Zemer 1974.

Study characteristics
Methods	Single‐center, cross‐over RCT 2 months of first treatment and then crossed over to second arm with no washout period Location: Israel
Participants	22 participants with FMF Gender: 4 females, 18 males
Interventions	Intervention: oral colchicine 0.5 mg 2 times daily for 2 months Control: placebo 2 times daily for 2 months Treatment 1 for 2 months, then cross‐over to alternate treatment for a further 2 months No washout period, but used paired t‐test to account for cross‐over design for the outcome 'number of attacks'
Outcomes	Number of participants experiencing an attack Frequency of attacks Outcomes measured at 1, 2, 3 and 4 months
Notes	The outcome data, except "number of patients experiencing an attack", could not be distinguished between phase I and II of the cross‐over study.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described.
Allocation concealment (selection bias)	Unclear risk	Not described.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "double‐blind". "They (participants) were not informed what drug was being tried or that administration of placebo was part of the program. None of them were known to be on any maintenance therapy or had taken part in a previous drug study."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The physicians of the follow‐up clinic were responsible for the referral of patients for the study and tabulating their attacks. They had no knowledge of whether the patient was receiving drug or placebo, or of the randomization schedule."
Incomplete outcome data (attrition bias) All outcomes	High risk	In the first treatment phase: 3 participants lost to follow‐up, 1 in the colchicine group and 2 in the control group, and no ITT analysis was performed. In the whole treatment process (quote): "Of the 22 patients who entered the study, nine failed to complete it."
Selective reporting (reporting bias)	Unclear risk	Protocol could not be reviewed; moreover, the methods section did not predefine outcome measurements.
Other bias	High risk	Difference in severity of FMF between groups were not described.

crFMF: colchicine‐resistant familial Mediterranean fever; CRP: C‐reactive protein; ESR: erythrocyte sedimentation rate; FMF: familial Mediterranean fever; HIDS: hyper‐immunoglobulin D syndrome; ITT: intention‐to‐treat; MEFV: Mediterranean fever; MKD: mevalonate kinase deficiency; PGA: Physician's Global Assessment; RCT: randomized controlled trial; SAA: serum amyloid A protein; SD: standard deviation; SE: standard error; TRAPS: tumor necrosis factor receptor‐associated periodic syndrome; WBC: white blood cell.