Health Technol Assess. 2021 Mar;25(23):1-138. doi: 10.3310/hta25230.
Crohn's disease is a lifelong condition that can affect any segment of the gastrointestinal tract. Some people with Crohn's disease may be at higher risk of following a severe course of disease than others and being able to identify the level of risk a patient has could lead to personalised management.
To assess the prognostic test accuracy, clinical impact and cost-effectiveness of two tools for the stratification of people with a diagnosis of Crohn's disease by risk of following a severe course of disease.
The data sources MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were searched to inform the systematic reviews on prognostic accuracy, clinical impact of the prognostic tools, and economic evaluations. Additional data sources to inform the review of economic evaluations were NHS Economic Evaluation Database, Database of Abstracts of Reviews of Effects and the Health Technology Assessment Database.
Systematic reviews of electronic databases were carried out from inception to June 2019 for studies assessing the prognostic accuracy and clinical impact of the IBDX (Crohn's disease Prognosis Test; Glycominds Ltd, Lod, Israel) biomarker stratification tool and the PredictSURE-IBD™ (PredictImmune Ltd, Cambridge, UK) tool. Systematic reviews of studies reporting on the cost-effectiveness of treatments for Crohn's disease were run from inception to July 2019. Two reviewers independently agreed on studies for inclusion, assessed the quality of included studies and validated the data extracted from studies. Clinical and methodological heterogeneity across studies precluded the synthesis of data for prognostic accuracy. A de novo economic model was developed to compare the costs and consequences of two treatment approaches - the 'top-down' and 'step-up' strategies, with step-up considered standard care - in people at high risk of following a severe course of Crohn's disease. The model comprised a decision tree and a Markov cohort model.
Sixteen publications, including eight original studies ( = 1478), were deemed relevant to the review of prognostic accuracy. Documents supplied by the companies marketing the prognostic tools were also reviewed. No study meeting the eligibility criteria reported on the sensitivity or specificity of the IBDX biomarker stratification tool, whereas one study provided estimates of sensitivity, specificity and negative predictive value for the PredictSURE-IBD tool. All identified studies were observational and were considered to provide weak evidence on the effectiveness of the tools. Owing to the paucity of data on the two tools, in the base-case analysis the accuracy of PredictSURE-IBD was assumed to be 100%. Accuracy of IBDX was assumed to be 100% in a scenario analysis, with the cost of the tests being the only difference between the analyses. The incremental analysis of cost-effectiveness demonstrated that top-down (via the use of PredictSURE-IBD in the model) is more expensive and generates fewer quality-adjusted life-years than step-up (via the standard care arm of the model).
Despite extensive systematic searches of the literature, no robust evidence was identified of the prognostic accuracy of the biomarker stratification tools IBDX and PredictSURE-IBD.
Although the model indicates that standard care dominates the tests, the lack of evidence of prognostic accuracy of the two tests and the uncertainty around the benefits of the top-down and step-up treatment approaches mean that the results should be interpreted as indicative rather than definitive.
This study is registered as PROSPERO CRD42019138737.
This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in ; Vol. 25, No. 23. See the NIHR Journals Library website for further project information.
克罗恩病是一种终身疾病，可影响胃肠道的任何部位。一些患有克罗恩病的人可能比其他人更容易出现严重的疾病过程，能够识别患者的风险水平可能会导致个性化的管理。
评估两种工具对克罗恩病诊断患者严重疾病风险分层的预后准确性、临床影响和成本效益。
MEDLINE、EMBASE、Cochrane 系统评价数据库和 Cochrane 对照试验中心注册库等数据来源用于为预后准确性的系统评价提供信息，临床影响的预后工具，以及经济评估。告知经济评估综述的其他数据源包括 NHS 经济评估数据库、疗效评价摘要数据库和卫生技术评估数据库。
从开始到 2019 年 6 月，对评估 IBDX（克罗恩病预后测试；Glycominds Ltd，Lod，以色列）生物标志物分层工具和 PredictSURE-IBD™（PredictImmune Ltd，剑桥，英国）工具的预后准确性和临床影响的电子数据库进行系统评价。从开始到 2019 年 7 月对报告克罗恩病治疗成本效益的研究进行系统评价。两名审查员独立同意纳入研究，评估纳入研究的质量，并验证从研究中提取的数据。研究之间的临床和方法学异质性排除了对预后准确性进行数据综合的可能性。开发了一个新的经济模型，以比较两种治疗方法 - “自上而下”和“逐步上升”策略的成本和后果，逐步上升被认为是标准护理 - 在患有严重克罗恩病风险的人群中。该模型包括决策树和马尔可夫队列模型。
纳入了 16 篇出版物，包括 8 篇原始研究（=1478 人），认为与预后准确性综述相关。还审查了营销预后工具的公司提供的文件。没有符合资格标准的研究报告 IBDX 生物标志物分层工具的敏感性或特异性，而一项研究提供了 PredictSURE-IBD 工具的敏感性、特异性和阴性预测值的估计。所有确定的研究都是观察性的，被认为对工具的有效性提供了薄弱的证据。由于缺乏关于两种工具的数据，在基线分析中，PredictSURE-IBD 的准确性假设为 100%。在情景分析中，IBDX 的准确性假设为 100%，成本分析是两种分析的唯一区别。增量成本效益分析表明，自上而下（通过在模型中使用 PredictSURE-IBD）比逐步上升（通过模型中的标准护理臂）更昂贵，并且产生更少的质量调整生命年。
尽管对文献进行了广泛的系统搜索，但没有发现生物标志物分层工具 IBDX 和 PredictSURE-IBD 的预后准确性的可靠证据。
尽管该模型表明标准护理优于测试，但缺乏对两种测试的预后准确性的证据，以及自上而下和逐步上升治疗方法的益处存在不确定性，这意味着结果应被解释为指示性而非决定性的。
本研究由英国国家卫生研究院（NIHR）证据综合计划资助，并将在；第 25 卷，第 23 期。有关该项目的更多信息，请访问 NIHR 期刊库网站。
