A Market Shaping Approach for the Biopharmaceutical Industry: Governing Innovation Towards the Public Interest.

Enhancing research and development and ensuring equitable pricing and access to cutting-edge treatments are both vital to a biopharmaceutical innovation system that works in the public interest. However, despite delivering numerous therapeutic advances, the existing system suffers from major problems: a lack of directionality to meet key needs, inefficient collaboration, high prices that fail to reflect the public contribution, and an overly-financialized business model.

Automated Quality Assessment and Image Selection of Ultra-Widefield Fluorescein Angiography Images through Deep Learning.

Purpose: Numerous angiographic images with high variability in quality are obtained during each ultra-widefield fluorescein angiography (UWFA) acquisition session. This study evaluated the feasibility of an automated system for image quality classification and selection using deep learning. Methods: The training set was comprised of 3543 UWFA images. Ground-truth image quality was assessed by expert image review and classified into one of four categories (ungradable, poor, good, or best) based on contrast, field of view, media opacity, and obscuration from external features. Two test sets, including randomly selected 392 images separated from the training set and an independent balanced image set composed of 50 ungradable/poor and 50 good/best images, assessed the model performance and bias. Results: In the randomly selected and balanced test sets, the automated quality assessment system showed overall accuracy of 89.0% and 94.0% for distinguishing between gradable and ungradable images, with sensitivity of 90.5% and 98.6% and specificity of 87.0% and 81.5%, respectively. The receiver operating characteristic curve measuring performance of two-class classification (ungradable and gradable) had an area under the curve of 0.920 in the randomly selected set and 0.980 in the balanced set. Conclusions: A deep learning classification model demonstrates the feasibility of automatic classification of UWFA image quality. Clinical application of this system might greatly reduce manual image grading workload, allow quality-based image presentation to clinicians, and provide near-instantaneous feedback on image quality during image acquisition for photographers. Translational Relevance: The UWFA image quality classification tool may significantly reduce manual grading for clinical- and research-related work, providing instantaneous and reliable feedback on image quality.

Exploring the evidence base for national and regional policy interventions to combat resistance.

The effectiveness of existing policies to control antimicrobial resistance is not yet fully understood. A strengthened evidence base is needed to inform effective policy interventions across countries with different income levels and the human health and animal sectors. We examine three policy domains-responsible use, surveillance, and infection prevention and control-and consider which will be the most effective at national and regional levels. Many complexities exist in the implementation of such policies across sectors and in varying political and regulatory environments. Therefore, we make recommendations for policy action, calling for comprehensive policy assessments, using standardised frameworks, of cost-effectiveness and generalisability. Such assessments are especially important in low-income and middle-income countries, and in the animal and environmental sectors. We also advocate a One Health approach that will enable the development of sensitive policies, accommodating the needs of each sector involved, and addressing concerns of specific countries and regions.

Current state of hereditary angioedema management: a patient survey.

Hereditary angioedema (HAE) is a chronic disease with a high burden of disease that is poorly understood and often misdiagnosed. Availability of treatments, including C1 esterase inhibitor (C1INH) replacement, ecallantide, and icatibant, marks a significant advance for HAE patients. We aimed to better understand the current state of HAE care, from a patient perspective, after the introduction of several novel therapies. One session of the United States Hereditary Angioedema Association 2013 patient summit was devoted to data collection for this study. Patients attending the summit were self-selected, and HAE diagnosis was self-reported. Survey questions assessed patient characteristics, burden of disease, and treatment. Participant responses were captured using an audience response system. We surveyed 149 (80%) type I and II HAE (HAE-C1INH) and 37 (20%) HAE with normal C1INH (HAE-nlC1INH) patients. HAE-C1INH (72%) and HAE-nlCINH patients (76%) equally reported that HAE had a significant impact on quality of life (QOL). A third of HAE-C1INH patients were diagnosed within one year of their first HAE attack, but another third reported a delay of more than 10 years. Most HAE-C1INH (88%) and HAE-nlC1INH (76%) patients had on-demand treatment available. HAE-C1INH patients frequently had an individual treatment plan (76%) compared with 50% of HAE-nlC1INH patients. Most HAE-C1INH patients went to the emergency department (ED) or were hospitalized less than once every six months (80%). Our findings show that HAE management is improving with good access to on-demand and prophylactic treatment options. However, HAE patients still have a significant burden of disease and continued research and educational efforts are needed.

Before and after, the impact of available on-demand treatment for HAE.

Availability of effective treatment for acute attacks is expected to transform the care of hereditary angioedema (HAE) patients. We felt that it would be of interest to test these assumptions by examining the perceptions of HAE patients regarding the impact that these therapies have had on their lives. Patients at a United States HAE Association summit meeting were asked to rate the burden of HAE currently and compare by recall with 2009 when these therapies were not available. Questions covered five domains: psychological/emotional status, ability to carry out daily activities, fear of suffocation, worry about their children inheriting HAE, and medication side effects. Data were analyzed using Wilcoxon signed-rank tests or analysis of variance. Responses were obtained from 134 self-identified HAE subjects: 85 type I, 21 type II, and 28 with normal C1 inhibitor (C1INH). Burden of disease showed significant improvement in all domains except worry about children inheriting HAE. With the introduction of newer therapies, subjects with the most severe burden of illness improved more than those with milder burdens. However, significant burden of illness remained. The availability of the current treatments has substantially improved the quality of life for HAE patients in the United States, similar to a survey of Danish HAE patients regarding the introduction of home treatment. Nevertheless, our study shows that a substantial burden of illness remains for HAE patients.

Cost-effectiveness of a novel molecular test for cytologically indeterminate thyroid nodules.

CONTEXT: Determining which patients with thyroid nodules require surgery is limited by cytologically indeterminate findings. A new approach for preoperative molecular classification of cytologically indeterminate thyroid nodules has a reported sensitivity of 91% and specificity of 75%; however, its cost-effectiveness has yet to be assessed. OBJECTIVE: Our objective was to evaluate the 5-yr cost-effectiveness of routine use of a molecular test in adult patients with indeterminate fine-needle aspiration biopsy results from a societal perspective. DESIGN: A 16-state Markov decision model was developed. Probabilities, costs, and quality-adjusted life years (QALY) were estimated from literature review, U.S. Department of Health and Human Services data, Medicare reimbursement schedules, and expert opinion. SETTING AND SUBJECTS: Decision analysis of a hypothetical group of adult patients with cytologically indeterminate thyroid nodules was conducted. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratio was calculated as incremental cost (measured in U.S. dollars) divided by incremental effectiveness (measured in QALY). RESULTS: Modifying current practice with use of the molecular test resulted in 74% fewer surgeries for benign nodules with no greater number of untreated cancers. Over 5 yr, mean discounted cost estimates were $12,172 for current practice and $10,719 with the molecular test. Current practice and molecular test use produced 4.50 and 4.57 QALY, respectively. CONCLUSIONS: Use of this novel molecular test for differential diagnosis of cytologically indeterminate thyroid nodules can potentially avoid almost three fourths of currently performed surgeries in patients with benign nodules. Compared with current practice based on cytological findings alone, use of this test may result in lower overall costs and modestly improved quality of life for patients with indeterminate thyroid nodules.