Macchiarini 1991

Methods	Italy; RCT
Participants	Number of participants: 52 (Between January 1979 and December 1980) Number randomised: Experimental group (adjuvant chemo immunotherapy CAV + BCG ): 26 Control group (adjuvant chemotherapy CAV): 26 Number evaluated: Experimental group: 26, age: 53.8% < Median (57.5 yrs), 46.2% > Median (57.5 yrs) Control group: 26, age: 46.2% < Median (57.5 yrs), 53.8% > Median (57.5 yrs) Diagnosis: Patients stages II and III NSCLC following complete surgical resection Inclusion: eligible patients should: Patients aged < 76 years with no prior history of malignancy except for non‐melanoma skin cancer, or in situ cervical cancer, or both; no previous treatment by chemotherapy, immunotherapy, or thoracic radiation; Karnofsky performance status > 69; histologically confirmed NSCLC classified postsurgically as stage II or III disease; adequate renal, liver, bone marrow, and cardiopulmonary functions.
Interventions	Experimental group: Chemotherapy including cyclophosphamide (1 g/m² iv, day 1), doxorubicin (45 mg/m² iv, day 1), and vincristine (1.2 mg/m² iv, day 1) was started within 4 weeks after operation and repeated every 3 weeks. Intrapleural BCG consisted of 5.5 per 10⁸ colony‐forming units of BCG Pasteur administered into the pleural space as a single dose between postoperative days 4 and 14. 14 days after BCG administration, Isionazide (INH), 300 mg/day, was administered orally for 12 weeks. Control group: Chemotherapy including cyclophosphamide (1 g/m² iv, day 1), doxorubicin (45 mg/m² iv, day 1), and vincristine (1.2 mg/m² iv, day 1) was started within 4 weeks after operation and repeated every 3 weeks.
Outcomes	Duration of follow‐up (median): 111 months OS (survival time), disease‐free survival
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label design
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	62 randomised participants were included in analysis (100%)
Selective reporting (reporting bias)	High risk	previous protocol was unavailable, and no pre‐specified primary outcome was reported.
Other bias	Low risk	No obvious potential source of bias