Makinen 2002.

Methods	Study design: phase II placebo‐controlled double‐blind RCT Intention‐to‐treat: yes Country: Finland
Participants	Number randomised: N = 54 (VEGF‐AdV n = 18; VEGF‐P/L n = 17; control n = 19) Losses to follow‐up and withdrawals: at 3 months: VEGF‐Ad n = 3; VEGF‐P/L n = 1; control n = 2) Age (mean years (range)): VEGF‐AdV 70 (53 to 86); VEGF‐P/L 74 (55 to 84); control 73 (61 to 86) Gender (M): VEGF‐AdV 50.0%; VEGF‐P/L 35.3%; control 42.1% Inclusion criteria: angiographically proven atherosclerotic infrainguinal stenosis or occlusion suitable for PTA Exclusion criteria: type 1 diabetes; malignancy; osteomyelitis; fertile women age < 50 years; signs of active inflammation; abnormal prostate‐specific antigen or carcinoembryonic antigen values; poor cooperation
Interventions	Treatment: 2 × 10¹⁰ pfu VEGF‐AdV, intra‐articular catheter administration following PTA VEGF‐P/L (2000 µg VEGF plasmid plus 2000 µL DOTMA:DOPE) intra‐articular catheter administration following PTA Control: placebo, Ringer's lactate, intra‐articular catheter administration following PTA
Outcomes	Follow‐up times: 1 and 3 months, median follow‐up 24 months for safety outcomes Outcomes: Ischaemic status using Rutherford Classification, ABI, Vascular assessment, Restenosis rate
Notes	Study period: not specified
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation done before beginning of study; block of 9 people; used a procedure based on random digits
Allocation concealment (selection bias)	Unclear risk	Insufficient information provided to determine allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Used control placebo treatment; "treatment and follow up were made in double‐blinded manner"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"Treatment and follow up were made in double‐blinded manner"; image analysis was carried out by blinded assessors who did not have access to follow‐up laboratory or clinical information
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants accounted for and dropouts clearly explained
Selective reporting (reporting bias)	Low risk	All outcomes reported
Other bias	Unclear risk	Supported by a grant from Kuopio University Hospital, Ark Therapeutics Ltd., Boston Scientific Inc., and Valentis