Amaryan 2003.

Study characteristics
Methods	Single‐centre, parallel RCT Location: Armenia Conducted from January 2001 to January 2002
Participants	24 people with FMF, diagnosed according to the Tel‐Hashomer criteria, without prior colchicine therapy 14 participants randomized to ImmunoGuard and 10 to placebo Age: 3–15 years Gender: 10 girls, 14 boys
Interventions	Intervention: ImmunoGuard (containing Andrographolide, Eleuteroside E, Schisandrins and Glycyrrhizin) 4 tablets orally, 3 times daily for 1 month Control: placebo (containing lactose 170 mg, calcium hydrophosphate, potato starch, microcrystalline cellulose, magnesium stearate, silicagel) 4 tablets orally, 3 times daily for 1 month
Outcomes	Acute‐phase response, including: ESR, WBC count, CRP Clinical assessment scores (combined score for duration, frequency and severity of attacks) Participants' self‐assessment scores (self‐evaluation with health diary – before and after treatment – of the severity of symptoms, mainly abdominal, chest pains, temperature, arthritis, myalgia, erysipelas‐like erythema) Adverse events All outcomes measured at 1 month
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Using simple randomization procedure. Quote: "Each jar of tablets was given a sequential number (1, 2, 3…) with the code concealed to the investigator. The sequential numbers were matched with the order of arrival of the participants."
Allocation concealment (selection bias)	Low risk	Quote: "Each jar was given a sequential number (1, 2, 3…) with the code concealed to the investigator. The sequential numbers were matched with the order of arrival of the participants."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "The current study is a double blind placebo‐controlled trial." "Placebo tablets were organoleptically and visually identical to the verum ImmunoGuard."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Stated as double‐blind, but we do not know whether outcome assessment was blinded. The review's secondary outcome of acute‐phase response was not influenced by lack of blinding.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Of the 24 patients who completed the clinical trial, 23 patients had complete laboratory results."  Comment: 1 (< 5%) participant in the control group lost to follow‐up.
Selective reporting (reporting bias)	Low risk	Protocol could not be reviewed; however, comparison of methods section and results section indicated all outcome measurements were reported.
Other bias	Low risk	No other source of bias identified.