Clinical research designs for emerging treatments for Alzheimer disease: Moving beyond placebo-controlled trials

Archives of Neurology

Volumn 55, Issue 11, 1998, Pages 1425-1429

  Knopman, David ^{a,b,c,d,e,f,g}   Kahn, Jeffrey ^a   Miles, Steven ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

^b PFIZER INC   (United States)

^c Athena Neurosciences Inc   (United States)

^d BAYER CORPORATION   (United States)

^e NOVARTIS PHARMA AG   (Switzerland)

^f WYETH AYERST RESEARCH   (United States)

^g Forest Pharmaceutical Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA TOCOPHEROL; DONEPEZIL; TACRINE;

ALZHEIMER DISEASE; ARTICLE; CLINICAL TRIAL; DRUG EFFICACY; DRUG RESEARCH; DRUG SAFETY; DRUG TOLERABILITY; HUMAN; METHODOLOGY; PRIORITY JOURNAL; VALIDATION PROCESS;

EID: 0031759502     PISSN: 00039942     EISSN: None     Source Type: Journal    
DOI: 10.1001/archneur.55.11.1425     Document Type: Article

References (31)

1. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med. 1987; 317;141-145.
2. Alderson P. Equipoise as a means of managing uncertainty: personal, communal and proxy. J Med Ethics. 1996;22:135-139.
3. Council for International Organization of Medical Sciences. International ethical guidelines for biomedical research involving human subjects. Geneva, Switzerland: World Health Organization; 1993.
4. Rothman KJ, Michels KB. The continuing unethical use of placebo controls. N Engl J Med. 1994;331:394-398.
5. Shuster E. Fifty years later: the significance of the Nuremberg Code. N Engl J Med. 1997;337:1436-1440.
6. Cleophas TJ, Van der Meulen J, Kalmansohn RB. Phase III trials: specific problems associated with the use of a placebo control group. Int J Clin Pharmacol Ther. 1997;35:47-50.
7. Collier J. Confusion over use of placebos in clinical trials. BMJ. 1995;311: 821-822.
8. De Deyn PP, D'Hooge R. Placebos in clinical practice and research. J Med Ethics. 1996;22:140-146.
9. Clark PI, Leaverton PE. Scientific and ethical issues in the use of placebo controls in clinical trials. Annu Rev Public Health. 1994;15:19-38.
10. Palter SF. Ethics of clinical trials. Semin Reprod Endocrinol. 1996;14:85-92.
11. Knapp MJ, Knopman DS, Solomon PR, Pendlebury WW, Davis CS, Gracon SI. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. JAMA. 1994;271:985-991.
12. Rogers SL, Doody R, Mohs R, Friedhoff LT. E2020 produces both clinical global and cognitive test improvement in patients with mild to moderately severe Alzheimer's disease: results of a 30-week phase III trial. Neurology. 1998;50: 136-145.
13. Morris J, Cyrus P, Orazem J, et al. Metrifonate benefits cognitive, behavioral, and global function in patients with AD. Neurology. 1998;50:1222-1230.
14. Corey-Bloom J, Anand R, Veach J, for the ENA 713 B352 Study Group. A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer's disease. Int J Geriatr Psychopharm. 1998;1:55-65.
15. Wilcock G, Wilkinson D. Galanthamine hydrobromide: interim results of a group comparative, placebo controlled study of efficacy and safety in patients with a diagnosis of senile dementia of the Alzheimer type. Neurobiol Aging. 1996;17 (suppl 4s):S144.
16. Thai LJ, Schwartz G, Sano M, et al. A multicenter double-blind study of controlled-release physostigmine for the treatment of symptoms secondary to Alzheimer's disease. Neurology. 1996;47:1389-1395.
17. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. N Engl J Med. 1997; 336:1216-1222.
18. Freedman B, Glass KC, Weijer C. Placebo orthodoxy in clinical research, II: ethical, legal, and regulatory myths. J Law Med Ethics. 1996;24:252-259.
19. Freedman B, Weijer C, Glass KC. Placebo orthodoxy in clinical research, I: empirical and methodological myths. J Law Med Ethics. 1996;24:243-251.
20. Beck TM, Ciociola AA, Jones SE, et al. Efficacy of oral ondansetron in the prevention of emesis in outpatients receiving cyclophosphamide-based chemotherapy: The Ondansetron Study Group. Ann Intern Med. 1993;118:407-413.
21. Markman M. When regulatory requirements conflict with ethical study design: the case of oral ondansetron. Cancer Invest. 1994;12:654-656.
22. Citron ML. Placebos and principles: a trial of ondansetron. Ann Intern Med. 1993; 118:470-471.
23. American Psychiatric Association. Practice guidelines for major depressive disorder in adults. Am J Psychiatry. 1993;150(suppl 4):1-26.
24. Hass WK, Easton JD, Adams HP Jr, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. N Engl J Med. 1989;321:501-507.
25. Ray WA, Griffin MR, Avorn J. Evaluating drugs after their approval for clinical use. N Engl J Med. 1993;329:2029-2032.
26. Gram L, Schmidt D. Innovative designs of controlled clinical trials in epilepsy. Epilepsia. 1993;34(suppl 7):S1-S6.
27. Fields WS, Maslenikov V, Meyer JS, et al. Joint study of extracranial arterial occlusion, V: progress report of prognosis following surgery or non-surgical treatment for transient cerebral ischemic attacks and cervical carotid artery lesions. JAMA. 1970;211:1993-2003.
28. NASCET Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991;325: 445-453.
29. Ware JH, Antman EM. Equivalence trials. N Engl J Med. 1997;337:1159-1161.
30. Wechsler H, Grosser GH, Greenblatt M. Research evaluating antidepressant medications on hospitalized mental patients: a survey of published reports during a five year period. J Nerv Ment Dis. 1965;141:231-239.
31. Leber P. Slowing the progression of Alzheimer disease: methodological issues. Alzheimer Dis Assoc Disord. 1997;11 (suppl 5):S10-S21.