Ahmad 2015.

Methods	Prospective cohort study Setting: hospital leg ulcer clinic Country: UK Duration of follow‐up: 6 months Treatments: compression bandaging (3‐layer or 4‐layer)
Participants	30 participants with VLUs (recalcitrant ulcers) Median age (range): 62 (36‐79) years vs 70 (40‐92) years (healed vs non‐healed) Sex (M:F): 4:5 vs 10:11 (healed vs non‐healed) Stage of ulcer: not reported Ulcer duration: median (range): 12 (3‐84) months vs 19 (2‐180) months (healed vs non‐healed) Ulcer size at baseline: median (range): 6 (2‐165) cm² vs 9 (3‐140) cm² (healed vs non‐healed) Wound infection: not reported Number of wounds: 30 (if bilateral, only 1 limb assessed) Inclusion criteria: confirmed VLU; incompetence of superficial veins or thrombosed deep veins on duplex scan Exclusion criteria: ABPI < 0.8, immunosuppressed, unable to tolerate compression therapy
Prognostic factors	Active uPA (continuous data); total uPA (including receptor bound and complexed to PAI‐1 and PAI‐2). Level of active uPA (quote: "below sensitivity of bioimmunoassay"). Measurement method ELISA: total uPA antigen measurements by ELISA IMUBIND (American Diagnostica). Active uPA measured by bioimmunoassay with the WHO uPA standard. Activity and antigen measurements normalised against soluble protein concentration (Coomassie Plus protein assay). Time of measurement: collected before start of compression therapy Wound fluid sampling method: occlusive dressings (exudate collected from under Opsite (Smith & Nephew) dressing)
Notes	uPA activity measured too, but in all ulcer exudates the level was below the sensitivity of the bioimmunoassay.
Risk of bias
Bias	Authors' judgement	Support for judgement
Selection bias	Unclear risk	Moderate: unclear if consecutive participants, but representative; people at a dedicated ulcer clinic (but inclusion criterion for review was any with VLU).
Attrition bias	Low risk	No missing data
Prognostic factor measurement	High risk	Inappropriate biomarker measure: ELISA for total uPA (including bound and complexed uPA); active bioimmunoassay with uPA WHO standard. Activity below sensitivity level
Outcome measurement	Unclear risk	Moderate: unclear if blinded; defined as complete re‐epithelialisation after 6 months
Adjustment factors	High risk	None of the key adjustment factors taken into account in the design or analysis
Analysis and reporting	High risk	Results reported only for total uPA
Overall risk of bias	High risk