Hostname: page-component-78c5997874-m6dg7 Total loading time: 0 Render date: 2024-11-17T18:06:48.451Z Has data issue: false hasContentIssue false
  • English
  • Français

Designing dementia treatment studies: Diagnosis, efficacy criteria, and duration

Published online by Cambridge University Press:  16 April 2020

R Spiegel  and
P Irwin
R Spiegel
Affiliation:
Sandoz Pharma Ltd, Drug Registration and Regulatory Affairs, CH-4002Basel, Switzerland
P Irwin
Affiliation:
Sandoz Pharmaceuticals Corporation, Clinical Research, East Hanover, NJ07936, USA
Get access

Summary

Development of treatments for dementia is beset by special problems in defining the diagnosis, establishing efficacy criteria, and specifying the necessary duration of study. There is need for agreement among clinicians and scientists on diagnostic subgroups of dementia. Similarly, there is a need for harmonization of the regulatory guidelines in Europe, Japan, and the United States regarding the decision set of variables on which to base efficacy claims. The duration of trials must be based upon the intended claim: transient symptomatic benefit, maintained symptomatic benefit, or a therapeutic effect on disease progression. Claims other than transient benefit require long-term trials, suggested to be of at least six months in duration. Problems with long-term studies include slow patient accrual, high dropout rates, changing milieu, low return on investment, and lack of unanimity regarding regulatory requirements. Regulatory authorities must come to some accord, consonant with current clinical/scientific wisdom and consensus, regarding diagnosis, efficacy criteria, and feasible study duration, in order to attract continued sponsor investment in the development of antidementia treatments.

Keywords

dementiaclinical trialsstudy designharmonizationguidelines
Type
Research Article
Information
European Psychiatry , Volume 11 , Issue 3: Issues of Concern in the Standardization and Harmonization of Psychotropic Drug Trials in Europe , 1996 , pp. 149 - 154
Copyright
Copyright © Elsevier, Paris 1996

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

Presented, in part, to the European Committee for Standardization of Clinical Trials with Psychotropics, Strasbourg, 26–27 May 1994.

References

Amaducci, L, Angst, J, Bech, P, et al.Consensus Conference on the Methodology of Clinical Trials of “Nootropics” Munich, June 1989 Pharmacopsychiatry 1990 23; 171–175CrossRefGoogle Scholar
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. (Third Edition — Revised) Washington, DC: APA, 1987Google Scholar
Blessed, G, Tomlinson, BE, Roth, MThe association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 1968; 114: 797–811CrossRefGoogle ScholarPubMed
CPMP CPMP Working Party on Efficacy of Medicinal Products: Antidementia Medicinal products. Draft 5. Washington, DC: Commission of the European Communities, 1992Google Scholar
Crum, RM, Anthony, JC, Bassett, SS, Folstein, MFPopulation-based norms for the mini-mental state examination by age and educational level. JAMA 1993; 269: 2386–2391CrossRefGoogle ScholarPubMed
De Jong, R, Osterlund, OW, Roy, GWMeasurement of quality-of-life changes in patients with Alzheimer's Disease. Clin Therapeut 1989; 11: 545–554Google Scholar
FDA Task Force Antidementia drug assessment symposium. Ad hoc FDA Dementia Assessment Task Force Neurobiol Aging 1991 12 379–382CrossRefGoogle Scholar
Folstein, MF, Folstein, SE, McHugh, PRMini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiat Res 1975; 12: 189–201CrossRefGoogle ScholarPubMed
Huber, F, Koeberle, S, Prestele, H, Spiegel, REffects of long-term ergoloid mesylates (‘Hydergine’) administration in healthy pensioners: 5-year results. Curr Med Res Opin 1986; 10: 235–279CrossRefGoogle Scholar
Hughes, ChP, Berg, L, Danzinger, WL, Coben, LA, Martin, RLA new clinical scale for the staging of dementia. Br J Psychiatry 1982; 140: 566–572CrossRefGoogle ScholarPubMed
ICH The 2nd International Conference on Harmonization (ICH-2). Orlando, Florida 1993Google Scholar
Irwin, P, Singer, JA guide for clinical studies with potential antipsychotic or antidepressant medications. Clin Research Practices & Drug Reg Affairs 1988; 6: 293–411Google Scholar
Katz, S, Ford, AB, Moskowitz, RW, Jackson, B, Jaffe, MStudies of illness in the aged: The Index of ADL, a standardized measure of biological and psychosocial function. JAMA 1963; 185: 914–919CrossRefGoogle ScholarPubMed
Knapp, MJ, Knopman, DS, Solomon, PR, Penlebury, WW, Davis, CS, Gracon, SIA 30-week randomized controlled trial of high-dose Tacrine in patients with Alzheimer's disease. JAMA 1994; 271: 985–991CrossRefGoogle ScholarPubMed
Knopman, D, Gracon, SObservations on the short-term ‘natural history’ of probable Alzheimer's disease in a controlled clinical trial. Neurology 1994; 44: 260–265CrossRefGoogle Scholar
Lawton, MPScales to measure competence in everyday activities. Psychopharmacol Bull 1988; 24: 609–614Google ScholarPubMed
Lawton, MP, Brody, EMAssessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969; 9: 179–186CrossRefGoogle ScholarPubMed
Leach, J, Levy, RReflection on the NINCDS/ ADRDA criteria for the diagnosis of Alzheimer's disease. Editorial Int J Geriat Psychiat 1994; 9: 173–179CrossRefGoogle Scholar
Leber, PGuidelines for the Clinical Evaluation of Antidementia Drugs. First Draft. Brussels: FDA, 1990Google Scholar
Leber, PGlobal Assessment Measures. Letter to Companies involved in antidementia research. Washington, DC: FDA, 1991Google Scholar
Lucca, U, Comelli, M, Tettamanti, M, Tiraboschi, P, Spagnoli, ARate of progression and prognostic factors in Alzheimer's disease: a prospective study. J Amer Geriat Soc 1993; 41: 45–49CrossRefGoogle ScholarPubMed
Mattis, SMental state examination for organic mental syndromes in the elderly patient In: Bellak, L, Karasu, TBGeriatric Psychiatry Washington, DC: Grune & Stratton, 1976; 77–121Google Scholar
McKhann, G, Drachman, D, Folstein, M, Katzman, R, Price, D, Stadlan, EMClinical diagnosis of Alzheimer's disease. Report of the NINCDS-ADRDA Work Group. Neurology 1984; 34: 939–944CrossRefGoogle ScholarPubMed
Reisberg, B, Ferris, SH, deleon, MJ, Crook, TThe Global Deterioration Scale (GDS): An instrument for the assessment of primary degenerative dementia (PDD). Am J Psychiat 1982; 139: 1136–1139Google Scholar
Rosen, WG, Mohs, RC, Davis, KLA new rating scale for Alzheimer's disease. Am J Psychiat 1984; 141: 1356–1364Google ScholarPubMed
Spiegel, R, Brunner, C, Ermini-Fünfschilling, D, et al.A new behavioral assessment scale for geriatric out- and in-patients: the NOSGER (Nurses' Observation Scale for Geriatric Patients). JAmer Geriat Soc 1991; 39: 339–347CrossRefGoogle ScholarPubMed
Stern, RG, Mohs, RC, Davidson, M, Schmeidler, J, Silverman, J, Kramer-Ginsberg, E, Searcey, T, Bierer, L, Davis, KLA longitudinal study of Alzheimer's disease: Measurement, rate, and predictors of cognitive deterioration. Am J Psychiat 1994; 151: 390–396Google ScholarPubMed
Tremmel, L, Spiegel, RClinical experience with the NOSGER (Nurses' Observation Scale for Geriatric Patients): Tentative normative data and sensitivity to change. Int J Geriat Psychiat 1993; 8: 311–317CrossRefGoogle Scholar
Submit a response

Comments

No Comments have been published for this article.