Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study

Ron L H Handels, Pauline Aalten, Claire A G Wolfs, Marcel OldeRikkert, Philip Scheltens, Pieter Jelle Visser, Manuela A Joore, Johan L Severens, Frans R J Verhey, Ron L H Handels, Pauline Aalten, Claire A G Wolfs, Marcel OldeRikkert, Philip Scheltens, Pieter Jelle Visser, Manuela A Joore, Johan L Severens, Frans R J Verhey

Abstract

Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model.

Methods/design: In a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered.Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period.A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers.

Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems.

Trial registration: NCT01450891.

References

    1. Prince M, Jackson J. World Alzheimer Report. , ; 2009.
    1. Wimo A, Winblad B, Jonsson L. The worldwide societal costs of dementia: Estimates for 2009. Alzheimers Dement. 2010;6(2):98–103. doi: 10.1016/j.jalz.2010.01.010.
    1. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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. 1984;34(7):939–944. doi: 10.1212/WNL.34.7.939.
    1. Knopman DS, DeKosky ST, Cummings JL, Chui H, Corey-Bloom J, Relkin N, Small GW, Miller B, Stevens JC. Practice parameter: diagnosis of dementia (an evidence-based review), Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56(9):1143–1153. doi: 10.1212/WNL.56.9.1143.
    1. Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, Rossor M, Scheltens P, Tariska P, Winblad B. Recommendations for the diagnosis and management of Alzheimer’s disease and other disorders associated with dementia: EFNS guideline. Eur J Neurol. 2007;14(1):e1–e26.
    1. Dubois B, Feldman HH, Jacova C, Cummings JL, Dekosky ST, Barberger-Gateau P, Delacourte A, Frisoni G, Fox NC, Galasko D. et al.Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol. 2010;9(11):1118–1127. doi: 10.1016/S1474-4422(10)70223-4.
    1. Albert MS, Dekosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC. et al.The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):270–279. doi: 10.1016/j.jalz.2011.03.008.
    1. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R. et al.The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263–269. doi: 10.1016/j.jalz.2011.03.005.
    1. Jack CR, Albert MS, Knopman DS, McKhann GM, Sperling RA, Carrillo MC, Thies B, Phelps CH. Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):257–262. doi: 10.1016/j.jalz.2011.03.004.
    1. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR, Kaye J, Montine TJ. et al.Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280–292. doi: 10.1016/j.jalz.2011.03.003.
    1. Van den Bruel A, Cleemput I, Aertgeerts B, Ramaekers D, Buntinx F. The evaluation of diagnostic tests: evidence on technical and diagnostic accuracy, impact on patient outcome and cost-effectiveness is needed. J Clin Epidemiol. 2007;60(11):1116–1122. doi: 10.1016/j.jclinepi.2007.03.015.
    1. Knottnerus JA, Buntinx F. The evidence base of clinical diagnosis: theory and methods of diagnostic research. 2. Wiley-Blackwell Pub./BMJ Books, Oxford Hoboken, NJ; 2009.
    1. Schaafsma JD, van der Graaf Y, Rinkel GJ, Buskens E. Decision analysis to complete diagnostic research by closing the gap between test characteristics and cost-effectiveness. J Clin Epidemiol. 2009;62(12):1248–1252. doi: 10.1016/j.jclinepi.2009.01.008.
    1. Cushman LA, Scherer MJ. Psychological assessment in medical rehabilitation. 1. American Psychological Association, Washington, DC; 1995.
    1. Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993;43(11):2412–2414.
    1. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982;140:566–572. doi: 10.1192/bjp.140.6.566.
    1. Almeida OP, Almeida SA. Short versions of the geriatric depression scale: a study of their validity for the diagnosis of a major depressive episode according to ICD-10 and DSM-IV. Int J Geriatr Psychiatry. 1999;14(10):858–865. doi: 10.1002/(SICI)1099-1166(199910)14:10<858::AID-GPS35>;2-8.
    1. Cummings JL. The neuropsychiatric inventory: Assessing psychopathology in dementia patients. Neurology. 1997;48(5):S10–S16. doi: 10.1212/WNL.48.5_Suppl_6.10S.
    1. Gelinas I, Gauthier L, McIntyre M, Gauthier S. Development of a functional measure for persons with Alzheimer’s disease: the disability assessment for dementia. Am J Occup Ther. 1999;53(5):471–481. doi: 10.5014/ajot.53.5.471.
    1. Vernooij-Dassen MJ, Felling AJ, Brummelkamp E, Dauzenberg MG, van den Bos GA, Grol R. Assessment of caregiver’s competence in dealing with the burden of caregiving for a dementia patient: a Short Sense of Competence Questionnaire (SSCQ) suitable for clinical practice. J Am Geriatr Soc. 1999;47(2):256–257.
    1. Vernooij-Dassen MJ. Dementia and Homecare: Determinants of the sense of Competence of Primary Caregivers and the effect of Professionally Guided Caregiver Support. Swets & Zeitlinger, Lisse; 1993.
    1. Brand N, Jolles J. Learning and retrieval rate of words presented auditorily and visually. J Gen Psychol. 1985;112(2):201–210. doi: 10.1080/00221309.1985.9711004.
    1. Rey A. L’examen clinique en psychologie. Presses Universitaries De France, Oxford England; 1958.
    1. Lindeboom J, Schmand B, Tulner L, Walstra G, Jonker C. Visual association test to detect early dementia of the Alzheimer type. J Neurol Neurosurg Psychiatry. 2002;73(2):126–133. doi: 10.1136/jnnp.73.2.126.
    1. Wechsler D. Wechsler Memory Scale – 3rd edition: Administration and Scoring Manual. The Psychological Corporation, San Antonio; 1997.
    1. Natu MV, Agarwal AK. Digit Letter Substitution Test (DLST) as an alternative to Digit Symbol Substitution Test (DSST) Human Psychopharmacology: Clinical and Experimental. 1995;10(4):339–343. doi: 10.1002/hup.470100414.
    1. Stroop JR. Studies of interference in serial verbal reactions. J Exp Psychol. 1935;18(6):643–662.
    1. Reitan RM. Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills. 1958;8:271–276.
    1. Reitan RM. Trail Making Test: Manual for administration, scoring, and interpretation. Indiana University, Bloomington; 1956.
    1. Brooks R. EuroQol: The current state of play. Health Policy. 1996;37(1):53–72. doi: 10.1016/0168-8510(96)00822-6.
    1. Lamers LM, Stalmeier PF, McDonnell J, Krabbe PF, van Busschbach JJ. Measuring the quality of life in economic evaluations: the Dutch EQ-5D tariff. Ned Tijdschr Geneeskd. 2005;149(28):1574–1578.
    1. Lamers LM, McDonnell J, Stalmeier PF, Krabbe PF, Busschbach JJ. The Dutch tariff: results and arguments for an effective design for national EQ-5D valuation studies. Health Econ. 2006;15(10):1121–1132. doi: 10.1002/hec.1124.
    1. Jonsson L, Andreasen N, Kilander L, Soininen H, Waldemar G, Nygaard H, Winblad B, Jonhagen ME, Hallikainen M, Wimo A. Patient- and proxy-reported utility in Alzheimer disease using the EuroQoL. Alzheimer Dis Assoc Disord. 2006;20(1):49–55. doi: 10.1097/01.wad.0000201851.52707.c9.
    1. Wolfs CA, Dirksen CD, Kessels A, Willems DC, Verhey FR, Severens JL. Performance of the EQ-5D and the EQ-5D + C in elderly patients with cognitive impairments. Health Qual Life Outcomes. 2007;5:33. doi: 10.1186/1477-7525-5-33.
    1. Dolan P. Modeling valuations for EuroQol health states. Med Care. 1997;35(11):1095–1108. doi: 10.1097/00005650-199711000-00002.
    1. Brooks RG, Rabin R, De Charro F. The measurement and valuation of health status using EQ-5D: a European perspective: evidence from the EuroQol BIOMED Research Programme. Kluwer Academic Pub, Dordrchet; Boston; 2003.
    1. Logsdon RG, Gibbons LE, McCurry SM, Teri L. Assessing quality of life in older adults with cognitive impairment. Psychosom Med. 2002;64(3):510–519.
    1. Thorgrimsen L, Selwood A, Spector A, Royan L, de Madariaga Lopez M, Woods RT, Orrell M. Whose quality of life is it anyway? The validity and reliability of the Quality of Life-Alzheimer’s Disease (QoL-AD) scale [comment] Alzheimer Dis Assoc Disord. 2003;17(4):201–208. doi: 10.1097/00002093-200310000-00002.
    1. Spector A, Thorgrimsen L, Woods B, Royan L, Davies S, Butterworth M, Orrell M. Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial [comment] Br J Psychiatry. 2003;183:248–254. doi: 10.1192/bjp.183.3.248.
    1. Brouwer WB, van Exel NJ, van Gorp B, Redekop WK. The CarerQol instrument: a new instrument to measure care-related quality of life of informal caregivers for use in economic evaluations. Qual Life Res. 2006;15(6):1005–1021. doi: 10.1007/s11136-005-5994-6.
    1. Wimo A, Winblad B. Resource utilization in dementia. Brain & Aging. 2003;3:48–60.
    1. Koopmanschap MA, Meerding WJ, Evers S, Severens J, Burdorf A, Brouwer W. Handleiding voor het gebruik van PRODISQ versie 2.1 (PROductivity and DISease Questionnaire). Een modulaire vragenlijst over de relatie tussen ziekte en productiviteitskosten. Toepasbaar bij economische evaluaties van gezondheidszorgprogramma’s voor patiënten en werknemers. Rotterdam/Maastricht. , ; 2004.
    1. van Roijen L, Essink-Bot ML, Koopmanschap MA, Bonsel G, Rutten FF. Labor and health status in economic evaluation of health care. The Health and Labor Questionnaire. Int J Technol Assess Health Care. 1996;12(3):405–415. doi: 10.1017/S0266462300009764.
    1. Jack CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010;9(1):119–128. doi: 10.1016/S1474-4422(09)70299-6.
    1. Gabel MJ, Foster NL, Heidebrink JL, Higdon R, Aizenstein HJ, Arnold SE, Barbas NR, Boeve BF, Burke JR, Clark CM. et al.Validation of consensus panel diagnosis in dementia. Arch Neurol. 2010;67(12):1506–1512. doi: 10.1001/archneurol.2010.301.
    1. Brook RH, Chassin MR, Fink A, Solomon DH, Kosecoff J, Park RE. A method for the detailed assessment of the appropriateness of medical technologies. Int J Technol Assess Health Care. 1986;2(1):53–63. doi: 10.1017/S0266462300002774.
    1. Mauskopf JA, Paul JE, Grant DM, Stergachis A. The role of cost-consequence analysis in healthcare decision-making. Pharmacoeconomics. 1998;13(3):277–288. doi: 10.2165/00019053-199813030-00002.
    1. Briggs AH, Claxton K, Sculpher MJ. Decision modelling for health economic evaluation. Oxford University Press, Oxford; 2006.
    1. Visser PJ, Scheltens P, Verhey FR. Do MCI criteria in drug trials accurately identify subjects with predementia Alzheimer's disease?J Neurol Neurosurg. Psychiatry. 2005;76(10):1348–1354.
    1. Claxton K. The irrelevance of inference: a decision-making approach to the stochastic evaluation of health care technologies. J Health Econ. 1999;18(3):341–364. doi: 10.1016/S0167-6296(98)00039-3.
    1. Mueller SG, Weiner MW, Thal LJ, Petersen RC, Jack C, Jagust W, Trojanowski JQ, Toga AW, Beckett L. The Alzheimer's disease neuroimaging initiative. Neuroimaging Clin N Am. 2005;15(4):869–877. doi: 10.1016/j.nic.2005.09.008. xi-xii.
    1. Visser PJ, Verhey FR, Boada M, Bullock R, De Deyn PP, Frisoni GB, Frolich L, Hampel H, Jolles J, Jones R, Minthon L, Nobili F, Olde Rikkert M, Ousset PJ, Rigaud AS, Scheltens P, Soininen H, Spiru L, Touchon J, Tsolaki M, Vellas B, Wahlund LO, Wilcock G, Winblad B. Development of screening guidelines and clinical criteria for predementia Alzheimer's disease. The DESCRIPA Study. Neuroepidemiology. 2008;30(4):254–265. doi: 10.1159/000135644.
    1. Visser PJ, Kester A, Jolles J, Verhey F. Ten-year risk of dementia in subjects with mild cognitive impairment. Neurology. 2006;67(7):1201–1207. doi: 10.1212/01.wnl.0000238517.59286.c5.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit