Modelling disease progression in Alzheimer's disease: a review of modelling methods used for cost-effectiveness analysis.

The literature reporting economic evaluations related to the treatment of Alzheimer's disease (AD) has developed over the last decade. Most analyses have used economic models to estimate the cost effectiveness of drugs for the treatment of AD. This review considers the range of methods used in the published cost-effectiveness literature to model AD progression and the effect of interventions on the progression of AD. The review builds on and updates an earlier systematic review of cost-effectiveness studies on drugs for AD. Systematic and rigorous methods were used to search the literature for economic evaluations estimating the cost effectiveness of donepezil, rivastigmine, galantamine or memantine in AD. The literature search covered a wide range of electronic databases (e.g. MEDLINE, EMBASE), and included literature from the inception of databases up to the end of 2005. The search identified 22 published economic evaluations. An outline and brief critical review of the identified studies is provided, and thereafter the methods used to model disease progression were considered in more detail. The review employs recent guidance on good practice in decision-analytic modelling in HTA to critically review the modelling methods used. Using this guidance, the models are assessed against the broad criteria of model structure, data inputs and assessment of uncertainty and inconsistency. Concerns were noted over the model structure employed in all models. The reliance on cognitive scores to model AD, the progression of the disease, and the effect of treatment on costs and consequences is regarded as a serious limitation in almost all of the studies identified. There are also limitations over the data used to populate published models, especially around the failure of studies to document and establish the basis for the modelling of treatment effects. It is also clear that studies modelling AD progression, and subsequently the cost effectiveness of treatment, have not addressed uncertainty or consistency (internal and/or external) in sufficient detail. Further research is required on more appropriate methods for the modelling of AD progression. In the meantime, future economic evaluations of treatment need to be more explicit on the methods used to model AD, and the data used to populate models.