San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA.
Departments of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
Geroscience. 2022 Dec;44(6):2925-2931. doi: 10.1007/s11357-022-00671-8. Epub 2022 Oct 19.
Treatments that target fundamental processes of aging are expected to delay several aging-related conditions simultaneously. Testing the efficacy of these treatments for potential anti-aging benefits will require clinical trials with endpoints that reflect the potential benefits of slowing processes of aging. There are several potential types of endpoints to capture the benefits of slowing a process of aging, and a consensus is needed to standardize and compare the results of these trials and to guide the analysis of observational data to support trial planning. Using biomarkers instead of clinical outcomes would substantially reduce the size and the duration of clinical trials. This requires validation of surrogate markers showing that treatment induced change in the marker reliably predicts the magnitude of change in the clinical outcome. The surrogate marker must also reflect the biological mechanism for the effect of treatment on the clinical outcome. "Biological age" is a superficially attractive marker for such trials. However, it is essential to establish that treatment induced change in biological age reliably predict the magnitude of benefits in the clinical outcome. Reaching consensus on clinical outcomes for geroscience trials and then validating potential surrogate biomarkers requires time, effort, and coordination that will be worthwhile to develop surrogate outcomes that can be trusted to efficiently test the value of many anti-aging treatments under development.
预计靶向衰老基本过程的治疗方法将同时延迟多种与衰老相关的疾病。为了测试这些治疗方法在潜在抗衰老方面的疗效，需要进行临床试验，其终点反映了减缓衰老过程的潜在益处。有几种潜在的终点类型可以捕捉减缓衰老过程的益处，需要达成共识来标准化和比较这些试验的结果，并指导观察性数据的分析，以支持试验计划。使用生物标志物而不是临床结果将大大减少临床试验的规模和持续时间。这需要验证替代标志物，表明治疗引起的标志物变化可靠地预测临床结果的变化幅度。替代标志物还必须反映治疗对临床结果的影响的生物学机制。“生物年龄”是此类试验的一个表面上很有吸引力的标志物。然而，至关重要的是要确定治疗引起的生物年龄变化可靠地预测临床结果的益处幅度。就衰老科学试验的临床结果达成共识，然后验证潜在的替代生物标志物，需要时间、精力和协调，这将是值得的，以开发可以信任的替代结果，从而有效地测试许多正在开发的抗衰老治疗方法的价值。
