阿尔茨海默病与住院费用和质量调整生命年的关系:英国生物库中传统分析和孟德尔随机分析的证据

Padraig Dixon, Emma Louise Anderson
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引用次数: 0

摘要

背景阿尔茨海默病和其他痴呆症是渐进性神经退行性疾病,对认知功能有深远影响。关于阿尔茨海默病对医疗成本和质量调整生命年(QALYs)的影响,缺乏经济学证据。我们采用了两种研究设计来模拟阿尔茨海默病与医疗成本和 QALYs 之间的关系。我们首先估算了阿尔茨海默病与这些核心经济结果之间关系的传统多变量模型。然而,这些类型的模型可能会受到疾病、过程或特征的干扰,而这些疾病、过程或特征会独立影响阿尔茨海默病以及医疗成本和 QALYs 中的一项或两项。因此,我们还探索了一种补充方法,即在孟德尔随机分析中使用种系遗传变异作为工具变量。我们将近期阿尔茨海默病全基因组关联研究中发现的单核苷酸多态性(SNPs)作为工具变量。我们研究了英国生物库队列中住院费用和 QALYs 的结果数据。结果 分析了多达 310,838 人的数据。在英国生物库招募时或招募前报告的阿尔茨海默病病例为 55 例。在随访过程中又发现了 284 例偶发病例。对发病病例的多变量观察分析表明,发病病例对成本有显著影响(病例成本为 1140 英镑,95% 置信区间 (CI):825 英镑至 1140 英镑):825英镑至1,456英镑)和QALY(-25%,95% CI:-28%至-21%)。孟德尔随机估计的成本(3,082 英镑,95% CI:-7,183 英镑至 13,348 英镑)和 QALYs(-32%,95% CI:-149% 至 85%)非常不精确,这可能是由于最具预测性的一组 SNPs 在阿尔茨海默病状态中解释的变异比例较小(0.9%)。意义 传统的多变量模型表明,阿尔茨海默病对住院费用和 QALYs 有重要影响,尽管这一发现是基于极少数病例得出的,其中可能包括早发性痴呆。孟德尔随机化非常不精确。对临床病例进行更大规模的全球基因组研究、提高对疾病结构的认识以及对直至老年和死亡的队列进行随访,将有助于克服这些挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Associations of Alzheimer's disease with inpatient hospital costs and with quality-adjusted life years: Evidence from conventional and Mendelian randomization analyses in the UK Biobank
BACKGROUND Alzheimer`s disease and other dementias are progressive neurodegenerative disorders with profound impacts on cognitive function. There is a shortage of economic evidence relating to the impact Alzheimer`s disease on healthcare costs and quality-adjusted life-years (QALYs). METHODS. We employed two study designs to model the association between Alzheimer`s disease and healthcare costs and QALYs. We first estimated conventional multivariable models of the association between Alzheimer`s disease and these core economic outcomes. However, these types of model may be confounded by diseases, processes, or traits that independently affect Alzheimer`s disease and either or both of healthcare costs and QALYs. We therefore also explored a complementary approach using germline genetic variation as instrumental variables in a Mendelian randomization analysis. We used single nucleotide polymorphisms (SNPs) identified in recent genome-wide association studies of Alzheimer`s disease as instruments. We studied outcome data on inpatient hospital costs and QALYs in the UK Biobank cohort. RESULTS Data from up to 310,838 individuals were analyzed. N=55 cases of Alzheimer`s disease were reported at or before recruitment into UK Biobank. A further N=284 incident cases were identified over follow-up. Multivariable observational analysis of the prevalent cases suggested significant impacts on costs (GBP1,140 in cases, 95% Confidence Interval (CI): GBP825 to GBP1,456) and QALYs (-25%, 95% CI: -28% to -21%). Mendelian randomization estimates were very imprecise for costs (GBP3,082, 95% CI: -GBP7,183 to GBP13,348) and QALYs (-32%, 95% CI: -149% to 85%), likely due to the small proportion of variance (0.9%) explained in Alzheimer`s disease status by the most predictive set of SNPs. IMPLICATIONS Conventional multivariable models suggested important impacts of Alzheimer`s disease on inpatient hospital costs and QALYs, although this finding was based on very few cases which may have included instances of early-onset dementia. Mendelian randomization was very imprecise. Larger GWAS of clinical cases, improved understanding of the architecture of the disease, and the follow-up of cohorts until old age and death will help overcome these challenges.
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