Hostname: page-component-797576ffbb-6mkhv Total loading time: 0 Render date: 2023-12-04T16:57:51.340Z Has data issue: false Feature Flags: { "corePageComponentGetUserInfoFromSharedSession": true, "coreDisableEcommerce": false, "useRatesEcommerce": true } hasContentIssue false

Facilitating Regulation: The Dance of Statistical Significance and Clinical Meaningfulness in Standardizing Technologies for Dementia

Published online by Cambridge University Press:  01 September 2008

Janice E. Graham
Department of Bioethics, Faculty of Medicine, Dalhousie University, 5849 University Avenue, Room C-315, Halifax, NS B3H 4H7Canada E-mail:
Get access


Regulatory activities are intended to safeguard the health of citizens by ensuring that new drug therapies meet the highest standards of safety, efficacy and quality. Recent initiatives emphasize streamlining and speeding up approval, and are intent on harmonizing standards for international competitive advantage. In Canada and the United Kingdom, a second order of evaluation is necessary in order to have the costs of a federally licensed drug covered under provincial or state health insurance programmes resulting in wider patient access to potentially cost-prohibitive products. While new therapies can get approved by federal regulatory scientists based upon acceptable evidence from data meeting the standards of safety, quality and efficacy, the determination of the formulary committees, such as the UK National Institute for Health and Clinical Excellence (NICE), or the Canadian Common Drug Review (CDR), take into consideration the economic costs and benefits of the therapeutic agent. This analysis considers the technical-political-social-moral positions taken by various actors involved in legitimizing and contesting the effectiveness of cholinesterase inhibitors (ChEIs) for treating people with Alzheimer’s disease. It examines ambiguities in the ‘norms of appropriateness and legitimacy’ of clinician researchers, and the construction and legitimization of what is appropriate in clinical research and regulatory practices.

Copyright © London School of Economics and Political Science 2008

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.)


Abraham, J. (2002). The pharmaceutical industry as a political player. Lancet, 360(9344), 14981502.Google Scholar
Aisen, P.S. (2000). Anti-inflammatory therapy for Alzheimer’s disease: Implications of the prednisone trial. Acta Neurologica Scandinavica Suppl. 176: 8589.Google Scholar
Alzheimer’s Society. (2006). NICE fails dementia. Country Doctor. URL (accessed November 2007): Scholar
American Psychiatric Association. (1987). Diagnostic and statistical manual of mental disorders, 3rd edn—Revised, Washington, DC: American Psychiatric Association.Google Scholar
American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders, 4th edn.Washington, DC: American Psychiatric Association.Google Scholar
Badiou, A. (2001). Ethics: An essay on the understanding of evil. trans.Hallward, P.. London and New York: Verso.Google Scholar
Baker, F.M., Ogunniyi, A., & Osuntokun, B.O. (1995). A pilot study of dementia in Ibadan, Nigeria. Journal of Geriatric Psychiatry and Neurology, 8, 6570.Google Scholar
Baron, J.-C. (2006). Monitoring changes in brain anatomy with time. Alzheimer’s Disease & Dementia, 2(3), Suppl 1: S45–6.Google Scholar
Bassett, K., Wright, J.M., Puil, L., Perry, T.L.Jr, Heran, B., & Cole, C. (2002). Cyclooxygenase-2 inhibitor update: Journal articles fail to tell the full story. Canadian Family Physician, 48, 14551460. Also available as Therapeutics Letter, 43(2001), URL (accessed February 2007):; Scholar
BBC News. (2006). The drug improved both our lives. BBC News Online, 10 October. URL (accessed February 2007): Scholar
Björkman, I.K., Bernstein, C.B., Schmidt,, I.K., & Holmström,, I. (2005). The role of drug and therapeutics committees: Perception of chairs and information officers. International Journal of Health Care Quality Assurance, 18(4), 235248.Google Scholar
Black, J. (1998). Regulation as facilitation: Negotiating the genetic revolution. Modern Law Review, 61, 621660.Google Scholar
Black, J. (2005). Toward’s worlds: Frameworks for understanding regulatory innovation. In Black, J., Lodge, M. & Thatcher, M. (Eds), Regulatory innovation: A comparative analysis, 16–44. Cheltenham, UK: Edward Elgar.Google Scholar
Blennow, K., & Zetterberg, H. (2006). Pinpoint plaques with PIB. Nature Medicine, 12, 753754.Google Scholar
Brayne, C., & Calloway, P. (1988). Normal ageing, impaired cognitive function, senile dementia of the Alzheimer’s type: A continuum? Lancet, 1(8597), 12651267.Google Scholar
Buckholtz, N.S., & Radebaugh, T.S. (1994). National Institute on Aging collaborative studies in the standardization of cognitive measures. Alzheimer Disease and Associated Disorders, 8, Suppl 1, S214S216.Google Scholar
Burville, P.W. (1993). A critique of current criteria for early dementia in epidemiological studies. International Journal of Geriatric Psychiatry, 8, 553559.Google Scholar
Cacabelos, R. (2008). Pleiotropic effects of Apolipoprotein E in dementia: Influence on functional genomics and pharmacogenetics. In Fisher, A., Maurizio, M., Stocchi, F. & Hanin, I. (Eds), Advances in Alzheimer’s and Parkinson’s Disease. New York: Springer.Google Scholar
Canadian Study of Health and Aging Working Group (CSHA) (1994). Canadian Study of Health and Aging: Study methods and prevalence of dementia. Canadian Medical Association Journal, 150, 899913.Google Scholar
Caulfield, T. (2001). Globalization, conflicts of interest and clinical research: An overview of trends and issues. Widener Law Symposium Journal, 8, 3245.Google Scholar
Chui, H.C., Victoroff, J.I., Margolin, D., Jagust, W., Shankle, R., & Katzman, R. (1992). Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer’s Disease Diagnostic and Treatment Centers. Neurology, 42, 473480.Google Scholar
Corder, E.H., Saunders, A.M., Strittmatter, W.J., Schmechel, D.E., Gaskell, P.C., Small, G.W. et al. (1993). Gene dose of Apoliprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science, 261, 921923.Google Scholar
Corner, L., & Bond, J. (2006). The impact of the label of mild cognitive impairment on the individual’s sense of self. Philosophy, Psychology and Psychiatry, 13(2), 312.Google Scholar
Courtney, C., Farrell, D., Gray, R., Hills, R., Lynch, L., Sellwood, E. et al. (2004). Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): Randomised double-blind trial. Lancet, 363(9427), 21052115.Google Scholar
Coyle, J.T., Proce, D.L., & DeLong, M.R. (1983). Alzheimer’s disease: A disorder of cortical cholinergic innervation. Science, 219, 11841190.Google Scholar
Dalziel, W.B. (1994). Dementia: No longer the silent epidemic. Canadian Medical Association Journal, 151, 11407–1409.Google Scholar
Davis, K.I, & Mohs, R.C. (1986). Cholinergic drugs in Alzheimer’s disease. New England Journal of Medicine, 315, 12861287.Google Scholar
Day, M. (2006). NICE says anti-dementia drugs should be used only for moderate Alzheimer’s disease. British Medical Journal, 333, 774.Google Scholar
Eco, U. (1990). The limits of interpretation. Bloomington: Indiana UP.Google Scholar
Eisai Ltd. (2008). Court of Appeal makes decision following ruling that NICE process on anti-dementia medicines unfair. URL (accessed June 2008): Scholar
Ernst, R., & Hay, J. (1997). Economic research on Alzheimer disease: A review of the literature. Alzheimer Disease Associated Disorders, 11, 135145.Google Scholar
Evans, R., & Bosely, S. (2006). Drug firms’ lobby tactics revealed. The Guardian, 28 September. URL (accessed February 2007):,,1882581,00.htmlGoogle Scholar
Feinstein, A.R. (1987). Clinimetrics. New Haven, CT: Yale UP.Google Scholar
Feinstein, A.R. (1994). ‘Clinical judgment’ revisited: The distraction of quantitative models. Annals of Internal Medicine, 120, 799805.Google Scholar
Feldman, H.H., Gauthier, S., Chertkow, H., Conn, D.K., Freedman, M., & Chris, M.; 2nd Canadian Conference on Antidementia Guidelines. (2006). Progress in clinical neurosciences: Canadian guidelines for the development of antidementia therapies: A conceptual summary. Canadian Journal of Neurological Science, 33, 626.Google Scholar
Ferri, C.P., Prince, M., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M. et al. ; Alzheimer’s Disease International. (2006). Global prevalence of dementia: a Delphi consensus study. Lancet, 366(9503): 21122117.Google Scholar
Freedman, B. (1987). Equipoise and the ethics of clinical research. New England Journal of Medicine, 317, 141145.Google Scholar
Fujimura, J.H. (1996). Crafting science: A sociohistory of the quest for the genetics of cancer. Cambridge, MA: Harvard UP.Google Scholar
Fujimura, J.H. (1998). Authorizing knowledge in science and anthropology. American Anthropologist, 100, 347360.Google Scholar
Goate, A. (2006). Segregation of a missense mutation in the amyloid ß-protein precursor gene with familial Alzheimer’s disease. Journal of Alzheimer’s Disease, 9, 341347.Google Scholar
Goate, A., Chartier-Hardin, M.C., Mullan, M., Brown, J., Crawford, F., Fidani, L. et al. (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature, 349, 704706.Google Scholar
Graham, J. (2001). Harbinger of hope or commodity fetishism: Re-cognizing dementia in an age of therapeutic agents. International Psychogeriatrics, 13(2), 131134.Google Scholar
Graham, J., & Bassett, R. (2006). Reciprocal relations: The recognition and co-construction of caring with Alzheimer’s disease. Journal of Aging Studies, 20(4), 335349.Google Scholar
Graham, J., & Ritchie, K. (2006). Mild cognitive impairment: Ethical considerations for nosological flexibility in human kinds. Philosophy, Psychology and Psychiatry, 13(2), 3143.Google Scholar
Graham, J., Mitnitski, A.B., Mogilner, A.J., & Rockwood, K. (1999). The dynamics of cognitive aging: Distinguishing functional age and disease from chronological age in a population. American Journal of Epidemiology; 150, 10451054.Google Scholar
Graham, J., Rockwood, K., Beattie, B.L., McDowell, I., Eastwood, M.R., & Gauthier, S. (1996). Standardization of the diagnosis of dementia in the Canadian Study of Health and Aging. Neuroepidemiology, 15, 246256.Google Scholar
Graham, J., Rockwood, K., Beattie, B.L.Eastwood, R., Gauthier, S., Tuokko, H. et al. (1997). Prevalence and severity of cognitive impairment with and without dementia in an elderly population. Lancet, 349(9068), 17931796.Google Scholar
Groves, K. (2006). The influence of pharmaceutical marketing activity, practice characteristics and physician profile on physician prescribing behaviour. PhD dissertation, Dalhousie University, Nova Scotia, Canada.Google Scholar
Hardy, J., & Cullen, K. (2006). Amyloid at the blood vessel wall. Nature Medicine, 12, 756757.Google Scholar
Hofman, A., Rocca, W.A., Brayne, C., Breteler, M.M.B., Clarke, M., Cooper, B. et al. (1991). The prevalence of dementia in Europe: A collaborative study of 1980–1990 findings. International Journal of Epidemiology, 20, 736748.Google Scholar
Joffres, C., Graham, J., & Rockwood, K. (2000). A qualitative analysis of the clinician interview-based impression of change (plus): Methodological issues and implications for clinical research. International Psychogeriatrics, 12, 401415.Google Scholar
Jorm, A.F., Korten, A.E., & Henderson, A.S. (1987). The prevalence of dementia: A quantitative integration of the literature. Acta Psychiatrica Scandinavica, 76, 465479.Google Scholar
Kaduszkiewicz, H. (2006). An innovative approach to involve patients in measuring treatment effects in drug trials. Canadian Medical Association Journal, 174, 11171118.Google Scholar
Kaduszkiewicz, H., Zimmermann, T., Beck-Bornholdt, H.-P., & van den Bussche, H. (2005). Cholinesterase inhibitors for patients with Alzheimer’s disease: Systematic review of randomised clinical trials. British Medical Journal, 331, 321327.Google Scholar
Keating, P., & Cambrosio, A. (2003). Biomedical platforms. Cambridge, MA: MIT Press.Google Scholar
Kendall, T., & McGoey, L. (2007). Truth, disclosure and the influence of industry on the development of NICE guidelines: An interview with Tim Kendall. BioSocieties, 2, 129140.Google Scholar
Kielhofner, G., & Barrett, L. (1998). Meaning and misunderstanding in occupational forms: A study of therapeutic goal setting. American Journal of Occupational Therapy, 52, 345353.Google Scholar
Kleinman, A. (1995). Writing at the margin: Discourse between anthropology and medicine. Berkeley: U California Press.Google Scholar
Knopman, D.S., Knapp, M.J., Gracon, S.I., & Davis, C.S. (1994). The Clinician Interview-Based Impression (CIBI): A clinician’s global change rating scale in Alzheimer’s disease. Neurology, 44, 23152321.Google Scholar
Kodish, E., Murray, T., & Whitehouse, P. (1996). Conflict of interest in university–industry research relationships: Realities, politics and values. Academic Medicine, 71(12), 12871290.Google Scholar
Lanctôt, K.L., Herrmann, N., Yau, K.K., Khan, L.R., Liu, B.A., LouLou, M.M. et al. (2003). Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: A meta-analysis. Canadian Medical Association Journal, 169, 557564.Google Scholar
Larrieu, S., Letenneur, L., Orgogozo, J.M., Fabrigoule, C., Amieva, H., Le Carret, N. et al. (2002). Incidence and outcome of mild cognitive impairment in a population-based prospective cohort. Neurology, 59, 15941599.Google Scholar
Latour, B., & Woolgar, S. (1986). Laboratory life: The construction of scientific facts. Princeton. NJ: Princeton UP.Google Scholar
Leber, P.D. (1990). Guidelines for the clinical evaluation of anti-dementia drugs, 1st draft. Rockville, MD: US Food and Drug Administration.Google Scholar
Leber, P.D. (1997a). Slowing the progression of Alzheimer disease: Methodologic issues. Alzheimer Disease & Associated Disorders, 11, 1020.Google Scholar
Leber, P.D. (1997b). Developing safe and effective anti-dementia drugs. In Becker, R., & Giacobini, E. (Eds), Alzheimer disease: From molecular biology to therapy, 579–584. Boston, MA. Birkhäuser.Google Scholar
Ledford, H. (2008). Drug markers questioned. Nature, 452, 510511.Google Scholar
Lee, V.M.-Y., & Trojanowski, J.Q. (2006). Progress from Alzheimer’s tangles to pathological tau points towards more effective therapies now. Journal of Alzheimer’s Disease, 9, 257262.Google Scholar
Lemmens, T., Liclur, L.L.M., & Singer, P.A. (1998). Bioethics for clinicians: 17. Conflict of interest in research, education and patient care. Canadian Medical Association Journal, 159, 960965.Google Scholar
Lexchin, J., Bero, L.A., Djulbegovic, B., & Clark, O. (2003). Pharmaceutical industry sponsorship and research outcome and quality: Systematic review. British Medical Journal, 326, 11671170.Google Scholar
Lopez, O.L., Larumbe, M.R., Becker, J.T., Rezek, D., Rosen, J., Klunk, W. et al. (1994). Reliability of NINDS-AIREN clinical criteria for the diagnosis of vascular dementia. Neurology, 44, 12401245.Google Scholar
Lopez, O.L., Swihart, A.A., Becker, J.T., Reinmuth, O.M., Reynolds, C.F., Rezek, D.L. et al. (1990). Reliability of NINCDS-ADRDA clinical criteria for the diagnosis of Alzheimer’s disease. Neurology, 40, 15171522.Google Scholar
Mallinson, T., Kielhofner, G., & Mattingly, C. (1996). Metaphor and the meaning in a clinical interview. American Journal of Occupational Therapy, 50, 338346.Google Scholar
Mandavilli, A. (2006). The Amyloid code. Nature Medicine, 12, 746751.Google Scholar
March, J.G., & Olsen, J.P. (1984). The new institutionalism: Organizational factors in political life. American Political Science Review, 78, 734749.Google Scholar
Marks, H.M. (1997). The progress of experiment: Science and therapeutic reform in the United States, 1900–1990. Cambridge: Cambridge UP.Google Scholar
Marx, J.L. (1987). Alzheimer’s drug trial put on hold. Science, 238, 10411042.Google Scholar
McAllister, J.C. (2000). Fortresses and formularies: Response 3. American Journal of Health-System Pharmacy, 57, 859860.Google Scholar
McKeith, I., Perry, R.H., Fairbairn, A.F., Jabeen, S., & Perry, E.K. (1992). Operational criteria for senile dementia of Lewy body type. Psychological Medicine, 22, 911922.Google Scholar
McKeith, I., Mintzer, J., Arsland, D., Burn, D., Chiu, H., Cohen-Mansfield, D. et al. (2004). Dementia with Lewy bodies. Lancet Neurology, 3, 1928.Google Scholar
McKeith, I.G., Dickson, D.W., Lowe, J., Emre, M., O’Brien, J.T., Cummings, J. et al. (2005). Diagnosis and management of dementia with Lewy bodies. 3rd Report of the DLB Consortium. Neurology, 65, 18631872.Google Scholar
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E.M. (1984). Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology, 34, 939944.Google Scholar
McKhann, G.M., Albert, M.S., Grossman, M., Miller, B., Dickson, D., Trojanowski, J. et al. (2001). Clinical and pathological diagnosis of frontotemporal dementia: Report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Archives of Neurology, 58, 18031809.Google Scholar
Medical News Today. (2006). ABPI condemns NICE’s decision on Alzheimer’s medicines, UK. Medical News Today Online, 12 October. URL (accessed February 2006): Scholar
Mendez, M.F., Mastri, A.R., Sung, J.H., & Frey, W.H. (1992). Clinically diagnosed Alzheuner disease: Neuropathologic findings in 650 cases. Alzheimer Disease and Associated Disorders, 6, 3543.Google Scholar
Mintzes, B., Barer, M.L., Kravitz, R.L., Bassett, K., Lexchin, J., Kazanjian, A. et al. (2003). How does direct-to-consumer advertising (DTCA) affect prescribing? A survey in primary care environments with and without legal DTCA. Canadian Medical Association Journal, 169, 405412.Google Scholar
Mitnitski, A.B., Graham, J., Mogilner, A.J., & Rockwood, K. (1997). Vector diagnostics in dementia derived from Bayes’ theorem. American Journal of Epidemiology, 146, 665671.Google Scholar
Morris, J.C., Heyman, A., Moms, R.C., Hughes, J.P., Van Belle, G., Fillenbaum, G. et al. (1989). The consortium to establish a registry for Alzheimer’s disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer’s disease. Neurology, 39, 11591165.Google Scholar
Mulnard, R.A., Cotman, C.W., Kawas, C., van Dyck, C.H., Sano, M., Doody, R. et al. (2000). Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: A randomized controlled trial. Alzheimer’s Disease Cooperative Study. Journal of the American Medical Association, 283, 10071015.Google Scholar
National Institute for Clinical Excellence (NICE) (2001). Guidance on the use of donepezil, rivastigmine and galantamine for the treatment of Alzheimer’s disease: Technology appraisal guidance No. 19. URL (accessed February 2007):’_full_guidance.pdfGoogle Scholar
National Institute for Health and Clinical Excellence (NICE) (2006). Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer’s disease: Technology appraisal guidance No. 111. URL (accessed February 2007): Scholar
National Institute for Health and Clinical Excellence (NICE) (2008). Amendment of technology appraisal 111. URL (accessed June 2008): Scholar
Neary, D., Snowden, J.S., Gustafson, L., Passant, U., Stuss, D., Black, S. et al. (1998). Frontotemproal lobar degeneration: A consensus on clinical diagnostic criteria. Neurology, 51, 15461554.Google Scholar
O’Connor, D.W. (1990). The contribution of CAMDEX to the diagnosis of mild dementia in community surveys. Psychiatry Journal of University of Ottawa, 15, 216220.Google Scholar
Ostbye, T., & Crosse, E. (1994). Net economic cost of dementia in Canada. Canadian Medical Association Journal, 151, 14571464.Google Scholar
Osuntokun, B.O., Hendrie, H.C., Ogunniyi, A.O., Hall, K.S., Lekwauwa, U.G., Brittain, H.M. (1992). Cross-cultural studies in Alzheimer’s disease. Ethnicity and Disease, 2, 352357.Google Scholar
Osuntokun, B.O., Ogunniyi, A.O., Lekwauwa, U.G., & Oyediran, A.B. (1991). Epidemiology of age-related dementias in the Third World and aetiological clues of Alzheimer’s disease. Tropical and Geographical Medicine, 43, 345351.Google Scholar
PausJenssen, M.A., Singer, P.A., & Detsky, A.S. (2003). Ontario’s formulary committee: How recommendations are made. PharmacoEconomics, 21, 285294.Google Scholar
Pericak-Vance, M.A. (1991). Linkage studies in familial Alzheimer’s disease: Evidence for chromosome 19 linkage. American Journal of Human Genetics, 48, 10341050.Google Scholar
Perras, C., Shukla, V.K., Lessard, C., Skidmore, B., Bergman, H., & Gauthier, S. (2005). Cholinesterase inhibitors for Alzheimer’s disease: A systemic review of randomized controlled trials [Technology report no. 58]. Ottawa: Canadian Coordinating Office for Health Technology Assessment/Canadian Agency for Drugs and Technologies in Health. URL (accessed February 2007): Scholar
Poirier, J., Delisle, M.C., Quirion, R., Aubert, I., Farlow, M., Lahiri, D. et al. (1995). Apolipoprotein E allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. Proceedings of the National Academy of Sciences, 92, 1226012264.Google Scholar
Ritchie, K., Leibovici, D., Ledésert, B., & Touchon, J. (1996). A typology of sub-clinical senescent cognitive disorder. British Journal of Psychiatry, 168, 470476.Google Scholar
Rocca, W.A., Hofman, A., Brayne, C., Breteler, M.M., Clarke, M., Copeland, J.R et al. (1991a). Frequency and distribution of Alzheimer’s disease in Europe: A collaborative study of 1980–1990 prevalence findings. Annals of Neurology, 30, 381390.Google Scholar
Rocca, W.A., Hofman, A., Brayne, C., Breteler, M.M., Clarke, M., Copeland, J.R. et al. (1991b). The prevalence of vascular dementia in Europe: Facts and fragments from 1980–1990. Annals of Neurology, 30, 817824.Google Scholar
Rockwood, K., & Graham, J. (1997). Protocol for defining the expectations and effects of treatment with an anti-dementia medication (donepezil) in patients with Alzheimer’s disease. The Atlantic Canadian Alzheimer’s Disease Investigations of Expectations.Google Scholar
Rockwood, K., & MacKnight, C. (2001). Assessing the clinical importance of statistically significant improvement in anti-dementia drug trials. Neuroepidemiology, 20, 5156.Google Scholar
Rockwood, K., Graham, J., & Fay, S. (2002). Goal setting and attainment in patients with Alzheimer’s disease treated with donepezil. Journal of Neurology, Neurosurgery, and Psychiatry, 73, 500507.Google Scholar
Rockwood, K., Fay, S., Song, X., MacKnight, C., & Gorman, M. (2006). Attainment of treatment goals by people with Alzheimer’s disease receiving galantamine: A randomized control trial. Canadian Medical Association Journal, 174, 10991105.Google Scholar
Rogers, S.L., & Friedhoff, L.T. (1996). The efficacy and safety of donepezil in patients with Alzheimer’s disease: Results of a US multicentre, randomized, double-blind, placebo-controlled trial. The Donepezil Study Group. Dementia, 7(6), 293303.Google Scholar
Rogers, S.L., Farlow, M.R., Doody, R.S., Mohs, R., & Friedhoff, L.T. (1998). A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Donepezil Study Group. Neurology, 50, 136145.Google Scholar
Román, G.C., Tatemichi, T.K., Erkinjuntii, T., Cummings, J.L., Masedu, J.C., Garcia, J.H. et al. (1993). Vascular dementia: Diagnostic criteria for research studies. Neurology, 43, 250260.Google Scholar
Rosen, W.G., Mohs, R.C., & Davis, K.L. (1984). A new rating scale for Alzheimer’s disease. American Journal of Psychiatry, 141, 13561364.Google Scholar
Schellenberg, G.G., Bird, T.D., Wijsman, E.M., Orr, H.T., Anderson, L., Nemens, E. et al. (1992). Genetic linkage evidence for a familial Alzheimer’s disease locus on chromosome 14. Science, 258, 668671.Google Scholar
Schneider, L.S. (2004). AD2000: Donepezil in Alzheimer’s disease (Commentary). Lancet, 363(9427), 21002101.Google Scholar
Schneider, L.S. (2006). The post-modern world of Alzheimer’s disease: How much is an ADAS–Cog point worth in central London? Journal of Geriatric Psychiatry, 21, 913.Google Scholar
Schneider, L.S., Olin, J.T., Doody, R.S., Clark, C.M., Morris, J.C., Reisberg, B. et al. (1997). Validity and reliability of the Alzheimer’s Disease Cooperative Study—clinical global impression of change. The Alzheimer’s Disease Cooperative Study. Alzheimer Disease and Associated Disorders, 11(Suppl 2), S2232.Google Scholar
Selkoe, D.J. (2006). The ups and downs of Aß. Nature Medicine, 12, 758759.Google Scholar
St George-Hyslop, P.H., Ranzi, R.E., Polinsky, R.J., Haines, J.L., Nee, L., Watkins, P.C. et al. (1987). The genetic defect causing familial Alzheimer’s disease maps on chromosome 21. Science, 235, 885890.Google Scholar
Stern, R.G., Mohs, R.C., Davidson, M., Schmeidler, J., Silverman, J., Kramer-Ginsberg, E. et al. (1994). A longitudinal study of Alzheimer’s disease: Measurement, rate and predictors of cognitive deterioration. American Journal of Psychiatry, 151, 390396.Google Scholar
Strathern, M. (2000). Audit cultures: Anthropological studies in accountability, ethics, and the academy. London: Routledge.Google Scholar
Summers, W.K., Majovski, L.V., Marsh, G.M., Tachiki, K., & Kling, A. (1986). Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. New England Journal of Medicine, 315, 12411245.Google Scholar
Talon, D., Chard, J., & Dieppe, P. (2000). Relation between agendas of the research community and the research consumer. Lancet, 355, 20372040.Google Scholar
Thal, L.J. (2002). How to define treatment success using cholinesterase inhibitors. International Journal of Geriatric Psychiatry, 17, 388390.Google Scholar
Therapeutics Initiative. (2005). Therapeutics letter no. 56: Drugs for Alzheimer’s disease. URL (accessed February 2007):;; Scholar
Timmermans, S., & Berg, M. (1997). Standardization in action: Achieving local universality through medical protocols. Social Studies of Science, 27, 273305.Google Scholar
Tuokko, H., Garrett, D.D., McDowell, I., Silverberg, N., & Kristjansson, B. (2003). Cognitive decline in high-functioning older adults: Reserve or ascertainment bias? Aging and Mental Health, 7, 259270.Google Scholar
Wachbroit, R. (1998). The question not asked: The challenge of pleiotropic genetic tests. Kennedy Institute of Ethics Journal, 8, 131144.Google Scholar
Watkins, P.B., Zimmerman, H.J., Knapp, M.J., Gracon, S.I., & Lewis, K.W. (1994). Hepatotoxic effects of tacrine administration in patients with Alzheimer’s disease. Journal of the American Medical Association, 271, 992998.Google Scholar
Whitehouse, P. (2003). Lessons and responses in Alzheimer disease research. Journal of the American Medical Association, 290, 115.Google Scholar
Willison, D.J., & MacLeod, S.M. (1999). The role of research evidence in pharmaceutical policy making: Evidence when necessary but not necessarily evidence. Journal of Evaluation in Clinical Practice, 5, 243249.Google Scholar
Winblad, B., Brodaty, H., Gauthier, S., Morris, J.C., Orgogozo, J.M., Rockwood, K. et al. (2001). Pharmacotherapy of Alzheimer’s disease: Is there a need to redefine treatment success? International Journal of Geriatric Psychiatry, 16, 653666.Google Scholar
Wolfe, N., Reed, B.R., Eberling, J.L., & Jagust, W.J. (1995). Temporal lobe perfusion on single photon emission computed tomography predicts the rate of cognitive decline in Alzheimer’s disease. Archives of Neurology, 52, 257262.Google Scholar
World Health Organization. (1959). Mental health problems in aging and the aged, 6th Report of the Expert Committee on Mental Health, Technical Report Series No. 171. Geneva: WHO.Google Scholar
World Health Organization. (1979). Psychogeriatric care in the community, Public Health in Europe No. 10. Copenhagen: WHO Regional Office for Europe.Google Scholar
World Health Organization. (1993). The ICD-10 classification of mental and behavioural disorders: Diagnostic criteria for research. Geneva: World Health Organization.Google Scholar
World Health Organization. (2008). Norms and standards: Quality, safety and efficacy of medicines. URL (accessed April 2008): Scholar
Wright, J.M. (2002). The double-edged sword of COX-2 selective NSAIDs. Canadian Medical Association Journal, 167, 11311137.Google Scholar
Zareparsi, S., Reddick, A.C., Branham, K.E.H., Moore, K.B., Jessup, L., Thoms, S. et al. (2004). Association of Apolipoprotein E alleles with susceptibility to age-related macular degeneration in a large cohort from a single center. Investigative Ophthalmology and Visual Science, 45, 13061310.Google Scholar