Prentice 1997.

Methods	Multicentred, international (UK, Europe) open‐label randomised trial. Adult studies (104‐10) and paediatric studies (104‐14) are presented in the same paper
Participants	Neutropenic children and adults (ANC < 0.5x109/L) with pyrexia of unknown origin (96 hours of fever defined as a temperature ≥ 38°C not responding to broad‐spectrum antibacterial therapy)
Interventions	Liposomal amphotericin B versus conventional amphotericin B Liposomal amphotericin B (Ambisome® 1 and 3mg/kg/day) was compared with conventional amphotericin B (1mg/kg/day) Therapy was continued until resolution of fever (<38°C), recovery of neutrophils to above or equal to 0.5x109/L for 3 consecutive days, patient death, unresolved toxicity, patient or physician request to withdraw
Outcomes	Primary endpoint::safety Secondary endpoints: efficacy or treatment response which was defined by a minimum of 3 consecutive days without fever (<38°C) that continued until study end, indicated by recovery of neutrophils to 0.5x109/L. Failure was defined as patients who remained febrile at the of study, patients who developed a systemic fungal infection on study and patients in whom a further systemic fungal agent was added
Notes	Paediatric and adult population. Authors contacted for further data (5/12/2008). No further data were available The study contains two difference concentrations of liposomal amphotericin B (1mg/kg and 3mg/kg). These have been pooled for some comparisons. Toxicity endpoints are only expressed as percentages without clear denominators. It was therefore necessary to calculate numbers from percentages.
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Randomisation was done centrally and each participating centre was provided with a set of blinded, numbered envelopes which required sequential opening. The arms were balanced per centre and per block of six patients.
Allocation concealment?	Low risk	Blinded, numbered envelopes were provided by study investigators preventing allocation concealment.
Blinding? All outcomes	High risk	The trial was open labelled.
Incomplete outcome data addressed? All outcomes	High risk	Patients enrolled: 204 children and 134 adults. Of 204 randomised children, 202 reported with 2 charts not available for review. Toxicity endpoints were expressed as percentages in both adults and children. Nephrotoxicity data was calculated from 305 adults and children however 338 subjects were evaluable for safety. It was not clear from the report why these patients were not included in the analysis.
Free of selective reporting?	Unclear risk	Given the incomplete outcome data, selective reporting is potentially a problem.
Free of other bias?	Low risk	The study appeared to be free from other sources of bias.