Slowing the progression of Alzheimer disease: methodologic issues - PubMed (original) (raw)
. 1997:11 Suppl 5:S10-21; discussion S37-9.
Affiliations
- PMID: 9348423
Slowing the progression of Alzheimer disease: methodologic issues
P Leber. Alzheimer Dis Assoc Disord. 1997.
Abstract
The evidence to support a claim that a new drug will slow the progression of Alzheimer disease (AD) must derive from epistemologically valid research methods. Although agency regulations do not specify the magnitude of an effect that a drug must possess to be granted a claim as a treatment for AD, the evidence to support any claim must be adduced in adequate and well-controlled clinical investigations and must meet the standard of "substantial evidence." Because a claim presented in drug product labeling may not be false or misleading in any particular, a distinction must be made between treatments that provide a "symptomatic" benefit and those that alter the course of dementia. Examples of some of the difficulties likely to be encountered by sponsors seeking to develop evidence to support a claim that a new drug slows the progression of dementia are presented. A suggestion is made for a clinical trial design, designated as the "randomized start design," that may be useful in such a question. Why this design might overcome many of the difficulties, both practical and ethical, present in the "discontinuation" design, the design ordinarily proposed to assess a drug's effect on disease progression, is discussed.
Similar articles
- A new proposal for randomized start design to investigate disease-modifying therapies for Alzheimer disease.
Zhang RY, Leon AC, Chuang-Stein C, Romano SJ. Zhang RY, et al. Clin Trials. 2011 Feb;8(1):5-14. doi: 10.1177/1740774510392255. Clin Trials. 2011. PMID: 21335586 - Comparing the power of the discontinuation design to that of the classic randomized design on time-to-event endpoints.
Capra WB. Capra WB. Control Clin Trials. 2004 Apr;25(2):168-77. doi: 10.1016/j.cct.2003.11.005. Control Clin Trials. 2004. PMID: 15020035 - Protocols to demonstrate slowing of Alzheimer disease progression. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines. The Disease Progression Sub-Group.
Bodick N, Forette F, Hadler D, Harvey RJ, Leber P, McKeith IG, Riekkinen PJ, Rossor MN, Scheltens P, Shimohama S, Spiegel R, Tanaka S, Thal LJ, Urata Y, Whitehouse P, Wilcock G. Bodick N, et al. Alzheimer Dis Assoc Disord. 1997;11 Suppl 3:50-3. Alzheimer Dis Assoc Disord. 1997. PMID: 9305517 - Diagnosis of dementia and treatment of Alzheimer's disease. Pharmacologic management of disease progression and cognitive impairment.
van Reekum R, Simard M, Farcnik K. van Reekum R, et al. Can Fam Physician. 1999 Apr;45:945-52. Can Fam Physician. 1999. PMID: 10216793 Free PMC article. Review. - Outcome measures in clinical trials on medicinal products for the treatment of dementia: a European regulatory perspective.
Broich K. Broich K. Int Psychogeriatr. 2007 Jun;19(3):509-24. doi: 10.1017/S1041610207005273. Epub 2007 Apr 16. Int Psychogeriatr. 2007. PMID: 17433121 Review.
Cited by
- Challenges to demonstrating disease-modifying effects in Alzheimer's disease clinical trials.
Cummings JL. Cummings JL. Alzheimers Dement. 2006 Oct;2(4):263-71. doi: 10.1016/j.jalz.2006.07.001. Alzheimers Dement. 2006. PMID: 19595897 Free PMC article. - A novel approach to delayed-start analyses for demonstrating disease-modifying effects in Alzheimer's disease.
Liu-Seifert H, Andersen SW, Lipkovich I, Holdridge KC, Siemers E. Liu-Seifert H, et al. PLoS One. 2015 Mar 17;10(3):e0119632. doi: 10.1371/journal.pone.0119632. eCollection 2015. PLoS One. 2015. PMID: 25781335 Free PMC article. - Clinical trial design issues in mild to moderate Alzheimer disease.
Knopman DS. Knopman DS. Cogn Behav Neurol. 2008 Dec;21(4):197-201. doi: 10.1097/WNN.0b013e318190cf75. Cogn Behav Neurol. 2008. PMID: 19057167 Free PMC article. Review. - Optimum Design of Disease-modifying Trials on Alzheimer's Disease.
Xiong C, Luo J, Gao F, Chen L, Yan Y. Xiong C, et al. Stat Biopharm Res. 2012 Aug 30;4(3):216-227. doi: 10.1080/19466315.2011.634757. Stat Biopharm Res. 2012. PMID: 23626866 Free PMC article. - FDA: evidentiary standards for drug development and approval.
Katz R. Katz R. NeuroRx. 2004 Jul;1(3):307-16. doi: 10.1602/neurorx.1.3.307. NeuroRx. 2004. PMID: 15717032 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Medical