Donepezil, rivastigmine, galantamine and memantine for ...

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Economic analysis
sensitive to disease stage (and earlier reporting of
data suggests responses are sensitive to setting of
care), 161 yet caregiver values do not appear to be
associated with disease severity. HUI3 produces
considerably lower utility scores for patients. The
HUI3 has a broader descriptive system and
identifies more states considered worse than dead
than did the HUI2.
There are limitations with the study; it is a crosssectional
study and one-time assessments can be
affected by many factors present on a particular
day, the HUI2 questionnaire has not been
validated for use in AD, 161 responses are from
proxies (caregivers) not patients, and there may be
many other factors (e.g. co-morbid conditions)
that influence the respondents. In general proxies
tend to rate disability at a higher level (i.e. rate it
as if it has a larger impact on health-related QoL)
than do patients, 167 although with AD proxies are
the only practical option. The sample may not be
representative of the treatment population, as they
were from selected sites and were required to have
an active caregiver. Furthermore, the utilities are
derived indirectly using a multi-attribute model
based on a community sample, with responses
unrelated to AD (i.e. generic health state
descriptions were used).
Neumann 166 in an earlier presentation, reported
health state values for AD by severity and location
(community or nursing home) (Table 66).
Kerner and colleagues, 168 in a US study, report
health state utility data from a sample of 159
patients with a diagnosis of probable or possible AD
patients (and their caregivers), and 52 control
patients, recruited as part of a longitudinal study on
AD care-giving. This study reports data collected
using the Quality of Well-being Scale (QWB). The
QWB assesses QoL across levels of functioning (i.e.
TABLE 66 Data on AD health state values reported by
Neumann 164
AD stage/setting Patients Caregivers
Mild AD
Community 0.68 0.86
Nursing home
Moderate AD
0.71 0.86
Community 0.54 0.86
Nursing home 0.48 0.86
Severe AD
Community 0.37 0.86
Nursing home 0.31 0.86
using descriptive scales for mobility, physical activity
and social activity) and a range of symptoms.
Responses to the questionnaire provide a profile
which is used in conjunction with tariff values for
the QWB. The QWB uses decrements in well-being
(from a position of 1.0 reflecting
asymptomatic/optimum function) based on weights
derived from a US sample of the general
population, for health states described using the
three QWB descriptive scales, and additional
decrements based on reported symptoms. 169 Kerner
and colleagues report an overall QWB score of 0.51
(SD 0.06) for AD patients, compared with 0.74 (SD
0.12) in controls. Results are not presented by
stages of disease severity (the sample was spread
evenly over CDR stages of disease).
Sano and colleagues, 170 in a US study, report
findings from an experimental empirical study
which elicited health state values for AD health
state descriptions (using CDR stages 1 and 3; mild
dementia and severe dementia) from both experts
familiar with AD and students unfamiliar with AD.
The study used the visual analogue scale (VAS)
and time trade-off (TTO) health state valuation
techniques. The authors report findings from
expert raters for CDR1 and CDR3 states as 0.75
and 0.26, respectively, for VAS, and 0.67 and 0.31,
respectively, for TTO. Student responses are
reported as 0.65 and 0.30 for VAS and 0.58 and
0.29 for TTO in CDR 1 and 3, respectively.
Mortality and AD
AD is reported to be the fourth most common
cause of death after heart disease, cancer and
stroke and is also associated with an increased
mortality rate in comparison with the general
population mortality rate. 112,129,171 Studies have
taken different approaches to assessing the impact
that AD has on life span; some report a hazard
ratio for the increased risk of death for AD
patients in comparison with the mortality risk in
the general population, whereas others have
developed models to try to predict the expected
survival time for a person with AD.
In the UK, Burns and colleagues 172 estimated
standardised mortality ratios (SMRs) for AD
patients in the age groups 65–75, 75–84 and
>85 years, with SMRs of 5.00, 4.07, and 2.80,
respectively. Combining these data with UK
mortality data presents annual mortality estimates
for AD at 15.4, 30.3 and 48.5% in the 65–75,
75–84 and >85 years age groups, respectively.
The data from Burns and colleagues 172 are based