Oprica 2007.

Methods	Parallel design, randomised controlled trial
Participants	52 participants from a single centre, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden Inclusion criteria: male and female participants who had moderate or severe inflammatory acne vulgaris (at least grade 3 on the face, back, or chest according to the Leeds technique); age range 15–35 years Exclusion criteria: papulo‐pustular acne with no nodules or very severe forms (acne fulminans); use of oral/topical acne treatments within 8 weeks of the start of treatment; use of drugs that may interfere with tetracycline (i.e. retinoids, anticoagulants, antacids, iron preparations, hepatic enzyme inducers); pregnant women or those who, wanted to become pregnant; breastfeeding mothers; systemic or psychiatric diseases (including drug and alcohol abuse); any dermatological condition that might interfere with the evaluation of acne; acne due to secondary causes; participation in any other clinical trial; hypersensitivity or allergy to the study medication Age: for all participants, ranged from 15 to 35 years Age: by group, median ± SD (years) Group 1 (n = 25): 19 ± 5.5 Group 2 (n = 24): 18 ± 6 Gender: male/female Group 1 (n = 25): 15/10 Group 2 (n = 24): 17/7 Disease duration: median ± SD (years): Group 1 (n = 25): 4 ± 4.2 Group 2 (n = 24): 3 ± 5.4 Acne severity: moderate or severe acne
Interventions	Group 1 (tetracycline/adapalene) (n = 25): tetracycline hydrochloride (500 mg twice daily, one hour before meals) plus topical adapalene once a day in a thin film on the affected area, for 24 weeks Group 2 (oral isotretinoin) (n = 24): oral isotretinoin 1 mg/ kg/day, in two divided doses, for 24 weeks
Outcomes	Improvement in lesion‐counting and acne‐grading system described by Burke & Cunliffe (Burke 1984). At each visit (baseline, follow‐up visits at 2, 4, 6 months of treatment, and 2 months after cessation of treatment) lesions were counted on the face, back, and chest and categorised into non‐inflammatory (open and closed comedones), superficial inflammatory (papules, pustules), and deep inflammatory (nodules)* Participants’ perception and assessment regarding the two treatments, evaluated by the Dermatology Life Quality Index (DLQI) (Finlay 1994) completed by all participants before the treatment started and after the end of the therapy phase*. Microbiological assessments of the skin from five areas (forehead, right cheek, left cheek, back, and chest). Samples were taken at each visit Frequency of alterations in laboratory parameters of participants before the treatment started and after 2, 4, and 6 months of therapy*: Group 1: complete blood count, and a 12‐hour fasting blood chemistry panel; Group 2: blood counts, liver enzymes, triglycerides, fasting total cholesterol, low‐density lipoproteins, and high‐density lipoproteins. Frequency of possible side effects of the drugs detected by questioning participants at each visit* * Indicates outcomes which matched those prespecified for this review
Funding body	Edward Welander and Finsen Foundations; F. Hoffman‐La Roche Ltd Co
Notes	There was no report of demographic data for all initially randomised participants (52)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were assigned randomly to one of 2 treatment groups, using a computer‐generated randomisation code..." Comment: The trial described an adequate method for the random sequence generation
Allocation concealment (selection bias)	Low risk	Quote: "...randomisation code known only to a person not involved in the trial." Comment: There was an adequate concealment of the allocation sequence
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "In our open study, both treatments improved the clinical condition". Comment: Participants and personnel were not blinded; they were aware of the treatment arm to which participants were allocated
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "In our open study, both treatments improved the clinical condition". Comment: The study had an open design. However, there was no information regarding blinding of outcome assessors
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "A total of 52 patients were randomised; 26 to receive TET/ADA and 26 to receive ISO. Of these, 3 patients abandoned the study after randomisation and were not included in further analyses. Overall, 7 patients in the ISO group and 6 patients in the TET/ADA group abandoned the study at different times. The therapy was regarded as completed due to a very good clinical response before the end of 6 months in one patient from the ISO group." "Analysis of clinical efficacy parameters was performed on the intention‐to‐treat population, which included all patients who had at least one post‐baseline evaluation. For patients who prematurely discontinued the treatment, the last observations were carried forward." Comment: Despite having cited the term "intention‐to‐treat", actually authors performed a "per protocol" analysis, since analysis did not included data from all initially randomised participants
Selective reporting (reporting bias)	Low risk	Comment: No protocol available; however, there was an adequate report of outcomes listed in methods section
Other bias	Unclear risk	Comment: The study might be at risk of inappropriate influence of funders, as it was sponsored and promoted by a pharmaceutical company