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Comparison of Alternative Outcome Measures for Antiepileptic Drug Trials

Comparison of Alternative Outcome Measures for Antiepileptic Drug Trials Abstract • Studies to determine the efficacy of antiepileptic drugs often use seizure frequency as an outcome measure. Time to kth seizure (k up to 12) was investigated as an alternative endpoint. Monte Carlo simulations, based on seizure behavior in previous clinical trials, were used to evaluate crossover studies with these endpoints. Tests on seizure frequency exhibited the highest power. However, tests on time to the 12th seizure, for a sample size of 50, approached the power of tests on seizure frequency with a sample size of 20. Including patients with less severe epilepsy (two vs four seizures per month) did not change the power of tests on time to the kth seizure and lowered it only moderately for tests on seizure frequency. The simulation methodology presented can be adapted to evaluate other design variations. References 1. Gram L, Bentsen KD, Parnas J, et al: Controlled trials in epilepsy: A review . Epilepsia 1982;23:491-519.Crossref 2. Van Belle G, Temkin NR: Design strategies in the clinical evaluation of new antiepileptic drugs , in Pedley TA, Meldrum BS (eds): Recent Advances in Epilepsy . New York, Churchill Livingstone Inc, 1983, pp 93-111. 3. Hills M, Armitage P: The two-period crossover clinical trial . Br J Clin Pharmacol 1979;8:7-20. 4. Shofer JB: Application of Monte Carlo Meth ods to Explore Alternative Outcome Measures in Antiepileptic Drug Trials, thesis. University of Washington, Seattle, 1985. 5. Temkin NR: Contagious models for epileptic seizure count data. Read before the Western North American Regional Annual Meeting of the Biometric Society, Los Angeles, June 26, 1979. 6. Hopkins A, Davies P, Dobson C: Mathematical models of patterns of seizures: Their use in the evaluation of drugs . Arch Neurol 1985;42:463-467.Crossref 7. Krall RL, Penry JK, Kupferberg HJ, et al: Antiepileptic drug development: I. History and a program for progress . Epilepsia 1978;19:393-408.Crossref 8. Anderson S, Hauck WW: A new procedure for testing equivalence in comparative bioavail-ability and other clinical trials . Commun Stat Theory Meth 1983;12:2663-2692.Crossref 9. Wilensky AJ, Ojemann LM, Temkin NR, et al: Clorazepate and phenobarbital as antiepileptic drugs: A double-blind study . Neurology 1981;31:1271-1276.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Comparison of Alternative Outcome Measures for Antiepileptic Drug Trials

Archives of Neurology , Volume 43 (9) – Sep 1, 1986

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Publisher
American Medical Association
Copyright
Copyright © 1986 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1986.00520090017009
Publisher site
See Article on Publisher Site

Abstract

Abstract • Studies to determine the efficacy of antiepileptic drugs often use seizure frequency as an outcome measure. Time to kth seizure (k up to 12) was investigated as an alternative endpoint. Monte Carlo simulations, based on seizure behavior in previous clinical trials, were used to evaluate crossover studies with these endpoints. Tests on seizure frequency exhibited the highest power. However, tests on time to the 12th seizure, for a sample size of 50, approached the power of tests on seizure frequency with a sample size of 20. Including patients with less severe epilepsy (two vs four seizures per month) did not change the power of tests on time to the kth seizure and lowered it only moderately for tests on seizure frequency. The simulation methodology presented can be adapted to evaluate other design variations. References 1. Gram L, Bentsen KD, Parnas J, et al: Controlled trials in epilepsy: A review . Epilepsia 1982;23:491-519.Crossref 2. Van Belle G, Temkin NR: Design strategies in the clinical evaluation of new antiepileptic drugs , in Pedley TA, Meldrum BS (eds): Recent Advances in Epilepsy . New York, Churchill Livingstone Inc, 1983, pp 93-111. 3. Hills M, Armitage P: The two-period crossover clinical trial . Br J Clin Pharmacol 1979;8:7-20. 4. Shofer JB: Application of Monte Carlo Meth ods to Explore Alternative Outcome Measures in Antiepileptic Drug Trials, thesis. University of Washington, Seattle, 1985. 5. Temkin NR: Contagious models for epileptic seizure count data. Read before the Western North American Regional Annual Meeting of the Biometric Society, Los Angeles, June 26, 1979. 6. Hopkins A, Davies P, Dobson C: Mathematical models of patterns of seizures: Their use in the evaluation of drugs . Arch Neurol 1985;42:463-467.Crossref 7. Krall RL, Penry JK, Kupferberg HJ, et al: Antiepileptic drug development: I. History and a program for progress . Epilepsia 1978;19:393-408.Crossref 8. Anderson S, Hauck WW: A new procedure for testing equivalence in comparative bioavail-ability and other clinical trials . Commun Stat Theory Meth 1983;12:2663-2692.Crossref 9. Wilensky AJ, Ojemann LM, Temkin NR, et al: Clorazepate and phenobarbital as antiepileptic drugs: A double-blind study . Neurology 1981;31:1271-1276.Crossref

Journal

Archives of NeurologyAmerican Medical Association

Published: Sep 1, 1986

References