Morrell Liz, Wordsworth Sarah, Schuh Anna, Middleton Mark R, Rees Sian, Barker Richard W
Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation, Radcliffe Department of Medicine, University of Oxford, Room 4403, Level 4, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.
Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Roosevelt Drive, Headington, Oxford, OX3 7LF, UK.
BMC Health Serv Res. 2018 May 31;18(1):393. doi: 10.1186/s12913-018-3162-2.
One of the functions of the reformed Cancer Drugs Fund in England is as a managed access fund, providing conditional funding for cancer drugs where there is uncertainty in the economic case, and where that uncertainty can be addressed by data collection during two years' use in the NHS. Our study characterises likely sources of such uncertainty, through a review of recent NICE Technology Appraisals.
Discussions of uncertainty in NICE Appraisal Committees were extracted from published Single Technology Appraisals of cancer drugs, 2014-2016, and categorised inductively. The location of the comments within the structured Appraisal document was used as a proxy for the degree of concern shown by the Committee.
Twenty-nine appraisals were analysed, of which 23 (79%) were recommended for funding. Six main sources of uncertainty were identified. Immaturity of survival data, and issues relating to comparators, were common sources of uncertainty regardless of degree of concern. Uncertainties relating to quality of life, and the patient population in the trial, were discussed frequently but rarely occurred in the more uncertain appraisals. Concerns with trial design, and cost uncertainty, were less common, but a high proportion contributed to the most uncertain appraisals. Funding decisions were not driven by uncertainty in the evidence base, but by the expected cost per QALY relative to acceptance thresholds, and the resultant level of uncertainty in the decision.
The reformed CDF is an improvement on its predecessor. However the main types of uncertainty seen in recent cancer appraisals will not readily be resolved solely by 2 years' RWD collection in the reformed CDF; where there are no ongoing trials to provide longer-term data, randomised trials rather than RWD may be needed to fully resolve questions of relative efficacy. Other types of uncertainty, and concerns with generalisability, may be more amenable to the RWD approach, and it is these that we expect to be the focus of data collection arrangements in the reformed CDF.
英国改革后的癌症药物基金的职能之一是作为一个管理式准入基金，在经济情况存在不确定性且这种不确定性可通过在国民医疗服务体系（NHS）中两年的使用期内收集数据来解决时，为癌症药物提供有条件的资金。我们的研究通过回顾近期的英国国家卫生与临床优化研究所（NICE）技术评估，对这种不确定性的可能来源进行了描述。
从2014 - 2016年已发表的癌症药物单一技术评估中提取NICE评估委员会关于不确定性的讨论内容，并进行归纳分类。将评论在结构化评估文件中的位置用作委员会所显示关注程度的代理指标。
分析了29项评估，其中23项（79%）被推荐给予资金。确定了六个主要的不确定性来源。生存数据的不成熟以及与对照相关的问题，无论关注程度如何，都是常见的不确定性来源。与生活质量以及试验中的患者群体相关的不确定性被频繁讨论，但在不确定性更高的评估中很少出现。对试验设计的担忧以及成本不确定性不太常见，但很大一部分导致了最具不确定性的评估。资金决策并非由证据基础中的不确定性驱动，而是由相对于接受阈值的每质量调整生命年（QALY）预期成本以及决策中由此产生的不确定性水平驱动。
改革后的癌症药物基金比其前身有所改进。然而，近期癌症评估中所见的主要不确定性类型不会仅通过改革后的癌症药物基金中两年的真实世界数据（RWD）收集就轻易得到解决；在没有正在进行的试验来提供长期数据的情况下，可能需要随机试验而非真实世界数据才能完全解决相对疗效问题。其他类型的不确定性以及对可推广性的担忧，可能更适合采用真实世界数据方法，而这些正是我们预计改革后的癌症药物基金数据收集安排的重点。
