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Conceptualizing disease: building unifying models to support
the development of PROs and cost-effectiveness analyses.
A case study in Alzheimer's Disease (AD)
Wild D, Mealing S, Gallop K, Nixon A, Lloyd A, Briggs A, Sculpher M
Oxford Outcomes Ltd, Oxford, United Kingdom
INTRODUCTION
Conceptual models are used in Patient Reported Outcomes (PRO) research to explore a
(as measured using the ADAD-COG instrument), the presence of extrapyramidial symptoms,
disease or treatment. They are developed for a number of reasons including the selection,
and the presence of hallucinations or delusions.
adaptation or development of a PRO measure and the development of an endpoint model.
In the long term module, mathematical functions were used to calculate the time
They have long been used in psychology and health education to explore the relations
dependant probabilities of moving from pre-FTC to FTC, and from either state to death.
between concepts.
Baseline characteristics and change in ADAS-COG during the short term module were used as
Approaches similar to conceptual models are also used by decision analysts and health
independent variables in all risk equations. The model has been implemented as a patient level
economists to understand the underlying mechanism and natural history of a particular
simulation (Caro et al, 2001) and, after modification, a closed cohort Markov model (Loveman
disease. These models typically form the basis from which a cost-effectiveness model is
et al, 2006).
constructed. However, in the models constructed by a health economist here is perhaps less emphasis on patient experience than those constructed by a PRO analyst where this is more
Figure 2 Economic Model
of the focus.
However, there is we believe considerable potential for using a shared approach to
Cohort of AD patients
developing models which will meet the aims of both groups. Such a unified approach we
Std. Care + Drug therapy
believe can only lead to greater validity and a convergence of the science.
Cost = £328/mnth
Cost = £328/mnth
METHODS
To explore the potential for a shared approach the authors reviewed two models of
the same disease - Alzheimer's disease (AD). The authors reviewed the structure of a
health economic model of the disease which described the progression from diagnosis
Cost = £937/mnth
Cost = £937/mnth
to death. They also reviewed a published QoL model of AD from a patient perspective (Jonker et al, 2004). The patient oriented conceptual model and the economic model are presented below:
Conceptual Model
The introduction of drugs used to treat AD has increased levels of interest in measuring quality
of life (QoL) in dementia patients (Brod et al, 1999). Jonker et al (2004) propose a model of
QOL in dementia (see figure 2). The conceptual model of AD developed by Jonker et al (2004) extends work by Lawton
A large number of points of overlap were identified. These included the impacts of AD on day
(1994). Lawton suggested a hierarchical view of QoL in dementia, with psychological
to day functioning of the patient which will have an impact on caregiver burden, and will
well-being as the ultimate outcome. This model includes the interrelationships between
influence the ability of the caregiver to work and impact on other resource utilisation. This may,
dimensions. The model is disease specific, however, not all dimensions of the model are
in turn, have an impact on the time to institutionalisation which is where the major cost burden
influenced by the disease. The model identifies the causal pathways that link different types
of outcomes. According to this model, QoL can be measured at three levels. The relative
If the economic and conceptual modeling had been undertaken concurrently, however,
importance of the domains may vary across patients, although it is assumed that for all
the conceptual models insight into the multi-factorial influences on patients' health (in terms of
patients with dementia, a number of these are important and contribute to psychological
psychological well-being) may have led to different approaches to the economic modeling. In
well-being, the central outcome measure. The model focuses on the dementia patient, and
particular, although a patient's entry into full time care may represent a step-change in the cost
does not consider the subsequent impact on the caregiver's QoL, if the patient is being
of caring for AD patients, it is not clear whether this is a major driver for patients' health status.
cared for at home. The model is more generic and less detailed than other conceptual
Structuring the economic model around health states, defined in terms of the key determinants
models, which perhaps makes it less useful from a health economic perspective.
of psychological health on which medical interventions may impact, would be an alternative approach. These health states would effectively use patients' health (as reported by patients
Figure 1 – Conceptual Model
and their carers) to characterize the natural history of AD, including the likely increase in severity over time. The costs of care (including that related to institutionalization) would be quantified as a function of that severity.
Evaluation of each domain
The synergy found between PRO and health economic models lead us to suggest that there is merit in developing many models simultaneously and as early as possible in the drug
Personal aspects not
Personal aspects
development life cycle. This is likely to increase the validity of each of the models, as well as
related to dementia
related to dementia
having a positive impact on related research, for example, the development of health states for utility elicitation.
Personal aspects not related to dementia
Brod, M., Stewart, A. L., Sands, L, et al (1999) Conceptualization and measurement of quality of
AD is a common and incurable ailment of the elderly. It is degenerative and during the later
life in dementia: The dementia quality of life instrument (DQOL).
Gerontologist, 39, 25-35
stages of the illness individuals are unable to undertake everyday tasks and thus require large amounts of specialist care. AD thus constitutes a significant burden on the budget of any
Caro, J. J., Getsios, D., Migliaccio-Walle, K., Raggio, G., Ward, A., AHEAD Study Group., (2001)
health care provider.
Assessment of health economics in Alzheimer's disease (AHEAD) based on need for full time
The economic model is based around the concept of the need for full time care (FTC -
care.
Neurology, 25, 57 (6) 964-71
either in an institution or at home). The rationale behind this approach being that prior to this point, care tends to be less intensive and is usually provided by family and friends and thus
Jonker, C., Gerritsen, D. L., Bosboom, P. R., Van der Steen, J. T. (2004) A model of quality of life
the cost to heath care providers is relatively minor. The need for full time care is also a proxy
measures in patients with dementia: Lawton's next step,
Dementia and Geriatric Cognitive
for severe disease and is associated with a reduction in an individuals' quality of life. Three
Disorders, 18, 159-164
licensed products exist (galantamine, rivastigmine and donepezil) that aim to extend the period of time a patient can live without the need to full time care. The schematic of the
Lawton, M. P., (1994) Quality of life in Alzheimer disease,
Alzheimer Disease and Associated
model is shown in figure 1.
Disorders, 8 (suppl 3), 138-150
Structurally, the model has two components. A short term module covering an initial six month period, and a long term module with a 10 year time horizon. At the start of
Loveman, E., Green, C., Kirby, J., Takeda, A., Picot, J., Payne, E., Clegg, A. (2006) The clinical
the model, matched cohorts of patients were generated using the following patient
and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer's
characteristics: Age, age at onset of disease, duration of illness, gender, cognitive function
disease,
Health Technology Assessment, 10 (1), 1-160
Source: http://www.soshall.co.uk/oxfordoutcomes.eu/images/conference_material/posters/HE/Conceptualizing%20disease%20building%20unifying%20models%20to%20support%20-%20Copy.pdf
Opioid Prescribing Tool Kit Nathaniel Katz, MD, MS Tufts University School of Medicine Boston, MA Analgesic Research Needham, MA © Nathaniel Katz, MD, MS 2006. All rights reserved. Funded in part by the Massachusetts Department of Public Health. Production support provided by Fusion Medical Education, LLC, Wakefield, MA
Journal of Neurochemistry, 2005, 95, 1421–1437 Supersensitivity of P2X7 receptors in cerebrocortical cell culturesafter in vitro ischemia Kerstin Wirkner,* Attila Ko¨falvi, ,1 Wolfgang Fischer,* Albrecht Gu¨nther,*,à Heike Franke,*Helke Gro¨ger-Arndt,*,§ Wolfgang No¨renberg,* Emı´lia Madara´sz, E. Sylvester Vizi, Dietmar Schneider,à Bea´ta Sperla´gh and Peter Illes*,§