Taher 2012.

Methods	Multinational, prospective, randomised, double‐blind, placebo‐controlled phase 2 study.
Participants	166 participants were randomised. 95 non‐transfusion‐dependent β‐thalassaemia, 22 α‐thalassaemia, 49 HbE/β‐thalassaemia 148 participants completed 1 year of the study. Inclusion criteria ≥ 10 years of age with Non‐transfusion‐dependent β‐thalassaemia Iron overload (R2‐MRI‐measured LIC ≥ 5 mg Fe/g dry weight) Serum ferritin > 300 ng/mL at screening based on 2 consecutive values ≥ 14 days apart were eligible Participants were required to have not received transfusions within 6 months or chelation therapy within 1 month before study entry Exclusion criteria People with previous exposure to DFX Anticipated regular transfusions; unplanned transfusions during the study were allowed HbS variants of thalassaemia syndromes Active hepatitis B (positive hepatitis B surface antigen with negative hepatitis B surface Ab) or hepatitis C (positive hepatitis C virus Ab and detectable hepatitis C virus RNA with alanine aminotransferase [ALT] above the normal range) Cirrhosis Levels of ALT > 5 x ULN Serum creatinine > ULN or creatinine clearance ≤ 60 mL/min on 2 measurements Significant proteinuria (urine protein/urine creatinine ratio > 1.0 mg/mg) on 2 measurements Follow‐up: 1 year
Interventions	4 groups: DFX (n = 55): 5 mg/kg/day DFX (n = 55): 10 mg/kg/day Placebo (n = 28): 5 mg/kg/day Placebo (n = 28): 10 mg/kg/day ‐ Doses were doubled at 24 weeks for patients with LIC > 7 mg Fe/g dry weight and LIC reduction < 15% from baseline ‐ Dose adjustment recommendations were also provided based on continuous safety assessments ‐ If serum ferritin was <100 ng/mL or LIC was <3 mg Fe/g dry weight at any visit, treatment was to be suspended until LIC increased to ≥ 5 mg Fe/g dry weight and serum ferritin to > 300 ng/m
Outcomes	LIC Number and proportion of patients with a LIC decrease of ≥ 3 mg Fe/g dry weight, those with ≥ 30% reduction in LIC, and those with LIC ≤ 7, ≤ 5, and ≤ 3 mg Fe/g dry weight Serum ferritin Correlation of serum ferritin and LIC AEs Serious AEs Adherence
Notes	Study was sponsored by Novartis Pharma AG. Novartis was involved in design and statistical analysis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"[...] patients were block randomised [...]". No details given on how random sequence was generated.
Allocation concealment (selection bias)	Low risk	"[...] patients were block randomised using an interactive voice response system. After confirming that the patient fulfilled the inclusion/exclusion criteria, the investigator contacted the interactive voice response system to obtain a randomisation number linking the patient to a treatment arm."
Blinding (performance bias and detection bias) All outcomes	Unclear risk	"Because blinding of dose was not possible, blinding was only applied to the treatment received. All persons were blinded to the treatment from the time of randomisation until database lock."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Attrition was 12.7%, 10.9% and 8.9% for the DFX 5 mg, DFX 10 mg and the placebo group, respectively In the journal publication, the authors state that "efficacy was assessed for the full analysis set (all randomised patients).[...] If there was no LIC measurement available at week 52, the last available post‐baseline LIC measurement was carried forward." Number of participants analysed on clinicaltrials.gov doesn't include all randomised patients for continuous outcomes.
Selective reporting (reporting bias)	High risk	Extensive data set available on ClinicalTrials.gov (along with prespecified protocol), but AEs and SAEs were not reported separately for the core phase In the journal publication AEs and drug‐related AEs were not reported completely
Other bias	Low risk	No other bias detected.

AE: adverse event
 ALP: alkaline phosphatase
 ALT: alanine aminotransferase
 AST: aspartate aminotransferase
 A‐V: atrio‐ventricular
 CBC: complete blood count
 CONSORT: consolidated standards of reporting trials
 DFO: deferoxamine
 DFP: deferiprone
 DFX: deferasirox
 ECG: electrocardiogram
 EF: ejection fraction
 EOS: eosinophil count
 Fe: iron
 FT₃: serum‐free triiodothyronine
 FT₄: serum‐free thyroxine
 GI: gastrointestinal
 HBV: hepatitis B virus
 ITT: intention‐to‐treat
 LVEF: left ventricular ejection fraction
 LIC: liver iron concentration
 MRI: magnetic resonance imaging
 QoL: quality of life
 PCR: polymerase chain reaction
 RBCs: red blood cells
 RNA: ribonucleic acid
 SD: standard deviation
 SQUID: superconducting quantum interference device
 TGA: antithyroglobulin
 TSH: thyroid‐stimulating hormone
 TPO: antithyroid peroxidase
 UIBC: unsaturated iron binding capacity
 ULN: upper limit of normal
 WBC: white blood count