Krege 1996.

Methods	Study design: multicentre, prospective, randomised clinical trial Number of study centres: 14 Study dates: August 1985 to September 1992, follow‐up 20.2 months Participants randomly assigned: 327
Participants	Inclusion criteria: histologically confirmed stage pTa/T1 grades 1–3 bladder cancer complete resection of tumour, inconspicuous cystoscopy after 6 weeks > 3000/mL leukocytes; > 100,000/mL thrombocytes; serum creatinine < 2.0 mg Exclusion criteria: primary stage pTa grade 1 tumours metastasis, upper urinary tract tumour, hydronephrosis, other malignant disease or active tuberculosis intravesical chemotherapy during the last 6 months or previous radiation acute urinary infection
Interventions	Group A: 112 participants randomised to TUR alone Group B: 113 participants randomised to TUR followed by intravesical MMC 20 mg in 50 mL saline Group C: 102 participants randomised to TUR followed by intravesical BCG 120 mg Connaught strain in 50 mL saline, plus concomitant subcutaneous BCG 0.5 mg. Procedure: at 6 weeks after TUR, participants underwent subsequent urethrocystoscopy, and in case of residual tumour a second TUR was performed; instillation was done only after complete resection of the tumour, 7 days after secondary resection at the earliest; MMC was instilled via a catheter and kept in the bladder for 2 hours. Instillations were performed every 2 weeks during year 1 and once a month during year 2; BCG was instilled intravesically for 1 hour. At the same time BCG 0.5 mg was applied subcutaneously. Therapy was continued once weekly for 6 weeks and once a month for 4 months; in case of tumour recurrence TUR was repeated.
Outcomes	Time to recurrence, progression rate and adverse effects
Funding sources	Supported by a grant from the Ministry of Science and Technology, Germany.
Declarations of interest	No information reported.
Notes	Sample size calculations demanded the admission of 402 participants into the study. However, despite an extended recruitment phase to September 1992, only 337 participants were enrolled.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Comment: randomised by permuted block method after stratification with respect to primary or recurrent tumours, as well as the canters involved to ensure balanced group sizes within strata after every 6 participants. We assumed that sequence generation was done adequately.
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: nearly all participants were included in statistical analysis (Group B 112/113, Group C 102/102).
Incomplete outcome data (attrition bias) Adverse effect outcomes	Unclear risk	Comment: no precise information on participants included in analyses.
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	High risk	Quote: "(...) despite an extended recruitment phase (...), only 337 patients were found." Comment: sample size calculations showed a need for 134 participants per treatment arm. Thus, the reduced number of study participants might have had led to reduced power to detect any effects. Study was supported by a grant from the Ministry of Science and Technology, Germany. Conflicts of interests are not reported. We assumed there was no other potential risk of bias.