Pennell 2014.

Methods	Prospective, multinational, randomised, open‐label, parallel‐group, phase 2 study; Non‐inferiority study.
Participants	197 participants were randomised 160 participants completed one year of treatment Age (mean (SD)): 19.8 (6.4) years (range: 10 ‐ 40 years) Gender (male/female): 115/82 Setting and countries: 22 centres across 11 countries Inclusion criteria: People with β‐thalassaemia major, Diamond‐Blackfan anaemia, low/intermediate 1 myelodysplastic syndromes, or sideroblastic anaemia Aged ≥ 10 years Myocardial T2* 6 to 20 ms without clinical symptoms of cardiac dysfunction (shortness of breath at rest or exertion, orthopnoea, exercise intolerance, lower‐extremity edema, arrhythmias) LVEF ≥ 56%, R2 magnetic resonance imaging LIC ≥ 3 mg Fe/g dry weight Lifetime history of ≥ 50 U red blood cell transfusions Receiving ≥ 10 U/y of red blood cell transfusion Only people with β‐thalassaemia major fulfilled the inclusion criteria and were enrolled in the study Exclusion criteria: Serum creatinine above the ULN Significant proteinuria (urinary protein/creatinine ratio ≥ 1.0 mg/mg in a non‐first‐void urine sample at baseline) ALT > 5 times the ULN only if their LIC was < 10 mg Fe/g dry weight Considerable impaired GI function or GI disease History of clinically relevant ocular and/or auditory toxicity related to iron chelation therapy History of HIV seropositivity or malignancy within the past 5 years Follow‐up: 12 months
Interventions	Two groups: DFX (n = 96): Once‐daily starting dose was 20 mg/kg per day for 2 weeks, followed by 30 mg/kg per day for 1 week, and then continued with 40 mg/kg per day DFO (n = 91): 50 to 60 mg/kg per day via subcutaneous infusion over 8 to 12 hours, 5 to 7 days a week; dose adjustment recommendations were provided based on continuous assessment of efficacy and safety markers
Outcomes	Ratio of geometric mean myocardial T2* with DFX divided by the ratio of geometric mean for DFO LVEF LIC Serum ferritin Furthermore, safety, compliance, dose interruptions/reductions and laboratory parameters (serum creatinine, blood creatinine, ALT) were measured.
Notes	Study was sponsored by Novartis Pharma AG. Novartis Pharma AG was involved in design of the study, conducted the statistical analysis and paid a medical writer who assisted with writing the article. Some of the authors received research grant funding, honoraria or lecture fees from Novartis Pharmaceuticals and/or other pharmaceutical companies.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"[...]patients were randomised in a 1:1 ratio [...]" "Randomization was based on permuted blocks; stratification by centre was not conducted."
Allocation concealment (selection bias)	Unclear risk	No details given with regard to concealment of allocation.
Blinding (performance bias and detection bias) All outcomes	High risk	"Core laboratories were blinded to treatment allocation." "In order to eliminate potential unrecognised biases, the core clinical trial team was blinded to the treatment assignment prior to the database lock for the primary analysis." "Open‐label trial" No placebo treatment mentioned. Due to different administration routes, blinding is not likely in particular of performance bias.
Incomplete outcome data (attrition bias) All outcomes	High risk	ITT was done regarding myocardial T2*, but the number of included patients (n=180) was lower than the number of randomised patients (n=197) Apart from that, per‐protocol analysis was done for the other outcomes.
Selective reporting (reporting bias)	High risk	Only most common AE (≥ 5%) and drug related AE ≥ 2 participants were reported
Other bias	Low risk	No other bias detected.