ArticleNPJ digital medicine2021
Exploring the feasibility of using real-world data from a large clinical data research network to simulate clinical trials of Alzheimer's disease.
Article in NPJ digital medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00478205 (Double-Blind, Parallel-Group Comparison of 23 mg Donepezil Sustained Release), which is not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Double-Blind, Parallel-Group Comparison of 23 mg Donepezil Sustained Release (SR) to 10 mg Donepezil Immediate Release (IR) in Patients With Moderate to Severe Alzheimer's Disease
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials: A Systematic Review.JAMA network open · 2023Pooled it
- Design and Implementation of Observational Studies Emulating a Target Trial.JAMA network open · 2026Article
- A Framework for Generating Realistic Synthetic Tabular Data in a Randomized Controlled Trial Setting.Statistics in medicine · 2025Article
- Longitudinal tau aggregation, atrophy, and cognitive decline in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Federated target trial emulation using distributed observational data for treatment effect estimation.NPJ digital medicine · 2025Article
- Federated Target Trial Emulation using Distributed Observational Data for Treatment Effect Estimation.medRxiv : the preprint server for health sciences · 2025Article
- Synthetic Data in Healthcare and Drug Development: Definitions, Regulatory Frameworks, Issues.CPT: pharmacometrics & systems pharmacology · 2025Review
- Real-world evidence: state-of-the-art and future perspectives.Journal of comparative effectiveness research · 2025Review
- Drug repurposing for Alzheimer's disease and other neurodegenerative disorders.Nature communications · 2025Review
- Temporal Ensemble Logic for Integrative Representation of the Entirety of Clinical Trials.LIPIcs : Leibniz international proceedings in informatics · 2025Article
- Article
- Envisioning the Future of Personalized Medicine: Role and Realities of Digital Twins.Journal of medical Internet research · 2024Article
- The Digital Therapeutics Real-World Evidence Framework: An Approach for Guiding Evidence-Based Digital Therapeutics Design, Development, Testing, and Monitoring.Journal of medical Internet research · 2024Article
- Artificial intelligence and open science in discovery of disease-modifying medicines for Alzheimer's disease.Cell reports. Medicine · 2024Review
- A comparative study of clinical trial and real-world data in patients with diabetic kidney disease.Scientific reports · 2024Article
- High-throughput target trial emulation for Alzheimer's disease drug repurposing with real-world data.Nature communications · 2023Article
- Characteristics and Admission Preferences of Pediatric Emergency Patients and Their Waiting Time Prediction Using Electronic Medical Record Data: Retrospective Comparative Analysis.Journal of medical Internet research · 2023Article
- A review of research on eligibility criteria for clinical trials.Clinical and experimental medicine · 2023Review
- Machine Learning in Clinical Trials: A Primer with Applications to Neurology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Emulation of the control cohort of a randomized controlled trial in pediatric kidney transplantation with Real-World Data from the CERTAIN Registry.Pediatric nephrology (Berlin, Germany) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
In this study, we explored the feasibility of using real-world data (RWD) from a large clinical research network to simulate real-world clinical trials of Alzheimer's disease (AD). The target trial (i.e., NCT00478205) is a Phase III double-blind, parallel-group trial that compared the 23 mg donepezil sustained release with the 10 mg donepezil immediate release formulation in patients with moderate to severe AD. We followed the target trial's study protocol to identify the study population, treatment regimen assignments and outcome assessments, and to set up a number of different simulation scenarios and parameters. We considered two main scenarios: (1) a one-arm simulation: simulating a standard-of-care (SOC) arm that can serve as an external control arm; and (2) a two-arm simulation: simulating both intervention and control arms with proper patient matching algorithms for comparative effectiveness analysis. In the two-arm simulation scenario, we used propensity score matching controlling for baseline characteristics to simulate the randomization process. In the two-arm simulation, higher serious adverse event (SAE) rates were observed in the simulated trials than the rates reported in original trial, and a higher SAE rate was observed in the 23 mg arm than in the 10 mg SOC arm. In the one-arm simulation scenario, similar estimates of SAE rates were observed when proportional sampling was used to control demographic variables. In conclusion, trial simulation using RWD is feasible in this example of AD trial in terms of safety evaluation. Trial simulation using RWD could be a valuable tool for post-market comparative effectiveness studies and for informing future trials' design. Nevertheless, such an approach may be limited, for example, by the availability of RWD that matches the target trials of interest, and further investigations are warranted.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.