Modelling the cost effectiveness of treatments for Parkinson's disease: a methodological review

The objective of this review was to assess models of cost effectiveness for Parkinson's disease (PD) published after July 2002 and to derive recommendations for future modelling. A systematic literature search was performed in the databases PubMed, Current Contents, EMBASE, EconLit, the Cochrane Database of Systematic Reviews, and DARE (Database of Abstracts of Reviews of Effectiveness), NHS EED (Economic Evaluation Database) and HTA (Health Technology Assessment) of the UK NHS Centre for Review and Dissemination (July 2002 to March 2010). Only fully published studies using decision trees, Markov models, individual simulation models or sets of mathematical equations were included. Most of the 11 studies identified used Markov models (n?=?9) and two employed were based on decision trees. Based on the Hoehn & Yahr (HY) scale, authors evaluated the cost effectiveness of drug treatments (n?=?6), surgical approaches such as deep brain stimulation (n?=?1) or striatal cell grafting (n?=?1), and diagnostic procedures such as single photon emission computed tomography (SPECT) testing (n?=?3) over a time horizon of 1 year to lifetime. Costs were adapted to address a societal and/or healthcare provider/third-party payer perspective. All but one of the interventions investigated were considered cost effective or cost saving. Cost-effectiveness modelling in PD between 2003 and 2010 showed only minor improvement when compared with our earlier review of models published from 1998 up to 2003. Cost-effectiveness modelling recommendations were complied with to only a limited extent, leaving room for quality improvement. More advanced modelling approaches may, so far, be under-represented, but may be used in the future, driven by the research question. Adverse events of treatment, co-morbidities or disease complications are not yet sufficiently included in the models to adequately represent clinical reality.     

Frequency of dementia, depression, and other neuropsychiatric symptoms in 1,449 outpatients with Parkinson’s disease

Neuropsychiatric symptoms (NPS) of Parkinson’s disease (PD) are of growing diagnostic and therapeutic importance. Data on their prevalence and characteristics have been primarily derived from highly selective clinical populations. We have conducted a national study in the outpatient care sector to provide a fuller characterization of the frequency of dementia, depression, and other NPS in PD outpatients. We also examined associations with biosocial and neurological variables. A nationwide representative sample of 1,449 PD outpatients was examined with a standardized clinical interview. PD severity was rated with the Hoehn and Yahr (HY) scale and the Unified Parkinson’s Disease Rating Scale. Depression was measured with the Montgomery-Asberg Depression Rating Scale. Cognitive impairment and dementia were assessed with the Mini-Mental State Exam and according to diagnostic criteria. Logistic regression analyses were used to investigate associations. At least one NPS occurred in 71% of all patients with PD. The estimated prevalences (ranges) by age group and HY-stage were: depression, 25% (13.2–47.9%), dementia, 29% (12.2–59.4%), and psychotic syndromes, 12.7% (3.1–40.9%). Other frequent complications were sleep disturbances (49%) and anxiety (20%). Depression was associated with gender but not with age. Dementia was associated with age. The rates and comorbidity of depression and dementia were driven by PD severity. NPS were highly prevalent in our comprehensive patient sample, largely representative of management problems occurring in an outpatient setting. PD outpatients are at an increased risk for all neuropsychiatric conditions, increasing with PD severity but not with age or age of onset (except dementia), revealing challenging symptom patterns.     

Cost‐effectiveness of deep brain stimulation in patients with Parkinson's disease

In addition to medical treatment, deep brain stimulation has become an alternative therapeutic option in advanced Parkinson's disease. High initial costs of surgery have to be weighted against long‐term gains in health‐related quality of life. The objective of this study was to assess the cost‐effectiveness of deep brain stimulation compared with long‐term medical treatment. We performed a cost‐utility analysis using a lifetime Markov model for Parkinson's disease. Health utilities were evaluated using the EQ‐5D generic health status measure. Data on effectiveness and adverse events were obtained from clinical studies, published reports, or meta‐analyses. Costs were assessed from the German health care provider perspective. Both were discounted at 3% per year. Key assumptions affecting costs and health status were investigated using one‐way and two‐way sensitivity analyses. The lifetime incremental cost‐utility ratio for deep brain stimulation was €6700 per quality‐adjusted life year (QALY) and €9800 and €2500 per United Parkinson's Disease Rating Scale part II (motor experiences of daily living) and part III (motor examination) score point gained, respectively. Deep brain stimulation costs were mainly driven by the cost of surgery and of battery exchange. Health status was improved and motor complications were reduced by DBS. Sensitivity analysis revealed that battery life time was the most influential parameter, with the incremental cost‐utility ratio ranging from €20,000 per QALY to deep brain stimulation dominating medical treatment. Deep brain stimulation can be considered cost‐effective, offering a value‐for‐money profile comparable to other well accepted health care technologies. Our data support adopting and reimbursing deep brain stimulation within the German health care system. © 2013 Movement Disorder Society     

Caffeic acid phenethyl ester prevents cerebellar granule neurons (CGNs) against glutamate-induced neurotoxicity

Caffeic acid phenethyl ester (CAPE) is an active component of propolis obtained from honeybee hives and is found to have the following properties: anti-mitogenic, anti-carcinogenic, anti-inflammatory, immunomodulatory, and antioxidant. Recent reports suggest that CAPE also has a neuronal protective property against ischemic injury. Since excitotoxicity may play an important role in ischemia, in this study, we investigated whether CAPE could directly protect neurons against excitotoxic insult. We treated cultured rat cerebellar granule neurons (CGNs) with excitotoxic concentrations of glutamate in the presence or absence of CAPE and found that CAPE markedly protected neurons against glutamate-induced neuronal death in a concentration-dependent fashion. Glutamate-induced CGNs death is associated with time-dependent activation of caspase-3 and phosphorylation of p38, both events of which can be blocked by CAPE. Treating CGNs with specific inhibitors of these two enzymes together exerts a synergistic neuroprotective effect, similar to the neuroprotective effect of CAPE exposure. These results suggest that CAPE is able to block glutamate-induced excitotoxicity by inhibiting phosphorylation of p38 and caspase-3 activation. This finding may further help understanding of the mechanism of glutamate-induced neuronal death and CAPE-induced neuroprotection against excitotoxicity.