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      A New Approach to the Development of Disease‐Modifying Therapies for PD; Fighting Another Pandemic

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      , MD 1 , 2 , , MD 1 , , MD 1 , 3 , , MD, FRCPC, FRCP(hon) 1 , 4 ,
      Movement Disorders
      John Wiley & Sons, Inc.
      Parkinson's disease, disease‐modifying therapy, regulatory approval

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          Abstract

          A disease‐modifying therapy that slows disease progression and development of disability is the major unmet need in the treatment of Parkinson's disease. Recent scientific advances suggest many promising and exciting new interventions. However, despite these opportunities, the cost, time and uncertainty of being able to receive an indication as a disease‐modifying therapy has caused many pharmaceutical companies to abandon development of potentially disease‐modifying drugs. We propose a new approach to development of these agents that will reduce the cost and facilitate approval of putative disease‐modifying drugs that should prove acceptable to pharmaceutical companies and regulatory agencies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

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          Most cited references30

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          Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

          Summary Background Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. Methods We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach. Findings Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable). Interpretation Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. Funding Bill & Melinda Gates Foundation.
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            Innovation in the pharmaceutical industry: New estimates of R&D costs.

            The research and development costs of 106 randomly selected new drugs were obtained from a survey of 10 pharmaceutical firms. These data were used to estimate the average pre-tax cost of new drug and biologics development. The costs of compounds abandoned during testing were linked to the costs of compounds that obtained marketing approval. The estimated average out-of-pocket cost per approved new compound is $1395 million (2013 dollars). Capitalizing out-of-pocket costs to the point of marketing approval at a real discount rate of 10.5% yields a total pre-approval cost estimate of $2558 million (2013 dollars). When compared to the results of the previous study in this series, total capitalized costs were shown to have increased at an annual rate of 8.5% above general price inflation. Adding an estimate of post-approval R&D costs increases the cost estimate to $2870 million (2013 dollars).
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              The Emerging Evidence of the Parkinson Pandemic

              Neurological disorders are now the leading source of disability globally, and the fastest growing neurological disorder in the world is Parkinson disease. From 1990 to 2015, the number of people with Parkinson disease doubled to over 6 million. Driven principally by aging, this number is projected to double again to over 12 million by 2040. Additional factors, including increasing longevity, declining smoking rates, and increasing industrialization, could raise the burden to over 17 million. For most of human history, Parkinson has been a rare disorder. However, demography and the by-products of industrialization have now created a Parkinson pandemic that will require heightened activism, focused planning, and novel approaches.
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                Author and article information

                Contributors
                cwolanow@aol.com
                Journal
                Mov Disord
                Mov Disord
                10.1002/(ISSN)1531-8257
                MDS
                Movement Disorders
                John Wiley & Sons, Inc. (Hoboken, USA )
                0885-3185
                1531-8257
                07 October 2020
                January 2021
                : 36
                : 1 ( doiID: 10.1002/mds.v36.1 )
                : 59-63
                Affiliations
                [ 1 ] Clintrex Research Corporation Sarasota Florida USA
                [ 2 ] Center for Health & Technology University of Rochester Rochester New York USA
                [ 3 ] Cooper Medical School of Rowan University Camden New Jersey USA
                [ 4 ] Department of Neurology and Department of Neuroscience Mount Sinai School of Medicine New York New York USA
                Author notes
                [*] [* ] [Corrections added on Oct 27, 2020 after first online publication: Copyright line updated.]* Correspondence to: C. Warren Olanow, Department of Neurology and Department of Neuroscience, Icahn School of Medicine at Mount Sinai, Mount Sinai School of Medicine, New York, NY 10029, USA; E‐mail: cwolanow@ 123456aol.com

                Article
                MDS28310
                10.1002/mds.28310
                7891378
                33026697
                3ae94625-18bc-439d-8d4f-054aeae28d98
                © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 August 2020
                : 31 August 2020
                : 01 September 2020
                Page count
                Figures: 0, Tables: 1, Pages: 5, Words: 4238
                Categories
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                2.0
                January 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.7 mode:remove_FC converted:18.02.2021

                Medicine
                parkinson's disease,disease‐modifying therapy,regulatory approval
                Medicine
                parkinson's disease, disease‐modifying therapy, regulatory approval

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