riepe_book.qxp 14/1/08 02:51 Page 52
Alzheimer’s Disease
Figure 1: Measurement of Patient Performance
solely on the consideration of effectiveness data. Considering the economic
impact due to the large numbers of individuals affected, several
governments have asked for re-appraisals to be performed. In Germany,
the IQWIG issued a report with conclusions similar to those of licensing
Imaginary boundary score
authorities, medical associations and independent organisations.
Progression on treatment
However, the discussion is supplemented by arguments about the
‘relevance’ of the effect for the individual patient. There are also
limitations in gathering reliable information about the impairments,
needs and preferences of patients with AD and their care-givers,
Onset of treatment especially with progressing disease and the resulting impairment of
communicative capabilities on the part of the patient. The fact that
impairments may fluctuate or may surface only under certain
conditions is also explicitly discussed.
Natural progression
In the view of the author, ‘relevance’ or ‘clinical benefit’ cannot be
defined in scientific terms, but rather represent a judgement on the
Time
worth of a treatment, or an assessment of its effect versus its expense; as
Measurement of patient performance in any outcome variable is subject to variability of such, they go beyond the principles of evidence-based medicine. Only on
fluctuations (e.g. blood pressure, metabolism and fatigue; intercurrent subclinical diseases) so
that at onset of treatment the true performance may be better or worse than the imaginary
consideration of these additional judgement domains – i.e. beyond just
boundary score. Natural course of disease and treatment effects are rather to be considered
‘effectiveness’ – can tests to determine whether a substance should be
as fans in the individual patient and in line with standard deviations (arrows) only in groups
of patients. It thus cannot be determined in the individual patient whether that patient is a
applied set strict upper and lower boundaries. From an evidence-based
treatment failure or treatment responder.
medicine point of view there is insufficient evidence to propose such a
procedure. From a scientific point of view, the test–re-test reliability of
functional and behavioural condition of the patient. It is recommended the MMSE
25,26
and the variability of progression of disease in individual
that the choice of drug should be guided by acquisition costs and patients due to a multitude of internal (genetic background) or external
expectations of adverse event profiles and treatment adherence. In this (fluctuations of blood pressure, metabolism and fatigue; intercurrent
guideline, memantine is not recommended as a treatment option. The subclinical diseases) reasons precludes the fixing of strict boundaries, and
NICE guidance is binding for physicians in the UK. no grade I evidence supports the proposed procedure (see Figure 1).
Discussion and Conclusion In light of the lack of scientifically founded procedures, it thus needs to
Evidence-based medicine helps individual physicians to decide the best be concluded – based on several grade I studies and supported by
choice of treatment for individual patients.
24
The results of double-blind, biological and physiological considerations – that treatment with
placebo-controlled studies and meta-analyses of these studies are cholinergic drugs is indicated in subjects with mild to moderate AD and
considered best evidence regarding the objective appraisal of the efficacy treatment with memantine is indicated in moderate to severe AD.
of treatments. Based on these kinds of studies, licensing authorities such as Treatment needs to be continued as long as the main diagnosis of AD is
the European Medicines Agency (EMEA) and the US Food and Drug still valid and no contraindications arise. How to proceed with treatment
Administration (FDA) came to the conclusion that there is sufficient on transition from the moderate to the severe stages of disease is
evidence to license cholinergic drugs (donepezil, galantamine, rivastigmine) unsupported by systematic evidence at present and needs to be decided
and the antiglutamatergic drug memantine for the treatment of mild to at the level of the individual patient. Cessation of any kind of specific
moderate and moderate to severe AD, respectively. Similarly, committees antidementia therapy in advanced stages of disease does not rest on
of medical associations and independent organisations such as the evidence-based data at present; any such decision needs to consider the
Cochrane Collaboration came to the same conclusion. These appraisals rest specifics of each individual patient and his or her care-giver. ■
1. Bachman DL, Wolf PA, Linn R, et al., Neurology, 11. Hodges JR, The Oxford Handbook of Memory, Oxford, New 20. Birks J, Cochrane Database Syst Rev, 2006;(1):CD005593.
1992;42(1):115–19. York: Oxford University Press, 2000:441–59. 21. McShane R, Areosa SA, Minakaran N, Cochrane Database Syst
2. Erkinjuntti T, Ostbye T, Steenhuis R, Hachinski V, 12. Bittner D, Gron G, Schirrmeister H, et al., Dement Geriatr Rev, 2006;19(2):CD003154.
N Engl J Med, 1997;337(23):1667–74. Cogn Disord, 2005;19(1):24–30. 22. IQWIG, Cholinesterasehemmer bei Alzheimer Demenz.
3. Small GW, Rabins PV, Barry PP, et al., JAMA, 13. Everitt BJ, Robbins TW, Annu Rev Psychol, 1997;48:649–84. Abschlussbericht 05-19A, Köln: Institut für Qualitätssicherung
1997;278(16):1363–71. 14. Bartus RT, Dean RL, Beer B, Lippa AS, Science, und Wirtschaftlichkeit im Gesundheitswesen (IQWIG), 2007.
4. Grady CL, Haxby JV, Horwitz B, et al., J Clin Exp 1982;217(4558):408–14. 23. NICE, TA111 Alzheimer’s disease – donepezil, galantamine,
Neuropsychol, 1988;10(5):576–96. 15. Bancher C, Jellinger K, Lassmann H, et al., Eur Arch Psychiatry rivastigmine (review) and memantine: quick reference guide
5. Almkvist O, Acta Neurol Scand Suppl, 1996;165:63–71. Clin Neurosci, 1996;246(3):137–46. (amended September 2007), London: National Institute of
6. Hyman BT, Van Horsen GW, Damasio AR, Barnes CL, Science, 16. Chapman PF, White GL, Jones MW, et al., Nat Neurosci, Clinical Excellence (NICE), 2007.
1984;225(4667):1168–70. 1999;2(3):271–6. 24. Sackett DL, Rosenberg WM, Gray JA, et al., BMJ,
7. Ball MJ, Fisman M, Hachinski V, et al.,Lancet, 17. Knopman DS, DeKosky ST, Cummings JL, et al., Neurology, 1996;312(7023):71–2.
1985;1(8419):14–16. 2001;56(9):1143–53. 25. Clark CM, Sheppard L, Fillenbaum GG, et al., Arch Neurol,
8. Hyman BT, Van Hoesen GW, Kromer LJ, Damasio AR, Ann 18. Gron G, Brandenburg I, Wunderlich AP, Riepe MW, Neurobiol 1999;56(7):857–62.
Neurol, 1986;20(4):472–81. Aging, 2005; in press. 26. Mendiondo MS, Ashford JW, Kryscio RJ, Schmitt FA, Stat
9. Hyman BT, Neurobiol Aging, 1997;18(Suppl. 4):S27–S32. 19. Riepe MW, Frolich L, Benesch R, Leitlinien für Diagnostik und Med, 2000;19(11–12):1607–16.
10. Gron G, Bittner D, Schmitz B, et al., Ann Neurol, Therapie in der Neurologie, Stuttgart: Thieme-Verlag,
2002;51(4):491–8. 2005:144–52.
52 EUROPEAN NEUROLOGICAL DISEASE 2007
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