Cummings 2008.

Methods	Randomised placebo‐controlled trial
Participants	4538 women between 60 and 85 years of age (mean 68) who had bone mineral density T score ≤ −2.5 at the hip or lumbar spine or T score ≤ −2.0 with radiological evidence of vertebral fracture
Interventions	Tibolone 1.25 mg/d Placebo Administered for 34 months (median)
Outcomes	Vaginal bleeding, vaginal infection, endometrial cancer and endometrial hyperplasia, breast cancer, stroke, coronary heart disease, venous thromboembolism, mortality from any cause
Notes	Timing: July 2001 to Feb 2006, when trial was stopped because increased risk of stroke was identified Location: Europe, the Americas Multi‐centre: 80 sites in 22 countries All participants received 2 to 4 tablets of calcium + vit D daily
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	No details on random generation of the allocation sequence, but use of an interactive voice response system should keep risk of selection bias very low
Allocation concealment (selection bias)	Low risk	Centralised interactive voice response system
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo‐controlled and identical looking interventions
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	32 of 4538 participants not evaluated for not receiving any dose of the interventions under study
Selective reporting (reporting bias)	Low risk	Study reported data on outcomes as indicated in the protocol. Additional data on vaginal bleeding, vaginal infection, endometrial cancer and endometrial hyperplasia, breast cancer, stroke, coronary heart disease, venous thromboembolism and mortality from any cause were available in the study publication and were included in this review
Conflict of interest	High risk	Financed by the drug manufacturer. Study authors have conflicts of interest