ReviewEpilepsia2023
Time-to-event clinical trial designs: Existing evidence and remaining concerns.
Review in Epilepsia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Pooled it
- Trial
- Trial
- Trial
- Monitoring Antiseizure Medication Change Using Ultra Long-Term Electroencephalogram: A Multicenter Study.Annals of neurology · 2026Article
- Article
- Article
- Patterns of seizure frequency reduction in clinical trial participants with lower baseline seizure frequency.Epilepsia · 2026Article
- L-Relationship between uncertainty and average seizure frequency in clinical trials of antiseizure medications.Epilepsia · 2026Article
- Ask a Simple Question, Design an Elegant Study and the Rest is History.Epilepsy currents · 2026Article
- Exploring the Effectiveness of Adjunctive Cenobamate in Focal Epilepsy: A Time-Based Analysis.CNS drugs · 2025Article
- Factors associated with placebo response rate in randomized controlled trials of antiseizure medications for focal epilepsy.Epilepsia · 2025Article
- Demonstration of Group-Level and Individual-Level Efficacy Using Time-to-Event Designs for Clinical Trials of Antiseizure Medications.Neurology · 2024Article
- The present and future of seizure detection, prediction, and forecasting with machine learning, including the future impact on clinical trials.Frontiers in neurology · 2024Review
- A single-center survey on physical activity barriers, behaviors and preferences in adults with epilepsy.Epilepsy & behavior : E&B · 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
8 authors at 7 institutions in 5 countries.
Funding
Abstract
Well-designed placebo-controlled clinical trials are critical to the development of novel treatments for epilepsy, but their design has not changed for decades. Patients, clinicians, regulators, and innovators all have concerns that recruiting for trials is challenging, in part, due to the static design of maintaining participants for long periods on add-on placebo when there are an increasing number of options for therapy. A traditional trial maintains participants on blinded treatment for a static period (e.g., 12 weeks of maintenance), during which participants on placebo have an elevated risk of sudden unexpected death in epilepsy compared to patients on an active treatment. Time-to-event trials observe participants on blinded treatment until a key event occurs (e.g., post-randomization seizure count matches pre-randomization monthly seizure count). In this article, we review the evidence for these designs based on re-analysis of prior trials, one published trial that used a time-to-second seizure design, and experience from an ongoing blinded trial. We also discuss remaining concerns regarding time-to-event trials. We conclude that, despite potential limitations, time-to-event trials are a potential promising mechanism to make trials more patient friendly and reduce placebo exposure, which are urgent needs to improve safety and increase recruitment to trials.
Indexed as
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.