Trial reportEpilepsia2022
Reappraisal of the Medical Research Council Antiepileptic Drug Withdrawal Study: Contamination-adjusted and dose-response re-analysis.
Trial report in Epilepsia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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
6 citing papers in PubMed.
- Reappraisal of the Medical Research Council Antiepileptic Drug Withdrawal Study: Contamination-adjusted and dose-response re-analysis.Epilepsia · 2022Trial
- Risk factors of recurrence for epilepsy patients after antiseizure medication withdrawal: what we do and do not know?Journal of neurology · 2025Review
- Patient Perspectives on Antiseizure Medication Discontinuation: A Mixed-Methods Exploration of Risk Perception, Tolerance, and Counseling.Neurology. Clinical practice · 2025Article
- Variation in seizure risk increases from antiseizure medication withdrawal among patients with well-controlled epilepsy: A pooled analysis.Epilepsia open · 2024Article
- Video-EEG-monitoring to guide antiseizure medication withdrawal.Neurological research and practice · 2023Article
- The sense of stopping migraine prophylaxis.The journal of headache and pain · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
objectiveThe 1991 Medical Research Council (MRC) Study compared seizure relapse for seizure-free patients randomized to withdraw vs continue of antiseizure medications (ASMs). We re-analyzed this trial to account for crossover between arms using contamination-adjusted intention to treat (CA ITT) methods, to explore dose-response curves, and to validate predictions against external data. ITT assesses the effect of being randomized to withdraw, as-treated analysis assesses the confounded effect of withdrawing, but CA ITT assesses the unconfounded effect of actually withdrawing.
methodsCA ITT involves two stages. First, we used randomized arm to predict whether patients withdrew their ASM (logistic) or total daily ASM dose (linear). Second, we used those values to predict seizure occurrence (logistic).
resultsThe trial randomized 503 patients to withdraw and 501 patients to continue ASMs. We found that 316 of 376 patients (88%) who were randomized to withdraw decreased their dose at every pre-seizure visit, compared with 35 of 424 (8%) who were randomized to continue (p < .01). Adjusted odds ratios of a 2-year seizure for those who withdrew vs those who did not was 1.3 (95% confidence interval [CI] 0.9-1.9) in the as-treated analysis, 2.5 (95% CI 1.9-3.4) comparing those randomized to withdraw vs continue for ITT, and 3.1 (95% CI 2.1-4.5) for CA ITT. Probabilities (withdrawal vs continue) were 28% vs 24% (as-treated), 40% vs 22% (ITT), and 43% vs 21% (CA ITT). Differences between ITT and CA ITT were greater when varying the predictor (reaching zero ASMs) or outcome (1-year seizures). As-treated dose-response curves demonstrated little to no effects, but larger effects in CA ITT analysis. MRC data overpredicted risk in Lossius data, with moderate discrimination (areas under the curve ~0.70). SIGNIFICANCE: CA ITT results (the effect of actually withdrawing ASMs on seizures) were slightly greater than ITT effects (the effect of recommend withdrawing ASMs on seizures). How these findings affect clinical practice must be individualized.
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