Collins R, Fenwick E, Trowman R, Perard R, Norman G, Light K, Birtle A, Palmer S, Riemsma R
Centre for Reviews and Dissemination, University of York, UK.
Health Technol Assess. 2007 Jan;11(2):iii-iv, xv-xviii, 1-179. doi: 10.3310/hta11020.
A systematic review was undertaken and an economic model constructed to evaluate the clinical effectiveness and cost-effectiveness of docetaxel (Taxotere, Sanofi-Aventis) in combination with prednisone/prednisolone for the treatment of metastatic hormone-refractory prostate cancer (mHRPC). The main comparators considered were other established chemotherapy regimens and best supportive care.
Twenty-one resources (including MEDLINE, EMBASE and the Cochrane Library) were searched to April 2005.
Two reviewers independently assessed studies for inclusion. Data from included studies were extracted and quality assessed. Where appropriate, outcomes were synthesised using formal analytic approaches. A new economic model was developed in order to establish the cost-effectiveness of docetaxel compared with a range of potential comparators. A separate review was undertaken to identify sources of utility data required to estimate quality-adjusted life-years (QALYs). Sensitivity analyses were also undertaken to explore the robustness of the main analysis to alternative assumptions related to quality of life. Monte Carlo simulation was used to propagate uncertainty in input parameters through the model in such a way that the results of the analysis could be presented with their uncertainty. The impact of uncertainty surrounding the decision was established using value of information and implementation approaches.
Seven randomised controlled trials were identified that met the inclusion criteria. A direct comparison of docetaxel plus prednisone versus mitoxantrone plus prednisone in an open-label randomised trial showed improved outcomes for docetaxel plus prednisone in terms of overall survival, quality of life, pain and prostate-specific antigen decline. Two other chemotherapy regimens that included docetaxel: docetaxel plus estramustine and docetaxel plus prednisone plus estramustine, also showed improved outcomes in comparison with mitoxantrone plus prednisone. Indirect comparison suggested that docetaxel plus prednisone seems to be superior to corticosteroids alone in terms of overall survival. Conclusions on cost-effectiveness were primarily informed by the results of the in-house model. This indicated that mitoxantrone plus a corticosteroid is probably cheaper and more effective than corticosteroid alone. Compared with mitoxantrone plus prednisone/prednisolone, the use of docetaxel plus prednisone/prednisolone (3-weekly) appears cost-effective only if the NHS is prepared to pay 33,000 pounds per QALY. The incremental cost-effectiveness ratio associated with docetaxel plus prednisone (3-weekly) remained fairly robust to these variations with estimates ranging from 28,000 pounds to 33,000 pounds per QALY. Value of information analysis revealed that further research is potentially valuable. Given a maximum acceptable ratio of 30,000 pounds per QALY, the expected value of information was estimated to be approximately 13 million pounds.
This systematic review of the research suggests that docetaxel plus prednisone seems to be the most effective treatment for men with mHRPC. The economic model suggests that treatment with docetaxel plus prednisone/prednisolone is cost-effective in patients with mHRPC provided the NHS is prepared to pay 33,000 pounds per additional QALY. Future research should include the direct assessment of quality of life and utility gain associated with different treatments, including the effect of adverse events of treatment, using generic instruments, which are suitable for the purposes of cost-effectiveness analyses.
进行一项系统评价并构建一个经济模型，以评估多西他赛（泰索帝，赛诺菲 - 安万特公司）联合泼尼松/泼尼松龙治疗转移性激素难治性前列腺癌（mHRPC）的临床有效性和成本效益。主要的对照方案为其他已确立的化疗方案以及最佳支持治疗。
检索了截至2005年4月的21种资源（包括MEDLINE、EMBASE和Cochrane图书馆）。
两名评价者独立评估纳入研究。提取纳入研究的数据并进行质量评估。在适当情况下，采用正式分析方法综合结果。开发了一个新的经济模型，以确定多西他赛与一系列潜在对照方案相比的成本效益。进行了一项单独评价，以确定估计质量调整生命年（QALY）所需的效用数据来源。还进行了敏感性分析，以探讨主要分析对与生活质量相关的替代假设的稳健性。使用蒙特卡罗模拟在模型中传播输入参数的不确定性，以便能够呈现分析结果及其不确定性。利用信息价值和实施方法确定围绕决策的不确定性的影响。
确定了7项符合纳入标准的随机对照试验。在一项开放标签随机试验中，多西他赛加泼尼松与米托蒽醌加泼尼松的直接比较显示，多西他赛加泼尼松在总生存期、生活质量、疼痛和前列腺特异性抗原下降方面有更好的结果。另外两种包含多西他赛的化疗方案：多西他赛加雌莫司汀以及多西他赛加泼尼松加雌莫司汀，与米托蒽醌加泼尼松相比也显示出更好的结果。间接比较表明，多西他赛加泼尼松在总生存期方面似乎优于单独使用皮质类固醇。成本效益结论主要基于内部模型的结果。这表明米托蒽醌加一种皮质类固醇可能比单独使用皮质类固醇更便宜且更有效。与米托蒽醌加泼尼松/泼尼松龙相比，仅当英国国家医疗服务体系（NHS）准备为每个QALY支付33,000英镑时，使用多西他赛加泼尼松/泼尼松龙（每3周一次）似乎才具有成本效益。与多西他赛加泼尼松（每3周一次）相关的增量成本效益比对于这些变化仍然相当稳健，估计范围为每个QALY 28,000英镑至33,000英镑。信息价值分析表明进一步的研究可能具有价值。假设每个QALY的最大可接受比率为30,000英镑，信息的预期价值估计约为1300万英镑。
这项研究的系统评价表明，多西他赛加泼尼松似乎是治疗mHRPC男性患者最有效的治疗方法。经济模型表明，对于mHRPC患者来说，如果NHS准备为每个额外的QALY支付33,000英镑，那么使用多西他赛加泼尼松/泼尼松龙进行治疗具有成本效益。未来的研究应包括使用适用于成本效益分析目的的通用工具，直接评估与不同治疗相关的生活质量和效用增益，包括治疗不良事件的影响。
