Effects of Droxidopa Treatment for Neurogenic Orthostatic Hypotension in Patients Concomitantly on Dopa Decarboxylase Inhibitors (P3.6-048)
Objective: To assess long-term efficacy of droxidopa for treatment of neurogenic orthostatic hypotension (nOH) in patients concomitantly on dopa decarboxylase (DDC) inhibitors (DDCIs)Background: nOH is a non-motor symptom of Parkinson disease (PD). Treatment of PD frequently includes DDCIs. Droxidopa, a treatment for symptomatic nOH, is converted to norepinephrine by DDC.Design/Methods: Patients were enrolled in a prospective cohort study comparing outcomes before initiation of droxidopa and after 1, 3, and 6 months of treatment. Patients recorded monthly number of falls using a questionnaire and dizziness/lightheadedness using Orthostatic Hypotension Symptom Assessment, Item 1 (OHSA-1). Post-hoc analysis compared outcomes in patients on DDCIs vs without DDCIs. “DDCI treatment” defined as receiving carbidopa alone or in combination with levodopa or entacapone. Influence of DDCIs was compared across time points using generalized linear mixed models adjusting for repeated measures within individuals.Results: 168 patients were included (PD: 32.1%, autonomic failure: 66.1%, other: 1.8%). 61.8% of patients on DDCIs (n=55) reported ≥1 fall at baseline vs 46.9% of patients not on DDCIs (n=113). Patients on DDCIs experienced significant reduction in fall rate (30.1%, 36.4 point reduction) and improvement in OHSA-1 scores (−1.8) from baseline to 6 months (both P<0.05). Patients not on DDCIs also experienced significant OHSA-1 scores improvement (−1.9, P<0.05), but fall rate reduction was not significant (39.8%, 6.2 point reduction, P=0.49). The differences in change from baseline to 6 months for fall risk and OHSA-1 score were not significant between groups (P=0.15, P=0.96, respectively). DDCI users (66.6%) had a greater prevalence of >1 falls vs nonusers (46.6%) at baseline.Conclusions: These post-hoc analyses suggest that DDCI users and nonusers experienced reductions in fall rate and dizziness/lightheadedness with droxidopa. Additional studies are needed to examine the impact of DDCIs on droxidopa because the current study was not powered for subgroup analyses and data were patient self-reported.Disclosure: Dr. Kymes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck and CVS Health. Dr. Kymes holds stock and/or stock options in Lundbeck that is greater than $10,000 in value which sponsored research in which Dr. Kymes was involved as an investigator. Dr. Francois has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck and Creativ-Ceutical. Dr. Francois holds stock and/or stock options in Lundbeck. Dr. Sullivan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck. Dr. McLeod has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Xcenda, LLC. Dr. Duhig has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Xcenda, LLC. Dr. Ogbonnaya has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Xcenda LLC. Dr. Quillen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Xcenda LLC. Dr. Cannon has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck. Dr. Biaggioni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck, Theravance Biopharma. Dr. Biaggioni has received research support from Lundbeck (investigator-initiated grant) and Theravance Biopharma (Clinical Trial). Dr. Shibao has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck. Dr. Shibao h s received research support from Lundbeck. Dr. Yue has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Xcenda LLC. Dr. Hauser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie Inc., Acorda Therapeutics, Academy for Continued Healthcare Learning, Acadia Pharmaceuticals, Inc., Adamas Pharmaceuticals, AstraZeneca, ApoPharma, Back Bay Life Science, Biotie Therapies, Bracket, Cerecor, Inc., ClearView Healthcare Partners, ClinicalMind Medical and Therapeutic Communications, CNS Ratings, LLC., Cowen and Company, Cynapsus Therapeutics, DDB Health LLC, Decision Resources Group (DRG), Eli Lilly & Company, eResearch Technology, Inc., Expert Connect, Extera Partners, GE Healthcare, Health Advances, HealthLogix, Health and Wellness Partners, Huron Consulting Group, Impax Laboratories, Impel Neuropharma, Intec Pharma Ltd., Jazz Pharmaceuticals, Kashiv Pharma LLC, Kyowa Kirin Pharmaceutical Development, Ltd., LCN Consulting, LifeMax, Life Sciences, Lundbeck LLC, The Lockwood Group, MEDACorp, Medscape, Medtronic, Michael J. Fox Foundation, Mitsubishi Tanabe Pharmaceuticals, Movement Disorder Society, National Institutes of Health (NIH), Neurocea LLC, Neurocrine Biosciences, Neuroderm, Neuropore Therapies, Orbes Medical Group, Outcomes Insights, Parkinson Study Group, Peerview Press, Pennside Partners, Pfizer, Inc., Pharma Two B, Ltd, Phase Five Communications, Prescott Medical Group, Prexton Therapeutics, Prilenia Development Ltd., Projects in Knowledge, Putnam Associates, Quintiles, RMEI Medical Education for Better Outcomes, SAI Med Partners LLC, Sarepta Therapeutics, Schlesinger Associates, Scion Neurostim, LLC, Seagrove Partners, LLC, Slingshot Insights, Sunovion Pharmaceuticals, Inc., Sun Pharma, Teva Pharmaceutical Industries, US WorldMeds, Vista Research, WebMD, Windrose Consulting Group. Dr. Hauser has received royalty, license fees, or contractual rights payments from the University of South Florida. Dr. Hauser has received research support from AbbVie Inc., Acorda Therapeutics, AstraZeneca, Axovant Sciences , Biogen Inc., Cavion, Enterin Inc., Impax Laboratories, LLC., Intec Pharma Ltd, Jazz Pharmaceuticals, NeuroDerm Ltd., Lundbeck, Michael J Fox Foundation for Parkinson’s Research, F. Hoffman-La Roche, Dart NeuroScience LLC, Prexton Therapeutics, Revance Therapeutics Inc., Sunovion Pharmaceuticals.
Non-profit drug research and development: the case study of Genethon
2019 J Mark Access Health Policyhttps://www.doi.org/10.1080/20016689.2018.1545514 Non-profit, ethics, orphan drugs, pharmaceutical industry, pricing, research and development,
Non-profit drug research and development (R&D) has the potential to deliver innovative treatments at affordable prices. Using the case study methodology, we discuss some ethical and economic issues, including the possible impact of non-profit companies on innovation efforts from for-profit firms. Like other non-profits, Genethon is willing to adopt an ethical attitude toward their donors by pricing their products affordably. It remains to be seen if the approach to internalize the marketing authorization, manufacturing and distribution activities prove to be efficient and sustainable. Also, the firm faces an ethical dilemma because lower prices of innovative drugs can dry the for-profit R&D in the area and prevent patient access to future innovations.
The mediating role of depression in pathways linking positive and negative symptoms in schizophrenia. A longitudinal analysis using latent variable structural equation modelling
2019 Psychol Medhttps://www.doi.org/10.1017/s0033291719000321 Depression, longitudinal studies, negative symptoms, positive symptoms, schizophrenia,
BACKGROUND: The interaction between positive, negative and depressive symptoms experienced by people with schizophrenia is complex. We used longitudinal data to test the hypothesis that depressive symptoms mediate the links between positive and negative symptoms. METHODS: We analyzed data from the European Schizophrenia Cohort, randomly sampled from outpatient services in France, Germany and the UK (N = 1208). Initial measures were repeated after 6 and 12 months. Depressive symptoms were identified using the Calgary Depression Scale for Schizophrenia (CDSS), while positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Latent variable structural equation modelling was used to investigate the mediating role of depression assessed at 6 months in relation to the longitudinal association between positive symptoms at baseline and negative symptoms at 12 months. RESULTS: We found longitudinal associations between positive symptoms at baseline and negative symptoms at 12 months, as well as between both of these and CDSS levels at 6 months. However depression did not mediate the longitudinal association between PANSS scores; all the effect was direct. CONCLUSIONS: Our findings are incompatible with a mediating function for depression on the pathway from positive to negative symptoms, at least on this timescale. The role of depression in schizophrenic disorders remains a challenge for categorical and hierarchical diagnostic systems alike. Future research should analyze specific domains of both depressive and negative symptoms (e.g. motivational and hedonic impairments). The clinical management of negative symptoms using antidepressant treatments may need to be reconsidered.
Comparison of persistence and adherence between fixed-dose combinations and two-pill combinations in Japanese patients with type 2 diabetes
2019 Curr Med Res Opinhttps://www.doi.org/10.1080/03007995.2018.1551192 Adherence, diabetes mellitus, fixed-dose, persistence, two-pill,
OBJECTIVE: To compare treatment patterns, persistence and adherence between fixed-dose combinations (FDCs) and two-pill combinations (TPCs) of oral antidiabetic drug (OAD) classes in Japanese patients with type 2 diabetes mellitus (T2DM) using administrative claims databases (Japan Medical Data Center [JMDC] and Medical Data Vision [MDV]). METHODS: This was a retrospective, longitudinal cohort analysis conducted between 2011 and 2015, in patients with T2DM receiving OADs as FDC or TPC. Outcomes included prescribing patterns, treatment persistence and adherence. RESULTS: Data from 3474 and 3066 patients receiving FDCs, and 4325 and 5192 patients receiving TPCs from the JMDC and MDV databases, respectively, was extracted. The most common OAD combination received by over half of all patients was dipeptidyl peptidase-4 inhibitor (DPP-4i) + thiazolidinediones (TZDs) (64.1% [JMDC] and 70.5% [MDV]). Overall, 12-month persistence rates were higher in patients receiving FDCs compared with TPCs (70.4 vs. 66.2% [JMDC], 75.6 vs. 55.7% [MDV]). In the JMDC population receiving FDCs or TPCs, persistence rates were highest with DPP-4i schedules (67.5-83.5%). Median time to discontinuation was significantly longer with biguanide + TZD, and DPP-4i + TZD FDC schedules (p < .05) than TPC; adherence rates were >/=80% across all antidiabetic drug classes in both database populations. CONCLUSIONS: Persistence with and adherence to OADs in Japanese patients with T2DM were greater with FDCs than with TPCs, which may suggest increased patient satisfaction due to reduced treatment burden. Further studies are warranted to investigate the impact of adherence and persistence of FDCs of OADs on glycemic control.
Estimation of the costs attributable to vitamin K antagonist treatment in patients with non-valvular atrial fibrillation from a French societal perspective
2019 J Mark Access Health Policyhttps://www.doi.org/10.1080/20016689.2018.1564506 N,
Background: Little is known about the costs associated with vitamin K antagonist (VKA) treatment in patients with non-valvular atrial fibrillation (NVAF) in France.
Objectives: To evaluate monthly per-patient costs attributable to VKA treatment in NVAF patients from a French societal perspective.
Study design: Retrospective data were obtained from 7 international normalised ratio (INR) monitoring centres in France. Patients older than 18 years of age with NVAF treated with VKA were recruited. Additional patient-level data assessing resource use corresponding with VKA treatment were collected via self-completed questionnaires. Unit costs applicable to 2015 were multiplied by resource use and summed to generate VKA treatment costs.
Results: 363 patients were included; 53% were men. The majority of patients received fluindione (72%). The number of INR tests per patient per month was 1.69 (95% CI, 1.59–1.80). The monthly patient cost was €39.72 (€36.23–43.21) from the French societal perspective. Direct medical costs comprised 76% of overall costs, with drug costs representing 7.4% (€2.4); direct non-medical and indirect costs comprised 10% and 14% respectively.
Conclusions: Costs associated with VKA treatment in NVAF cannot be estimated only with drug costs. When direct and indirect attributable costs associated with VKA treatment are considered, the VKA treatment costs are more substantial.
President Trump’s prescription to reduce drug prices: from the campaign trail to American Patients First
2019 Journal of market access & health policyhttps://www.doi.org/10.1080/20016689.2019.1579597 American Patients First (APF), President Trump, Trump administration, campaign, drug prices,
Background: Drug prices in the United States are the highest in the world, restricting access to the domestic lower income population. President Trump campaigned heavily on promises to reduce drug prices.Methods: A literature review was conducted through PUBMED, EMBASE, Media and grey literature to consolidate and analyze publications addressing President Trump’s promises from the campaign trail as well as the shortcomings and achievements of the Trump administration.Results: Major promises ranged from repealing and replacing Obamacare, expanding coverage, allowing cross-state insurance purchasing, and reducing drug prices. Main accomplishments of the Trump administration have been two executive orders (13765 and 13813), the proposition of the American Health Care Act, and the passing of the Tax Cuts and Jobs Act of 2017. The American Patients First blueprint further revealed the administration’s strategies for lowering drug prices. The administration has also engaged in unconventional strategies, such as via bilateral leverage directly with trade partners.Conclusion: The Trump administration has not yet been able to fulfill the major campaign promises, primarily the ones requiring legislative and/or administrative action. If enough legislative action is accomplished to implement the Trump administration’s promises, the effects on the pharmaceutical industry could be direct, yet minimal, unless Medicare can directly negotiate with manufacturers.
Management and clinical practice of multiple face and scalp actinic keratosis in France
2019 J Mark Access Health Policyhttps://www.doi.org/10.1080/20016689.2019.1605787 Actinic keratosis, cancerization zone, cryotherapy, face and scalp, photodynamic therapy, topical treatments,
Background: Actinic keratosis (AK) is characterized by the occurrence of thick and scaly skin areas caused by damage from ultraviolet radiation. The management of AK aims to reduce lesions and prevent their recurrence by regular monitoring. French guidelines, last updated in 2009, reflect European guidelines for the management of face and scalp AK. However, they do not address all current, available options. Objective: To assess the management of face and scalp AK in French clinical practice. Methods: A two-part online questionnaire comprising a survey among French dermatologists and an analysis of patient medical records was performed to describe AK patients treated with topical therapy, patients’ profiles, and characteristics of the affected lesion areas. Results: Decisions for topical treatments for face and scalp AK made by dermatologists were mainly driven by the lesion size. According to the last 10 patients they have seen, dermatologists were prescribing physical therapy in 53% of the cases, a combination of topical and physical therapy in 27% and topical only in 20%. Patient records revealed the average surface area targeted for treatment was 139 +/- 113cm(2). Conclusions: Discrepancies between the guidelines on the treatment of face and scalp AK and clinical practice exist. Further research may help to standardize the treatment.
Treatment patterns, persistence and adherence rates in patients with type 2 diabetes mellitus in Japan: a claims-based cohort study
2019 BMJ Openhttps://www.doi.org/10.1136/bmjopen-2018-025806 adherence, administrative claims-based study, antidiabetic drug therapy, dipeptidyl peptidase-4 inhibitors, persistence, type 2 diabetes, Nippon Boehringer Ingelheim, Eli Lilly Japan K.K., Kissei Pharmaceutical,, Medtronic Japan, MSD, Novartis Pharma KK, Novo Nordisk Pharma, Sanofi KK and, Takeda Pharmaceutical and contract research fees for collaborative research with, the Japan Diabetes Foundation. HK, KK, AO and YS are employees of Takeda, Pharmaceutical. SH was an employee of Takeda Pharmaceutical at the time the study, was conducted. FG and YO are employees of Creativ-Ceutical K.K.,
OBJECTIVE: To determine real-world trends in antidiabetic drug use, and persistence and adherence, in Japanese patients with type 2 diabetes mellitus (T2DM). DESIGN: Retrospective evaluation of administrative claims data (2011-2015) using the Japan Medical Data Center (JMDC) and Medical Data Vision (MDV) databases. SETTING: Analysis of two administrative claims databases for Japanese patients with T2DM. PARTICIPANTS: Adults (aged >/=18 years) with an International Classification of Diseases, 10th Revision code of T2DM and at least one antidiabetic drug prescription. MAIN OUTCOME MEASURES: Treatment patterns in untreated (UT) or previously treated (PT) patients receiving antidiabetic therapy; persistence with treatment at 12 months; adherence to treatment at 12 months. RESULTS: 40 908 and 90 421 patients were included from the JMDC and MDV databases, respectively. The most frequently prescribed therapy at the index (first prescription) date was dipeptidyl peptidase-4 inhibitor (DPP-4i) in UT patients (JMDC: 44.0%, MDV: 54.8%) and combination therapy in PT patients (74.6%, 81.1%). Most common combinations were DPP-4i plus: biguanide (BG; 11.4%, 10.9%), sulfonylurea (SU; 8.4%, 11.0%) or BG+SU (7.8%, 9.1%). In UT or PT patients from either database whose index prescription was for any antidiabetic drug class(es) other than DPP-4i, the most frequent add-on or switch was to DPP-4i. 12-month persistence with index monotherapy was highest with DPP-4i and BG. Adherence was high (>/=80%) for all monotherapy schedules, except insulin and glucagon-like peptide-1 agonist, and for the five most frequent two-drug and three-drug combinations. Persistence was greater in elderly UT patients and in those receiving =5 medications, but comparatively worse in UT patients with >/=3 index antidiabetic drug classes. CONCLUSIONS: The findings indicate that DPP-4i is the most commonly used antidiabetic drug class in Japanese patients with T2DM, and persistence and adherence to this antidiabetic drug class are high.
Oncology from an HTA and Health Economic Perspective
2019 Recent Results Cancer Reshttps://www.doi.org/10.1007/978-3-030-01207-6_3 Cost-Benefit Analysis, Decision Making, Medical Oncology/*economics, *Models, Economic, Neoplasms/*economics, Randomized Controlled Trials as Topic, Research Design, *Technology Assessment, Biomedical, Cost-effectiveness, Decision-making, Health technology assessment, Oncology drugs,
In this chapter, we will present and discuss the challenges of assessing oncology products from a health economic perspective. We will provide a brief introduction on the need for economic evaluation in health care and focus on cost-effectiveness and comparative aspects of the evaluation of oncology products, which are of paramount interest to HTA decision-making bodies using economic evaluation in their decision-making framework. As the burden of oncology is well-documented, we do not discuss it in detail here. Before we address the specific issue of oncology, we will briefly define the critical aspects of HTA assessment and also define what a cost-effectiveness analysis is and why economic modelling is the most appropriate tool to assess the cost-effectiveness of oncology products. We will touch upon the prices of oncology drugs and the questions that high prices raise regarding funding and availability. We then present an overview of the general structure of an oncology cost-effectiveness model. Usually, this is quite simple, representing response, progression, advanced-stage disease and death. Despite the relative simplicity of these models, some issues may render the evaluation more complex; we will touch upon these in this chapter: Issue with clinical inputs due to the design of randomised clinical trials (e.g. cross-over designs involving a treatment switch) Need for survival extrapolation and limitations of current parametric models Rare conditions with limited economic and comparative evidence available High pace of clinical development Finally, we will conclude with a discussion of the uncertainty around the evaluation of oncology products and the major evolution expected in health economics in oncology.
Cost-effectiveness of fluocinolone acetonide implant (ILUVIEN(R)) in UK patients with chronic diabetic macular oedema considered insufficiently responsive to available therapies
2019 BMC Health Serv Reshttps://www.doi.org/10.1186/s12913-018-3804-4 Cost-effectiveness, Diabetic macular oedema, Fluocinolone acetonide implant, Incremental cost-effectiveness ratio, Treatment cost,
BACKGROUND: Diabetic macular oedema (DMO) may lead to visual loss and blindness. Several pharmacological treatments are available on the National Health Service (NHS) to United Kingdom patients affected by this condition, including intravitreal vascular endothelial growth factor inhibitors (anti-VEGFs) and two types of intravitreal steroid implants, releasing dexamethasone or fluocinolone acetonide (FAc). This study aimed to assess the value for money (cost-effectiveness) of the FAc 0.2 mug/day implant (ILUVIEN(R)) in patients with chronic DMO considered insufficiently responsive to other therapies. METHODS: We developed a Markov model with a 15-year time horizon to estimate the impact of changes in best-corrected visual acuity in DMO patients on costs and quality-adjusted life years. The model considered both eyes, designated as the “study eye”, defined at model entry as phakic with an ongoing cataract formation or pseudophakic, and the “fellow eye”. The model compared the FAc 0.2 mug/day implant with a 700 mug dexamethasone implant (pseudophakic patients only) or with usual care, defined as a mixture of laser photocoagulation and anti-VEGFs (phakic and pseudophakic patients). Costs were estimated from the perspective of the NHS and Personal Social Services; full NHS prices were used for drugs. RESULTS: In patients who were pseudophakic at baseline, at 36 months, the FAc implant provided an additional gain of 4.01 and 3.64 Early Treatment Diabetic Retinopathy Study (ETDRS) letters compared with usual care and the dexamethasone implant, respectively. Over the 15-year time horizon, this translated into 0.185 additional quality-adjusted life years (QALYs) at an extra cost of pound3066 compared with usual care, and 0.126 additional QALYs at an extra cost of pound1777 compared with dexamethasone. Thus, incremental cost-effectiveness ratios (ICERs) were pound16,609 and pound14,070 per QALY gained vs. usual care and dexamethasone, respectively. In patients who were phakic at baseline, the FAc 0.2 mug/day implant provided an additional gain of 2.96 ETDRS letters at 36 months compared with usual care, which, over 15 years, corresponded to 0.11 additional QALYs at an extra cost of pound3170, resulting in an ICER of pound28,751 per QALY gained. CONCLUSION: The FAc 0.2 mug/day implant provided good value for money compared with other established treatments, especially in pseudophakic patients.