Robinson M, Palmer S, Sculpher M, Philips Z, Ginnelly L, Bowens A, Golder S, Alfakih K, Bakhai A, Packham C, Cooper N, Abrams K, Eastwood A, Pearman A, Flather M, Gray D, Hall A
Nuffield Institute for Health, University of Leeds, UK.
Health Technol Assess. 2005 Jul;9(27):iii-iv, ix-xi, 1-158. doi: 10.3310/hta9270.
To identify and prioritise key areas of clinical uncertainty regarding the medical management of non-ST elevation acute coronary syndrome (ACS) in current UK practice.
Electronic databases. Consultations with clinical advisors. Postal survey of cardiologists.
Potential areas of important uncertainty were identified and 'decision problems' prioritised. A systematic literature review was carried out using standard methods. The constructed decision model consisted of a short-term phase that applied the results of the systematic review and a long-term phase that included relevant information from a UK observational study to extrapolate estimated costs and effects. Sensitivity analyses were undertaken to examine the dependence of the results on baseline parameters, using alternative data sources. Expected value of information analysis was undertaken to estimate the expected value of perfect information associated with the decision problem. This provided an upper bound on the monetary value associated with additional research in the area.
Seven current areas of clinical uncertainty (decision problems) in the drug treatment of unstable angina patients were identified. The agents concerned were clopidogrel, low molecular weight heparin, hirudin and intravenous glycoprotein antagonists (GPAs). Twelve published clinical guidelines for unstable angina or non-ST elevation ACS were identified, but few contained recommendations about the specified decision problems. The postal survey of clinicians showed that the greatest disagreement existed for the use of small molecule GPAs, and the greatest uncertainty existed for decisions relating to the use of abciximab (a large molecule GPA). Overall, decision problems concerning the GPA class of drugs were considered to be the highest priority for further study. Selected papers describing the clinical efficacy of treatment were divided into three groups, each representing an alternative strategy. The strategy involving the use of GPAs as part of the initial medical management of all non-ST elevation ACS was the optimal choice, with an incremental cost-effectiveness ratio (ICER) of 5738 pounds per quality-adjusted life-year (QALY) compared with no use of GPAs. Stochastic analysis showed that if the health service is willing to pay 10,000 pounds per additional QALY, the probability of this strategy being cost-effective was around 82%, increasing to 95% at a threshold of 50,000 pounds per QALY. A sensitivity analysis including an additional strategy of using GPAs as part of initial medical management only in patients at particular high risk (as defined by age, ST depression or diabetes) showed that this additional strategy was yet more cost-effective, with an ICER of 3996 pounds per QALY compared with no treatment with GPA. Value of information analysis suggested that there was considerable merit in additional research to reduce the level of uncertainty in the optimal decision. At a threshold of 10,000 pounds per QALY, the maximum potential value of such research in the base case was calculated as 12.7 million pounds per annum for the UK as a whole. Taking account of the greater uncertainty in the sensitivity analyses including clopidogrel, this figure was increased to approximately 50 million pounds.
This study suggests the use of GPAs in all non-ST elevation ACS patients as part of their initial medical management. Sensitivity analysis showed that virtually all of the benefit could be realised by treating only high-risk patients. Further clarification of the optimum role of GPAs in the UK NHS depends on the availability of further high-quality observational and trial data. Value of information analysis derived from the model suggests that a relatively large investment in such research may be worthwhile. Further research should focus on the identification of the characteristics of patients who benefit most from GPAs as part of medical management, the comparison of GPAs with clopidogrel as an adjunct to standard care, follow-up cohort studies of the costs and outcomes of high-risk non-ST elevation ACS over several years, and exploring how clinicians' decisions combine a normative evidence-based decision model with their own personal behavioural perspective.
识别并确定当前英国实践中关于非ST段抬高型急性冠状动脉综合征（ACS）药物治疗的关键临床不确定性领域，并按优先顺序排列。
电子数据库。与临床顾问的磋商。对心脏病专家的邮政调查。
识别潜在的重要不确定性领域，并对“决策问题”进行优先排序。采用标准方法进行系统的文献综述。构建的决策模型包括一个应用系统综述结果的短期阶段和一个纳入英国观察性研究相关信息以推断估计成本和效果的长期阶段。进行敏感性分析以检验结果对基线参数的依赖性，使用替代数据源。进行信息期望值分析以估计与决策问题相关的完美信息的期望值。这为该领域额外研究的货币价值提供了一个上限。
确定了不稳定型心绞痛患者药物治疗中当前的七个临床不确定性领域（决策问题）。涉及的药物有氯吡格雷、低分子量肝素、水蛭素和静脉注射糖蛋白拮抗剂（GPA）。识别出12份已发表的关于不稳定型心绞痛或非ST段抬高型ACS的临床指南，但很少有包含关于特定决策问题的建议。对临床医生的邮政调查显示，对于小分子GPA的使用存在最大分歧，对于阿昔单抗（一种大分子GPA）使用决策存在最大不确定性。总体而言，关于GPA类药物的决策问题被认为是进一步研究的最高优先事项。描述治疗临床疗效的选定论文分为三组，每组代表一种替代策略。将GPA作为所有非ST段抬高型ACS初始药物治疗一部分的策略是最佳选择，与不使用GPA相比，增量成本效益比（ICER）为每质量调整生命年（QALY）5738英镑。随机分析表明，如果医疗服务机构愿意为每个额外的QALY支付10000英镑，该策略具有成本效益的概率约为82%，在每个QALY阈值为50000英镑时增加到95%。一项敏感性分析包括一种仅在特定高危患者（根据年龄、ST段压低或糖尿病定义）中将GPA作为初始药物治疗一部分的额外策略，结果表明该额外策略更具成本效益，与不使用GPA治疗相比，ICER为每QALY 3996英镑。信息价值分析表明，进行额外研究以降低最佳决策中的不确定性水平有很大价值。在每个QALY阈值为10000英镑时，在基础案例中此类研究对整个英国的最大潜在价值计算为每年1270万英镑。考虑到包括氯吡格雷在内的敏感性分析中更大的不确定性，这一数字增加到约5000万英镑。
本研究建议将GPA用于所有非ST段抬高型ACS患者作为其初始药物治疗的一部分。敏感性分析表明，仅治疗高危患者几乎可以实现所有益处。GPA在英国国民医疗服务体系（NHS）中的最佳作用的进一步明确取决于是否有更多高质量的观察性和试验数据。从模型得出的信息价值分析表明，对这类研究进行相对大量的投资可能是值得的。进一步的研究应侧重于识别作为药物治疗一部分最能从GPA中获益的患者特征，将GPA与氯吡格雷作为标准治疗辅助手段进行比较，对高危非ST段抬高型ACS患者的成本和结局进行数年的随访队列研究，以及探索临床医生的决策如何将基于规范证据的决策模型与他们自己的个人行为观点相结合。
