AIMS: To estimate the impact of anti-vascular endothelial growth factor (VEGF) agents on visual impairment and blindness avoided in patients with diabetic macular edema (DME) and on associated patient and caregiver productivity loss in Japan. METHODS: This study compared the impact of current care (estimated at 53.8% utilization of anti-VEGF agents using current data) with that of hypothetical care (characterized by a higher utilization of anti-VEGF agents [80.0%], as estimated by an expert panel) of DME patients. A population-based Markov model (two-eye approach) simulated visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) transitions over 5 years with DME treatments (intravitreal aflibercept, ranibizumab, and triamcinolone acetonide, and grid/focal laser) in patients with DME. Patient and caregiver productivity loss was determined using the human capital method. RESULTS: In total, 570,000 DME patients were included in the model over 5 years. Increased utilization of anti-VEGF agents resulted in 6,659 fewer cases of severe visual impairment (SVI; 26-35 ETDRS letters) or blindness (0-25 ETDRS letters) compared with the current care approach (26,023 vs 32,682 cases; 20.38% reduction) over this period. Increased utilization of anti-VEGF agents also contributed to productivity loss savings of yen12.58 billion (US $115.64 million) (i.e., 17.01%) at the end of year 5. The total overall saving over 5 years was yen45.83 billion (US $421.27 million) (13.45%). LIMITATIONS: Few Japanese data were available, and assumptions were made for some inputs. Vision changes dependent on the function of both eyes were not studied. Only intravitreal (not sub-Tenon’s) injections of triamcinolone were considered in this model. Direct costs were not considered. CONCLUSIONS: Increased utilization of anti-VEGF agents can reduce SVI and legal blindness in patients with DME in Japan. This would also be associated with substantial savings in patient and caregiver productivity loss.

AIMS: There have been no systematic literature reviews (SLRs) evaluating the identified association between outcomes (e.g. clinical, functional, adherence, societal burden) and Quality of Life (QoL) or Healthcare Resource Utilization (HCRU) in schizophrenia. The objective of this study was to conduct a SLR of published data on the relationship between outcomes and QoL or HCRU. MATERIALS AND METHODS: Electronic searches were conducted in Embase and Medline, for articles which reported on the association between outcomes and QoL or HCRU. Inclusion and exclusion criteria were applied to identify the most relevant articles and studies and extract their data. A summary table was developed to illustrate the strength of associations, based on p-values and correlations. RESULTS: One thousand and two abstracts were retrieved; 5 duplicates were excluded. 997 abstracts were screened and 95 references were retained for full-text screening. 31 references were included in the review. The most commonly used questionnaire, which also demonstrated the strongest associations (defined as a p < 0.0001 and/or correlation +/- 0.70), was the Positive and Negative Syndrome Scale (PANSS) associated with HCRU and QoL (the SF-36, the Schizophrenia Quality of Life questionnaire [S-QOL-18], the Quality of Life Scale [QLS]). Other robust correlations included the Clinical Global Impression - Severity (CGI-S) with QoL (EQ5D), relapse with HCRU and remission with QoL (EQ5D). Lastly, functioning (Work Rehabilitation Questionnaire [WORQ] and Personal and Social Performance Scale [PSP]) was found to be associated to QoL (QLS and Subjective Well-being under Neuroleptics Questionnaire [SWN]). LIMITATIONS: This study included data from an 11-year period and other instruments less frequently used may be further investigated. CONCLUSIONS: The evidence suggests that the PANSS is the clinical outcome that currently provides the most frequent and systematic associations with HCRU and QoL endpoints in schizophrenia.

Background: The relative efficacy and safety can vary among drugs over time. Sumatriptan, a first choice drug for acute migraine, can illustrate this phenomenon. Objective: To assess the evolution of the relative efficacy and tolerability of oral sumatriptan against placebo between its approval in 1991 and 2006. Methods: A systematic literature review of randomized controlled trials (RCTs) of adults suffering from acute migraine episodes was performed using Medline. Meta-analyses estimated odds ratios of the occurrence of pain-free at 2 hours and of any adverse event. Results: Out of the 67 RCTs identi.fied, pain-free at 2 hours and adverse events were reported in 25 and 28 studies, respectively. For pain-free, the relative effect of sumatriptan increases considerably over time, despite an increase in the absolute placebo effect. The odds ratio (95% CI) equaled 3.13 (1.67-5.86) around approval (1991-1994) and increased up to 4.14 (3.67-4.67) on the following decade. No specific variation was observed in the relative tolerability effect of sumatriptan over placebo over time. Conclusions: The relative effect of sumatriptan evolved substantially over time. This phenomenon may impact the results of network meta-analysis and indirect comparisons performed to evaluate the potential of a new drug, compared to widely prescribed older drugs.

Objective: To assess the long-term effectiveness of droxidopa in reducing the risk of falling and fear of falling (FoF) in patients with neurogenic orthostatic hypotension (nOH)Background: nOH, a sustained blood pressure drop upon standing, may increase fall incidence, which can trigger FoF and future fall risk. Droxidopa is approved to treat nOH symptoms; fall benefits were suggested in pivotal trials.Design/Methods: Patients newly initiating droxidopa enrolled in an open-label, prospective cohort study. The number of falls in the past month and FoF were recorded at baseline, 1, 3, and 6 months using a falls questionnaire and the Short Falls Efficacy Scale-International. P values were calculated using paired t test for continuous measures and generalized estimating equations with multinomial distributions for categorical measures.Results: 179 patients were enrolled (Parkinson disease, 33%; autonomic failure without identifiable cause, 65%; other, 2%); 135, 119, and 105 remained at 1, 3, and 6 months. Patients reported fewer falls in the previous month at 1, 3, and 6 months vs baseline (P≤0.01, P=0.06, P&lt;0.05, respectively). Among patients who fell ≥1 time at baseline, fewer falls were reported during droxidopa treatment; 59% fell ≥3 times at baseline and only 36% fell ≥3 times at 6 months. At 1, 3, and 6 months, significantly less concern about falling vs baseline were indicated by reductions in FoF scores (all P&lt;0.0001) and categorical changes in level of concern about falling (all P&lt;0.01).Conclusions: In this “real-world” study patients taking droxidopa were at a lower risk of falling after 1, 3, and 6 months of treatment. Those who fell ≥1 time in the prior month reported fewer falls per month vs baseline. Patients reported reduced FoF during treatment. These results suggest persistence of beneficial effects at 6 months of treatment, but conclusions are limited by the lack of a control cohort.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. 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. Shibao has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck. Dr. Shibao has 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, LL ., Cowen and Company, Cynapsus Therapeutics, DDB Health LLC, Decision Resources Group (DRG), Eli Lilly &amp; 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. 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).

Abstract Aim To characterize patients with neurogenic bladder (NGB), their treatment patterns, healthcare resource utilization, and associated costs based on records from a primary care database in the United Kingdom. Methods This was a retrospective, descriptive, observational study of anonymized data from the Clinical Practice Research Datalink and Hospital Episode Statistics databases (selection period, 1 January 2004 to 31 December 2016). Adults with a definitive or probable diagnosis of NGB and ≥1 referral to a urologist were included. Results The study cohort included 3913 patients with definitive (n?=?363) or probable (n?=?3550) NGB. Patients had a mean of 8.6 (standard deviation [SD], 7.6) comorbidities, and mean Anticholinergic Cognitive Burden Scale score of 6.6 (SD, 5.9). During 12 months? follow-up, urinary tract infection (UTI) and urinary incontinence were the most common complications. Most patients (92.2%) received ≥1 prescription for an antimuscarinic agent or mirabegron, and 53.9% of patients received prescriptions for UTI-specific antibiotics. The mean number of visits to a general practitioner for any cause was 67.7 (SD, 42.6) per individual. Almost half (46.7%) of the study cohort visited a specialist during the 12-month follow-up period, and 11.0% had ≥1 hospital admission. Total mean per patient costs for healthcare resource utilization was £2395. Conclusions The burden of illness, healthcare resource needs, and associated costs among patients with NGB are considerable. Drug prescribing patterns are consistent with the symptoms and complications of NGB, although increased awareness of drugs with anticholinergic activity among prescribers may help to reduce the cumulative anticholinergic burden in this vulnerable population.

The goal of the treatment of a disease has moved from treating organs and diseases through symptoms, biological parameters and imaging towards treating a human being as a whole. The treatments should deliver benefits that patients can personally perceive. However, the patient’s perspective does not always match the one of those surrounding them. Illustratively, patients’ symptom assessments are more predictable for daily health status, whereas clinicians’ symptom measurements are more related to clinical outcomes. The term, patient-reported outcomes (PROs), includes any data that are reported directly by the patient without an intermediary, such as a family member or a healthcare professional. The use of PROs in oncology trials is increasing and the U.S. Food and Drug Administration has published guidelines on the review and evaluation of PROs. However, while PROs are increasingly used in clinical trials, they are rarely used in daily clinical practice. Further, healthcare payers are concerned with issues related to relevance, quality, and interpretability of these outcomes.

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&lt;0.05). Patients not on DDCIs also experienced significant OHSA-1 scores improvement (−1.9, P&lt;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 &gt;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 &amp; 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 (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.