Impact of non-binding FDA guidances on primary endpoint
selection in Alzheimer's disease trials

J 2022

Impact of non-binding FDA guidances on primary endpoint selection in Alzheimer's disease trials

YU, Jeffrey C.; Jakub HLÁVKA; Elizabeth JOE; Frances J. RICHMOND; Darius N. LAKDAWALLA et al.

Základní údaje

Originální název

Impact of non-binding FDA guidances on primary endpoint selection in Alzheimer's disease trials

Autoři

YU, Jeffrey C.; Jakub HLÁVKA; Elizabeth JOE; Frances J. RICHMOND a Darius N. LAKDAWALLA

Vydání

ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS, HOBOKEN, WILEY, 2022

Další údaje

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Označené pro přenos do RIV

DOI

https://doi.org/10.1002/trc2.12280

UT WoS

000772386600001

Klíčová slova anglicky

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

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 30. 1. 2025 09:29, Mgr. Alžběta Karolyiová

Anotace

V originále

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.

Citovat

YU, Jeffrey C.; Jakub HLÁVKA; Elizabeth JOE; Frances J. RICHMOND a Darius N. LAKDAWALLA. Impact of non-binding FDA guidances on primary endpoint selection in Alzheimer's disease trials. ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS. HOBOKEN: WILEY, 2022, roč. 8, č. 1, 13 s. Dostupné z: https://doi.org/10.1002/trc2.12280.

@article{2472549,
   author = {Yu, Jeffrey C. and Hlávka, Jakub and Joe, Elizabeth and Richmond, Frances J. and Lakdawalla, Darius N.},
   article_location = {HOBOKEN},
   article_number = {1},
   doi = {https://doi.org/10.1002/trc2.12280},
   keywords = {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},
   journal = {ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS},
   title = {Impact of non-binding FDA guidances on primary endpoint selection in Alzheimer's disease trials},
   url = {https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.12280},
   volume = {8},
   year = {2022}
}

TY  - JOUR
ID  - 2472549
AU  - Yu, Jeffrey C. - Hlávka, Jakub - Joe, Elizabeth - Richmond, Frances J. - Lakdawalla, Darius N.
PY  - 2022
TI  - Impact of non-binding FDA guidances on primary endpoint selection in Alzheimer's disease trials
JF  - ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS
VL  - 8
IS  - 1
PB  - WILEY
KW  - Alzheimer's disease
KW  - Clinical Dementia Rating Sum of Boxes
KW  - clinical trials
KW  - composite endpoints
KW  - Food and Drug Administration
KW  - guidance documents
KW  - legal
KW  - mild cognitive impairment
KW  - primary endpoints
KW  - prodromal
KW  - regulatory
UR  - https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.12280
N2  - 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.
ER  -

YU, Jeffrey C.; Jakub HLÁVKA; Elizabeth JOE; Frances J. RICHMOND a Darius N. LAKDAWALLA. Impact of non-binding FDA guidances on primary endpoint selection in Alzheimer's disease trials. \textit{ALZHEIMERS \&{}amp; DEMENTIA-TRANSLATIONAL RESEARCH \&{}amp; CLINICAL INTERVENTIONS}. HOBOKEN: WILEY, 2022, roč.~8, č.~1, 13 s. Dostupné z: https://doi.org/10.1002/trc2.12280.

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