Witjes 1996b.

Methods	Study design: multicentre, prospective, randomised clinical trial Number of study centres: 27 Study dates: 1987–1990, follow‐up 36 months (2–81 months) Participants randomly assigned: 437
Participants	Inclusion criteria: histologically confirmed primary or recurrent papillary transitional cell carcinoma stage Ta or T1 after complete TUR; people with primary or concomitant Cis were also eligible. Exclusion criteria: previously treated with intravesical or systemic cytotoxic agents or radiotherapy; recurrent severe bacterial urinary tract infections; bladder cancer other than transitional cell carcinoma or with a second primary malignancy (exception of basal cell or squamous cell carcinoma of the skin).
Interventions	Group A: MMC 30 mg in 50 mL saline Group B: BCG‐RIVM 5 × 108 bacilli in 50 mL saline Group C: BCG‐Tice 5 × 108 bacilli in 50 mL saline Procedure: MMC instilled once a week for 1 month (weeks 1–4) and thereafter once a month for a total of 6 months; BCG was administered once a week for 6 weeks. Treatments start 7–20 days after TUR; if a recurrence was detected in the MMC group, complete resection was carried out and the MMC treatment continued monthly for another 3 months; if disease recurred within 6 months in the BCG treatment group, a second course of 6 weekly instillations was administered after complete tumour resection; if a recurrence was observed after completion of intravesical treatment or if the T category increased to T2 or higher, participants went off the study; further treatment was left to the discretion of the individual urologist.
Outcomes	Recurrence‐free survival, progression‐free survival, adverse effects
Funding sources	No information reported.
Declarations of interest	No information reported.
Notes	Dutch South East Cooperative Trial. 1 pathologist determined stage and grade.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Comment: restricted block‐wise (block size 6 equals 3 treatments times 2 participants per treatment) randomisation was used.
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	Unclear risk	Outcome not reported.
Incomplete outcome data (attrition bias) Adverse effect outcomes	Low risk	Comment: all participants were considered in the analyses (Group A 136/136, Group B 134/134, Group C 140/140).
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.