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
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


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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

Supersensitivity of p2x7 receptors in cerebrocortical cell cultures after invitro ischemia

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*,§