Clifford 2012.

Study characteristics
Methods	RCT, DB, parallel groups, single application, 12‐week duration. Patches applied to both feet, up to 1120 cm2 Oral pain medication continued without change. Transdermal opioids (morphine equivalent ≤ 80 mg/day) permitted, but not topical analgesics, or implanted medical device for pain relief Rescue medication: during application participants allowed oral oxycodone solution (1 mg/mL) and local cooling; after application allowed hydrocodone/paracetamol (5/500 mg) for ≤ 5 days, and paracetamol (≤ 3 g/day) throughout Pain assessed daily (average pain for last 24 hours). PGIC assessed at 12 weeks. Clinic visits at 4, 8, 12 weeks
Participants	HIV‐associated distal sensory neuropathy for ≥ 2 months Exclusion: previous use of NGX‐4010 (capsaicin) N = 494 M = 432, F = 62 Mean age: 50 years Baseline pain: 30 mm to 90 mm (mean 60 mm)
Interventions	(1) Capsaicin patch 8% 30 min, n = 167 (2) Capsaicin patch 8% 60 min, n = 165 (3) Placebo patch 30 min, n = 73 (4) Placebo patch 60 min, n = 89 Topical local anaesthetic applied for 60 min, then patch applied for 30 or 60 min Control patch contained 0.04% capsaicin to mimic AEs
Outcomes	PI: 11‐point numeric pain rating scale (responder: ≥ 30% reduction from baseline) PGIC: 7‐point scale (reporting: slightly, much and very much improved) AEs Withdrawals
Notes	Oxford Quality Score: R1, DB2, W1. Total = 4/5
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described; "allocation scheme prepared by Fisher Clinical Services"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not described as identical; "low‐dose capsaicin control patches were used instead of placebo to provide effective blinding ..."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Modified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis
Size	Unclear risk	50 to 200 participants per treatment arm.