Steinherz 1993.

Study characteristics
Methods	Method of randomisation not clear (stratified according to risk group, degree of leukocyte count elevation, age, FAB morphology, and presence or absence of lymphoma syndrome)
Participants	44 participants (aged 1 to 19 years; median 7 years; 11 girls and 33 boys) with ALL (31 high risk and 13 average risk) treated with daunorubicin, cytosine arabinoside, cyclophosphamide, vincristine, prednisone, L‐asparaginase, methotrexate, 6‐MP, thioguanine, and sometimes spinal (12 Gy for participants with CNS disease at diagnosis; N = 3, nm in which treatment group) and /or cranial irradiation. No prior anthracycline therapy; no prior cardiac radiotherapy; prior cardiac dysfunction nm
Interventions	Daunorubicin (peak dose 120 mg/m2) with either bolus (push) infusion (N = 22; median cumulative dose 360 mg/m2 (range 120 to 585 mg/m2) for 18 participants with an echocardiogram) or continuous (48 hours) infusion (N = 22; median cumulative dose 400 mg/m2 (range 120 to 558 mg/m2) for 18 participants with an echocardiogram)
Outcomes	Heart failure (i.e. subclinical heart failure defined as a LVSF of less than 29% or a 10% unit or more decrease from baseline to 29% (borderline function) or median change in LVSF as measured by echocardiography)
Notes	Median length of follow‐up 54+ months (minimal 25+ months) No funding documented
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, although due to the nature of the interventions, this was most likely not the case
Blinding of outcome assessment (detection bias): subclinical heart failure (dichotomous and/or continuous)	Unclear risk	No information on blinding of outcome assessors was provided for subclinical heart failure
Incomplete outcome data (attrition bias): subclinical heart failure (dichotomous and/or continuous)	Low risk	All participants were included in the analysis
Selective reporting (reporting bias)	High risk	There was no reference to a protocol provided in the manuscript (and we did not search for it), but not all expected outcomes were reported in a useful manner
Other bias	Unclear risk	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 groups; no prior cardiotoxic treatment) Difference in length of follow‐up between treatment arms: unclear (not reported)