Casper 1991.

Study characteristics
Methods	Method of randomisation not clear (stratified according to presence or absence of microscopically positive margins)
Participants	82 participants (aged 18 to 87 years; 39 women and 44 men) with high‐grade non‐metastatic soft tissue sarcoma treated with doxorubicin. No prior anthracycline therapy; prior cardiac radiotherapy possible for 2 participants in the bolus group and 3 participants in the continuous infusion group; no prior cardiac dysfunction
Interventions	Doxorubicin (peak dose 60 mg/m2) every 3 weeks for a total of 9 cycles with either bolus (5 to 10 min) infusion (N = 39; median cumulative dose 420 mg/m2; range 60 to 540 mg/m2) or continuous infusion (72 h) (N = 43; median cumulative dose nm; range 120 to 540 mg/m2)
Outcomes	Heart failure (i.e. clinical heart failure defined as congestive heart failure; subclinical heart failure defined as a 10% or more decrease in LVEF at rest as measured by radionuclide cineangiograms) OS (definition nm)
Notes	One participant randomised to bolus therapy actually received the drug by continuous infusion. We performed an intention‐to‐treat analysis, but the data presented in this table are for 38 participants in the bolus and 44 participants in the continuous infusion group. One participant in the bolus group and 3 participants in the continuous infusion group never received treatment Length of follow‐up nm The study was supported by a grant from the National Institutes of Health, but no information on the influence of funders was provided
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): clinical heart failure	Unclear risk	No information on blinding of outcome assessors was provided for clinical heart failure.
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
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
Incomplete outcome data (attrition bias): clinical heart failure	Unclear risk	Not documented how many participants were included in the analysis of clinical heart failure
Incomplete outcome data (attrition bias): subclinical heart failure (dichotomous and/or continuous)	High risk	Only 84.1% of participants were included in the analysis
Incomplete outcome data (attrition bias): overall survival	Low risk	All participants were included in the analysis
Selective reporting (reporting bias)	Low risk	There was no reference to a protocol provided in the manuscript (and we did not search for it), but all expected outcomes were reported
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 prior cardiotoxic treatment was balanced between treatment groups; all other items were balanced between treatment groups) Difference in length of follow‐up between treatment arms: unclear (not reported)