A novel approach to delayed-start analyses for demonstrating disease-modifying effects in Alzheimer's disease

PLoS ONE

Volumn 10, Issue 3, 2015, Pages

  Liu Seifert, Hong ^a   Andersen, Scott W ^a   Lipkovich, Ilya ^a,b   Holdridge, Karen C ^a   Siemers, Eric ^a  

^a ELI LILLY AND COMPANY   (United States)

^b IQVIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SOLANEZUMAB; MONOCLONAL ANTIBODY;

ALZHEIMER DISEASE; ANALYTICAL ERROR; ARTICLE; CLINICAL STUDY; CONTROLLED STUDY; DELAYED START ANALYSIS; DISEASE COURSE; DRUG EFFICACY; DRUG SCREENING; DRUG WITHDRAWAL; METHODOLOGY; PLACEBO EFFECT; SIMULATION; BIOLOGICAL MODEL; FEMALE; HUMAN; MALE; PATHOPHYSIOLOGY; PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC);

ALZHEIMER DISEASE; ANTIBODIES, MONOCLONAL, HUMANIZED; CLINICAL TRIALS, PHASE III AS TOPIC; FEMALE; HUMANS; MALE; MODELS, BIOLOGICAL; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84924975684     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0119632     Document Type: Article

References (36)

1. th ed. Washington, DC: American Psychiatric Association; 2000.
2. Bynum JP, Rabins PV, Weller W, Niefeld M, Anderson GF, Wu AW. The relationship between a dementia diagnosis, chronic illness, Medicare expenditures, and hospital use. J Am Geriatr Soc. 2004; 52: 187-194. PMID: 14728626
3. Holtzman DM, Morris JC, Goate AM. Alzheimer' s disease: the challenge of the second century. Sci Trans Med. 2011; 3: 1-17.
4. James BD, Leurgans SE, Hebert LE, Scherr PA, Yaffe K, Bennett DA. Contribution of Alzheimer disease to mortality in the United States. Neurology. 2014; 82: 1045-1050. doi: 10.1212/WNL.0000000000000240 PMID: 24598707
5. Alzheimer's Disease International. World Alzheimer report 2010: the global economic impact of dementia. 2010. Available: http://preview.alz.org/documents/national/World-Alzheimer-Report-2010.pdf.
6. Galimberti D, Scarpini E. Disease-modifying treatments for Alzheimer's disease. Ther Adv Neurol Disord. 2011; 4: 203-216. doi: 10.1177/1756285611404470 PMID: 21765871
7. Leber P. Slowing the progression of Alzheimer disease: methodological issues. Alzheimer Dis Assoc Disord. 1997; 11: S10-21. PMID: 9348423
8. Davis KL, Thal LJ, Gamzu ER, Davis CS, Woolson RF, Gracon SI, et al. A double-blind, placebocongrolled multicenter study of tacrine for Alzheimer's disease. N Engl J Med. 1992; 327: 1253-1259. PMID: 1406817
9. Bhattaram VA, Siddiqui O, Kapcala LP, Gobburu JV. Endpoints and analyses to discern disease-modifying drug effects in early Parkinson's disease. AAPS J. 2009; 11: 456-464. doi: 10.1208/s12248-009-9123-2 PMID: 19521783
10. Zhang RY, Leon AC, Chuang-Stein C, Romano SJ. A new proposal for randomized start design to investigate disease-modifying therapies for Alzheimer disease. Clinical Trials. 2011; 8: 5-14. doi: 10.1177/1740774510392255 PMID: 21335586
11. Olanow CW, Rascol O, Hauser R, Feigen PD, Jankovic J, Langston W, et al. A double-blind, delayed-start trial of rasagiline in Parkinson's disease. NEJM. 2009; 361: 1268-78. doi: 10.1056/NEJMoa0809335 PMID: 19776408
12. FDA. Guidance for industry: non-inferiority clinical trials draft guidance. 2010; Available: http://www.fda.gov/downloads/Drugs/.../Guidances/UCM202140.pdf.
13. Hung HMJ, Wang SJ, Tsong Y, Lawrence J, O'Neil RT. Some fundamental issues with non-inferiority testing in active controlled trials. Stat Med. 2003; 22: 213-225. PMID: 12520558
14. Verbeke G, Molenberghs G. Linear mixed models for longitudinal data. New York, NY: Springer; 2000.
15. Mallinckrodt CH, Clark WS, David SR. Accounting for dropout bias using mixed-effects models. J Biopharm Stat. 2001; 11: 9-21. PMID: 11459446
16. Molenberghs G, Kenward MG. Missing data in clinical studies. Chichester: John Wiley & Sons; 2007.
17. Mallinckrodt CH, Lane PW, Schnell D, Peng Y, Mancuso JP. Recommendations for the primary analysis of continuous endpoints in longitudinal clinical trials. Drug Inf J. 2008; 42: 303-319.
18. National Research Council. The prevention and treatment of missing data in clinical trials. Panel on handling missing data in clinical trials. Committee on National Statistics, Division of Behavioral and Social Sciences and Education. Washington, DC: The National Academies Press; 2010.
19. Mallinckrodt CH, Prucka WR, Molenberghs G. Statistical issues relevant to CNS drug development (Chapter 7). In: Kalali et al. editors. Essentials in CNS drug development. New York, Cambridge Press; 2012.
20. Mallinckrodt CH. The prevention and treatment of missing data: a practical guide. New York: Cambridge University Press; 2013.
21. st ed. Hoboken, NJ: John Wiley and Sons; 2004.
22. Molenberghs G, Thijs H, Jansen I, Beunckens C, Kenward MG, Mallinckrodt C, et al. Analyzing incomplete longitudinal clinical trial data. Biostatistics. 2004; 5: 445-464. PMID: 15208205
23. Schwartz TA, Denne JS. A two-stage sample size recalculation procedure for placebo- and active-controlled non-inferiority trials. Statist Med. 2006; 25: 3396-3406. PMID: 16900573
24. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Guidance for industry, Non-Inferiority Clinical Trials, Draft Guidance, 2010. Available: http://www.fda.gov/downloads/Drugs/Guidances/UCM202140.pdf
25. Ito K, Ahadieh S, Corrigan B, French J, Fullerton T, Tensfeldt T; Alzheimer's Disease Working Group. Disease progression meta-analysis model in Alzheimer's disease. Alzheimers Dement. 2010; 6: 39-53. doi: 10.1016/j.jalz.2009.05.665 PMID: 19592311
26. Sperling RA, Jack CR Jr, Aisen PS. Testing the right target and right drug at the right stage. Sci Transl Med. 2011; 3: 111cm33. doi: 10.1126/scitranslmed.3002609 PMID: 22133718
27. Katz R. FDA: evidentiary standards for drug development and approval. NeuroRx. 2004; 1: 307-316. PMID: 15717032
28. Mani RB. Establishing claims for long term therapeutic disease progression: a US regulatory perspective. In: ISCTM Autumn Meeting, Toronto, Canada, 6-7 October 2008, Session V. Nashville: ISCTM.
29. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Summary minutes of the Peripheral and Central Nervous System Drugs Advisory Committee Meeting. October 17, 2011; Available: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCommittee/UCM284387.pdf.
30. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Guidance for industry, Alzheimer's disease: developing drugs for the treatment of early stage disease. 2013. Available: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM338287.pdf.
31. Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 2014; 370: 311-321. doi: 10.1056/NEJMoa1312889 PMID: 24450890
32. Carlson C, Sundell K, Estergard W, Raskin J, Liu-Seifert H, Case M, et al. Efficacy of solanezumab in patients with mild or moderate Alzheimer's disease: Pooled analyses findings from two phase III studies. Alzheimer's Dement. 2013; 9 Supplement:P139.
33. Uenaka K, Nakano M, Willis BA, Friedrich S, Ferguson-Sells L, Dean RA, et al. Comparison of Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of the Amyloidß Monoclonal Antibody Solanezumab in Japanese and White Patients with Mild to Moderate Alzheimer Disease. Clin Neuropharm. 2012; 35: 25-29.
34. Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT, the Donepezil Study Group. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology. 1998; 50: 136-145. PMID: 9443470
35. Rösler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, et al. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial. BMJ. 1999; 318: 633-640. PMID: 10066203
36. Wilcock GK, Lilienfeld S, Gaens E, Galantamine International-1 Study Group. Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomized controlled trial. BMJ. 2000; 321: 1-7. PMID: 10875807