Friedrich 2007.

Methods	Study design: multicentre, prospective, randomised open‐label clinical trial Number of study centres: unclear Study dates: 1995–2002, follow‐up 2.9 years Participants randomly assigned: 495
Participants	Inclusion criteria: histologically confirmed primary transitional cell carcinoma of the bladder or tumour recurrence after TUR without prior adjuvant therapy with intermediate‐risk pTa G1 tumour (size > 3 cm, recurrent or multifocal tumour) or pTa G2 up to pT1 tumour (G1–3) pT1 G3 tumours in case of a unifocal small tumour (diameter 2.5 cm) Exclusion criteria: muscle‐invasive tumour or a concomitant Cis evidence of lymph node or distant metastasis pT1 G3 tumour > 2.5 cm pregnancy, mental disease, reduced kidney function or a second malignant disease
Interventions	Group A: 6 weekly instillations of MMC 20 mg (MMC 6 week) Group B: 6 weekly instillations of BCG RIVM (BCG 6 week) Group C: 6 weekly instillations of MMC 20 mg followed by monthly instillations of MMC 20 mg for 3 years (MMC 3 years) Procedure: instillation was performed with a volume of 20 mL after emptying the bladder; participants received 20 mg of MMC or RIVM 2 108 cfu; adjuvant intravesical therapy was started 4 weeks after TUR (after second TUR in case of a pT1 tumour). In case of recurrence, treatment was stopped.
Outcomes	Recurrence‐free survival, adverse effects
Funding sources	Quote: "The work was supported in part by Fa. Medac GmbH, Wedel, Germany. Dr Pichlmeier is an employee of Medac GmbH."
Declarations of interest	Quote: "None of the authors will benefit financially from the publication of the manuscript."
Notes	Quote: "None of the authors will benefit financially from the publication of the manuscript. The work was supported in part by Fa. Medac GmbH, Wedel, Germany. Dr Pichlmeier is an employee of Medac GmbH." Our meta‐analyses included groups A and B. Group C was considered in the sensitivity analyses.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomisation was performed by use of a stratified permuted block randomisation scheme, balanced for treatment groups. Stratification was performed by hospital or private urologists." Comment: therefore, we assumed this item to be of low risk for bias.
Allocation concealment (selection bias)	Unclear risk	Comment: no information
Blinding of participants and personnel (performance bias) all outcomes	High risk	Comment: no information on blinding. We assumed that there was no blinding and that the outcomes might have been influenced by differences in performance due to a lack of blinding.
Blinding of outcome assessment (detection bias) overall survival	Unclear risk	Outcome not reported.
Blinding of outcome assessment (detection bias) recurrence and progression free survival	High risk	Comment: no information on blinding. We assumed that there was no blinding. We assumed that the absence of blinding might have had an effect on the detection and measurement of subjective outcomes.
Blinding of outcome assessment (detection bias) serious and non‐serious adverse effects	High risk	Comment: no information on blinding. We assumed that there was no blinding. We assumed that the absence of blinding might have had an effect on the detection and measurement of subjective outcomes.
Blinding of outcome assessment (detection bias) quality of life	Unclear risk	Outcome not reported.
Incomplete outcome data (attrition bias) Survival outcomes	Low risk	Comment: all participants were considered in the analysis (Group A 179/179, Group B 163/163, Group C 153/153).
Incomplete outcome data (attrition bias) Adverse effect outcomes	Low risk	Comment: all participants were considered in the analyses (Group A 179/179, Group B 163/163, Group C 153/153).
Incomplete outcome data (attrition bias) Quality of life outcomes	Unclear risk	Outcome not reported.
Selective reporting (reporting bias)	Unclear risk	Comment: no study protocol available.
Other bias	Low risk	Comment: we assumed that there was no risk for other bias.