outcome data (attrition bias) All outcomes	Low risk	Data accounted for outcomes and analysed as ITT
Selective reporting (reporting bias)	Unclear risk	Prespecified outcomes reported
Other bias	High risk	Funded by Roche