Skip to main content Accessibility help
×
Home
  • Print publication year: 2012
  • Online publication date: May 2012

24 - Amyotrophic Lateral Sclerosis

from Section 6

Summary

Enrichment designs are being increasingly used in fields such as chronic pain research because they may better reflect routine clinical practice than other study designs. Researchers use a variety of methods to perform the first stage of an enrichment design trial. This chapter examines the varied strategies involved in developing a trial using an enrichment design, the advantages and disadvantages of this method and considers the issues when planning a study using enrichment strategies. Issues related to washout periods were considered in the trial using the enrichment design to examine the use of gabapentin for treatment of postherpetic neuralgia (PHN). The distinction between enrichment by response and enrichment by expected mechanism of action is significant. An enrichment design is well suited to examine treatments with small effect sizes in a general population with increased efficiency, particularly those treatments with a greater expected effect in a particular subpopulation of subjects.

References:

1. LankaV, CudkowiczM. Therapy development for ALS: Lessons learned and path forward. Amyotroph Lateral Scler 2008; 9: 131–40.
2. BensimonG, LacomblezL, and MeiningerV. The ALSRSG. A Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis. N Engl J Med 1994; 330: 585–91.
3. RosenDR, SiddiqueT, PattersonD, et al. Mutations in Cu/Zn superoxide dismutase are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362: 59–62.
4. RentonAE, MajounieE, WaiteA, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-F70. Neuron 2011; 72(2): 257–68.
5. RothsteinJD. Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann Neurol 2009; 65(S1): S3–S9.
6. ClevelandDW and RothsteinJD. From Charcot to Lou Gehrig: Deciphering selective motor neuron death in ALS. Nature Reviews Neuroscience 2001; 2(11): 806–19.
7. DimosJT, RodolfaKT, NiakanKK, et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 2008; 321: 1218–21.
8. ScottS, KranzJE, ColeJ, et al. Design, power, and interpretation of studies in the standard murine model of ALS. Amyotroph Lateral Scler 2008; 9: 4–15.
9. CedarbaumJ, StamblerN, MaltaE, et al. The ALSFRS-R: a revised ALS functional rating scale that incorporated assessments of respiratory function. J Neurol Sci 1999; 169: 13–21.
10. QureshiM, SchoenfeldDA, PaliwalY, et al. The natural history of ALS is changing: Improved survival. Amyotroph Lateral Scler 2009; 10: 324–31.
11. McGuireV, Longstreth Jr W, KoepsellT, et al. Incidence of amyotrophic lateral sclerosis in three counties in western Washington State. Neurology 1996; 47: 571–3.
12. KurtzkeJ and KurlandL. The epidemiology of neurologic disease. In: JoyntR, editor. Clinical Neurology. Philadelphia, J.B. Lippincot. 1989; 1–43.
13. KurtzkeJF. Risk factors in amyotrophic lateral sclerosis. Adv Neurol 1991; 56: 245–70.
14. TraynorBJ, CoddMB, CorrB, et al. Clinical features of amyotrophic lateral sclerosis according to the El Escorial and Airlie House diagnostic criteria: A population-based study. Arch Neurol 2000; 57: 1171–6.
15. BrooksB, MillerR, SwashM, et al. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 15: 293–9.
16. GordonPH, ChengB, KatzIB, et al. The natural history of primary lateral sclerosis. Neurology 2006; 66: 647–53.
17. ConteA, MediaF, LuigettiM, et al. Survival in ALS patients after tracheostomy. 20th Symposium on ALS/MND. Berlin. 2009.
18. TraynorBJ, ZhangH, ShefnerJM, et al. Functional outcome measures as clinical trial endpoints in ALS. Neurology 2004; 63: 1933–5.
19. CudkowiczME, ShefnerJM, SchoenfeldDA, et al. A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis. Neurology 2003; 61: 456–64.
20. GoonetillekeA, Modarres-SadeghiH and GuiloffR. Accuracy, reproducibility, and variability of hand-held dynamometry in motor neuron disease. J Neurol Neurosurg Psych 1994; 57: 326–32.
21. BeckM, GiessR, WurffelW, et al. Comparison of maximal voluntary isometric contraction and Drachman’s hand-held dynamometry in evaluating patients with amyotrophic lateral sclerosis. Muscle Nerve 1999; 22: 1265–70.
22. RaoulC, EstevezA, NishimuneH, et al. Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations. Neuron 2002; 35: 1067–83.
23. ShefnerJ, RutkoveSB, DavidW, et al. Modified incremental motor unit estimation in a longitudinal natural history study of subjects with ALS. 20th International Symposium on ALS/MND. Berlin. 2009.
24. KaufmannP, LevyG, MontesJ, et al. Excellent inter-rater, intra-rater, and telephone-administered reliability of the ALSFRS-R in a multicenter clinical trial. Amyotrophic Lateral Sclerosis 2007; 8: 42–6.
25. KasarskisEJ, Dempsey-HallL, ThompsonMM, et al. Rating the severity of ALS by caregivers over the telephone using the ALSFRS-R. Amyotroph Lateral Scler Other Motor Neuron Disord 2005; 6: 50–4.
26. AppelV, StewartS, SmithG, et al. A rating scale for amyotrophic lateral sclerosis: description and preliminary experience. Ann Neurol 1987; 22: 328–33.
27. SimmonsZ, FelgoiseSH, BremerBA, et al. The ALSSQOL: Balancing physical and nonphysical factors in assessing quality of life in ALS. Neurology 2006; 67: 1659–64.
28. CudkowiczME, AndresPL, MacdonaldSA, et al. Phase 2 study of sodium phenylbutyrate in ALS. Amyotrophic Lateral Sclerosis 2009; 10: 99–106.
29. TurnerMR, KiernanMC, LeighPN, et al. Biomarkers in amyotrophic lateral sclerosis. Lancet Neurol 2009; 8: 94–109.
30. FinkelsteinD and SchoenfeldD. Combining mortality and longitudinal measures in clinical trials. Stat Med 1999; 18: 1341–54.
31. CudkowiczM, BozikME, IngersollEW, et al. The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis. Nat Med 2011; 17(12): 1652–6.
32. CudkowiczME, KatzJ, MooreDH, et al. Toward more efficient clinical trials for amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis 2010; 11: 259–65.
33. SchoenfeldDA and CudkowiczM. Design of phase II ALS clinical trials. Amyotrophic Lateral Sclerosis 2008; 9: 16–23.
34. PetraK, JohnLPT, GilbertoL, et al. Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III. Annals of Neurology 2009; 66: 235–44.
35. GordonPH, CheungY-K, LevinB, et al. A novel, efficient, randomized selection trial comparing combinations of drug therapy for ALS. Amyotrophic Lateral Sclerosis 2008; 9: 212–22.
36. LevyG, KaufmannP, BuchsbaumR, et al. A two-stage design for a phase II clinical trial of coenzyme Q10 in ALS. Neurology 2006; 66: 660–3.
37. MillerR, BradleyW, CudkowiczM, et al. Phase II/III randomized trial of TCH346 in patients with ALS. Neurology 2007; 69: 776–84.
38. GordonPH, MooreDH, MillerRG, et al. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol 2007; 6: 1045–53.
39. CudkowiczM, GreenblattD, ShefnerJ, et al. Ceftriaxone in ALS: results of stages 1 and 2 of an adaptive design safety, pharmacokinetic and efficacy trial. 20th International Symposium on ALS/MND. Berlin. 2009.
40. LacomblezL, BensimonG, LeighP, et al. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet 1996; 347: 1425–31.
41. AggarwalS and CudkowiczM. ALS drug development: reflections from the past and a way forward. Neurotherapeutics 2008; 5: 516–27.
42. BedlackRS, PastulaD, WelshE, et al. Scrutinizing enrollment in ALS clinical trials: Room for improvement?Amyotroph Lateral Scler 2008; 9: 257–65.
43. CzaplinskiA, YenAA, SimpsonEP, et al. Slower disease progression and prolonged survival in contemporary patients with amyotrophic lateral sclerosis: Is the natural history of amyotrophic lateral sclerosis changing?Arch Neurol 2006; 63: 1139–43.
44. TestaD, LovatiR, FerrariniM, et al. Survival of 793 patients with amyotrophic lateral sclerosis diagnosed over a 28-year period. Amyotroph Lateral Scler Other Motor Neuron Disord 2004; 5: 208–12.
45. TraynorBJ, AlexanderM, CorrB, et al. Effect of a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996–2000. J Neurol Neurosurg Psychiatry 2003; 74: 1258–61.
46. DattwylerRJ, HalperinJJ, PassH, et al. Ceftriaxone as effective therapy in refractory lyme disease. J Inf Dis 1987; 155: 1322–4.
47. ForshewDA and BrombergMB. A survey of clinicians’ practice in the symptomatic treatment of ALS. Amyotroph Lateral Scler Other Motor Neuron Disord 2003; 4: 258–63.
48. MillerRG, JacksonCE, KasarskisEJ, et al. Practice Parameter update: The care of the patient with amyotrophic lateral sclerosis: Drug, nutritional, and respiratory therapies (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2009; 73: 1218–26.
49. BatshawM, MacArthurR, and TuchmanM. Alternative pathway therapy for urea cycle disorders: twenty years later. J Pediatr 2001; 138(Suppl 1): S46–55.
50. LeighN, Groups atNAaEAI-S. The treatment of ALS with recombinant insulin-like growth factor (rhIGF-1): pooled analysis of two clinical trials. Neurology 1997; 1997(Suppl 1): A217–A8.