D'Angio 1981.

Methods	Method of randomisation not clear (patients were stratified by institution, age and risk group)
Participants	316 children (age nm; 151 boys and 165 girls) with Wilms' tumour (stage II, III or IV; primary disease) No prior treatment Prior cardiac dysfunction nm
Interventions	Chemotherapy without doxorubicin (N = 159) versus chemotherapy including doxorubicin (N = 157) Cumulative doxorubicin dose nm (according to protocol 300 mg/m2); peak dose (i.e. the maximal dose received in one week) 60 mg/m2; infusion duration nm All patients underwent radiotherapy (dose adjusted to age; location adjusted to stage of disease) All patients underwent surgery (radical nephrectomy) No cardioprotective interventions
Outcomes	Overall survival (defined as time from surgery to death without regard to cause) Event‐free survival (defined as the length of time between initial surgery and the earliest detection of abdominal recurrence, distant metastasis or death (whether or not tumour related)) Cardiotoxicity (clinical heart failure defined as cardiac death)
Notes	Length of follow‐up nm Age in treatment and control group nm Long‐term follow‐up data of this study have been published (Green 2004) on 275 of 316 patients: 227 patients with stage II or III disease with favourable or unfavourable histology (as opposed to D'Angio 1981 where data were presented for favourable and unfavourable histology separately) and 48 patients with stage IV disease. The length of follow‐up was nm but at least part of the patients had a follow‐up of 16 years. Since in the stage IV group 20 patients were included in the no anthracycline group and 28 in the anthracycline group, as opposed to the original data where 22 patients were randomised to the anthracycline group and 27 to the non‐anthracycline group, intention‐to‐treat analyses were not possible.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	It was stated that this was a randomised study, but no further information on the methods of randomisation was provided
Allocation concealment (selection bias)	Unclear risk	It was stated that this was a randomised study, but no further information on the methods of randomisation was provided
Blinding of participants and personnel (performance bias)	Unclear risk	No information on blinding of participants and personnel was provided
Blinding of outcome assessment (detection bias): overall survival	Low risk	No information on blinding of outcome assessors was provided, but since this is not applicable for overall survival we judged this as a low risk of bias
Blinding of outcome assessment (detection bias): outcomes other than overall survival	Unclear risk	No information on blinding of outcome assessors was provided for event‐free survival and cardiotoxicity
Incomplete outcome data (attrition bias): overall survival	Unclear risk	It was not clear if all participants were included in the analyses
Incomplete outcome data (attrition bias): event‐free survival	Unclear risk	It was not clear if all participants were included in the analyses
Incomplete outcome data (attrition bias): anthracycline‐induced cardiotoxicity	Unclear risk	It was not clear if all participants were included in the analyses
Selective reporting (reporting bias)	Low risk	There was no protocol mentioned in the manuscript (and we did not search for it), but all expected outcomes were reported
Other bias	Unclear risk	Block randomisation in unblinded trials: unclear (see information provided at earlier associated risk of bias items) Baseline imbalance between treatment arms related to outcome (prior cardiotoxic treatment, age, sex and/or prior cardiac dysfunction): unclear (unclear if age, sex and prior cardiac dysfunction were balanced between treatment arms; no prior cardiotoxic treatment) Difference in length of follow‐up between treatment arms: unclear (not reported) Inappropriate influence of funders: unclear (the study was supported by a US Public Health Service Grant and by the National Institutes of Health, but no information on the influence of funders was provided)