Centre for Health Services Research, University of Queensland, Brisbane, QLD, Australia.
Department of Internal Medicine and Clinical Epidemiology, Princess Alexandra Hospital, Brisbane, QLD, Australia.
Age Ageing. 2024 Feb 1;53(2). doi: 10.1093/ageing/afae023.
Recent phase 3 randomised controlled trials of amyloid-targeting monoclonal antibodies in people with pre-clinical or early Alzheimer disease have reported positive results, raising hope of finally having disease-modifying drugs. Given their far-reaching implications for clinical practice, the methods and findings of these trials, and the disease causation theory underpinning the mechanism of drug action, need to be critically appraised. Key considerations are the representativeness of trial populations; balance of prognostic factors at baseline; psychometric properties and minimal clinically important differences of the primary efficacy outcome measures; level of study fidelity; consistency of subgroup analyses; replication of findings in similar trials; sponsor role and potential conflicts of interest; consistency of results with disease causation theory; cost and resource estimates; and alternative prevention and treatment strategies. In this commentary, we show shortcomings in each of these areas and conclude that monoclonal antibody treatment for early Alzheimer disease is lacking high-quality evidence of clinically meaningful impacts at an affordable cost.
最近，针对有临床前或早期阿尔茨海默病的人群的淀粉样蛋白靶向单克隆抗体的三期随机对照试验报告了阳性结果，这给人们带来了终于有了能够改变疾病进程的药物的希望。鉴于这些试验的方法和结果以及药物作用机制背后的疾病发病理论对临床实践具有深远的影响，需要对其进行批判性评估。关键考虑因素包括试验人群的代表性；基线预后因素的平衡；主要疗效结局测量的心理测量特性和最小临床重要差异；研究保真度的水平；亚组分析的一致性；类似试验中的发现的复制；赞助商的角色和潜在的利益冲突；结果与疾病发病理论的一致性；成本和资源估计；以及替代的预防和治疗策略。在这篇评论中，我们展示了这些方面的不足之处，并得出结论，即针对早期阿尔茨海默病的单克隆抗体治疗缺乏具有临床意义的、负担得起的高质量证据。
