Leyden 2006 (Part 2).

Methods	RCT: This had a multicenter, open‐label, treatment phase (Part 1) followed by a double‐blind randomised, parallel‐group maintenance phase (Part 2). Participants were then eligible to enter the double‐blind phase if they showed a 75% or greater global improvement at the end of the initial open‐label phase. Only the results of Part 2 have been included in this review because Part 1 was not randomised. The duration of the trial was 12 weeks (randomised phase). The method of randomisation was as follows: Participants were assigned a unique number obtained from a computer‐generated randomisation schedule. The trial was funded by Allergan Inc. There was no UV control. It was not stated whether all previous oral and topical treatment was stopped prior to the start of the trial, but all participants had received topical tazarotene gel and minocycline 100 mg daily during Part 1 of the study. Evaluation was at 12 weeks. The area evaluated was the face. The assessor was not specified. ITT results were given for all participants in the study and those randomised in the maintenance phase (Table 25, page 608).
Participants	The following are taken from page 606 of the trial. "189 participants enrolled, 137 completed open label phase, 110 [were] randomised to [the] maintenance phase." Randomised: 0.1% tazarotene gel each evening plus a placebo capsule twice‐daily, vehicle gel each evening plus minocycline capsule twice‐daily, or 0.1% tazarotene gel each evening plus a minocycline capsule twice‐daily. 20 participants did not complete the randomised phase of the study. The mean age was 22 years. Participants "enrolled from 5 investigational sites in the United States. The sites were referral or research centres, and enrolment was generally performed by investigators who recruited their existing participants or participants who responded to an advertisement." There were comparable demographics at baseline. Inclusion criteria of the trial "Participants were eligible for enrolment in the study if they were at least 12 years of age and had moderately‐severe to severe facial acne vulgaris, 10 to 100 facial non‐inflammatory acne lesions, 25 to 60 facial inflammatory acne lesions, and no more than 2 facial nodular cystic lesions" Participants were eligible to enter the double‐blind phase if they showed a 75% or greater global improvement at the end of the initial open‐label phase Exclusion criteria of the trial Antibiotic‐resistant acne vulgaris; PREG, BF, or planning pregnancy; uncontrolled systemic disease; participating in any other study in the preceding 30 days
Interventions	0.1% tazarotene gel each evening plus a placebo capsule twice‐daily Vehicle gel each evening plus a 100 mg minocycline hydrochloride capsule twice‐daily 0.1% tazarotene gel each evening plus a 100 mg minocycline capsule twice‐daily Concomitant therapy: none permitted Appearance: standard (open‐label) Instructions: pea‐sized amount to the face in a thin film 15 to 20 minutes after washing with a mild, non‐medicated cleanser and drying with a soft towel Skin hygiene: Quote (page 606): "Washing with a mild non‐medicated cleanser and drying with a soft towel. Participants were supplied with a noncomedogenic moisturiser to use if facial dryness developed. No other lotions, creams, medicated powders, or solutions were allowed on the treatment area." Empty stomach: no Compliance: measured as reported in Figure 1, page 607, but method of assessment was not specified Wash‐out periods: 14 days topical acne medications, 30 days oral antibiotics and investigational drugs, 12 weeks oestrogens or birth control pills if used for less than 12 weeks, 2 years for oral retinoids
Outcomes	Outcomes of the trial OC count, Cc count, PA count, PU count, TIL count, and NIL count Global improvement (7‐point scale), severity (0 to 6) TIL count, NIL count (overall disease severity, global response to treatment, mean percentage change in open ‐ plus closed ‐ comedone count, mean percentage change in papule plus pustule count ‐ overall disease severity was rated on a 7‐point scale, with 0 indicating none; 2, mild; 4, moderate; and 6, severe, with 1, 3, and 5 as intermediate grades. Global response to treatment was rated as 100% improvement, approximately 90% improvement, approximately 75% improvement, approximately 50% improvement, approximately 25% improvement, no change, or worsening) (primary outcome) Adverse drug reactions: Peeling, erythema, dryness, burning, and pruritus were assessed as a primary outcome measure. Both investigator or participant classified as none, trace, mild, moderate, marked, or severe
Notes	Country: United States Language: English Review version: 2012 The trial was financially sponsored, but disclosure was made. Quote (page 612): "The initial draft of the manuscript was reviewed by Allergan Inc, but the company did not prepare the manuscript or have the opportunity to approve the final version."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (page 606): "Participants who achieved at least 75% global improvement at week 12 were assigned a unique participant number obtained from a computer‐generated randomisation schedule (using a block size of 6) provided by the sponsor. The assignment of numbers was not necessarily continuous (because 1 investigator may have received noncontiguous blocks of numbers) but was always in blocks of 6." Comment: Yes, this was randomised.
Allocation concealment (selection bias)	Low risk	Small block randomisation was employed. Comment: It was possible to predict sequence in small block randomisation, but this was judged as probably low risk.
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote (page 606): "The labels on the medication containers were concealed." It was stated as double‐blind, but it was unclear if the appearance of products was identical.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants were accounted for at each time point (please see Figure 1, page 607).
Selective reporting (reporting bias)	Low risk	All outcomes were reported.