Cost-effectiveness evaluation to inform clinical trial design.
Cost-effectiveness evaluation to inform clinical trial design.
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成本效益评估为临床试验设计提供信息。
DOI：
10.1086/521934
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Ribaudo,HeatherJ
中科院分区：
文献类型：
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作者：
Ribaudo,HeatherJ
在本期杂志中，Schackman et al. [1]描述了一种治疗简化策略的成本效益分析，该策略涉及在初始抗逆转录病毒治疗方案（包括2种核苷类逆转录酶抑制剂和1种非核苷类逆转录酶抑制剂）期间HIV RNA水平目前受到抑制的患者单独给予阿扎那韦-利托那韦。最近的注意力集中在使用单一利托那韦增强的蛋白酶抑制剂作为对初始抗逆转录病毒方案成功应答的患者的维持治疗[2-4]。这种治疗策略的基本原理是可能减少甚至逆转与使用核苷逆转录酶抑制剂相关的毒性，并可能节省成本[4，5]。由于利托那韦增强的阿扎那韦耐受性良好，与其他蛋白酶抑制剂相比，血脂水平升高的可能性较低，并且在病毒学失败的情况下具有独特的耐药性特征，因此该方案已被提议作为此类维持治疗的特别有希望的候选药物[4，6]。最近的试点数据已经产生了有希望的结果，并建议将这种方法与当前的护理标准进行比较的大型随机试验是必要的[4，5]。与此同时，还有其他数据表明，该策略的病毒学失败率很高，并对该策略如何有效抑制解剖储库内的病毒复制表示担忧[7，8]。这些问题，沿着越来越多地使用标准治疗、固定剂量、3种药物、每日一次方案，引发了关于在发达国家使用该策略的合理性的问题。Schackman等人提出的分析目标。[1]目的是评估该策略的长期结果，从而帮助提供有关大型长期随机临床试验的优点和设计的信息。这种临床研究方法具有优点，并且在药物开发方面已经考虑了一段时间[9]。试验是昂贵的，及时进行，他们可能是不道德的，如果在研究结束时干预的临床影响是不可能影响目前的护理标准。使用这种经济学观点可以在数百人暴露于干预措施之前更好地了解干预措施的潜在有效性，并且还可以建议收集关键数据，选择人群和比较方案[10]。例如，在进行临床试验之前，对幽门螺杆菌预防胃癌的筛选评估进行经济建模，有助于确定筛选干预最有益的目标人群[11]。在Schackman等人提出的分析中，[1]，病毒学失败和耐药性被强调为定义该策略相对益处的关键参数，并指导中期分析关键停止边界的选择。建模的另一个好处是，它还可以帮助研究人员提高他们对可能需要改变临床实践的临床获益水平的理解，并指出研究的可接受性参数[12，13]-也就是说，它可以帮助定义2种治疗之间的临床重要差异，研究应该有把握检测或定义可接受的非劣效性区域。在简化策略的背景下，预期方案效价会有一些损失，因此很难定义可接受的非劣效性区域，在该区域内，该策略产生的获益可能会抵消这种效价损失。那个...
In this issue of the journal, Schackman et al.[1] describe a cost-effectiveness analysis of a treatment simplification strategy that involves administration of atazanavir-ritonavir alone for patients whose HIV RNA levels are currently suppressed during an initial antiretroviral regimen, which would consist of 2 nucleoside reverse-transcriptase inhibitors and a nonnucleoside reverse-transcriptase inhibitor. Attention has recently focused on using a single ritonavir-boosted protease inhibitor as maintenance therapy for patients who have successfully responded to their initial antiretroviral regimen [2–4]. The rationale given for such treatment strategies is the potential for a decrease in—and even a reversal of—toxicities associated with use of nucleoside reverse transcriptase inhibitors and for possible cost savings [4, 5]. Because ritonavir-boosted atazanavir is well tolerated, has a lower likelihood of elevated plasma lipid levels than do other protease inhibitors, and has a distinct resistance profile in the event of virologic failure, this regimen has been proposed as a particularly promising candidate for such maintenance therapies [4, 6]. Recent pilot data have yielded promising results and have suggested that larger, randomized trials comparing this approach with the current standard of care are warranted [4, 5]. At the same time, there have been other data suggesting a high rate of virologic failure with this strategy and a concern regarding how effectively the strategy suppresses viral replication within anatomic reservoirs [7, 8]. These concerns, along with the increasing use of standardof-care, fixed-dose, 3-drug, once-daily regimens, have raised questions regarding the rationale of use of this strategy in developed countries. The goal of the analysis presented by the Schackman et al.[1] was to evaluate the long-term outcomes of the strategy and, thus, to help provide information on the merits and design of a large, long-term, randomized clinical trial. Such an approach to clinical research has merits and has been considered for some time with regard to pharmaceutical drug development [9]. Trials are expensive and timely to undertake, and they may be unethical if the clinical impact of the intervention at the end of the study is unlikely to impact current standards of care. The use of such an economic perspective provides a better understanding of the potential effectiveness of an intervention before hundreds of individuals are exposed to it, and it can also suggest critical data to collect, the choice of population, and the comparator regimen [10]. For example, economic modeling of a screening evaluation for Helicobacter pylori to prevent gastric cancer prior to undertaking a clinical trial helped define the target population for which the screening intervention would be most beneficial [11]. In the case of the analysis presented by Schackman et al.[1], virologic failure with resistance was highlighted as a key parameter in defining the relative benefit of the strategy and guided the choice of critical stopping boundaries for interim analysis. An additional benefit of modeling is that it may also help researchers improve their understanding of the level of clinical benefit that might warrant a change in clinical practice and indicate the parameters of acceptability for the study [12, 13]—that is, it may help define the clinically important difference between 2 treatments that a study should be powered to detect or define the acceptable region of noninferiority. In the context of a simplification strategy, for which some loss in regimen potency is expected, it is challenging to define the acceptable region of noninferiority for which the benefits accruing from the strategy might offset this potency loss. The …