Impact of non-binding FDA guidances on primary endpoint selection in Alzheimer's disease trials
| Autoři | |
|---|---|
| Rok publikování | 2022 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS |
| Citace | |
| www | https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.12280 |
| Doi | http://dx.doi.org/10.1002/trc2.12280 |
| Klíčová slova | Alzheimer's disease; Clinical Dementia Rating Sum of Boxes; clinical trials; composite endpoints; Food and Drug Administration; guidance documents; legal; mild cognitive impairment; primary endpoints; prodromal; regulatory |
| Popis | Introduction The U.S. Food and Drug Administration (FDA)'s guidances help describe the agency's current thinking on regulatory issues and serve as a means of informal policymaking that is non-binding. This study examines the impact of two guidance documents for Alzheimer's disease (AD) trials. The first guidance in 2013 encouraged the use of cognitive/functional endpoints, while the second in 2018 modified such recommendation. Methods Using pivotal trial data, we applied a regression discontinuity in time (RDiT) framework to examine trialist response to these guidance documents. Results were stratified by disease-modifying therapy (DMT) status, and controlled for disease staging, FDA registration status, and trial phase. Results Among AD DMT trials, annual use of cognitive/functional composite endpoints significantly increased after the 2013 guidance (+12.9%, P < .001), and significantly decreased after the 2018 guidance (-19.9%, P = .022). Discussion Although guidance documents do not set new legal standards or impose binding requirements, our findings indicate they are broadly followed by AD trialists. |