EVTET 2000.

Methods	Stated purpose: to determine if HT alters risk of venous thromboembolism in high‐risk women Randomisation method: computer‐generated 1:1 block randomisation with fixed block sizes of 10 Allocation method: not described Stratification: by age < 60 years or ≥ 60 years; 37 (23 HT and 14 placebo) women did not attend all visits owing to premature termination of the study Blinding: double‐blind No. of women screened for eligibility: 328 No. randomised: 140 (71 HT, 69 placebo) No. analysed: 140 Losses to follow‐up: nil, although 37 (23 HT and 14 placebo) women did not attend all visits owing to premature termination of the study Adherence to treatment: 33 dropouts: 10 in HT group (2 wanted to be sure of being treated with oestrogen for postmenopausal symptoms, 8 had adverse effects), 23 in the placebo group (11 wanted to be sure of being treated with oestrogen for postmenopausal symptoms, 10 had adverse effects, 2 no reason stated) Analysis by intention to treat: Main findings were not reported by intention to treat because dropouts from the placebo group were not included in the denominator for the rate of recurrent thromboembolism. We included all randomised participants in analysis for this review. No. of centres: not stated Years of recruitment: February 1996‐March 1999 Design: stratified double triangular sequential design Funding: Novo‐Nordisk Pharmaceutical and research forum Ulleval University Hospital
Participants	Included Postmenopausal women with history of VTE, aged < 70 years, previous VTE verified by objective means (i.e. venography or ultrasonography in cases of DVT; lung scan, helical computed tomography or angiography in cases of PE) Excluded Current use or use of anticoagulants within past 3 months, familial antithrombin deficiency, any type of malignant disease including known, suspected or past history of carcinoma of the breast; acute or chronic liver disease or history of liver disease in which liver function tests had failed to return to normal; porphyria; known drug abuse or alcoholism; life expectancy less than 2 years; women who had taken part in other clinical trials within 12 weeks before study entry Mean age: 55.8 years Age range: 42‐69 years Means of recruitment: letters to family doctors, gynaecologists and hospitals, health bulletins and media Baseline equality of treatment groups: Baseline characteristics were similar for HT group and placebo group with regard to previous disease (coronary heart disease, hypertension, stroke, diabetes), smoking habits and serum lipids. All women had previously suffered at least 1 VTE, and the total number of previous VTEs was 75 in the placebo group and 77 in the HT group. Country: Norway
Interventions	HT arm: 2 mg oestradiol plus 1 mg norethisterone acetate 1 mg Control arm: placebo Duration: planned 2 years, stopped prematurely at median 1.3 years' follow‐up
Outcomes	Venous thrombosis Myocardial infarction Transient ischaemic attacks Stroke
Notes	Study was terminated early; only 140 women enrolled of 240 planned Power calculation: At a significance level of 5% and a power of 90%, sample size was estimated to a maximum of 240 women . After publication of results of the HERS study, which showed as a secondary endpoint increased risk of VTE, recruitment of women was discontinued in September 1998, until reviewed by the safety monitoring committee. The committee was also concerned about a non‐significant clustering of endpoints in 1 study group, without knowing treatment allocation. The committee advised on premature termination of the study, even though formal boundaries showing excess risk of VTE were not reached. The final decision on termination of the study was made in February 1999, and by the end of March 1999, all participants had completed a final follow‐up visit.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated 1:1 block randomisation with fixed block sizes of 10
Allocation concealment (selection bias)	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	Main findings were not reported by intention to treat because drop‐outs from the placebo group were not included in the denominator for the rate of recurrent thromboembolism.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinded participants and personnel ‐ "equal‐looking" placebo
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinded outcome assessment
Selective reporting (reporting bias)	Low risk	Retrospectively registered protocol on trials register. Reports all expected outcomes
Other bias	Low risk	No apparent source of other bias