Fox 2010.

Methods	RCT with 64 HIV‐positive patients (53 completed the study: 28 imiquimod arm and 25 patients in placebo arm) recruited in two anoscopy clinics. Initially planned recruitment of 120 patients, but after 64 patients had consented the manufacturer of imiquimod didn't supply more randomised study drug.
Participants	Age: intervention group median 41.8, range 35.2‐48.4); placebo group 42.3 years, range 34.9‐49.7). Smoker: intervention group smokers  n=13 and non‐smokers n=15. HAART for a minimum of 3 months prior to recruitment, >100 CD4 cells/ml or higher. No history of previous imiquimod use. Median CD4 cells count at enrolment (cells/µl): intervention group: 329 (258‐514); placebo group: 389 (262‐441). Median nadir CD4 cells counts  (cells/µl): intervention group: 88 (60‐182); placebo group: 98 (44‐169). Median duration of HSIL (months): intervention group: 2.5 (2.0‐ 7.5); placebo group: 3 (2‐14).
Interventions	‐ imiquimod versus placebo. Self‐application three times a week by inserting a finger no further than 2 cm into the canal anal and not using more than half a sachet. ‐ treatment three times a week for 4 months.
Outcomes	‐ Response to treatment at 8 weeks after the end of treatment (HRA and cytology) and 12 months of follow‐up. ‐ Compliance to treatment. ‐ Local side effects. ‐ Recurrences at one year of follow‐up.
Notes	Partial and non‐responders were all offered 4 months of open‐label treatment with imiquimod and ongoing 6‐monthly surveillance. All participants were offered ongoing 6‐monthly HRA and cytology.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported. “The randomization sequence was only known to 3M Health Care”.
Allocation concealment (selection bias)	Low risk	“Matching packs of imiquimod and placebo were supplied by 3M Health Care Ltd, Loughborough, UK. On recruitment, patients were allocated the next randomization number in the study”.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	“The study was not unblinded until all patients had completed the randomized stage”.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcomes were assessed by people who were not aware of the patient’s treatment allocation.
Incomplete outcome data (attrition bias) All outcomes	High risk	11/64 of participants is a 17.18%, a significant drop out rate. Description of reason for withdrawal of the patients who did not complete the study was partial (allocation of all drop outs is not reported).
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement.
Other bias	High risk	Study terminated earlier than previously designed due to “inability to obtain further supplies of randomized study drug after 64 patients had consented”. Knowgledge of a second phase with use of open‐label imiquimod may have influenced participants to withdrawal.