Kenemans 2009.

Methods	Randomised placebo‐controlled non‐inferiority trial
Participants	3148 postmenopausal women with vasomotor symptoms, in menopause for ≥ 12 months, who were surgically treated for breast cancer (T1‐3, N0‐2, M0) within the previous 5 years; excluded women with endometrial abnormalities at transvaginal ultrasonography. Mean time since menopause 6.2 years. Mean age 52.7 years. At study entry, 67% of participants were using tamoxifen
Interventions	Tibolone 2.5 mg/d Placebo Administered for 2.75 years
Outcomes	Unscheduled bleeding, vulvovaginal dryness, vaginal infection, urinary tract infection, insomnia, recurrence of breast cancer, endometrial cancer, venous thromboembolic events, cardiovascular and cerebrovascular events, mortality
Notes	Women who did not have adequate relief of their vasomotor symptoms were allowed to use concomitant non‐hormonal medication, such as soy products, clonidine and antidepressants Timing: from June 2002 to July 2007 (study prematurely interrupted for safety reasons) Location: USA, Europe, Asia, Australia Multi‐centre: 245 centres
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was done by use of a centralised interactive voice response system, stratified by centre, with a block size of 4
Allocation concealment (selection bias)	Low risk	Centralised interactive voice response system
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind fashion
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Not specified, but given the nature of outcomes assessed, their evaluation is likely to be "objective"
Incomplete outcome data (attrition bias) All outcomes	Low risk	98% of randomised participants were analysed; reasons given for withdrawals/dropouts
Selective reporting (reporting bias)	Low risk	Data on all outcomes indicated in the protocol were eventually available in the study publication
Conflict of interest	High risk	Financed by the drug producer. Some study authors with conflicts of interest