Singh 2008a.

Study characteristics
Methods	Study design Cross‐over RCT Study dates Duration of follow‐up: 7 days Time frame: not reported
Participants	Study characteristics Setting: multicentre Country: USA Inclusion criteria: ≥ 18 years; informed consent; Hb between 9.0 g/dL and 12.5 g/dL (90 to 125 g/L); serum ferritin level of ≤ 600 ng/mL (µg/L); TSAT ≤ 50%; negative serum pregnancy test result or not of childbearing potential; patients undergoing dialysis for at least 90 days Exclusion criteria: history of parenteral or oral iron therapy within 7 days; blood transfusion within 2 weeks; major surgery within 30 days; active infection; history of malignancy; cause of anaemia other than iron deficiency; allergy to iron products or to 2 or more drugs; and those who were breast‐feeding Baseline characteristics Number (analysed/randomised): intervention group (not reported/145); control group (not reported/158) HD: not reported PD: not reported Mean age ± SD (years): not reported for dialysis participants Sex (M/F): not reported for dialysis participants Dialysis type: HD, PD Dialysis vintage (years) (mean ± SD): not reported Comorbidities CVD: not reported Diabetes: not reported Hypertension: not reported Depression (clinician diagnosis): not reported
Interventions	Intervention classification Pharmacological intervention Indication: study reporting fatigue Intervention group Ferumoxytol (IV) 510 mg (17 mL) Control group Sterile saline placebo (IV) 0.9% (17 mL) Co‐interventions Not reported
Outcomes	Outcomes reported Fatigue outcome measures used: validation data available (fatigue was reported as an adverse event) Averse events (including fatigue and infection) Direct questioning of study patients: assessed at baseline and 7 days Serious adverse events: assessed at baseline and 7 days Death Life‐threatening event Hospitalisation Persistent or significant disability Congenital anomaly Changes from baseline in laboratory tests: assessed at baseline and 7 days Changes from baseline in vital signs: assessed at baseline and 7 days BP
Notes	Funding: National Institute of Health Grant T32‐DK007527‐23 and AMAG Pharmaceuticals Inc Conflicts of interest/disclosures: Drs Kausz and Brenner are employees of AMAG Pharmaceuticals, and Dr Singh is a member of the Clinical Studies Steering Committee of AMAG Pharmaceuticals Inc. Dr Singh receives research support from Amgen, Johnson and Johnson, AMAG, Roche, andWatson. He is on the speakers bureau for Johnson and Johnson and Watson. He has received consulting income from AMAG, Johnson and Johnson, and Amgen Trial registration identification number: NCT00255450 A priori published protocol was reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Eligible patients were randomly assigned in a 1:1 ratio (simple block randomisation) to either ferumoxytol or placebo by using a telephone‐based system (ClinPhone Interactive Voice Response System, East Windsor, NJ)." Comment: The interactive voice systems could be considered as a computer
Allocation concealment (selection bias)	Low risk	Quote: "Eligible patients were randomly assigned in a 1:1 ratio (simple block randomisation) to either ferumoxytol or placebo by using a telephone‐based system (ClinPhone Interactive Voice Response System, East Windsor, NJ)." Comment: Interactive system voice is considering as low risk of bias
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Patients, investigators, and study coordinators were blinded, with the exception of 1 individual at each site designated the Test Article Administrator, who administered study treatments." Comment: A double‐blind trial is considered as low risk of bias
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The blinded investigators and study coordinators, but not the Test Article Administrator, were involved in the assessment and attribution of adverse events. [...] All laboratory tests were performed at a central laboratory. [...] Relatedness of AEs to treatment was determined by the blinded site investigators. [...] Direct questioning of study patients regarding adverse events." Comment: Blinded investigators and study coordinators were involved in the assessment and attribution of adverse events (including fatigue)
Incomplete outcome data (attrition bias) All outcomes	High risk	The number of patients who completed the study was not clearly stated. It was unclear if there was evidence that the results were not biased by missing outcome data
Selective reporting (reporting bias)	High risk	Information about the protocol and the statistical analysis plan were reported. It was not reported if multiple eligible outcome measurements (scales and time points) were pre‐specified. It was unclear if the reported approach to analysing this outcome was pre‐specified or influenced by the results. Fatigue at the end of treatment was not reported in a format that was extractable for meta‐analysis (cross‐over study: data related to the first period were not clearly reported). All outcomes that should be addressed (fatigue, cardiovascular disease, and death) were not reported
Other bias	High risk	There was no evidence of different baseline characteristics, or different non‐randomised co‐interventions between groups. Government funding was unlikely to influence the data analysis but the pharmaceutical company could influence the data analysis and authors had conflicts of interest