Valentino 2012.

Study characteristics
Methods	Open‐label, multicentre, randomised, 2‐arm, parallel trial. Enrolled participants at 9 USA and 21 European sites between January 2006 and June 2010. Participants completed the 6‐month on‐demand period and were randomised to a 12‐month prophylaxis period (32 on standard and 34 on PK‐tailored prophylaxis).
Participants	Participants aged 7 to 65  years with moderately severe or severe haemophilia A, receiving on‐demand treatment. Baseline FVIII: < 1% Number of participants enrolled: 82. Number of participants randomised: 66.
Interventions	2 secondary prophylaxis arms: 1. Standard prophylaxis (20 – 40 IU/kg) every other day.(N = 32) 2. PK‐tailored prophylaxis (20 – 80 IU/kg) every third day.(N = 34) Follow‐up duration: 6 months on‐demand treatment followed by 12 months prophylaxis
Outcomes	Annualized bleeding rate.
Notes	Of note, this trial had a non‐randomised longitudinal cross‐over portion that compared prophylaxis versus on demand. Dates of trial: January 2006 to June 2010 Source of funding: Baxter Healthcare Corporation.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The randomization sequence was created using SAS version 8.2 (Cary, NC, USA), stratified by 0, 1–2 or ‡ 3target joints (defined as a joint in which ‡ 4 hemorrhages occurred within a period of 6 months, or > 20 lifetime hemarthroses)...".
Allocation concealment (selection bias)	Low risk	Quote: "...1:1 allocation to treatment regimens using a random block size of 2, and provided to the investigator via an automated assignment system as the subject neared completion of on‐demand treatment."
Blinding (performance bias and detection bias) Clinical Joint Function	Unclear risk	Not assessed.
Blinding (performance bias and detection bias) Bleeding	High risk	An open‐label trial.
Blinding (performance bias and detection bias) Radiologic Joint Score	Unclear risk	Not assessed.
Blinding of outcome assessment (detection bias) Bleeding	High risk	An open‐label trial.
Blinding of outcome assessment (detection bias) Clinical Joint Function	Unclear risk	Not assessed.
Blinding of outcome assessment (detection bias) Radiologic Joint Score	Unclear risk	Not assessed.
Incomplete outcome data (attrition bias) All outcomes	High risk	Unbalanced dropout rate across groups (N = 2 in standard prophylaxis arm; N = 11 in PK‐tailored prophylaxis arm). Reasons for dropout were included.
Selective reporting (reporting bias)	Low risk	Outcomes reported in protocol are present in report.
Other bias	Low risk	No other potential sources of bias identified.