Related Experiment Video

Updated: Sep 28, 2025

Assessment of Spontaneous Alternation, Novel Object Recognition and Limb Clasping in Transgenic Mouse Models of Amyloid-β and Tau Neuropathology

Assessment of Spontaneous Alternation, Novel Object Recognition and Limb Clasping in Transgenic Mouse Models of Amyloid-β and Tau Neuropathology

Published on: May 28, 2017

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

Jeffrey C Yu^1,2, Jakub P Hlávka^2,3, Elizabeth Joe⁴

¹School of Pharmacy University of Southern California Los Angeles California USA.

Alzheimer'S & Dementia (New York, N. Y.)

|March 31, 2022

Abstract

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.

Keywords:

Alzheimer's disease Clinical Dementia Rating Sum of Boxes Food and Drug Administration clinical trials composite endpoints guidance documents legal mild cognitive impairment primary endpoints prodromal regulatory

More Related Videos

Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451

Hybrid PET/MRI Imaging of Alzheimer's Disease Based on ¹⁸F-AV-1451

Published on: April 18, 2025

A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition

A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition

Published on: September 20, 2019

Related Concept Videos

Alzheimer's Disease: Treatment

Alzheimer's Disease: Treatment

Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...

Alzheimer's Disease: Overview

Alzheimer's Disease: Overview

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...

Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches

Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches

Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...

Clinical Trials: Overview

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...

Factors Affecting Drug Response: Overview

Factors Affecting Drug Response: Overview

When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...

Drug Regulation

Drug Regulation

Drug regulation encompasses the management of drug usage by evaluating its safety and efficacy through assessments conducted by regulatory authorities. Regrettably, the history of drug regulation is marred by several catastrophic events. One such incident is the Elixir Sulfanilamide tragedy, in which the toxic compound diethyl glycol was included in a sweet-tasting medication, leading to numerous fatalities. This event prompted the enactment of the Food, Drug, and Cosmetic Act in 1938. Under...

Articles linked to this work by shared authors, journal, and citation graph.

Protecting long-term care facilities in the next pandemic: Lessons regarding visitation and activity restrictions during COVID-19.

Geriatric nursing (New York, N.Y.)·2026

Valuing Dementia Interventions Under Uncertainty: A Comparison of Generalized and Risk-Adjusted Cost Effectiveness to Traditional Cost-Effectiveness Analyses.

Forum for health economics & policy·2026

Highly Novel Drugs Outperformed Less Novel Drugs In Gross And Net Revenues In The US, Driven Primarily By Utilization, 2013-19.

Health affairs (Project Hope)·2026

Pharmaceutical import landscape in Ethiopia: a cross-sectional study of importers' perspectives on business and regulatory challenges.

Tropical medicine and health·2026

PRBS Gas Challenges Reveal Impaired Chemoreflex and Cholinergic Dynamics in MCI.

Annals of biomedical engineering·2026

Real-World Treatment Adherence and Persistence with C5 Inhibitor Therapy Versus Satralizumab in Patients with Neuromyelitis Optica Spectrum Disorder in Japan.

Neurology and therapy·2026

See all related articles