Tice 2003.

Methods	Design: parallel‐group, active arms versus placebo Number screened: 1,191 (principal reasons for ineligibility: too few hot flushes (251), not interested (216) and medical conditions/medications (192)) Number randomly assigned: 252 Number dropped out: six (two taking Promensil (one too busy, one no improvement), two taking Rimostil (one nauseated, one on physician's advice), two taking placebo (one feared possible placebo, one too busy)) Number lost to follow‐up: Number analysed: 252 Intention‐to‐treat analysis: yes (also per‐protocol analysis) Power calculation: 90% power to detect at least a 15% greater reduction in hot flush frequency in the active arm compared with placebo; 25% placebo effect anticipated Duration: 12 weeks Timing: November 1999 to March 2001 Location: three US academic clinical research sites Funding: industry (Novogen Inc)
Participants	Inclusion criteria: women 45 to 60 years of age, experiencing at least 35 hot flushes/wk, FSH level 30 mIU/mL, documented bilateral oophorectomy or at least two consecutive months of amenorrhoea before enrolment, with at least six months of amenorrhoea during the year before entry Exclusion criteria: vegetarian, ate soy products > once a week, taking medications affecting isoflavone absorption or hormonal preparations during previous three months, significant gastrointestinal disease, > two alcoholic beverages per day, allergic to red clover, consumed < 80% of expected study tablets during the two‐week placebo run‐in Age, years: 52.3 (SD 2.8 to 3.4 in different arms) Recruitment method: newspaper and radio advertising, flyers, directed mailings
Interventions	Phytoestrogen: isoflavones Formulation: Promensil tablets, containing average of 41 mg total isoflavones per tablet (range 37 to 43 mg), with higher proportion of biochanin A and genistein than Rimostil Phytoestrogen: isoflavones Formulation: Rimostil tablets, containing average of 28.6 mg of total isoflavones per tablet (range 25.6 to 31.4 mg) with higher proportions of formononetin and daidzein than Promensil Placebo: contained < 0.04 mg total isoflavones per tablet Dose, duration and timing of administration: two tablets once daily for 12 weeks
Outcomes	Menopausal symptoms: daily diary cards for recording hot flushes and night sweats Quality of life: Greene Climacteric Scale Compliance: pill count Adverse effects: assessed at follow‐up, specific method unclear
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generated in random blocks of six, stratified by centre
Allocation concealment (selection bias)	Low risk	Allocation schedule maintained remotely, at pharmacy
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Stated as double‐blind: participants and researchers
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Stated as double‐blind: participants and researchers
Incomplete outcome data (attrition bias) All outcomes	Low risk	All randomly assigned participants analysed
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported