Levodopa-based device-aided therapies for the treatment of advanced Parkinson's disease: a social return on investment analysis.

Introduction: Parkinson's disease (PD) is an incurable, progressive, neurodegenerative disorder. As PD advances and symptoms progress, patients become increasingly dependent on family and carers. Traditional cost-effectiveness analyses (CEA) only consider patient and payer-related outcomes, failing to acknowledge impacts on families, carers, and broader society. This novel Social Return on Investment (SROI) analysis aimed to evaluate the broader impact created by improving access to levodopa (LD) device-aided therapies (DATs) for people living with advanced PD (aPD) in Australia. Methods: A forecast SROI analysis over a three-year time horizon was conducted. People living with aPD and their families were recruited for qualitative interviews or a quantitative survey. Secondary research and clinical trial data was used to supplement the primary research. Outcomes were valued and assessed in a SROI value map in Microsoft Excel™. Financial proxies were assigned to each final outcome based on willingness-to-pay, economic valuation, and replacement value. Treatment cost inputs were sourced from Pharmaceutical Benefits Schedule (PBS) and Medicare Benefits Scheme (MBS) published prices. Results: Twenty-four interviews were conducted, and 55 survey responses were received. For every $1 invested in access to LD-based DATs in Australia, an estimated $1.79 of social value is created. Over 3 years, it was estimated $277.16 million will be invested and $406.77 million of social return will be created. This value is shared between people living with aPD (27%), their partners (22%), children (36%), and the Australian Government (15%). Most of the value created is social and emotional in nature, including reduced worry, increased connection to family and friends, and increased hope for the future. Discussion: Investment in LD-based DATs is expected to generate a positive social return. Over 50% of the value is created for the partners and children of people living with aPD. This value would not be captured in traditional CEA. The SROI methodology highlights the importance of investing in aPD treatment, capturing the social value created by improved access to LD-based DATs.

Cost-Effectiveness of Device-Aided Therapies in Parkinson's Disease: A Structured Review.

BACKGROUND: Despite optimal dopaminergic treatment most patients in moderate to advanced stages of Parkinson's disease (PD) experience progressively increasing disabilities, necessitating a shift from oral medication to device-aided therapies, including deep brain stimulation (DBS), intrajejunal levodopa-carbidopa infusion (IJLI), and continuous subcutaneous apomorphine infusion (CSAI). However, these therapies are costly, limiting their implementation. OBJECTIVES: To perform a systematic review on cost-effectiveness analyses for device-aided therapies in PD. METHODS: References were identified by performing a systematic search in the PubMed and Web of Science databases in accordance with the PRISMA statement. In the absence of universal cost-effectiveness definitions, the gross domestic product per capita (GDP) in the country where a study was performed was used as a cut-off for cost-effectiveness based on cost per quality adjusted life year (QALY) gained. RESULTS: In total 30 studies were retrieved. All device-aided therapies improved quality of life compared to best medical treatment, with improvements in QALYs between 0.88 and 1.26 in the studies with long temporal horizons. For DBS, nearly all studies showed that cost per QALY was below the GDP threshold. For infusion therapies only three studies showed a cost per QALY below this threshold, with several studies with long temporal horizons showing costs below or near the GDP threshold. CONCLUSION: Of the device-aided therapies, DBS can be considered cost-effective, but the majority of infusion therapy studies showed that these were less cost-effective. However, long-term use of the infusion therapies appears to improve their cost-effectiveness and in addition, several strategies are underway to reduce these high costs.

Opicapone and Levodopa-Carbidopa Intestinal Gel Infusion: The Way Forward Towards Cost Savings for Healthcare Systems?

Combined catechol-O-methyl-transferase-inhibition and Levodopa-Carbidopa intestinal gel (LCIG) infusion has the potential to reduce LCIG daily dose and the costs of this therapy. In this retrospective analysis, we report on Parkinson's disease (PD) patients on LCIG with concomitant Opicapone. In 11 patients, the introduction of Opicapone led to LCIG daily dose being reduced by 24.8% (p = 0.05) without any significant worsening of dyskinesia. Three patients withdrew from Opicapone due to side effects or inefficacy. LCIG daily dose reduction could lead to cost savings of £142,820.63/year in the United Kingdom while maintaining clinical care.

Protocol of a randomized open label multicentre trial comparing continuous intrajejunal levodopa infusion with deep brain stimulation in Parkinson's disease - the INfusion VErsus STimulation (INVEST) study.

BACKGROUND: Both Deep Brain Stimulation (DBS) and Continuous intrajejunal Levodopa Infusion (CLI) are effective therapies for the treatment of Parkinson's disease (PD). To our knowledge, no direct head-to-head comparison of DBS and CLI has been performed, whilst the costs probably differ significantly. In the INfusion VErsus STimulation (INVEST) study, costs and effectiveness of DBS and CLI are compared in a randomized controlled trial (RCT) in patients with PD, to study whether higher costs of one of the therapies are justified by superiority of that treatment. METHODS: A prospective open label multicentre RCT is being performed, with ancillary patient preference observational arms. Patients with PD who, despite optimal pharmacological treatment, have severe response fluctuations, bradykinesia, dyskinesias, or painful dystonia are eligible for inclusion. A total of 66 patients will be randomized. There is no minimal inclusion in the patient preference arms. The primary health economic outcomes are costs per unit on the Parkinson's Disease Questionnaire-39 (PDQ-39) and costs per unit Quality-Adjusted Life Year (QALY) at 12 months. The main clinical outcome is patient-reported quality of life measured with the PDQ-39 at 12 months. Patients will additionally be followed during 36 months after initiation of the study treatment. DISCUSSION: The INVEST trial directly compares the costs and effectiveness of the advanced therapies DBS and CLI. TRIAL REGISTRATION: Dutch Trial Register identifier 4753, registered November 3rd, 2014; EudraCT number 2014-001501-32, Clinicaltrials.gov: NCT02480803.

Cost-utility analysis of levodopa carbidopa intestinal gel (Duodopa) in the treatment of advanced Parkinson's disease in patients in Scotland and Wales.

AIMS: To carry out a cost-utility analysis comparing the cost-effectiveness of levodopa carbidopa intestinal gel (LCIG) with standard of care (SOC) in patients with advanced Parkinson's Disease (aPD) unsuitable for apomorphine or deep brain stimulation (DBS). LCIG is the only treatment option in this small, but clinically important, population. METHODS: A Markov model with 25 disease states based on disease stage and off-time status plus death. Patients enter the model with aPD spending >50% of their waking day in the off-state. Patients progress through the model in 6-monthly cycles for 20 years to approximate lifetime treatment and capture long-term costs and effects of therapy. Inputs are based on LCIG clinical trials for clinical outcomes and health state utilities, the literature for health state transitions and use UK-based input data wherever possible (drug costs, disease/adverse event management costs, discontinuation rates, mortality rates). LIMITATIONS: Data collection can be challenging in this small, elderly population with advanced disease, therefore some model inputs were estimated, rather than collected directly. It was assumed that a reduction in off-time was the only benefit after the first year of treatment with LCIG; this is a conservative approach, since there may be additional clinical benefits. RESULTS: There is a considerable incremental gain in quality adjusted life years (QALYs) for patients treated with LCIG of 1.26 QALY with an associated incremental cost-effectiveness ratio (ICER) of £52,110. If the impact on caregivers is included, the ICER reduces to £47,266. CONCLUSIONS: In cases where there is an orphan population, with no alternative treatment options, HTA assessments have a broader decision-making framework and the ICER is interpreted in this context. In the setting of a very small population, with considerable unmet need, LCIG represents value for money, as reflected by funding approval across the UK.

[Pharmacoeconomic aspects of combined treatment of advanced stage of Parkinson's disease]. / Farmakoékonomicheskie aspekty kombinirovannoi terapii razvernutoi stadii bolezni Parkinsona.

AIM: To assess the cost-efficiency of the fixed levodopa/carbidopa/entacapone combination and the free combination of levodopa/carbidopa with rasagiline. MATERIAL AND METHODS: An analysis was performed using the Markov model including three clinical states: duration of off-time ≤25%, duration of off-time >25% and fatal outcome. Costs of the drugs were calculated based on the results of auctions for 2016 by IMS Health data. RESULTS: In basic variant (drugs containing levodopa, 5-times a day), costs of treatment with the fixed levodopa/carbidopa/entacapone combination were 2.45 times higher than with rasagiline + levodopa/carbidopa. When taking levodopa drugs 3 times a day, costs of treatment with levodopa/carbidopa/entacapone were 1.53 times higher. Costs of treatment with rasagiline in combination with levodopa/carbidopa were lower by 10.4% even in the least beneficial variant of sensitivity analysis (maximal cost of rasagiline, maximal cost of levodopa/carbidopa and minimal cost of the fixed levodopa/carbidopa/entacapone combination). In basic variant, the cost-efficiency of treatment with rasagiline in combination with levodopa/carbidopa at the advanced stage of Parkinson's disease was 281.4 thousand roubles/QALY. CONCLUSION: Rasagiline in combination with levodopa/carbidopa is clinically and economically expedient for treatment of patients at the advanced stage of Parkinson's disease because of the reduction of costs compared to the fixed levodopa/carbidopa/entacapone combination.

The cost-effectiveness of levodopa/carbidopa intestinal gel compared to standard care in advanced Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is an incurable, progressive neurological condition, with symptoms impacting movement, walking, and posture that eventually become severely disabling. Advanced PD (aPD) has a significant impact on quality-of-life (QoL) for patients and their caregivers/families. Levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of advanced levodopa-responsive PD with severe motor fluctuations and hyper-/dyskinesia when available combinations of therapy have not given satisfactory results. AIMS: To determine the cost-effectiveness of LCIG vs standard of care (SoC) for the treatment of aPD patients. METHODS: A Markov model was used to evaluate LCIG vs SoC in a hypothetical cohort of 100 aPD patients with severe motor fluctuations from an Irish healthcare perspective. Model health states were defined by Hoehn & Yahr (H&Y) scale-combined with amount of time in OFF-time-and death. SoC comprised of standard oral therapy ± subcutaneous apomorphine infusion and standard follow-up visits. Clinical efficacy, utilities, and transition probabilities were derived from published studies. Resource use was estimated from individual patient-level data from Adelphi 2012 UK dataset, using Irish costs, where possible. Time horizon was 20 years. Costs and outcomes were discounted at 4%. Both one-way and probabilistic sensitivity analyses were conducted. RESULTS: The incremental cost-effectiveness ratio for LCIG vs SOC was €26,944/quality adjusted life year (QALY) (total costs and QALYs for LCIG vs SoC: €537,687 vs €514,037 and 4.37 vs 3.49, respectively). LCIG is cost-effective at a payer threshold of €45,000. The model was most sensitive to health state costs. CONCLUSION: LCIG is a cost-effective treatment option compared with SoC in patients with aPD.

[Pharmacoeconomic study of the treatment of advanced Parkinson's disease]. / Estudio farmacoeconomico del tratamiento de la enfermedad de Parkinson avanzada.

INTRODUCTION: When oral or transdermal drug therapy in Parkinson's disease becomes less effective, there are three therapies using assisted devices that can reduce motor and non-motor complications: subcutaneous apomorphine infusion pump (SAIP), continuous levodopa/carbidopa duodenal infusion (LDI) and deep brain stimulation (DBS). AIM: Conduct a comparative pharmacoeconomic analysis of the use of SAIP, with LDI and DBS. As a secondary objective arises discuss the profile of the ideal candidate for each of the technicals. PATIENTS AND METHODS: Information on life years gained and quality adjusted life years (QALY) according to Hoehn and Yahr scale was obtained, as well as data on costs and resource use for each of the alternatives. The perspective of the analysis was the National Health System and the time horizon was 5 years for costs and patient´s lifetime for utilities. Outcome measures used were life years gained and QALYs, and incremental cost/utility ratio for comparison. RESULTS: Cost/utility ratio was obtained for each option: 31,956 euros/QALY for DBS, 38,249 euros/QALY for SAIP, and 75,206 euros/QALY for LDI. CONCLUSIONS: Our results allow us to add information about effectiveness of different treatments, as these are presented in gain of years lived in full health (QALY). Data obtained contribute to decision making that determine planning and management of each case, without forgetting patient and neurologist preferences, as well as budgetary limitations.

TITLE: Estudio farmacoeconomico del tratamiento de la enfermedad de Parkinson avanzada.Introduccion. Cuando el tratamiento farmacologico oral o transdermico de la enfermedad de Parkinson pierde eficacia, se dispone de tres terapias mediante dispositivos asistidos que pueden reducir las complicaciones motoras y no motoras: la apomorfina en infusion subcutanea (ASBI), la bomba de infusion duodenal continua de levodopa/carbidopa (IDL) y la estimulacion cerebral profunda (ECP). Objetivo. Efectuar un analisis farmacoeconomico comparativo del uso de ASBI con IDL y ECP; como objetivo secundario, discutir el perfil del candidato ideal para cada una de las tecnicas. Pacientes y metodos. Se extrajo informacion sobre datos de años de vida ganados y años de vida ganados ajustados por calidad (AVAC) segun la escala de Hoehn y Yahr, e informacion sobre costes y consumo de recursos para cada alternativa. La perspectiva del analisis fue la del Sistema Nacional de Salud, y el horizonte temporal fue de cinco años para los costes y toda la vida del paciente para las utilidades. Las medidas de resultado utilizadas fueron los años de vida ganados y AVAC, y en su comparacion se uso la ratio coste-utilidad incremental. Resultados. El coste-utilidad obtenido para cada opcion fue: 31.956 euros/AVAC para la ECP, 38.249 euros/AVAC para la ASBI y 75.206 euros/AVAC para la IDL. Conclusiones. Los resultados permiten evaluar la efectividad y utilidad de los diferentes tratamientos para la enfermedad de Parkinson avanzada, pues se presentan en ganancias de años vividos en plena salud. Los datos obtenidos contribuyen a la toma de decisiones que determinen la planificacion y gestion de cada caso, sin olvidar las preferencias del paciente y del neurologo, asi como las limitaciones presupuestarias.

Placebo effect of medication cost in Parkinson disease: a randomized double-blind study.

OBJECTIVE: To examine the effect of cost, a traditionally "inactive" trait of intervention, as contributor to the response to therapeutic interventions. METHODS: We conducted a prospective double-blind study in 12 patients with moderate to severe Parkinson disease and motor fluctuations (mean age 62.4 ± 7.9 years; mean disease duration 11 ± 6 years) who were randomized to a "cheap" or "expensive" subcutaneous "novel injectable dopamine agonist" placebo (normal saline). Patients were crossed over to the alternate arm approximately 4 hours later. Blinded motor assessments in the "practically defined off" state, before and after each intervention, included the Unified Parkinson's Disease Rating Scale motor subscale, the Purdue Pegboard Test, and a tapping task. Measurements of brain activity were performed using a feedback-based visual-motor associative learning functional MRI task. Order effect was examined using stratified analysis. RESULTS: Although both placebos improved motor function, benefit was greater when patients were randomized first to expensive placebo, with a magnitude halfway between that of cheap placebo and levodopa. Brain activation was greater upon first-given cheap but not upon first-given expensive placebo or by levodopa. Regardless of order of administration, only cheap placebo increased activation in the left lateral sensorimotor cortex and other regions. CONCLUSION: Expensive placebo significantly improved motor function and decreased brain activation in a direction and magnitude comparable to, albeit less than, levodopa. Perceptions of cost are capable of altering the placebo response in clinical studies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that perception of cost is capable of influencing motor function and brain activation in Parkinson disease.

Cost-effectiveness of continuous subcutaneous apomorphine in the treatment of Parkinson's disease in the UK and Germany.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting ∼ 5.2 million people worldwide. Continuous subcutaneous apomorphine (CSAI) represents an alternative treatment option for advanced PD with motor fluctuation. The purpose of this analysis was to estimate the cost-effectiveness of CSAI compared with Levodopa/carbidopa intestinal gel (LCIG), Deep-Brain-Stimulation (DBS) and Standard-of-care (SOC). METHODS: A multi-country Markov-Model to simulate the long-term consequences, disease progression (Hoehn & Yahr stages 3-5, percentage of waking-time in the OFF-state), complications, and adverse events was developed. Monte-Carlo simulation accounted for uncertainty. Probabilities were derived from RCT and open-label studies. Costs were estimated from the UK and German healthcare provider's perspective. QALYs, life-years (LYs), and costs were projected over a life-time horizon. RESULTS: UK lifetime costs associated with CSAI amounts to £78,251.49 and generates 2.85 QALYs and 6.28 LYs (€104,500.08, 2.92 QALYs and 6.49 LYs for Germany). Costs associated with LCIG are £130,011.34, achieves 3.06 QALYs and 6.93 LYs (€175,004.43, 3.18 QALYs and 7.18 LYs for Germany). The incremental-cost per QALY gained (ICER) was £244,684.69 (€272,914.58). Costs for DBS are £87,730.22, associated with 2.75 QALYs and 6.38 LYs (€105,737.08, 2.85 QALYs and 6.61 LYs for Germany). CSAI dominates DBS. SOC associated UK costs are £76,793.49; 2.62 QALYs and 5.76 LYs were reached (€90,011.91, 2.73 QALYs and 6 LYs for Germany). CONCLUSIONS: From a health economic perspective, CSAI is a cost-effective therapy and could be seen as an alternative treatment to LCIG or DBS for patients with advanced PD.

Real life cost and quality of life associated with continuous intraduodenal levodopa infusion compared with oral treatment in Parkinson patients.

Advanced-stage Parkinson's disease (PD) strongly affects quality of life (QoL). Continuous intraduodenal administration of levodopa (IDL) is efficacious, but entails high costs. This study aims to estimate these costs in routine care. 10 patients with advanced-PD who switched from oral medication to IDL were assessed at baseline, and subsequently at 3, 6, 9 and 12 months follow-up. We used the Unified PD Rating Scale (UPDRS) for function and 15D for Quality of Life (QoL). Costs were assessed using quarterly structured patient questionnaires and hospital registries. Costs per quality adjusted life year (QALY) were estimated for conventional treatment prior to switch and for 1-year treatment with IDL. Probabilistic sensitivity analysis was based on bootstrapping. IDL significantly improved functional scores and was safe to use. One-year conventional oral treatment entailed 0.63 QALY while IDL entailed 0.68 (p > 0.05). The estimated total 1-year treatment cost was NOK419,160 on conventional treatment and NOK890,920 on IDL, representing a cost of NOK9.2 million (€1.18 mill) per additional QALY. The incremental cost per unit UPDRS improvement was NOK25,000 (€3,250). Medication was the dominant cost during IDL (45% of total costs), it represented only 6.4% of the total for conventional treatment. IDL improves function but is not cost effective using recommended thresholds for cost/QALY in Norway.

[Pharmacoeconomic aspects of using levodopa/carbidopa intestinal gel in Parkinson's disease].

The application of levodopa/carbidopa intestinal gel (LCIG), which provides the more reliable control of the disease and decrease in progression rates compared to standard treatment, is a variant of treatment of severe forms of Parkinson's disease. An analysis of pharmacoeconomic aspects of LCIG use in foreign countries has shown that this treatment significantly improves expectancy of patients and reduces the costs of professional care. The approximate threshold values of costs per 1 QALY recommended for reimbursement of intervention costs are £30,000 in the United Kingdom and €50,000 in Sweden. In respect to intervention, LCIG can be regarded as an acceptable drug.

Cost analysis of the treatments for patients with advanced Parkinson's disease: SCOPE study.

OBJECTIVE: To perform a comparative long-term analysis of the associated healthcare costs for the therapeutic options in advanced Parkinson's Disease (PD): deep brain stimulation (DBS), continuous duodenal levodopa-carbidopa infusion (CDLCI), and continuous subcutaneous apomorphine infusion (CSAI). METHODS: Resource use associated with the pre-treatment period, procedure, and follow-up was assessed for the three therapies from the perspective of the Spanish national healthcare system. Resources consumption was measured with a Healthcare Resources Questionnaire (at nine advanced PD centres). Unit costs (Euro-Spain 2010) were applied to measure resource use to obtain the average total cost for each therapy over 5 years. RESULTS: Mean cumulative 5-year cost per patient was significantly lower with DBS (€88,014) vs CSAI (€141,393) and CDLCI (€233,986) (p < 0.0001). DBS was associated with the lowest cumulative costs from year 2, with a yearly average cost of €17,603 vs €46,797 for CDLCI (p = 0.001) and €28,279 for CSAI (p = 0.008). For every patient treated annually with CDLCI, two could be treated with DBS (or €29,194 could be saved) and for every patient treated with CSAI, €10,676 could be saved with DBS. The initial DBS investment (32.2% of the total 5-year costs) was offset by decreases in anti-Parkinsonian drugs and follow-up costs. CDLCI and CSAI required constant drug use (i.e., levodopa and carbidopa for CDLCI, apomorphine for CSAI), representing ∼95% of their total 5-year cost. LIMITATIONS: All costs were based on a questionnaire, not on actual clinical data. The study is not a cost-effectiveness analysis as there is a lack of comparable outcomes data. An expert panel was used due to the complexity and variability in the treatment of advanced PD. The sample size was relatively small. CONCLUSIONS: Overall, DBS requires less use of health resources than CDLCI or CSAI in advanced PD patients, mostly pharmacological. The initial DBS investment was offset at year 2 by reductions in the ongoing consumption of anti-Parkinsonian medication. For every patient treated annually with CDLCI or CSAI, substantial cost savings could be made with DBS.

Treatment patterns and associated costs with Parkinson's disease levodopa induced dyskinesia.

OBJECTIVES: This study examined the treatment patterns, direct healthcare costs and predictors of treatment costs associated with levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). METHODS: This retrospective cohort study followed PD patients for 1-year pre- and post-onset of LID, using a large US health insurance claims database from January 1, 2004 to December 31, 2008. Patients with LID were matched to patients without LID based on propensity scores to control for potential selection bias. Descriptive statistics and bootstrap techniques were employed to assess patient demographic and clinical characteristics and costs incurred. Factors influencing treatment costs were analyzed using a generalized linear model with log-link function and gamma distribution. Costs were adjusted to 2009 prices. RESULTS: After patients developed LID, their total treatment costs were increased from $18,645 during the 12 months preceding LID onset to $26,439 for the 12-month period subsequent to LID onset (incremental costs of $7795: P<0.001). PD-related costs increased from $3917 to $8110 (incremental costs of $4194: p<0.001) LID events, medical resource utilization, higher levodopa dosage, and use of alternative PD medications were associated with increases in total treatment costs. Few changes in medication treatment patterns were noted following the initial LID, with only slight increases in levodopa dosage and few additions of alternative agents. CONCLUSIONS: In the United States, PD patients with LID impose a significant economic burden when compared to patients without LID. Currently available, treatment strategies for dyskinesia should be used more frequently in PD management, and new treatment strategies should be considered as they may lower healthcare costs.

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.

Three year follow up of levodopa plus carbidopa treatment in a prevalent cohort of patients with Parkinson's disease in Hai, Tanzania.

It was previously thought that the prevalence of Parkinson's disease (PD) in developing countries, and in particular sub-Saharan Africa (SSA), was lower than the rest of the world. The Hai PD prevalence project [1] diagnosed 32 patients (the majority previously undiagnosed and untreated) with PD from a population of 161,000, giving age standardised prevalence rates of 64 (men) and 20 (women)/100,000, respectively. Subsequently, drug treatment has been commenced for all surviving patients with annual follow up. The aim of the study was to document response to treatment, development of side effects, progression of disease and feasibility and sustainability of supplying medication to patients in rural Tanzania. Eleven patients died before the start of medication, and a further four during follow up. One patient moved away from the study area. At the end of 3 years of treatment, 16 patients were surviving. Only one stopped medication due to side effects (dyskinesia). At 3 years, 9/16 experienced wearing off and a further three had dyskinesias. Non motor symptoms were a problem at initial assessment [2] and continued to be a problem for many of the patients. We have shown that it is possible to find, treat and follow up patients with PD in a rural sub-Saharan African setting. Availability of affordable medication locally is a major issue. Acknowledging that movement disorders and neurological diseases in general are an issue in this setting is important to drive education and training, and for allocation of funding from health care providers in SSA.

Pharmacological and electrical stimulation in chronic disorders of consciousness: new insights and future directions.

BACKGROUND: Chronic disorders of consciousness are costly and challenging conditions to treat. Although recent studies that have tested pharmacological and electrical stimulation for these conditions are promising, the optimal intervention, mechanisms of action and side effects of these experimental therapies are unclear. OBJECTIVE: To systematically review the clinical results of treatments for vegetative state (VS) and minimally conscious state (MCS) from the last 10 years. METHODS: MEDLINE, LILACS and SCOPUS were searched as data sources. Because the potential bias when search is limited to databases of peer-reviewed journals, reference lists were examined and experts in the field were contacted for other relevant or unpublished articles (i.e. negative studies). No negative unpublished studies were found. Studies were included related to therapeutic interventions in adult MCS or VS patients at least 3 and 12 months after non-traumatic and traumatic injuries, respectively. Eight studies met the inclusion criteria. The following interventions were reviewed: levodopa, amantadine, zolpidem, baclofen, dorsal column stimulation and deep brain stimulation. CONCLUSIONS: The adverse effects that were associated with these treatments were typically mild. Most of the studies demonstrated considerable improvements with the interventions, but their low strength of evidence limit the generalizability of the findings.

The association between adherence to levodopa/carbidopa/entacapone therapy and healthcare utilization and costs among patients with Parkinson's disease: a retrospective claims-based analysis.

BACKGROUND: Suboptimal adherence to long-term therapies is common and may potentially have adverse consequences on patient outcomes and healthcare costs. OBJECTIVE: To assess the association between adherence to levodopa/carbidopa/entacapone therapy and healthcare utilization and costs in patients with Parkinson's disease. METHODS: A retrospective historical cohort study, conducted in the US, using a health insurance claims database, with data spanning from 1 January 2000 to 31 December 2005. Subjects included patients with Parkinson's disease who were treated with levodopa (L), carbidopa (C) and entacapone (E) either as separate tablets (LC + E) or as a single-tablet formulation (LCE). The association between satisfactory adherence (defined as 'proportion of days covered' for LCE or LC + E during 1-year follow-up ≥80%) and healthcare utilization and costs was examined using multivariate regression to control for pretreatment adherence to LC and other patient characteristics. RESULTS: Compared with unsatisfactory adherence (n = 598), satisfactory adherence (n = 617) was associated with 39% fewer Parkinson's disease-related hospitalizations (95% CI 20, 54; p < 0.001), 47% lower all-cause inpatient costs (95% CI 18, 65; p = 0.004) and 18% lower all-cause total costs (95% CI 11, 24; p < 0.001). On an adjusted basis, all-cause total costs were $US3508 less for those with satisfactory versus unsatisfactory adherence. In both the LC + E and LCE groups, satisfactory adherence was associated with significant reductions in all-cause hospitalizations (39% and 46%, respectively), and all-cause total costs (10% and 31%, respectively). The association between adherence and total healthcare costs was stronger for patients receiving LCE. CONCLUSIONS: Better adherence to levodopa/carbidopa/entacapone therapy is associated with lower healthcare utilization and costs. Non-adherence to LCE is associated with a greater increase in costs than non-adherence to LC + E. Efforts should be made to ensure adherence to both therapies.

Reducing uncertainty in value-based pricing using evidence development agreements: the case of continuous intraduodenal infusion of levodopa/carbidopa (Duodopa®) in Sweden.

BACKGROUND: Value-based pricing (VBP), whereby prices are set according to the perceived benefits offered to the consumer at a time when costs and benefits are characterized by considerable uncertainty and are then reviewed ex post, is a much discussed topic in pharmaceutical reimbursement. It is usually combined with coverage with evidence development (CED), a tool in which manufacturers are granted temporary reimbursement but are required to collect and submit additional health economic data at review. Many countries, including the UK, are signalling shifts in this direction. Several countries, including Sweden, have already adopted this approach and offer good insight into the benefits and pitfalls in actual practice. OBJECTIVE: To describe VBP reimbursement decision making using CED in actual practice in Sweden. METHODS: Decision making by The Dental and Pharmaceutical Benefits Agency (TLV) in Sweden was reviewed using a case study of continuous intraduodenal infusion of levodopa/carbidopa (Duodopa®) in the treatment of advanced Parkinson's disease (PD) with severe motor fluctuations. RESULTS: The manufacturer of Duodopa® applied for reimbursement in late 2003. While the proper economic data were not included in the submission, TLV granted reimbursement until early 2005 to provide time for the manufacturer to submit a formal economic evaluation. The re-submission with economic data was considered inadequate to judge cost effectiveness, so TLV granted an additional extension of reimbursement until August 2007, at which time conclusive data were expected. The manufacturer initiated a 3-year, prospective health economic study and a formal economic model. Data from a pre-planned interim analysis of the data were loaded into the model and the cost-effectiveness ratio was the basis of the next re-submission. TLV concluded that the data were suitable for making a definite decision and that the drug was not cost effective, deciding to discontinue reimbursement for any new patients (current patients were unaffected). The manufacturer continued to collect data and to improve the economic model and re-submitted in 2008. New data and the improved model resulted in reduced uncertainty and a lower cost-effectiveness ratio in the range of Swedish kronor (SEK)430,000 per QALY gained in the base-case analysis, ranging up to SEK900,000 in the most conservative sensitivity analysis, resulting in reimbursement being granted. DISCUSSION: The case of Duodopa® provides excellent insight into VBP reimbursement decision making in combination with CED and ex post review in actual practice. Publicly available decisions document the rigorous, time-consuming process (four iterations were required before a final decision could be reached). The data generated as part of the risk-sharing agreement proved correct the initial decision to grant limited coverage despite lack of economic data. Access was provided to 100 patients while evidence was generated. CONCLUSIONS: Economic appraisal differs from clinical assessment, and decision makers benefit from analysis of naturalistic, actual practice data. Despite reviewing the initial trial-based, 'piggy-back' economic analysis, TLV was uncertain of the cost effectiveness in actual practice and deferred a final decision until observational data from the DAPHNE study became available. Second, acceptance of economic modelling and use of temporary reimbursement conditional on additional evidence development provide a mechanism for risk sharing between TLV and manufacturers, which enabled patient access to a drug with proven clinical benefit while necessary evidence to support claims of cost effectiveness could be generated.