London School of Hygiene and Tropical Medicine, London, UK; Department of Primary Care and Public Health, Imperial College London, London, UK.
Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK.
Atherosclerosis. 2018 Aug;275:434-443. doi: 10.1016/j.atherosclerosis.2018.05.047. Epub 2018 Jun 4.
Familial hypercholesterolaemia (FH) is widely underdiagnosed. Cascade testing (CT) of relatives has been shown to be feasible, acceptable and cost-effective in the UK, but requires a supply of index cases. Feasibility of universal screening (US) at age 1-2 years was recently demonstrated. We examined whether this would be a cost-effective adjunct to CT in the UK, given the current and plausible future undiagnosed FH prevalence.
Seven cholesterol and/or mutation-based US ± reverse cascade testing (RCT) alternatives were compared with no US in an incremental analysis with a healthcare perspective. A decision model was used to estimate costs and outcomes for cohorts exposed to the US component of each strategy. RCT case ascertainment was modelled using recent UK CT data, and probabilistic Markov models estimated lifetime costs and health outcomes for the cohorts screened under each alternative. 1000 Monte Carlo simulations were run for each model, and average outcomes reported. Further uncertainty was explored deterministically. Threshold analysis investigated the association between undiagnosed FH prevalence and cost-effectiveness.
A strategy involving cholesterol screening followed by diagnostic genetic testing and RCT was the most cost-effective modelled (incremental cost-effectiveness ratio (ICER) versus no US £12,480/quality adjusted life year (QALY); probability of cost-effectiveness 96·8% at £20,000/QALY threshold). Cost-effectiveness was robust to both deterministic sensitivity analyses and threshold analyses that modelled ongoing case ascertainment at theoretical maximum levels.
These findings support implementation of universal cholesterol screening followed by diagnostic genetic testing and RCT for FH, under a UK conventional willingness-to-pay threshold.
家族性高胆固醇血症（FH）广泛漏诊。在英国，对亲属进行级联检测（CT）已被证明是可行、可接受且具有成本效益的，但需要有索引病例的供应。最近已经证明，1-2 岁的普遍筛查（US）是可行的。我们研究了在目前和合理的未来 FH 未确诊患病率的情况下，这种方法是否会成为 CT 的一种具有成本效益的辅助手段。
在具有医疗保健视角的增量分析中，将七种基于胆固醇和/或突变的 US±反向级联检测（RCT）替代方案与无 US 进行比较。使用决策模型来估计每个策略中暴露于 US 成分的队列的成本和结果。RCT 病例确定使用最近的英国 CT 数据进行建模，概率马尔可夫模型估计每个替代方案下筛查队列的终生成本和健康结果。为每个模型运行了 1000 次蒙特卡罗模拟，并报告了平均结果。确定性地进一步探索了不确定性。阈值分析调查了未确诊 FH 患病率与成本效益之间的关联。
涉及胆固醇筛查，然后是诊断性基因检测和 RCT 的策略是最具成本效益的（与无 US 相比，增量成本效益比（ICER）为 12480 英镑/QALY；在 20000 英镑/QALY 阈值下，成本效益的概率为 96.8%）。成本效益对确定性敏感性分析和阈值分析均具有稳健性，这些分析模拟了理论上最大级别的持续病例确定。
这些发现支持在英国常规支付意愿阈值下，实施针对 FH 的普遍胆固醇筛查，然后是诊断性基因检测和 RCT。
