What clinical trial designs have been used to test antiepileptic drugs and do we need to change them?

Epileptic Disorders

Volumn 14, Issue 2, 2012, Pages 124-131

  Perucca, Emilio ^a  

^a UNIVERSITY OF PAVIA   (Italy)

Author keywords

Antiepileptic drug; Epilepsy; Randomised controlled trial; Regulatory guideline; Review; Trial design

Indexed keywords

ANTICONVULSIVE AGENT; CARBAMAZEPINE; ETIRACETAM; GABAPENTIN; LAMOTRIGINE; OXCARBAZEPINE; PLACEBO; VIGABATRIN;

ADD ON THERAPY; ADJUVANT CHEMOTHERAPY; CLINICAL TRIAL (TOPIC); CONFERENCE PAPER; DRUG APPROVAL; DRUG EFFICACY; DRUG SAFETY; EPILEPSY; HUMAN; MONOTHERAPY; PRACTICE GUIDELINE; PRIORITY JOURNAL; STUDY DESIGN; TREATMENT OUTCOME;

ANTICONVULSANTS; CLINICAL TRIALS AS TOPIC; EPILEPSY; HISTORY, 20TH CENTURY; HUMANS; REPRODUCIBILITY OF RESULTS; RESEARCH DESIGN;

EID: 84864573159     PISSN: 12949361     EISSN: 19506945     Source Type: Journal    
DOI: 10.1684/epd.2012.0511     Document Type: Conference Paper

References (47)

1. Arroyo S, Dodson WE, Privitera MD, et al. Randomized dose-controlled study of topiramate as first-line therapy in epilepsy. Acta Neurol Scand 2005; 112: 214-22.
2. Arzimanoglou A, Ben-Menachem E, Cramer J, Glauser T, Seeruthun R, Harrison M. The evolution of antiepileptic drug development and regulation. Epileptic Disord 2010; 12: 3-15.
3. Baulac M, Leon T, O'Brien TJ, Whalen E, Barrett J. A comparison of pregabalin, lamotrigine, and placebo as adjunctive therapy in patients with refractory partial-onset seizures. Epilepsy Res 2010; 91: 10-9.
4. Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: a summary of the Tenth Eilat Conference (EILAT X). Epilepsy Res 2010; 92: 89-124.
5. Brodie MJ, Perucca E, Ryvlin P, et al. Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology 2007; 68: 402-8.
6. Brodie MJ, Lerche H, Gil-Nagel A, et al. Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology 2010; 75: 1817-24.
7. Chadwick D. Monotherapy clinical trials of new antiepileptic drugs: design, indications, and controversies. Epilepsia 1997; 38: S16-20.
8. Coatsworth JJ. Studies on the Clinical Efficacy of Marketed Antiepileptic Drugs. NINDS Monograph # 12. Washington (DC): US Government Printing Office, 1971.
9. Coatsworth JJ, Penry JK. General principles. Clinical efficacy and use. In: Woodbury DM, Penry JK, Schmidt RP. Antiepileptic Drugs. New York: Raven Press, 1972: 87.
10. Committee for Proprietary Medicinal Products (CPMP). Note for guidance on clinical investigation of medicinal products in the treatment of epileptic disorders. (CPMP/EWP/566/98 rev 1). London: CPMP, 16 November 2000.
11. Committee for Medicinal Products for Human Use. Guidance on clinical investigation of medicinal products in the treatment of epileptic disorders. (CPMP/EWP/566/98 rev 2). London: Committee for Medicinal Products for Human Use, 22 July 2010.
12. Dam M, Ekberg R, Løyning Y, Waltimo O, Jakobsen K. A double-blind study comparing oxcarbazepine and carbamazepine in patients with newly diagnosed, previously untreated epilepsy. Epilepsy Res 1989; 3: 70-6.
13. Drug Amendments Act of 1962 (Public Law 87-781, 21 USC 355).
14. Fattore C, Perucca E. Novel medications for epilepsy. Drugs 2011; 71: 2151-78.
15. Faught E, Holmes GL, Rosenfeld WE, et al. Randomized, controlled, dose-ranging trial of carisbamate for partial-onset seizures. Neurology 2008; 71: 1586-93.
16. French JA, Wang S, Warnock B, Temkin N. Historical control monotherapy design in the treatment of epilepsy. Epilepsia 2010aa; 51: 1936-43.
17. French JA, Costantini C, Brodsky A, von Rosenstiel P; N01193 Study Group. Adjunctive brivaracetam for refractory partial-onset seizures: a randomized, controlled trial. Neurology 2010b; 75: 519-25.
18. Glauser T, Ben-Menachem E, Bourgeois B, et al. ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2006; 47: 1094-120.
19. Goa KL, Ross SR, Chrisp P. Lamotrigine. A review of its pharmacological properties and clinical efficacy in epilepsy. Drugs 1993; 46: 152-76.
20. Gram L, Bentsen KD, Parnas J, Flachs H. Controlled trials in epilepsy: a review. Epilepsia 1982; 23: 491-519.
21. Gram L, Klosterskov P, Dam M. Gamma-Vinyl GABA: a double-blind placebo-controlled trial in partial epilepsy. Ann Neurol 1985; 17: 262-6.
22. Grant SM, Heel RC. Vigabatrin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control. Drugs 1991; 41: 889-926.
23. Gruber CM Jr, Mosier JM, Grant P. Objective comparison of primidone and phenobarbital in epileptics. J Pharmacol Exp Ther 1957; 120: 184-7.
24. Halford JJ, Ben-Menachem E, Kwan P, et al. A randomized, double-blind, placebo-controlled study of the efficacy, safety, and tolerability of adjunctive carisbamate treatment in patients with partial-onset seizures. Epilepsia 2011; 52: 816-25.
25. Hauptmann A. Luminal bei Epilepsie. Münch med Wochenschr 1912; 59: 1907-9.
26. Hauptmann A. Erfahrungen aus der Behandlung der Epilepsie mit Luminal. Münch med Wochenschr 1919; 46: 1319-21.
27. Hills M, Armitage P. The two-period cross-over clinical trial. Br J Clin Pharmacol 1979; 8: 7-20.
28. Himwich HE. Report of committee on research 111: anticonvulsant and convulsant agents. Epilepsia (3rd series) 1952; 1: 145-52.
29. Karlawish JH, French J. The ethical and scientific shortcomings of current monotherapy epilepsy trials in newly diagnosed patients. Epilepsy Behav 2001; 2: 193-200.
30. Kwan P, Brodie MJ, Kalviainen R, Yurkevicz L, Weaver J, Knapp LE. Efficacy and safety of pregabalin versus lamotrigine in patients with newly diagnosed partial seizures: a phase 3, double-blind, randomised, parallel-group trial. Lancet Neurol 2011; 10: 881-90.
31. Marson AG, Williamson PR. Interpreting regulatory trials in epilepsy. Curr Opin Neurol 2009; 22: 167-73.
32. Matsuo F, Riaz A. Lamotrigine. In: Shorvon S, Perucca E, Engel J Jr. The Treatment of Epilepsy. 3rd edition. Oxford: Blackwell Publishers, 2009: 535-58.
33. Mattson RH, Cramer JA, Collins JF, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med 1985; 313: 145-51.
34. Merritt HH, Putnam TJ. Sodium diphenyl hydantoinate in the treatment of convulsive disorders. J Am Med Soc 1938; 111: 1068-73.
35. Perucca E. Designing clinical trials to assess antiepileptic drugs as monotherapy: difficulties and solutions. CNS Drugs 2008; 22: 917-38.
36. Perucca E. When clinical trials make history: demonstrating efficacy of new antiepileptic drugs as monotherapy. Epilepsia 2010; 51: 1933-5.
37. Perucca E, Tomson T. Monotherapy trials with the new antiepileptic drugs: study designs, practical relevance and ethical implications. Epilepsy Res 1999; 33: 247-62.
38. Perucca E, Tomson T. The pharmacological treatment of epilepsy in adults. Lancet Neurol 2011; 10: 446-56.
39. Perucca E, French J, Bialer M. Development of new antiepileptic drugs: challenges, incentives, and recent advances. Lancet Neurol 2007; 6: 793-804.
40. Rheims S, Perucca E, Cucherat M, Ryvlin P. Factors determining response to antiepileptic drugs in randomized controlled trials. A systematic review and meta-analysis. Epilepsia 2011; 52: 219-33.
41. Rimmer EM, Richens A. Double-blind study of gamma-vinyl GABA in patients with refractory epilepsy. Lancet 1984; 1: 189-90.
42. Ryvlin P, Cucherat M, Rheims S. Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials. Lancet Neurol 2011; 10: 961-8.
43. Sachdeo R. Monotherapy clinical trial design. Neurology 2007; 69: S23-7.
44. Shorvon SD. Drug treatment of epilepsy in the century of the ILAE: the first 50 years, 1909-1958. Epilepsia 2009; 50: 69-92.
45. Spangler R. The crotalin treatment of epilepsy. Epilepsia 1913; 3: 307-18.
46. White PT, Plott D, Norton J. Relative anticonvulsant potency of primidone; a double-blind comparison. Arch Neurol 1966; 14: 31-5.
47. Xiao Z, Li JM, Wang XF, et al. Efficacy and safety of levetiracetam (3,000 mg/day) as an adjunctive therapy in Chinese patients with refractory partial seizures. Eur Neurol 2009; 61: 233-9.