Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Preclinical Development: Overview01:28

Preclinical Development: Overview

5.7K
Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
5.7K
Clinical Trials: Overview01:11

Clinical Trials: Overview

4.5K
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...
4.5K
Drug Discovery: Overview01:26

Drug Discovery: Overview

10.9K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
10.9K
Drug Administration and Therapy Phases: Overview01:26

Drug Administration and Therapy Phases: Overview

1.1K
Drugs, the chemical agents used in diagnosing, treating, or preventing diseases, undergo a four-phase process of development: pharmaceutic, pharmacokinetics, pharmacodynamics, and therapeutic.
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
1.1K
In Vitro Drug Release Testing: Overview, Development and Validation01:10

In Vitro Drug Release Testing: Overview, Development and Validation

279
In vitro dissolution and drug release tests assess how quickly and how much of a drug is released from its dosage form into an aqueous medium under standardized laboratory conditions. These tests are essential tools in pharmaceutical development and quality assurance, offering insight into the drug's performance before clinical use.During formulation development, dissolution testing identifies incomplete or inconsistent drug release issues. It also supports decisions on selecting the optimal...
279
Drug Regulation01:25

Drug Regulation

2.7K
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...
2.7K

You might also read

Related Articles

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

Sort by
Same author

Simulation of long-term lecanemab treatment effect on Alzheimer's disease progression.

Alzheimer's & dementia (New York, N. Y.)·2026
Same author

Subgroup identification via Interaction Tree and Mixed Model for Repeated Measures with application to Alzheimer's disease.

Biometrics·2026
Same author

Statistical models for Alzheimer's disease clinical trials: Lessons learned from the DIAN-TU Platform Trial.

Journal of Alzheimer's disease : JAD·2026
Same author

Effect of Cognitive Reserve on Age at Symptom Onset and Cognitive Decline in Individuals With Dominantly Inherited Alzheimer Disease.

Neurology·2026
Same author

Testing disease progression under the proportional reduction in decline in Alzheimer's disease studies.

Journal of applied statistics·2026
Same author

Biomarkers.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Unveiling the procoagulant state in Alzheimer's disease: A novel PET imaging strategy.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Estimated labor market outcomes of people progressing from preclinical to early-stage Alzheimer's disease in the United States.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Amyloid exacerbates tau and alpha-synuclein pathologies, behavioral impairments, and neuroinflammation in a mixed dementia model.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Multimorbidity burden and patterns associated with DeepBrainNet-derived brain-age gap in dementia-free older adults: A community-based study.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Reply to "Shifting the emphasis of brain health literacy from individuals to systems to reduce inequalities".

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same journal

Shifting the emphasis of brain health literacy from individuals to systems to reduce inequalities.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
See all related articles

Related Experiment Video

Updated: Jan 7, 2026

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
05:10

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System

Published on: December 11, 2016

10.1K

Drug Development.

Yan Li1, Guoqiao Wang2

  • 1Washington University in St. Louis, St. Louis, MO, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

For preclinical Alzheimer's disease (AD) trials, using time-to-recurrent-event endpoints and blood-based biomarker enrichment enhances statistical power for detecting treatment effects more effectively than traditional methods.

More Related Videos

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
08:04

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing

Published on: May 11, 2021

3.3K
Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells
05:45

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Published on: October 10, 2025

451

Related Experiment Videos

Last Updated: Jan 7, 2026

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
05:10

Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System

Published on: December 11, 2016

10.1K
In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
08:04

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing

Published on: May 11, 2021

3.3K
Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells
05:45

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Published on: October 10, 2025

451

Area of Science:

  • Neurology
  • Clinical Trials
  • Biostatistics

Background:

  • Evaluating treatments for preclinical Alzheimer's disease (AD) presents challenges due to subtle cognitive decline.
  • Traditional endpoints like time-to-first-event may not fully capture treatment benefits in early-stage AD prevention trials.
  • Insights from the DIAN-TU platform trial highlight the need for improved endpoint and analysis strategies.

Purpose of the Study:

  • To propose and evaluate alternative endpoints and analysis models for preclinical AD prevention trials.
  • To enhance the detection of treatment effects in asymptomatic individuals with elevated amyloid levels.
  • To leverage insights from the DIAN-TU trial for optimizing future AD prevention study designs.

Main Methods:

  • Adoption of time-to-recurrent-event as a primary endpoint, defined by changes in CDR global or CDR-SB scores.
  • Application of Cox proportional hazards or frailty survival models for data analysis.
  • Exploration of blood-based biomarker (BBB) enrichment designs for participant stratification and power enhancement via stratified survival analysis or MMRM.

Main Results:

  • Time-to-recurrent-event endpoints provide a more comprehensive assessment of treatment effects over trial duration, increasing statistical power.
  • Combining BBB enrichment with stratified analysis significantly amplifies statistical power compared to non-enriched or non-stratified approaches.
  • Simulations and comparative analyses using DIAN-TU data will demonstrate the superiority of recurrent-event over first-event endpoints.

Conclusions:

  • Time-to-recurrent-event is a more effective and sensitive endpoint for preclinical AD trials.
  • Survival analysis offers clinically relevant insights by quantifying treatment effects in terms of hazard rate reduction or survival extension.
  • The proposed methods, including BBB enrichment, are crucial for improving the efficiency and power of AD prevention trials.