Evaluation of Postblock Hypersensitivity Using Quantitative Sensory Testing before, during, and after Axillary Brachial Plexus Block Resolution in Healthy Volunteers.

Alzheimer disease (AD) is a growing global public health challenge, driven by population aging, which currently affects over 57 million people worldwide. In recent years, there have been notable advances in therapeutic development and a rapid expansion of the drug development pipeline, highlighted by the approval of lecanemab in 2023 and donanemab in 2024. Given the clinical heterogeneity of AD, with manifestations extending beyond cognitive decline, efficacy in AD trials is assessed using a range of outcome measures (e.g., cognitive, functional, and behavioral abilities). However, a key concern remains whether these efficacy outcome measures are sufficient and whether the domains they assess are clinically meaningful. A previous review showed that clinical trials in mild cognitive impairment (MCI) and dementia conducted between 2004 and 2014 largely prioritized cognitive outcomes while overlooking other important domains. More recently, biomarker-based measures have been widely adopted, yet their clinical relevance remains uncertain, with limited high-strength evidence of association with clinical benefits. In response to these concerns, regulatory agencies including the European Medicines Agency (EMA), US Food and Drug Administration (FDA), Japan Pharmaceuticals and Medical Devices Agency (PMDA), and China National Medical Products Administration (NMPA) have all emphasized the importance of incorporating clinically meaningful outcomes that extend beyond isolated cognitive measures in confirmatory clinical trials for patients with MCI or mild-to-moderate dementia due to AD (). In 2023, 10 international professional societies jointly issued the , identifying 8 key clinical domains that capture not only cognition, function, and global status (as endorsed by regulators) but also behavioral and neuropsychiatric symptoms, caregiver and family quality of life (QoL), and significant disease-related life events. Regarding biomarkers, both the EMA and expert consensus discouraged their use as efficacy measures in clinical trials because of uncertain relevance to disease progression, whereas the FDA endorsed brain β-amyloid deposition as a surrogate outcome measure and the PMDA and NMPA encouraged the inclusion of biomarkers as secondary measures. Efficacy Measures Recommended for Confirmatory Trials of Interventions for Patients With Mild Cognitive Impairment or Mild-to-Moderate Dementia due to AD