A cost-effectiveness analysis of levodopa/carbidopa intestinal gel compared to standard care in late stage Parkinson's disease in the UK.

OBJECTIVE: Evaluation of cost-effectiveness of levodopa/carbidopa intestinal gel (LCIG), compared to standard care (SC) in patients with advanced Parkinson's disease (aPD) in the UK. DESIGN: Markov model to quantify costs and outcomes associated with LCIG versus SC in aPD patients at Hoehn and Yahr (H&Y) stages 3, 4 or 5 experiencing >50% OFF time per day. Time horizon was lifetime, LCIG treatment was assumed to last maximal 5 years after which patients revert to SC. Model comprised 12 aPD health states according to H&Y status and daily time spent in OFF state. Cost analyses are reported from a UK NHS and Personal Social Services perspective. Uncertainties were assessed through one-way sensitivity analyses. COMPARATORS: LCIG, providing patients with continuous dopaminergic stimulation to maximise functional ON time during the day and SC, defined as medically determined best available oral medication. MAIN OUTCOME MEASURES: Cost-effectiveness, based on quality adjusted life years gained, presented as an incremental cost-effectiveness ratio. RESULTS: Lifetime analysis yields an incremental cost per QALY of £36,024 for LCIG compared to SC (incremental cost £39,644, QALY gain 1.1). Results were sensitive to time on treatment, health state on treatment initiation, and estimates of long term benefit (OWSA results from £32,127 to £66,421 per QALY). Findings must be considered in the context of the study limitations which were mainly due to data availability constraints. CONCLUSIONS: LCIG is an effective treatment, reducing OFF time and improving quality of life in advanced PD. It provides value for money in levodopa-responsive aPD patients with severe motor fluctuations when no other treatment options are effective or suitable. Given LCIG is an orphan drug, it is reasonable to suggest that it may be considered cost-effective in the UK setting. However, further research is needed to complete current data gaps and increase robustness of the model.

The economic burden of advanced Parkinson's disease: an analysis of a UK patient dataset.

BACKGROUND: To evaluate the cost burden of patients with advanced Parkinson's disease (PD) according to the waking hours per day spent in OFF state. An analysis of resource use comprising medical services, professional care and informal care data from an observational, cross-sectional study was conducted. METHODS: A total of 60 physicians comprising 40 neurologists and 20 geriatricians across the UK participating in the Adelphi PD Disease Specific Programme took part. There were 302 PD patients at H&Y stages 3-5. Patients were characterised according to the percentage of time per day spent in OFF state (<25%, 26-50%, 51-75%, >75%). RESULTS: Average 12-monthly total costs increased according to the time spent in OFF state from £25,630 in patients spending less than 25% of their waking hours in OFF to £62,147 for patients spending more than 75% of their time in OFF. Overall, 7% of costs were attributed to direct medical care, while 93% were split between direct non-medical professional care (50%) and indirect informal care (43%). LIMITATIONS: Low patient numbers in the more advanced disease stages of PD led to very little or no data to directly inform some of the severe health states of the analysis. Data gaps were filled in with data derived from a regression analysis which may affect the robustness of the analysis. CONCLUSION: This study illustrates the increasing costs of advancing PD, in particular related to the time spent in OFF state, and identifies that the foremost cost burden is associated with the care needs of the patient rather than medical services.

Abnormality of taste and smell in Parkinson's disease.

BACKGROUND: Smell sense is impaired in classic Parkinson's disease (PD). An initial study found no change in taste threshold in non-demented PD subjects and pathological studies suggest that the first relay for taste, the nucleus of the solitary tract, is spared. We wished to determine if taste is abnormal in PD and whether it is associated with smell dysfunction. METHODS: Taste threshold was estimated using the Rion electrogustometer and olfaction by the University of Pennsylvania Smell Identification Test (UPSIT) in 75 non-demented PD patients and 74 controls. RESULTS: There was a significant impairment of taste threshold and severe disorder of smell identification in the PD group. Age, duration of symptoms, disability, and smoking had no important effect on threshold measurement and there was no correlation between taste and smell dysfunction. Sensitivity analysis suggested that a provisional diagnosis of PD would be confirmed if smell or taste were abnormal; conversely, the diagnosis would merit review if both modalities were normal. CONCLUSIONS: Impaired taste appreciation was found in about 27% of patients with clinically defined PD. There were no important effects from age, disease severity or smell sense. Given the sparing of the first and second order taste neurones in PD, disorder of taste in PD most likely signifies involvement of the frontal operculum or orbitofrontal cortex, in keeping with advanced disease, although confounding by drug effects and changes in salivary constitution could not be excluded completely.

Olfactory tests in the diagnosis of essential tremor.

Most patients with tremor-dominant Parkinson's disease (PD) have impaired smell function but it is unclear whether this is true for subjects with essential tremor (ET). If ET patients do not exhibit meaningful smell loss, then olfactory testing may help to distinguish PD from ET. We assessed olfactory function in 59 ET and 64 tremor-dominant PD patients using the University of Pennsylvania Smell Identification Test (UPSIT) and olfactory event-related potential (OERP). UPSIT scores were compared to those from 245 healthy controls, and OERPs were compared to those from 74 controls. Unlike the PD test scores, those of ET patients were indistinguishable from controls when the effects of age, age of onset, gender, and smoking were taken into account. ET patients with a family history of tremor scored significantly better than controls on the UPSIT, and their rate of decline with age was slower. The effect was not observed on OERP. Smell testing may help to distinguish between ET and tremor-predominant PD, and patients with family history of tremor may represent a subgroup whose olfactory function is enhanced by some unknown mechanism.

The economic impact of Parkinson's disease.

Patients with Parkinson's disease (PD) experience progressive disability and reduced quality of life due to both motor and non-motor complications. The cost of illness escalates as PD progresses, placing an economic burden on the healthcare system, society and patients themselves. Overall cost estimates vary from country to country, but the largest component of direct cost is typically inpatient care and nursing home costs, while prescription drugs are the smallest contributor. Indirect costs arising from lost productivity and carer burden tend to be high. The total cost in the UK has been estimated to be between pound 449 million and pound 3.3 billion annually, depending on the cost model and prevalence rate used. Management strategies that minimise the impact of disease progression and maximise quality of life should help ensure optimal resource utilisation.

Cost-effectiveness of levodopa/carbidopa/entacapone (Stalevo) compared to standard care in UK Parkinson's disease patients with wearing-off.

BACKGROUND AND METHODS: A Markov model was developed to evaluate the cost-effectiveness of levodopa/carbidopa/entacapone (LCE;Stalevo), in the treatment of patients with Parkinson's disease (PD) and end-of-dose motor fluctuations (wearing-off). LCE, with or without other antiparkinsonian medications, was compared to UK standard care, comprising traditional levodopa/ dopa-decarboxylase inhibitor (DDCI) with other antiparkinsonian medications (e.g. selegiline or dopamine agonists) added as needed. The costs and outcomes of both treatments were projected over a period of 10 years from the perspective (a) of society as a whole and (b) of the UK National Health Service (NHS). Sensitivity analyses, including second-order Monte Carlo simulations, were performed to assess the confidence level of the primary results. RESULTS: Treatment with LCE produced an average gain of +1.04 quality-adjusted life-years (QALYs) per patient (2.57 vs. 1.53) in the base-case analysis (discount rate 3.5%). This gain was accompanied by a reduction in the total 10-year direct cost of care to society of 10198 pounds per patient ( approximately E14800). From the societal perspective, therefore, LCE was dominant, producing better clinical outcomes with lower costs. This dominance was reiterated in all sensitivity analyses of society-focused analysis, including a shortening of the time-frame to 5 years. Although treatment with LCE resulted in an increase in direct costs per patient of 3239 pounds (25756 pounds versus 22517 pounds) to the NHS over the 10-year period analysed, the incremental cost-effectiveness ratio (ICER) of LCE was only 3105 pounds per QALY gained (approximately E4500). All ICERs to the NHS remained below 3800 pounds per QALY gained in univariate sensitivity analyses applying different discount rates. When a shorter, 5-year, time-horizon was analysed, the NHS-related ICER for LCE was 6526 pounds per QALY gained. All these ICERs are within the range usually considered to indicate acceptable or highly acceptable cost effectiveness (defined as < 30000 pounds per QALY gained). The results of the Monte Carlo simulations indicated that the likelihood of LCE being either 'dominant' or more effective at an 'acceptable cost' from either the societal or the NHS perspective was high, exceeding 96% in the base-case sensitivity analysis, and was 93% even when all the uncertainties associated with the model were taken into consideration simultaneously. In particular, compared to standard care, the probability that LCE would provide better outcomes at a lower cost to society as a whole was 77% in the base-case sensitivity analysis and 72% in the scenario involving the highest degree of uncertainty. CONCLUSIONS: In the UK the use of LCE to treat PD patients with wearing-off is beneficial to individual patients and likely to offer money savings to society as a whole, compared with UK standard therapy. The added cost of the medication itself is exceeded by the savings made in other direct costs of PD, mainly those relating to social care or PD-related private expenditures.

Randomized, double-blind, 3-month parallel study of the effects of pramipexole, pergolide, and placebo on Parkinsonian tremor.

We compared the antitremor effect of pramipexole, pergolide, or placebo in Parkinson's disease (PD). A double-blind, randomly controlled, parallel protocol was deployed to examine the effects of placebo, pergolide, and pramipexole [doses escalated to 1.5 mg three times daily (t.i.d.) over 3 months] on a compound Tremor Index (TI) and Unified Parkinson's Disease Rating Scale (UPDRS) part III. Thirty PD patients (19 men, 11 women; mean age 69 years, range 54-80 years; mean disease duration 3.9 years, range, 0.5-10 years) participated in the study, with 10 patients in each arm. Six subjects failed to complete the study (4 on pergolide and 2 on placebo). Analysis of covariance demonstrated strong evidence for a treatment effect on both TI and UPDRS III. There was no significant difference between the active treatments on either TI or UPDRS III. Both pergolide and pramipexole were significantly better than placebo. The results indicate that pergolide and pramipexole (1.5 mg t.i.d.) have similar anti-PD tremor and UPDRS III actions that are significantly superior to placebo. Patients on pergolide were more likely to drop out because of adverse events than those on pramipexole.

Double-blind, single-dose, cross-over study of the effects of pramipexole, pergolide, and placebo on rest tremor and UPDRS part III in Parkinson's disease.

Tremor is one of the cardinal signs of Parkinson's disease (PD) but its response to antiparkinsonian medication is variable. It has been postulated that pramipexole may have a stronger antiparkinsonian tremor effect than pergolide, another direct acting dopamine agonist medication, possibly because the former has preferential affinity for the dopamine D3 receptor. The purpose of this pilot study was to compare the effects of a single oral dose of either pramipexole (Pr) or pergolide (Pe) or placebo (Pl) on parkinsonian tremor and the motor (part III) subsection of the UPDRS. Ten patients (6 men, 4 women), mean age 65.3 years, mean duration from diagnosis of 2.6 years, with tremor dominant PD were recruited. On three separate occasions a single dose of pramipexole (salt) 500 microg, pergolide 500 microg or placebo were administered in random order to each patient, who were pretreated with domperidone and had their antiparkinsonian medication withheld from midnight before study. After each medication patients were assessed at baseline and then every 30 min for 4 hr using a 0 to 10 tremor rating scale and the UPDRS (part III) in a double-blind protocol. Adverse effects were systematically recorded. The results demonstrate that 500 microg of either pramipexole or pergolide reduced PD rest tremor scores to a similar degree, which at peak effect was significantly greater than placebo (respectively Pe v Pl: P < 0.006, Pr v Pl: P < 0.033). The two active drugs also had weaker beneficial effects on the UPDRS part III. Pergolide, however, was significantly more likely than pramipexole to cause nausea (P = 0.005) or vomiting (P = 0.014).