Eckermann Simon D, Martin Andrew J, Stockler Martin R, Simes R John
National Health and Medical Research Council, Clinical Trials Centre, University of Sydney, Locked Bag 77, Camperdown NSW, 1450.
Aust N Z J Public Health. 2003;27(1):34-40. doi: 10.1111/j.1467-842x.2003.tb00377.x.
To estimate the effects of key uncertainties on the effectiveness and cost-effectiveness of breast cancer prevention with tamoxifen.
The incremental cost-effectiveness ratio of tamoxifen therapy relative to placebo was estimated using decision analysis with Markov modelling of health states, outcomes and costs for a simulated cohort of women at high risk for breast cancer. Relative effects of tamoxifen's benefits and harms were estimated from meta-analyses of randomised controlled trials. Cost estimates were based on Australian treatment patterns and costs. The main outcome measure was cost per quality-adjusted life year (QALY) gained with costs and effects discounted at a 5% annual rate.
Tamoxifen therapy over five years reduces the incidence of breast cancer by approximately 1.4%, which is offset by an increase in endometrial cancer of 0.7% and pulmonary embolism of 0.2%. If the reduction is permanent (preventing new breast cancers emerging over five years and no further treatment effect thereafter), the model estimates an increase in life expectancy of 0.057 QALYs and an extra cost of $2,193; or $38,271/QALY gained. A model assuming further treatment effects of tamoxifen preventing new breast cancers emerging for up to 10 years results in an incremental cost of $19,354/QALY. However, if five years of tamoxifen therapy merely delays when these breast cancers appear (such that by 10 years there is no longer a reduced incidence), the incremental cost per QALY saved is estimated to be $199,149.
Tamoxifen is potentially cost-effective in preventing breast cancer in women at high risk. However, its cost-effectiveness as a preventive therapy is highly sensitive to whether these cancers are permanently prevented or their clinical presentation is only delayed. Long-term follow-up in randomised controlled trials is therefore crucial in forming health policy.
评估关键不确定性因素对他莫昔芬预防乳腺癌的有效性和成本效益的影响。
采用决策分析和马尔可夫健康状态模型，对模拟的乳腺癌高危女性队列的健康状况、结局和成本进行建模，估计他莫昔芬治疗相对于安慰剂的增量成本效益比。他莫昔芬利弊的相对影响通过随机对照试验的荟萃分析进行估计。成本估计基于澳大利亚的治疗模式和成本。主要结局指标是每获得一个质量调整生命年（QALY）的成本，成本和效果按每年5%的贴现率进行贴现。
他莫昔芬治疗五年可使乳腺癌发病率降低约1.4%，但子宫内膜癌发病率增加0.7%，肺栓塞发病率增加0.2%，抵消了部分益处。如果这种降低是永久性的（在五年内预防新的乳腺癌发生，此后不再有进一步的治疗效果），模型估计预期寿命增加0.057个QALY，额外成本为2193美元；即每获得一个QALY的成本为38271美元。一个假设他莫昔芬具有进一步治疗效果，可预防新的乳腺癌发生长达10年的模型得出，每QALY的增量成本为19354美元。然而，如果五年的他莫昔芬治疗仅仅是延迟了这些乳腺癌的出现时间（以至于到10年时发病率不再降低），则估计每挽救一个QALY的增量成本为199149美元。
他莫昔芬在预防高危女性乳腺癌方面可能具有成本效益。然而，其作为预防疗法的成本效益对这些癌症是被永久性预防还是仅被延迟临床表现高度敏感。因此，随机对照试验中的长期随访对于制定卫生政策至关重要。
