Reply to Commentary by Cummings (2022): Surrogate endpoints extend beyond biomarkers.
Reply to Commentary by Cummings (2022): Surrogate endpoints extend beyond biomarkers.
复制标题
DOI：
10.1002/trc2.12344
复制
发表时间：
2022
影响因子：
4.8
通讯作者：
Taylor, Rod S
中科院分区：
文献类型：
--
作者：
Manyara, Anthony Muchai;Ciani, Oriana;Taylor, Rod S
We thank Dr. Cummings for his support of the development of the SPIRIT/CONSORT-SURROGATE extensions and his correction that the primary outcome of the aducanumab trials in early Alzheimer’s disease is the Clinical Dementia Rating-Sum of Boxes (CDR-SB) rather than the biomarker of magnetic resonance imaging–assessed amyloid load. However, this reply gives us the opportunity to clarify that the concept of surrogate endpoints in trials extends beyond biomarkers and includes intermediate outcomes. 1 Unlike biomarkers, intermediate outcomes can be directly perceived and be valued by trial participants but are intended as a substitute and predictor for a more distal patientrelevant final outcome. Whether an intermediate outcome should be considered a patient-relevant final outcome or surrogate endpoint depends on the aims of a trial and how that trial informs health-care policy. 2 A key question for regulators, payers, health-care professionals, and patients for the assessment of new treatments in this field is whether intermediate outcomes such as CDR-SB or Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) should be valued as final outcomes in their own right or, rather, as surrogate endpoints for the more severe disease progression, including residential care facility admission and/or premature death. If the latter, validation is required that the treatment-related improvements in CDR-SB seen in recent trials is strongly associated with an improvement in these more distal outcomes. 3
