■为了在不妨碍新型抗菌剂开发的情况下限制抗菌剂的使用,有兴趣建立创新模型,根据对抗菌药物价值的评估,而不是使用的数量,为抗菌药物提供资金。该项目的目的是评估英格兰NHS中头孢地洛的人口水平健康益处,在其许可适应症内使用时,用于治疗严重的需氧革兰氏阴性细菌感染。结果用于告知国家健康与护理卓越研究所指导,以支持有关制造商与NHS英格兰之间合同价值的商业讨论。
■头孢地洛的健康益处首先是针对一系列高价值临床方案得出的。这些代表的用途预计会对患者的死亡风险和健康相关的生活质量产生重大影响。头孢地洛相对于其比较物的临床有效性是通过在网络荟萃分析中合成有关目的病原体对抗菌药物的敏感性的证据来估计的。使用决策模型量化了各种使用情景下头孢地洛与替代管理策略相比的患者水平成本和健康结果。结果报告为以质量调整生命年表示的增量净健康影响,根据英国公共卫生部的数据,使用感染人数预测将其缩放为20年人口值。高价值临床方案的估计结果外推到头孢地洛的其他预期用途。
■在具有金属β-内酰胺酶耐药机制的肠杆菌分离株中,基本情况网络荟萃分析发现,头孢地洛与粘菌素相对较低的易感性相关(比值比0.32,95%可信区间0.04至2.47),但结果无统计学意义。其他治疗也与较低的敏感性比粘菌素,但结果无统计学意义。在金属β-内酰胺酶铜绿假单胞菌基础病例网络荟萃分析中,头孢地洛相对于粘菌素具有较低的敏感性(比值比0.44,95%可信区间0.03至3.94),但结果无统计学意义。其他治疗没有易感性。在基本情况下,头孢地洛的患者水平获益在0.02和0.15质量调整寿命年之间,根据感染部位的不同,病原体和使用场景。头孢地洛在所有亚组中的益处存在高度不确定性。适合头孢地洛治疗的感染数量存在很大的不确定性,因此,针对当前感染人数的一系列情况,提出了人口水平的结果,随着时间的推移,感染的预期增加和耐药的出现率。人口层面的福利在不同的基本情况下变化很大,从896到3559质量调整寿命年,超过20年。
■这项工作提供了对头孢地洛在NHS预期使用范围内的价值的定量估计。
■鉴于现有证据,头孢地洛的价值估计是高度不确定的。
■未来对抗菌药物的评估将受益于对NHS数据联系的改进;支持敏感性研究的适当综合的研究;以及常规数据和决策模型的应用,以评估启用价值。
■没有进行这项研究的注册。
■该奖项由美国国立卫生与护理研究所(NIHR)卫生技术评估政策研究计划(NIHR奖项编号:NIHR135591)资助,通过健康和社会护理干预的经济评估方法政策研究单位进行,PR-PRU-1217-20401,并在《卫生技术评估》中全文发表;第一卷。28号28.有关更多奖项信息,请参阅NIHR资助和奖励网站。
该项目测试了估算抗生素对NHS价值的新方法,cefiderocol,因此,即使使用很少的药物,其制造商也可以获得公平的报酬,以降低细菌对产品产生抗药性的风险。临床医生说,头孢地洛的最大好处是用于由两种细菌(称为肠杆菌和铜绿假单胞菌)引起的复杂尿路感染和医院内获得的肺炎,具有称为金属β-内酰胺酶的抗性机制。因为没有相关的临床试验数据,我们通过对实验室感染产生细菌的研究进行系统的文献综述,并对其药物进行测试,估计了头孢地洛和替代疗法的有效性。我们将此与估计患者长期健康和生存的数据联系起来。一些证据是通过向临床医生询问他们认为基于他们的经验和现有证据的效果的详细问题来获得的。我们包括了替代疗法的副作用,其中一些会导致肾脏损伤。我们估计英国会有多少感染,它们是否会随着时间的推移而增加,以及对治疗的抵抗力如何随着时间的推移而改变。临床医生告诉我们,他们还将使用头孢地洛治疗腹内和血流感染,还有一些由另一种叫做窄食单胞菌的细菌引起的感染。我们估计会有多少这样的感染,并承担了与其他类型感染相同的健康益处。使用这些估计值计算NHS的总价值。我们还考虑了我们是否错过了任何其他有价值的元素。我们估计,在20年内,NHS的价值为1800万至7100万英镑。这反映出,如果由于支付这些费用而不是为其他NHS服务提供资金而导致的健康损失不超过使用这种抗菌剂的健康益处,则NHS可以为使用头孢地洛支付的最高费用。然而,这些估计是不确定的,因为用于产生它们的证据和必须作出的假设的限制。
UNASSIGNED: To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of
cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.
UNASSIGNED: The health benefit of
cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients\' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol.
UNASSIGNED: Among Enterobacterales isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase Pseudomonas aeruginosa base-case network meta-analysis,
cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of
cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years.
UNASSIGNED: This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS.
UNASSIGNED: Given existing evidence, the estimates of the value of
cefiderocol are highly uncertain.
UNASSIGNED: Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value.
UNASSIGNED: No registration of this study was undertaken.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.
This project tested new methods for estimating the value to the NHS of an antimicrobial, cefiderocol, so its manufacturer could be paid fairly even if very little drug is used in order to reduce the risk of bacteria becoming resistant to the product. Clinicians said that the greatest benefit of cefiderocol is when used for complicated urinary tract infections and pneumonia acquired within hospitals caused by two types of bacteria (called Enterobacterales and Pseudomonas aeruginosa), with a resistance mechanism called metallo-beta-lactamase. Because there were no relevant clinical trial data, we estimated how effective cefiderocol and alternative treatments were by doing a systematic literature review of studies that grew bacteria from infections in the laboratory and tested the drugs on them. We linked this to data estimating the long-term health and survival of patients. Some evidence was obtained by asking clinicians detailed questions about what they thought the effects would be based on their experience and the available evidence. We included the side effects of the alternative treatments, some of which can cause kidney damage. We estimated how many infections there would be in the UK, whether they would increase over time and how resistance to treatments may change over time. Clinicians told us that they would also use cefiderocol to treat intra-abdominal and bloodstream infections, and some infections caused by another bacteria called Stenotrophomonas. We estimated how many of these infections there would be, and assumed the same health benefits as for other types of infections. The total value to the NHS was calculated using these estimates. We also considered whether we had missed any additional elements of value. We estimated that the value to the NHS was £18–71 million over 20 years. This reflects the maximum the NHS could pay for use of cefiderocol if the health lost as a result of making these payments rather than funding other NHS services is not to exceed the health benefits of using this antimicrobial. However, these estimates are uncertain due to limitations with the evidence used to produce them and assumptions that had to be made.