ArticleAnnals of clinical and translational neurology2017
Monte Carlo simulations of randomized clinical trials in epilepsy.
Article in Annals of clinical and translational neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Anti-seizure efficacy and retention rate of carbamazepine is highly variable in randomized controlled trials: A meta-analysis.Epilepsia open · 2022Pooled it
- Trial
- Counterintuitive: reducing regression-to-the-mean worsens efficiency in simulated clinical trials.Seizure · 2026Article
- 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
- Epilepsy and Placebo: A Literature Review.Neurologic clinics · 2026Review
- Inductive reasoning with large language models: A simulated randomized controlled trial for epilepsy.Epilepsy research · 2025Article
- Factors associated with placebo response rate in randomized controlled trials of antiseizure medications for focal epilepsy.Epilepsia · 2025Article
- Monte Carlo Simulations in Nanomedicine: Advancing Cancer Imaging and Therapy.Nanomaterials (Basel, Switzerland) · 2025Review
- Demonstration of Group-Level and Individual-Level Efficacy Using Time-to-Event Designs for Clinical Trials of Antiseizure Medications.Neurology · 2024Article
- Article
- Review
- Minimum clinical utility standards for wearable seizure detectors: A simulation study.Epilepsia · 2024Article
- Inductive reasoning with large language models: a simulated randomized controlled trial for epilepsy.medRxiv : the preprint server for health sciences · 2024Article
- Prospective validation of a seizure diary forecasting falls short.medRxiv : the preprint server for health sciences · 2024Article
- Quantifying and controlling the impact of regression to the mean on randomized controlled trials in epilepsy.Epilepsia · 2023Article
- Review
- Flexible realistic simulation of seizure occurrence recapitulating statistical properties of seizure diaries.Epilepsia · 2023Article
- Epileptiform activity predicts epileptogenesis in cerebral hemorrhage.Annals of clinical and translational neurology · 2022Article
- Natural variability in seizure frequency: Implications for trials and placebo.Epilepsy research · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe placebo response in epilepsy randomized clinical trials (RCTs) has recently been shown to largely reflect underlying natural variability in seizure frequency. Based on this observation, we sought to explore the parameter space of RCT design to optimize trial efficiency and cost.
methodsWe used one of the world's largest patient reported seizure diary databases, SeizureTracker.com to derive virtual patients for simulated RCTs. We ran 1000 randomly generated simulated trials using bootstrapping (sampling with replacement) for each unique combination of trial parameters, sweeping a large set of parameters in durations of the baseline and test periods, number of patients, eligibility criteria, drug effect size, and patient dropout. We studied the resulting trial efficiency and cost.
resultsA total of 6,732,000 trials were simulated, drawing from 5097 patients in the database. We found that the strongest regression predictors of placebo response were durations of baseline and test periods. Drug effect size had a major impact on trial efficiency and cost. Dropout did not have a major impact on trial efficiency or cost. Eligibility requirements impacted trial efficiency to a limited extent. Cost was minimized while maintaining statistical integrity with very short RCT durations. DISCUSSION: This study suggests that RCT parameters can be improved over current practice to reduce costs while maintaining statistical power. In addition, use of a large-scale population dataset in a massively parallel computing analysis allows exploration of the wider parameter space of RCT design prior to running a trial, which could help accelerate drug discovery and approval.
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.