Ward 1976.

Methods	Cross‐over trial Three centres in London Period of inclusion: February 1973 to May 1974
Participants	Inclusion criteria Chronic, recurring, sterile pustulation with characteristic cyclical changes in the pustules (> 2 mm in diameter) from yellow to brown, followed by shedding of the dry scale Has not taken tetracycline within the previous 3 months Exclusion criteria During the preceding 2 months, disease consisted only of scaling, erythema, and/or tiny vesicles or brown macules < 2 mm in diameter Pregnancy Contraindication to tetracycline Participants were seen by an observer at intervals of 6 weeks Baseline data: clomocycline 170 mg thrice daily vs placebo (n = 60) Mean age, years: 52.4 ± 12.3 for women; 45.6 ± 13.8 for men Male/female: 12/48 Proportion of participants with psoriatic lesions elsewhere: not specified Withdrawal: 6 participants did not attend (4 after the first visit), 14 discontinued because of side effects (1 was on placebo and complained of heartburn and 13 were on clomocycline and complained of nausea and vomiting (6), vaginal thrush (1), constipation (1), heartburn (1), and miscellaneous symptoms (4))
Interventions	Intervention 1 A: clomocycline 170 mg thrice daily for 2 weeks, then twice a day for 10 weeks (60 participants; cross‐over design) Intervention 2 B: placebo (60 participants, cross‐over design) Co‐interventions: ointment or dilute Betnovate in petrolatum Duration of treatment: 3 months
Outcomes	No primary or secondary outcome pre‐specified Response (according to a diagram based on numbers of pustules and brown macules and extent of disease)
Notes	Funding: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Each patient received 3 months each of clomocycline and placebo in random order" Comment: insufficient information about the sequence generation process to permit judgement
Allocation concealment (selection bias)	Unclear risk	Comment: no information on method to guarantee allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "The paired packs were randomly labelled A and B using a restricted randomisation in tens, so that when treatment was started with pack A neither investigator nor patient knew whether it contained clomocycline or placebo" Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The paired packs were randomly labelled A and B using a restricted randomisation in tens, so that when treatment was started with pack A neither investigator nor patient knew whether it contained clomocycline or placebo" Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "Of sixty patients entering the trial twenty failed to complete the treatment. Six patients did not attend, four after the first visit. The remaining fourteen discontinued with side effects: one of these was on placebo and complained of heartburn; while the thirteen on clomocycline complained of nausea and vomiting (6), vaginal thrush (1), constipation (1), heartburn (1), miscellaneous symptoms (4)" Comment: 20 dropouts and no ITT analysis
Selective reporting (reporting bias)	Unclear risk	Comment: no protocol found to guarantee that all planned outcomes are presented in the results