bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying spatial technology clusters from patenting concentrations using heat map kernel density estimation
Authors: Stek Pieter E.
Published: December 2020

In this paper a methodology for identifying and delineating spatial technology clusters based on patenting concentration is developed. The methodology involves the automated geocoding of patent inventor addresses, the application of a home bias correction factor and a sensitivity analysis to determine the optimal parameters of the kernel density estimation interpolation distance and the minimum concentration threshold to identify clusters. The methodology’s performance is compared to a number of other cluster identification methods and it is validated across 18 individual sectors, including mature broad-based high-technology sectors and emerging niche sustainable energy technology sectors. The results suggest that the performance of the methodology exceed that of alternative cluster identification methods, although there is some variation in performance between different sectors. This demonstrates that the methodology provides researchers, practitioners and policy makers with a useful tool to gain insight into the spatial distribution of sectoral innovation activity at a global scale and sub-national regional level and to monitor changes over time, thereby supplementing more readily available global statistical data which is available at the national level.
Ontology, neural networks, and the social sciences
Authors: Strohmaier David
Published: December 2020

The ontology of social objects and facts remains a field of continued controversy. This situation complicates the life of social scientists who seek to make predictive models of social phenomena. For the purposes of modelling a social phenomenon, we would like to avoid having to make any controversial ontological commitments. The overwhelming majority of models in the social sciences, including statistical models, are built upon ontological assumptions that can be questioned. Recently, however, artificial neural networks (ANNs) have made their way into the social sciences, raising the question whether they can avoid controversial ontological assumptions. ANNs are largely distinguished from other statistical and machine learning techniques by being a representation-learning technique. That is, researchers can let the neural networks select which features of the data to use for internal representation instead of imposing their preconceptions. On this basis, I argue that neural networks can avoid ontological assumptions to a greater degree than common statistical models in the social sciences. I then go on, however, to establish that ANNs are not ontologically innocent either. The use of ANNs in the social sciences introduces ontological assumptions typically in at least two ways, via the input and via the architecture.
Analysis of stress pins for the local prestressing of cold forging tools
Authors: Killmann Martin , Merklein Marion
Published: December 2020

The trend towards lightweight design leads to an increasing demand for sophisticated part geometries with high functional integration. In order to use the advantages of cold forging regarding the time- and resource-efficient production of high-quality parts, high local stresses causing fatigue failure in geometrically complex tools have to be controlled. The objective of this manuscript is to analyse the use of stress pins for a local influence on the stress state within forging, especially in non-circular symmetrical cold forging dies. For this purpose, a closed-die forging process for elliptical parts is designed and analysed regarding the die stresses. Distinct areas with local compressive and tensile stresses occur in the process. To counteract the tensile stresses critical for fatigue failure, the effect of stress pins pressed into the die creating a local prestress is analysed. Around the pins, compressive radial and tensile tangential stresses occur. While large pin diameters, interferences and close positioning to the tensile area lead to an increasing prestressing effect, too high values of these parameters cause a detrimental superposition of tensile process and pin stresses. If used correctly, there is high potential to improve the stress state and tool life especially for locally stressed complex tools.
A novel reduced-dimensional dictionary grid screening strategy for SR-STAP
Authors: Cui Ning , Yu Zhongjun , Xing Kun
Published: December 2020

The traditional space-time adaptive processing (STAP) methods require large training samples to estimate the clutter covariance matrix. Sparse recovery STAP (SR-STAP) can get a highly accurate estimation in the case of insufficient samples and it alleviates the above problem of conventional STAP methods, however, the price of SR-STAP is that it involves a huge computational load in optimization, especially when the input data size is very big. This paper proposed a novel SR-STAP dictionary construction method that can significantly improve computational efficiency. We introduce the noise grids as the supplement of the spectrum-aid methods and design a second grids screening method based on the prior spectrum information. After the process of the proposed method, the dimension of the space-time dictionary has a sharp decrease compared to the over-complete dictionary, moreover, the sparsity of variable can be maintained better than the common spectrum-aid methods. The numerical experiments verify that the proposed method not only can significantly reduce the optimization time to far smaller than the SR-STAP but also more robust than spectrum-aid methods even in the small input size.
A novel chaotic manta-ray foraging optimization algorithm for thermo-economic design optimization of an air-fin cooler
Authors: Turgut Oguz Emrah
Published: December 2020

This research study aims to introduce chaos theory into the Manta Ray Foraging Optimization (MRFO) Algorithm and optimize a real-world design problem through the chaos-enhanced versions of this method. Manta Ray Foraging Optimization algorithm is a bio-inspired swarm intelligence-based metaheuristic algorithm simulating the distinctive food search behaviors of the manta rays. However, MRFO suffers from some intrinsic algorithmic inefficiencies such as slow and premature convergence and unexpected entrapment to the local optimum points in the search domain like most of the metaheuristic algorithms in the literature. Recently, random numbers generated by chaos theory have been incorporated into the metaheuristic algorithms to solve these problems. More than twenty chaotic maps are applied to the base algorithm and ten best performing methods are considered for performance evaluation on high-dimensional optimization test problems. Forty test problems comprising unimodal and multimodal functions have been solved by chaotic variants of MRFO and extensive statistical analysis is performed. Furthermore, thermo-economic design optimization of an air-fin cooler is maintained by the chaotic MRFO variants to assess their optimization capabilities over complex engineering design problems. Ten decisive design variables of an air fin cooler are optimized in terms of total annual cost rates and optimum solutions obtained by five best chaotic MRFO algorithms are compared to the preliminary design. A significant improvement is observed in the objective function values when MRFO with chaotic operators is applied to this considered thermal design problem.
Resection of Colorectal Liver Metastasis: Prognostic Impact of Tumor Burden vs KRAS Mutational Status
Authors: Tsilimigras Diamantis I. , Hyer Madison J. , Bagante Fabio , Guglielmi Alfredo , Ruzzenente Andrea , Alexandrescu Sorin , Poultsides George , Sasaki Kazunari , Aucejo Federico , Pawlik Timothy M.
Published: December 2020

BACKGROUND:

The prognostic impact of colorectal liver metastasis (CRLM) morphologic characteristics relative to KRAS mutational status after hepatic resection remains ill defined.

STUDY DESIGN:

Patients undergoing hepatectomy for CRLM between 2001 and 2018 were identified using an international multi-institutional database. Tumor burden score (TBS) was defined as distance from origin on a Cartesian plane that incorporated maximum tumor size (x-axis) and number of lesions (y-axis). Impact of TBS on overall survival (OS) relative to KRAS status (wild type [wtKRAS] vs mutated [mutKRAS]) was assessed.

RESULTS:

Among 1,361 patients, the median number of metastatic lesions was 2 (interquartile range [IQR] 1–3), and median size of the largest metastatic lesion was 3.0 cm (IQR 2.0–5.0 cm), resulting in a median TBS of 4.1 (IQR 2.8–6.1); KRAS status was wtKRAS (n = 420, 30.9%), mutKRAS (n = 251, 18.4%), and unknown (n = 690, 50.7%). Overall median and 5-year OS were 49.5 months (95%CI 45.2–53.8) and 43.2%, respectively. In examining the entire cohort, TBS was associated with long-term prognosis (5-year OS, low TBS: 49.4% vs high TBS: 36.7%), as was KRAS mutational status (5-year OS, wtKRAS: 48.2% vs mutKRAS: 31.1%; unknown KRAS: 44.0%)(both p < 0.01). Among patients with wtKRAS tumors, TBS was strongly associated with improved OS (5-year OS, low TBS: 59.1% vs high TBS: 38.4%, p = 0.002); however, TBS failed to discriminate long-term prognosis among patients with mutKRAS tumors (5-year OS, low TBS: 37.4% vs high TBS: 26.7%, p = 0.19). In fact, patients with high TBS/wtKRAS CRLM had comparable outcomes to patients with low TBS/mutKRAS tumors (5-year OS, 38.4% vs 37.4%, respectively; p = 0.59). On multivariable analysis, while TBS was associated with OS among patients with wtKRAS CRLM (hazard ratio 1.43, 95%CI 1.02–2.00; p = 0.03), TBS was not an independent predictor of survival among patients with mutKRAS CRLM (HR 1.36, 95%CI 0.92–1.99; p = 0.12).

CONCLUSIONS:

While TBS was associated with survival among patients with wtKRAS tumors, CRLM morphology was not predictive of long-term outcomes among patients with mutKRAS CRLM.
Uniformly positive entropy of induced transformations
Authors: BERNARDES NILSON C. , DARJI UDAYAN B. , VERMERSCH RÔMULO M.
Published: December 2020

Let

$(X,T)$
be a topological dynamical system consisting of a compact metric space X and a continuous surjective map

$T : X \to X$
. By using local entropy theory, we prove that

$(X,T)$
has uniformly positive entropy if and only if so does the induced system

$({\mathcal {M}}(X),\widetilde {T})$
on the space of Borel probability measures endowed with the weak* topology. This result can be seen as a version for the notion of uniformly positive entropy of the corresponding result for topological entropy due to Glasner and Weiss.
A new cobia (Teleostei, Rachycentridae) species from the Miocene St. Marys Formation along Calvert Cliffs, Maryland, USA
Authors: Godfrey Stephen J. , Carnevale Giorgio
Published: December 2020

The highly fossiliferous St. Marys Formation is exposed along Calvert Cliffs, Maryland, and comprises one of the best available records of late Miocene life in the northeastern United States. Rachycentron stremphaencus new species, a cobia from the late Miocene (Tortonian) of the St. Marys Formation is described herein on the basis of a single three-dimensional neurocranium. This fossil represents the earliest known occurrence of neurocranial remains of the genus Rachycentron in the record. Rachycentron stremphaencus differs from Rachycentron canadum (Linnaeus, 1766) in many ways. The most obvious include a different ornamentation of the outer surface of the cranial bones; a notably pronounced lateral ridge resulting in a considerable gradient from the dorsal-medial exposure of the frontal to its lateralmost supraorbital margin; the size, shape, and position of the sphenotic that is located in the posterior half of the neurocranium and its lateralmost edge being adjacent to the anteriormost extent of the wedge-shaped trough in the dorsal surface of the skull formed by the lateral and medial ridges; the two contralateral medial ridges forming a proportionately much wider trough on either side of the supraoccipital; the epioccipitals not reaching the rear edge of the neurocranium; and the lack of a conspicuous posterolateral prong of the intercalar.

UUID: http://zoobank.org/c8523bb4-2de2-4318-9a37-027f463a0441
OP366 Characterizing The Population At Risk Of Chronic Obstructive Pulmonary Disease In China Using A Real-World Population Survey
Authors: Koch Marco , Butt Thomas , Guo Wudong , Li Xue , Chen Yirong , Tan Diana , Liu Gordon G.
Published: December 2020

Introduction

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in China. However, early identification of patients with COPD in the community is challenging. This study used a real-world survey of the Chinese urban adult population to estimate the prevalence of COPD diagnosis or COPD-risk, examine the health outcomes and healthcare resource use of these groups, and investigate the sociodemographic factors associated with these statuses.

Methods

Respondents to the 2017 National Health and Wellness Survey in China (n = 19,994) were classified into: COPD (diagnosed), COPD-risk (undiagnosed), and control (undiagnosed, not at-risk) using their self-reported diagnosis and Lung Function Questionnaire (LFQ) score. These groups were compared by healthcare resource use and health outcomes (EuroQol [EQ-5D] and Work Productivity and Activity Impairment questionnaires). Factors associated with being in these groups were investigated using pairwise comparisons (t-tests and chi-square tests) and multivariable logistic regression.

Results

In total, 3,320 respondents (16.6%) had a suspected risk of COPD but did not report receiving a diagnosis. This was projected to 105.3 million people (16.9% of urban adults). Relative to the controls, COPD-risk and COPD-diagnosed respondents had higher healthcare resource use, lower productivity, and lower health-related quality of life (HRQoL) (p < 0.05). Age, smoking, alcohol consumption, weight, exercise, comorbidities, gender, education, employment, and air pollution were associated with increased odds of COPD-risk relative to the controls (p < 0.05).

Conclusions

A substantial group of individuals, undiagnosed, but with a risk of COPD, have impaired HRQoL, lower productivity, and elevated healthcare resource use. A range of sociodemographic factors are predictive of COPD risk, which may support targeted screening. Case-detection tools such as the LFQ may offer a convenient approach for identifying individuals for further definitive testing and appropriate treatment in China.
OP388 17-Year Disease Reduction Predicted By A Transmission Dynamic Model After Pneumococcal Conjugate Vaccine Introduction In The United States
Authors: Snedecor Sonya
Published: December 2020

Introduction

After the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in the United States (US) in the year 2000, the incidence of invasive pneumococcal disease (IPD) caused by the seven vaccine serotypes declined by 80 percent in vaccinated children and 30 percent in unvaccinated adults. A transmission dynamic equation model developed in 2009 captured the direct and indirect effects of vaccination in the early years after vaccination. Subsequently, the vaccine program switched to the 13-valent PCV and adult PCV13 vaccination. This work explores the accuracy of the mathematical model to predict long-term IPD due to changes in US immunization practices.

Methods

The model simulates the acquisition of asymptomatic carriage of pneumococci and the development of IPD among individuals aged <2, 2–4, 5–17, 18–49, 50–64, and ≥65 years. Pneumococcal serotypes were stratified into three categories: PCV7-type (4, 6B, 9V, 14, 18C, 19F, and 23F), PCV6-type (1, 3, 5, 6A, 7F, and 19A), and non-PCV-type (all others). Model parameters were calibrated using US IPD surveillance data from 1998–2006. Model results were compared to observed epidemiology.

Results

The model was previously shown to predict observed IPD well through 2007. After adjusting model parameters for PCV13 efficacy and adult vaccine coverage, modeled IPD closely replicated observed IPD. Observed baseline pre-vaccine incidence for children <2 years of age was 192 cases/100,000 and 13.5 cases in 2016, versus 18.5 cases estimated by the model. Similarly, observed versus modeled cases in the ≥65-year-old age group were 24 and 23.6 cases.

Conclusions

This epidemiologic model accurately simulates the observed US IPD surveillance data 17 years after initial introduction of PCV, highlighting the direct and indirect benefits of vaccination. Well-constructed mathematical models can accurately replicate real-world scenarios. Key input parameters of these models can then be modified to predict the impact of alternate scenarios, providing insights to inform public health policy-making.
OP410 Real-World Benefit Of Endovascular Repair Of Abdominal Aortic Aneurysms - Comparison Of GORE® Global Registry for Endovascular Aortic Treatment And National Institute for Clinical Excellence 2018 Guidance
Authors: O'Neill Frank , Baidoo Bismark , Waltham Matthew
Published: December 2020

Introduction

Endovascular aneurysm repair (EVAR) is routinely used for treatment of abdominal aortic aneurysm (AAA). In 2018, draft guidance from the National Institute for Clinical Excellence (NICE) suggested EVAR was not cost-effective compared to open surgical repair. The analysis was driven by clinical inputs from randomized control trials which may not reflect current clinical practice. Data from registries may inform more robust economic modelling. The Global Registry for Endovascular Aortic Treatment (GREAT) was initiated to collect contemporary real-world data on the performance of GORE® aortic endografts and includes long-term data on survival, re-interventions and resource use. This study compares the real-world values for mortality and resource use following elective EVAR as collected by GREAT with the 2018 NICE AAA draft guidance.

Methods

A total of 1,348 patients (88.7% men; mean age 73.1 years) undergoing elective AAA repair with the GORE® EXCLUDER device. Mortality, re-intervention and resource use was compared with the economic inputs for 2018 NICE draft guidance cost-utility analysis.

Results

All patients survived EVAR compared to the 0.4 percent mortality indicated in the NICE analysis. All-cause mortality was lower through 1, 3 and 5 years with values of 6.9, 14.8 and 16.2 percent respectively compared to the NICE base case. The average length of stay was 3.7 days in GREAT compared to 8.34 days in the NICE analysis. Short- and long-term re-interventions were also lower with real-world data (3.6% versus 7.3% and 5.5% versus 8.3%).

Conclusions

GREAT provides conflicting data on survival and resource use associated with EVAR compared to inputs of the 2018 NICE draft guidance These differences are likely to significantly alter incremental cost-effectiveness ratios. Robust cost-effectiveness modelling in health technology assessments should consider contemporary data, as it is likely more reflective of current clinical practice and more informative for clinical and economic decision making for AAA.
OP491 Beyond Horizon-Scanning And Early Identification Of Innovative Technologies – Development Of An Active Monitoring Framework
Authors: Aluko Patricia , Zanghelini Fernando , Ogunbayo Oladapo
Published: December 2020

Introduction

While horizon-scanning systems aim to identify innovative and potentially disruptive health technologies in development, a key challenge is variation in information collation and tracking of the pace of change prior to regulatory approval. An active and efficient monitoring process is crucial for timely notification of health technology assessment (HTA) stakeholders to enhance faster market and patient access. The National Institute for Health Research Innovation Observatory (NIHRIO) identifies and notifies its key HTA stakeholders in England of technologies that are within three to five-year timeframe to regulatory approval. Regular review of each technology is required to meet this remit.

Methods

A standardized monitoring framework was developed based on the knowledge and experience of the evidence synthesis specialists in NIHRIO, supplemented by literature to ensure consistency of setting review periods. This framework used predefined criteria that integrated the technology innovation (advanced therapies, orphan status, regulatory awards), trial data (phase, status, completion date, preliminary results) and estimated approval timelines obtained from the company or other sources (for example, press releases).

Results

The framework has been piloted and early findings showed improved consistency in the monitoring process between different analysts. It ensures that each technology is reviewed at least once a year; review timelines are set at three, six, nine or twelve months based on the predefined criteria. Estimated timeframes obtained from the companies are used to triangulate and streamline review periods, improving efficiency of the monitoring process.

Conclusions

Findings from the pilot work with the framework demonstrated improved consistency and efficiency of the technology monitoring process, which can be easily implemented to provide early awareness in an accurate and timely manner for HTA. This framework was designed using a systematic and transparent approach that integrated different data sources to set review periods. While most of the data used in defining the criteria are publicly available, commercially sensitive information provided by companies were also used which may not always be readily available. Implications for horizon-scanning organizations will be discussed.
OP615 Implementing EUnetHTA Products: The Implementation Experiences In Italy
Authors: Scalzo Alessandra Lo , Migliore Antonio , Paone Simona , Vicari Nicola
Published: December 2020

Introduction

The Italian National Agency for Regional Health Services (AGENAS) participation in the European network (EUnetHTA) allowed capacity building and the spread of knowledge, tools and methodologies built by the network. In the latest Joint Action, AGENAS is implementing both EUnetHTA tools/methdologies and assessments. This was done both by the “adaptation” of most relevant EunetHTA assessments to Italian context or by “traslation” of EUnetHTA assessments’ Summeries. Language barriers have been highlighted from local HTA partners who aknowledged that contents written in italian could have a higher potential for dissemination.

Methods

To adapt a EUnetHTA report we evaluate if the PICOD fits our context with clinicians and stakeholders. We thus update systematic review and/or add other context specific domains. The EUnetHTA report summaries were translated into Italian and reviwed by clinicians. The HTA Core Model® was incorporated into national processes (Procedure Manual, HTA report templates, assessment elements, the Planned and On going Projects (POP) database was also used.

Results

Implementation of EUnetHTA's tools and products consisted of i) Production of national assessment reports based on EUnetHTA assessments; ii) Dissemination of EUnetHTA assessment iii) Translation of EUnetHTA assessments summaries and publication on Agenas website iv) Use of EUnetHTA POP Database for the national HTA programme; v) Embedment Integration of the EUnetHTA HTA Core Model®

Conclusions

The use of the Core Model® allowed a better standardisation of AGENAS' outputs. The Assessement Element based structure assists authors with the choices of relevant research questions; and the Domain-based structure allowed an efficient division of work among the authors. The use of the Core Model® among European partners faciliated the adaptation of other national HTA reports to our context. The adaptation and translation of EUneHTA assessments provides more homogenous choices among Italian regions and European countries, and so does the use of the POP database as a source of information about technologies that are on other EU Countries agenda.
PP21 Use Of Real-World Evidence For Healthcare Decision Making: Infliximab Versus Etanercept And The Risk Of Tuberculosis
Authors: Rivera-Ramirez Paola Andrea , Fiestas-Saldarriaga Fabián Alejandro
Published: December 2020

Introduction

In the absence of direct evidence from randomized controlled trials (RCTs), real-world evidence (RWE) can play an important role in healthcare decision making. As part of a health technology assessment, we assessed the comparative risk of tuberculosis (TB) associated with using infliximab and etanercept in patients with rheumatoid arthritis.

Methods

We performed a systematic literature search using the PubMed database to identify relevant meta-analyses.

Results

We located two relevant meta-analyses: one based on RCTs and one based on observational studies. Evidence from seven RCTs on infliximab (2,686 patients; 12 TB events) and two RCTs on etanercept (663 patients; 2 TB events) suggested no significant differences in the risk of TB between the two treatments, compared with placebo. In contrast, evidence from ten observational studies that directly compared the two treatments (443,941 patients; 253 TB events) indicated a significantly higher risk of TB with infliximab than with etanercept.

Conclusions

Although RWE is prone to confounding and bias, in this case it had the advantage of providing direct comparisons with larger sample sizes and longer follow up than evidence from RCTs. As a result, RWE was used to inform decision making on the risk of TB with infliximab and etanercept in patients with rheumatoid arthritis.
PP159 Telemedicine In Paraguay: Contributions Of The Institute Of Health Sciences Research, National University Of Asunción
Authors: Rivas Ronald , Galván Pedro
Published: December 2020

Introduction

The modalities of telemedicine that have been developed and applied so far by the Department of Biomedical Engineering and Imaging at the National University of Asunción (IICS-UNA) are as follows: (i) telediagnosis: the remote sending of data, signals, and images for diagnostic purposes; (ii) general telediagnostic imaging; (iii) telemonitoring (including telemetry): remote monitoring of vital parameters to provide automatic or semi-automatic surveillance or alarm services in emergencies, epidemiology, or tele-public health; and (iv) tele-education: the use of telematic networks to provide virtual platforms for educating and training health professionals.

Methods

We conducted a comprehensive review of the scientific works developed by the IICS-UNA in order to evaluate the systematic implementation of Telemedicine in Paraguay. Documents, pilot projects (satellite telegraphy), telediagnostic research, telematics, tele-education, published articles, and statistical data (number of patients attending or studies performed, etcetera) relating to the implementation of the National Telemedicine System by the Ministry of Public Health and Social Welfare since 1999 were reviewed.

Results

Implementation of the telemedicine system has meant that 472,038 patients have attended referral centers nationwide, with 297,999 electrocardiographs, 165,323 computed tomography scans, and 8,697 electroencephalograms being conducted. Projects developed within the framework of the Telemedicine Research Line have included the following:

(i)

Development and validation of a clinical telemicroscopy system based on cellular telephony;

(ii)

Implementation of a telemetry system for temperature monitoring of the collection of biological samples from a biomedical research center; and

(iii)

Production and development of a virtual campus at the National University of Asunción.

Conclusions

Given the current healthcare environment, developing a line of research based on telemedicine is a proactive step, since telemedicine provides an alternative solution to the problem of access to the health system. That is why the IICS-UNA Biomedical Engineering and Imaging Department has developed telemedicine as one of its main lines of research.
PP188 Prevalence And Severity Of Erectile Dysfunction In Patients With Benign Prostatic Hyperplasia In China: A Cross-Sectional Survey
Authors: Zhou Liqun , Pei Zhengcun , Wen Xingqiao , Zhang Yanlei , Li Peng , Zhan Siyan
Published: December 2020

Introduction

Erectile dysfunction (ED) and benign prostatic hyperplasia (BPH) are highly prevalent among aging men. However, the rate of coexistence of these two conditions in China is still unclear, especially among men aged 45 to 60 years. Instruments such as the abbreviated five-item version of the International Index of Erectile Function (IIEF-5) and the International Prostate Symptom Score (IPSS) can be used to determine the presence of ED and the symptoms and severity of BPH, respectively. This study aimed to estimate the prevalence of ED in men with BPH and to assess its impact on the quality of life (QoL) of these patients.

Methods

Between October 2018 and March 2019 we enrolled 650 patients aged 45 to 65 years who were diagnosed with BPH by a urologist in nine first- and second-tier cities in China. Information on patients’ demographics, lifestyle, comorbidities, and medication use was collected through an electronic clinical outcome assessment tool. Patients with an IIEF-5 score of less than twenty-two were considered to have ED. The IPSS and the five-level EuroQol questionnaire (EQ-5D-5L) were used to assess BPH severity and overall health-related QoL.

Results

We enrolled 650 patients with BPH. Of these, only the 607 men who reported sexual intercourse attempts (mean age of 56.6 years, standard deviation 5.5) were included in the analysis because it was assumed that the other patients did not have ED. Signs of ED were present in ninety-seven percent of patients (IIEF-5 score < 22), and eighty-four percent had at least mild to moderate impairment (IIEF score < 17). Up to nineteen percent reported having physician-diagnosed ED previously, and twenty-eight percent had used medication for ED in the past six months. Compared to men without ED, those with ED and BPH had higher IPSS scores (13.2 versus 6.7, p < 0.05) and lower EQ-5D-5L scores (0.90 versus 0.97, p < 0.05).

Conclusions

Although the prevalence of ED in men with BPH in China is high, it is still underdiagnosed and undertreated. Co-existing ED in patients with BPH is associated with more severe BPH symptoms and lower quality of life.
PP229 Surrogate Outcomes In Health Technology Assessments Of Oncology Drugs: The Osimertinib Case
Authors: Rodriguez-Zuniga Milton , Rivera-Ramirez Paola , Fiestas-Saldarriaga Fabian
Published: December 2020

Introduction

Decision making in publicly funded healthcare systems must rely on patient-relevant outcomes that directly measure clinical benefit, such as overall survival and quality of life (QoL). However, studies that support market authorization of oncology drugs usually assess surrogate outcomes, without having previously demonstrated that these intermediate outcomes reliably predict clinical outcomes. As part of an HTA process, we evaluated the clinical benefit of osimertinib, compared with platinum-pemetrexed combination chemotherapy, in patients with epidermal growth factor receptor (EGFR) T790M mutation-positive advanced non-small cell lung cancer (NSCLC) that has progressed after first-line EGFR tyrosine kinase inhibitor (TKI) therapy.

Methods

We conducted a systematic search of the PubMed database for randomized controlled trials (RCT) published from inception to January 2019. The clinical outcomes of interest were overall survival and QoL. Where trials reported surrogate outcomes, we conducted additional PubMed searches for evidence of validity for predicting clinical outcomes and used guidance on surrogate outcome validation in oncology from the Institute for Quality and Efficiency in Health Care.

Results

Evidence on osimertinib, compared with chemotherapy, for patients with T790M-positive advanced NSCLC that has progressed after EGFR-TKI therapy was obtained from the AURA3 trial. In this study, overall survival data were immature and the results for QoL and symptom domains were not clinically meaningful. In addition, median progression-free survival (PFS) was six months longer for osimertinib than for chemotherapy. However, to date, no study has demonstrated that PFS reliably predicts longer survival or better QoL.

Conclusions

Our HTA suggested that, unless proven, PFS should not be used as a valid surrogate outcome for decision making in public health. For example, the results of the AURA3 trial showed that osimertinib has an effect on the surrogate outcome of PFS in patients with EGFR T790M-positive advanced NSCLC that has progressed after first-line EGFR-TKI therapy, but not on the clinically relevant outcomes of overall survival and QoL. Furthermore, currently available evidence has failed to prove that PFS reliably predicts outcomes that are clinically relevant. Despite this, osimertinib has been given marketing authorization and is widely recommended in clinical guidelines.
PP262 PapSEEK: Liquid Biopsy For Endometrial And Ovarian Cancer Screening
Authors: Hijas-Gómez Ana Isabel , Polo-de-Santos Mª Mar , Luengo-Matos Setefilla , Sánchez-Gómez Luís María
Published: December 2020

Introduction

Endometrial and ovarian cancer are the first and second leading causes of death from gynecological cancer in Spain. Survival is generally determined by stage at diagnosis, but there is no test currently used for early detection of both tumor types. PapSEEK is a test developed to diagnose endometrial and ovarian cancer by detecting aneuploidies and somatic mutations commonly associated with both tumor types through DNA next-generation sequencing (NGS) of liquid from Papanicolaou test (Pap smear) samples. The objective of this work was to assess the effectiveness and safety of PapSEEK.

Methods

PapSEEK was identified by the Early Awareness and Alert System, “SINTESIS-new technologies”, of the Agencia de Evaluación de Tecnologías Sanitarias in Spain (AETS-ISCIII). An early assessment of the technology was conducted through a literature search of the following databases: PubMed, Embase, the Web of Science, the Trip database, the International Clinical Trials Registry Platform, ClinicalTrials.gov, and The Cochrane Library. Clinical studies on the effectiveness and safety of PapSEEK published up to February 2019 were reviewed.

Results

The evidence comprised proof of concept and diagnostic accuracy studies, which showed good preliminary results regarding the accuracy of the test for diagnosing endometrial cancer (sensitivity ranged from 0.81 to 0.93), but not for ovarian cancer (sensitivity ranged from 0.33 to 0.45). The specificity for both tumor types ranged from 0.99 to 1.00. Since PapSEEK uses a sampling method that is routinely used in clinical practice (the Pap smear), no evidence was found in the literature on the safety of the test.

Conclusions

PapSEEK is a novel technology developed to diagnose endometrial and ovarian cancer by means of DNA-NGS of Pap smear samples. The identified studies showed good preliminary results regarding the ability of the test to diagnose endometrial cancer, but not ovarian cancer. PapSEEK may be useful as a screening tool for endometrial cancer. However, further research on PapSEEK is needed to prospectively evaluate its diagnostic accuracy, compare it with current tests used in the early diagnosis of both cancer types, evaluate its effect on patient survival and disease progression, and measure its economic impact.
PP265 Application Of A Case-Mix Method For Medical Consumables Management In Anhui Province, China Using Healthcare Big Data
Authors: Tong Lin , Xu Qing-hua , Ye Hong , Zhang Shuang , Cao Chen
Published: December 2020

Introduction

The case-mix method involves combining cases with similar complexities and medical services. The process of treating one episode of the disease and receiving treatment is the research unit, thus achieving different medical units. The feasibility of the calculation method is verified by calculating the public hospital consumption ratio, medical income, health materials expenditure indicators, and the differences between the various types of surgical combinations. A decision-making basis can then be provided for the creation of government indicator standards.

Methods

Medical records and data on the expenditure of medical consumables for the first and fourth quarters of 2017 were collected from seven third-class provincial hospitals. The medical consumption ratio for different diseases and surgical methods was calculated for the case-mix groups using a weighting method. Data were analyzed by descriptive statistics and the independent samples t-test.

Results

There were significant differences in the proportions of combined use for different types of diseases. The same combination also had significant differences between different hospitals. In the fourth quarter of 2017, the operating group's consumption ratio was significantly lower than in the first quarter (p = 0.000).

Conclusions

It is reasonable to calculate the proportion of consumption by combined weighted analysis, which is also fairer for hospitals with better technical levels. This calculation method can be used by governments to manage the use and cost of medical consumables in hospitals.
PP268 Eliciting Meaningful Patient Preferences In Rare Diseases – Swing Weighting With Immunoglobulin A Nephropathy Patients In The United States And China
Authors: Marsh Kevin , Zaour Nancy , Ho Kerrie-Anne , Joshi Ankit , Lo Rachel , George Aneesh Thomas , Cook Nigel S.
Published: December 2020

Introduction

Reimbursement agencies are increasingly using patient preference data to evaluate health technologies. Discrete choice experiments (DCE) are commonly used to elicit patient preferences, but they require large sample sizes to obtain meaningful results. For this reason, it is often not possible to use DCE to elicit patient preferences in rare diseases. This study assessed a swing weighting method for eliciting preferences from a small sample: patients with immunoglobulin A nephropathy (IgAN) in the United States (US) and China.

Methods

Attributes and levels were selected based on a review of clinical studies and qualitative research on patients. Computer-assisted, interview-based swing weighting exercises were piloted in a focus group with five participants each from the US and China. Preferences were then elicited in interviews with twenty-five patients in the US and fifteen patients in China. Consistency tests were used to assess internal validity. Qualitative data were collected on the reasons for patients’ preferences.

Results

Preference consistency: The weights for one attribute were elicited twice. The difference between initial and consistency test weights was not statistically significant (p < 0.1), although this may partly reflect the small sample sizes. Trade-offs: Qualitative data were used to demonstrate the validity of interpreting participants’ ratings as trade-offs. Using the partial value function for end-stage renal disease as an example, qualitative data demonstrated that patients were able to provide face-valid reasons for different shaped, non-linear preference functions. Robustness of treatment evaluation: Three hypothetical treatment profiles (using the attribute swings) were constructed. Preferences for these treatment profiles were robust to variations in patients’ preferences; all patients preferred one specific profile. This finding was not sensitive to changes in weights.

Conclusions

This study supports the feasibility of collecting valid and robust preference data from small groups of patients using swing weighting. Further work could be done to test the performance of swing weighting in larger sample sizes.
PP329 An Australian Cost-Effectiveness Analysis Of The EluviaTM Drug-Eluting Stent For Treatment Of Symptomatic Lower-Limb Peripheral Artery Disease
Authors: Gray William A. , Ariyaratne Thathya V. , Griffiths Robert I. , Elroy Peter W.M. , Amorosi Stacey L. , Akehurst Ronald L. , McGovern Alysha M. , Müller-Hülsbeck Stefan
Published: December 2020

Introduction

Despite advances in endovascular interventions, including the introduction of drug-eluting stents (DES), high target lesion revascularization (TLR) rates still burden the treatment of symptomatic lower-limb peripheral arterial disease (PAD). EluviaTM, a novel, sustained-release, paclitaxel-eluting DES, was shown to further reduce TLRs when compared with the paclitaxel-coated Zilver® PTX® stent, in the IMPERIAL randomized controlled trial. This evaluation estimated the cost-effectiveness of Eluvia when compared with Zilver PTX in Australia, based on 12-month clinical outcomes from the IMPERIAL trial.

Methods

A state-transition, decision-analytic model with a 12-month time horizon was developed from an Australian public healthcare system perspective. Cost parameters were obtained from the Australian National Hospital Cost Data Collection Cost Report (2016–17). All costs were captured in Australian dollars (AUD), where AUD 1 = USD 0.69 (June 2020). Complete sets of clinical parameters (primary patency loss, TLR, amputation, and death) and cost parameters from their respective distributions were bootstrapped in samples of 1,000 patients, for each intervention arm of the model. One-way and probabilistic sensitivity analyses were performed.

Results

At 12 months, modeled TLR rates were 4.5 percent for Eluvia and 8.9 percent for Zilver PTX, and mean total direct costs were AUD 6,537 [USD 4,511] and AUD 6,908 [USD 4,767], respectively (Eluvia average per patient savings; overall cohort=AUD 371 [USD 256]; diabetic cohort=AUD 625 [USD 431]). In probabilistic sensitivity analyses, Eluvia was cost-effective relative to Zilver PTX in 92.0 percent of all simulations at a threshold of $10,000 per TLR avoided. Eluvia was more effective and less costly (dominant) than Zilver PTX in 76.0 percent of simulations.

Conclusions

In the first year after the intervention, Eluvia was more effective and less costly than Zilver PTX, making Eluvia the dominant treatment strategy for treatment of symptomatic lower-limb PAD, from an Australian public healthcare system perspective. These findings should be considered when formulating policy and practice guidelines in the context of priority setting and making evidence-based resource allocation decisions for treatment of PAD in Australia.
PP339 A Budget Impact Model Of The EluviaTM Drug-Eluting Stent from The Australian Public Hospital And National Payer Perspective
Authors: Altaf Nishath , Ariyaratne Thathya V. , Peacock Adrian , Deltetto Irene , El-Hoss Jad , Thomas Shannon , Taylor Colman , Mwipatayi Patrice
Published: December 2020

Introduction

Improving long-term outcomes like target lesions revascularizations (TLRs) is a focus for endovascular interventions aimed at treating symptomatic lower-limb peripheral arterial disease (PAD). EluviaTM, a paclitaxel-eluting drug-eluting stent (DES) was shown to further reduce TLRs when compared with the paclitaxel-coated Zilver® PTX® stent in the IMPERIAL trial, a global, randomized controlled study. This budget-impact evaluation investigated cost-savings from Eluvia-use when compared with Zilver PTX, relying on the 12- to 24-month outcomes from the IMPERIAL trial.

Methods

A budget-impact model comparing Eluvia and Zilver PTX was developed from the Australian public healthcare payer, and an individual hospital perspective, with a 5-year time-horizon. Observed trial results were applied to each year's incident population and associated costs, and no extrapolation was conducted. The analysis used publicly available Australian national hospital cost data, population estimates, procedural statistics, epidemiological literature, and data from public hospital audits to verify eligible population for endovascular procedures (EVP) including DES. All costs were captured in Australian dollars (AUD), where AUD 1 = USD 0.69 (June 2020).

Results

Assuming 80-percent EVP eligibility, and a DES-use range of 10–28 percent, the 5-year model estimated potential national savings of AUD 4.3–12.1 million (M) [USD 3–8.3M] to the public healthcare payer, driven by reduced TLRs from Eluvia-use compared with Zilver-PTX. The model projected potential national savings of AUD 33.1–92.6M (USD 22.8–63.9M) to individual hospitals through reduced hospital bed days for adverse events (AE). The model forecasted 14,428–40,399 treated patients; 1,499–4,198 fewer TLRs; and 16,515–46,243 fewer hospital days for AE. At a state level, projected hospital savings were: New South Wales AUD 10.9–30.7M [USD 7.5–21.1M]; Victoria AUD 8.4–23.4M [USD 5.8–16.1M]; Queensland AUD 6.5–18.3M [USD 4.5–12.6M]; Western Australia AUD 3.4–9.5M [USD 2.3–6.5M]; South Australia AUD 2.3–6.4M [USD 1.6–4.4M].

Conclusions

Treatment of symptomatic lower-limb PAD with the Eluvia DES could lead to potential savings for the Australian healthcare system, at the national, state, and the local hospital level, based on improved patient outcomes.
PP400 Cost-Effectiveness Analysis Of Adding Bedaquiline To Drug Regimens For Multidrug-Resistant Tuberculosis Treatment In China
Authors: Zhang Fan , Liu Yuehua , Liu Zhao , Guo Zining , Yang Junting , Zhao Kun
Published: December 2020

Introduction

According to the World Health Organization, there were approximately 0.5 million new cases of rifampicin-resistant tuberculosis in 2018, of which 78 percent were multidrug-resistant tuberculosis (MDR-TB), and China has one of the largest shares of the global burden (14%). In recent years, the Chinese government has made progress in TB control and prevention, but for MDR-TB, treatment options are still limited and expensive, and novel drugs are not always available. This research aims to evaluate the cost-effectiveness of adding bedaquiline to a background regimen (BR) of drugs for MDR-TB treatment in China, and to provide evidence for government to improve public health policies.

Methods

A cohort-based Markov model was developed to evaluate the incremental cost-effectiveness ratio (ICER) of bedaquiline plus BR (BBR) versus BR alone in MDR-TB treatment, over a 10-year time horizon. Data were sourced from a phase II clinical trial, real-world data in China, published literature, and expert opinion. Outcomes were evaluated in quality-adjusted life years (QALYs) and life-years gained (LYG). The discount rate was 3.5%. Probabilistic and deterministic sensitivity analyses were conducted.

Results

The discounted costs per person for BBR was CNY 135,706 [USD 19,172], compared with CNY 92,465 [USD 13,063] for BR. The discounted utility per person for BBR was also higher than that for BR (3.943 QALYs versus 3.193 QALYs). The ICER of BBR was CNY 58,096 [USD 8,208]/QALY, which was lower than the willingness-to-pay threshold of CNY 212,676 [USD 30,046] (three-times the gross domestic product per capita). Therefore, BBR was considered to be cost-effective. The sensitivity analysis confirmed the robustness of the results. BBR remained cost-effective in the sensitivity analysis, with a 77.2 percent probability of being cost-effective versus BR.

Conclusions

In China, bedaquiline is not included in the National Reimbursement Medicine List, which results in a heavy financial burden for MDR-TB patients. From this study, BBR was cost-effective by significantly reducing time to sputum culture conversion and increasing QALYs and LYGs, which offset the higher drug costs.