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      The Cost Effectiveness of Levodopa-Carbidopa Intestinal Gel in the Treatment of Advanced Parkinson’s Disease in England

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          Abstract

          Background

          Parkinson’s disease is a progressive neurodegenerative disease, which significantly impacts patients’ quality of life and is associated with high treatment and direct healthcare costs. In England, levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of levodopa-responsive advanced Parkinson’s disease with troublesome motor fluctuations when available combinations of medicinal products are unsatisfactory.

          Objective

          We aimed to determine the cost effectiveness of LCIG compared to the standard of care for patients with advanced Parkinson’s disease in England, using real-world data.

          Methods

          A Markov model was adapted from previous published studies, using the perspective of the English National Health System and Personal and Social Services to evaluate the cost effectiveness of LCIG compared to standard of care in patients with advanced Parkinson’s disease over a 20-year time horizon. The model comprised 25 health states, defined by a combination of the Hoehn and Yahr scale, and waking time spent in OFF-time. The base case considered an initial cohort of patients with an Hoehn and Yahr score of ≥ 3, and > 4 h OFF-time. Standard of care comprised standard oral therapies, and a proportion of patients were assumed to be treated with subcutaneous apomorphine infusion or injection in addition to oral therapies. Efficacy inputs were based on LCIG clinical trials where possible. Resource use and utility values were based on results of a large-scale observational study, and costs were derived from the latest published UK data, valued at 2017 prices. The EuroQol five-dimensions-3-level (EQ-5D-3L) instrument was used to measure utilities. Costs and quality-adjusted life-years were discounted at 3.5%. Both deterministic and probabilistic sensitivity analyses were conducted.

          Results

          Total costs and quality-adjusted life-years gained for LCIG vs standard of care were £586,832 vs £554,022, and 2.82 vs 1.43, respectively. The incremental cost-effectiveness ratio for LCIG compared to standard of care was £23,649/quality-adjusted life-year. Results were sensitive to the healthcare resource utilisation based on real-world data, and long-term efficacy of LCIG.

          Conclusions

          The base-case incremental cost-effectiveness ratio was estimated to be within the acceptable thresholds for cost effectiveness considered for England.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40273-022-01132-y.

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          Most cited references52

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          Parkinson disease

          Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.
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            Parkinsonism: onset, progression, and mortality

            M Hoehn, M Yahr (1967)
            Neurology, 17(5), 427-427
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              Global, regional, and national burden of Parkinson's disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

              Summary Background Neurological disorders are now the leading source of disability globally, and ageing is increasing the burden of neurodegenerative disorders, including Parkinson's disease. We aimed to determine the global burden of Parkinson's disease between 1990 and 2016 to identify trends and to enable appropriate public health, medical, and scientific responses. Methods Through a systematic analysis of epidemiological studies, we estimated global, regional, and country-specific prevalence and years of life lived with disability for Parkinson's disease from 1990 to 2016. We estimated the proportion of mild, moderate, and severe Parkinson's disease on the basis of studies that used the Hoehn and Yahr scale and assigned disability weights to each level. We jointly modelled prevalence and excess mortality risk in a natural history model to derive estimates of deaths due to Parkinson's disease. Death counts were multiplied by values from the Global Burden of Disease study's standard life expectancy to compute years of life lost. Disability-adjusted life-years (DALYs) were computed as the sum of years lived with disability and years of life lost. We also analysed results based on the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings In 2016, 6·1 million (95% uncertainty interval [UI] 5·0–7·3) individuals had Parkinson's disease globally, compared with 2·5 million (2·0–3·0) in 1990. This increase was not solely due to increasing numbers of older people, because age-standardised prevalence rates increased by 21·7% (95% UI 18·1–25·3) over the same period (compared with an increase of 74·3%, 95% UI 69·2–79·6, for crude prevalence rates). Parkinson's disease caused 3·2 million (95% UI 2·6–4·0) DALYs and 211 296 deaths (95% UI 167 771–265 160) in 2016. The male-to-female ratios of age-standardised prevalence rates were similar in 2016 (1·40, 95% UI 1·36–1·43) and 1990 (1·37, 1·34–1·40). From 1990 to 2016, age-standardised prevalence, DALY rates, and death rates increased for all global burden of disease regions except for southern Latin America, eastern Europe, and Oceania. In addition, age-standardised DALY rates generally increased across the Socio-demographic Index. Interpretation Over the past generation, the global burden of Parkinson's disease has more than doubled as a result of increasing numbers of older people, with potential contributions from longer disease duration and environmental factors. Demographic and potentially other factors are poised to increase the future burden of Parkinson's disease substantially. Funding Bill & Melinda Gates Foundation.
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                Author and article information

                Contributors
                ray.chaudhuri@kcl.ac.uk
                simon.pickard@secondcityoutcomesresearch.com
                ali.alobaidi@abbvie.com
                yash.jalundhwala@abbvie.com
                lakshmi.kandukuri@abbvie.com
                carol.bao@abbvie.com
                julia.sus@abbvie.com
                glynn.jones5@gmail.com
                christian.ridley@abbvie.com
                julia.oddsdottir@iqvia.com
                seyavashnr@gmail.com
                matt.madinwarburton@gmail.com
                weiwei.xu@iqvia.com
                a.schrag@ucl.ac.uk
                Journal
                Pharmacoeconomics
                Pharmacoeconomics
                Pharmacoeconomics
                Springer International Publishing (Cham )
                1170-7690
                1179-2027
                21 March 2022
                21 March 2022
                2022
                : 40
                : 5
                : 559-574
                Affiliations
                [1 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Department of Basic and Clinical Neuroscience, , The Maurice Wohl Clinical Neuroscience Institute, King’s College London, ; Cutcombe Road, London, SE5 9RT UK
                [2 ]GRID grid.185648.6, ISNI 0000 0001 2175 0319, University of Illinois at Chicago, ; Chicago, IL USA
                [3 ]GRID grid.431072.3, ISNI 0000 0004 0572 4227, AbbVie Inc., ; North Chicago, IL USA
                [4 ]GRID grid.476021.6, ISNI 0000 0004 1797 2869, AbbVie Ltd, ; Maidenhead, Berkshire UK
                [5 ]GRID grid.482783.2, IQVIA, ; London, UK
                [6 ]IQVIA, Amsterdam, The Netherlands
                [7 ]GRID grid.83440.3b, ISNI 0000000121901201, Department of Clinical and Movement Neurosciences, , UCL Queen Square Institute of Neurology, University College London, ; London, UK
                Article
                1132
                10.1007/s40273-022-01132-y
                9095547
                35307793
                6bdd35b0-cb45-4f12-adfa-4425046f167e
                © Crown 2022

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 23 January 2022
                Funding
                Funded by: abbvie inc
                Categories
                Original Research Article
                Custom metadata
                © Springer Nature Switzerland AG 2022

                Economics of health & social care
                Economics of health & social care

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