The systematic review39 found marked heterogeneity in the concentration of 5-FU and drug vehicle, ranging from 1% in propylene glycol6364 or 1% cream,65 to 3% ointment,66 to 5% solution,67,68 ointment,69-73 or cream.54,55,74,75 Combination therapies have also been reported.68,76 To complicate issues further, variation in treatment site and outcomes was noted. An attempt to combine studies using meta-analysis techniques39 revealed that only three studies could be combined.70-72 This combination showed that overall efficacy (treatment period of 2-8 weeks and follow up period of 3-18 months) of 5% 5-FU ointment ranged from 79% (95% CI: 72-87%) using patient-level data (by pooling individual subjects' data) to 84% (77% to 91%) using study-level data (by using the reported effect size from each study, weighted by the reported variance).39 In the RCT, the authors demonstrated a significantly higher percentage reduction in the number of lesions (P<0-0001) and improvement in the investigators' global assessment (P< 0-001).

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