bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical working conditions and subsequent disability retirement due to any cause, mental disorders and musculoskeletal diseases: does the risk vary by common mental disorders?
Authors: Halonen Jaana I. , Mänty Minna , Pietiläinen Olli , Kujanpää Tero , Kanerva Noora , Lahti Jouni , Lahelma Eero , Rahkonen Ossi , Lallukka Tea
Published: December 2019

Purpose

Physical work exposures and common mental disorders (CMD) have been linked to increased risk of work disability, but their joint associations with disability retirement due to any cause, mental disorders or musculoskeletal diseases have not been examined.

Methods

The data for exposures and covariates were from the Finnish Helsinki Health Study occupational cohort surveys in 2000–2002, 2007 and 2012. We used 12,458 observations from 6159 employees, who were 40–60 years old at baseline. CMD were measured by the General Health Questionnaire (GHQ-12, cut-off point 3+). Four self-reported work exposures (hazardous exposures, physical workload, computer and shift work) were combined with CMD and categorized as “neither”, “work exposure only”, “CMD only”, and “both”. Associations with register-based disability retirement were assessed with Cox proportional hazards models for sample survey data adjusting for confounders over 5-year follow-up. Additionally, synergy indices were calculated for the combined effects.

Results

Those reporting CMD and high physical workload had a greater risk of disability retirement due to any cause (HR 4.26, 95% CI 3.60–5.03), mental disorders (HR 5.41, 95% CI 3.87–7.56), and musculoskeletal diseases (HR 4.46, 95% CI 3.49–5.71) when compared to those with neither. Synergy indices indicated that these associations were synergistic. Similar associations were observed for CMD and hazardous exposures, but not for combined exposures to CMD and computer or shift work.

Conclusions

Identification of mental health problems among employees in physically demanding jobs is important to support work ability and reduce the risk of premature exit from work due to disability.
Technoperformances: using metaphors from the performance arts for a postphenomenology and posthermeneutics of technology use
Authors: Coeckelbergh Mark
Published: December 2019

Postphenomenology and posthermeneutics as initiated by Ihde have made important contributions to conceptualizing understanding human–technology relations. However, their focus on individual perception, artifacts, and static embodiment has its limitations when it comes to understanding the embodied use of technology as (1) involving bodily movement, (2) social, and (3) taking place within, and configuring, a temporal horizon. To account for these dimensions of experience, action, and existence with technology, this paper proposes to use a conceptual framework based on performance metaphors. Drawing on metaphors from three performance arts—dance, theatre, and music—and giving examples from social media and other technologies, it is shown that we can helpfully describe technology use and experience as performance involving movement, sociality, and temporality. Moreover, it is argued that these metaphors can also be used to reformulate the idea that in such uses and experiences, now understood as “technoperformances”, technology is not merely a tool but also takes on a stronger, often non-intended role: not so much as “mediator” but as choreographer, director, and conductor of what we experience and do. Performance metaphors thus allow us to recast the phenomenology and hermeneutics of technology use as moving, social, and temporal—indeed historical—affair in which technologies take on the role of organizer and structurer of our performances, and in which humans are not necessarily the ones who are fully in control of the meanings, experiences, and actions that emerge from our engagement with the world, with technology, and with each other. This promises to give us a more comprehensive view of what it means to live with technology and how our lives are increasingly organized by technology—especially by smart technologies. Finally, it is argued that this has normative implications for an ethics and politics of technology, now understood as an ethics and politics of technoperformances.
Papal visits and abortions: evidence from Italy
Authors: Farina Egidio , Pathania Vikram
Published: December 2019

We investigate the impact of papal visits to Italian provinces on abortions from 1979 to 2012. Using administrative data, we find a 10–20% decrease in the number of abortions that commences in the 3rd month and persists until the 14th month after the visits. However, we find no significant change in the number of live births. A decline in unintended pregnancies best explains our results. Papal visits generate intense local media coverage, and likely make salient the Catholic Church’s stance against abortions. We show that papal visits lead to increased church attendance, and that the decline in abortions is greater when the Pope mentions abortion in his speeches.
Multivariate Gaussian and Student-t process regression for multi-output prediction
Authors: Chen Zexun , Wang Bo , Gorban Alexander N.
Published: December 2019

Gaussian process model for vector-valued function has been shown to be useful for multi-output prediction. The existing method for this model is to reformulate the matrix-variate Gaussian distribution as a multivariate normal distribution. Although it is effective in many cases, reformulation is not always workable and is difficult to apply to other distributions because not all matrix-variate distributions can be transformed to respective multivariate distributions, such as the case for matrix-variate Student-t distribution. In this paper, we propose a unified framework which is used not only to introduce a novel multivariate Student-t process regression model (MV-TPR) for multi-output prediction, but also to reformulate the multivariate Gaussian process regression (MV-GPR) that overcomes some limitations of the existing methods. Both MV-GPR and MV-TPR have closed-form expressions for the marginal likelihoods and predictive distributions under this unified framework and thus can adopt the same optimization approaches as used in the conventional GPR. The usefulness of the proposed methods is illustrated through several simulated and real-data examples. In particular, we verify empirically that MV-TPR has superiority for the datasets considered, including air quality prediction and bike rent prediction. At last, the proposed methods are shown to produce profitable investment strategies in the stock markets.
Location histogram privacy by Sensitive Location Hiding and Target Histogram Avoidance/Resemblance
Authors: Loukides Grigorios , Theodorakopoulos George
Published: December 2019

A location histogram is comprised of the number of times a user has visited locations as they move in an area of interest, and it is often obtained from the user in the context of applications such as recommendation and advertising. However, a location histogram that leaves a user’s computer or device may threaten privacy when it contains visits to locations that the user does not want to disclose (sensitive locations), or when it can be used to profile the user in a way that leads to price discrimination and unsolicited advertising (e.g., as “wealthy” or “minority member”). Our work introduces two privacy notions to protect a location histogram from these threats: Sensitive Location Hiding, which aims at concealing all visits to sensitive locations, and Target Avoidance/Resemblance, which aims at concealing the similarity/dissimilarity of the user’s histogram to a target histogram that corresponds to an undesired/desired profile. We formulate an optimization problem around each notion: Sensitive Location Hiding ($${ SLH}$$SLH), which seeks to construct a histogram that is as similar as possible to the user’s histogram but associates all visits with nonsensitive locations, and Target Avoidance/Resemblance ($${ TA}$$TA/$${ TR}$$TR), which seeks to construct a histogram that is as dissimilar/similar as possible to a given target histogram but remains useful for getting a good response from the application that analyzes the histogram. We develop an optimal algorithm for each notion, which operates on a notion-specific search space graph and finds a shortest or longest path in the graph that corresponds to a solution histogram. In addition, we develop a greedy heuristic for the $${ TA}$$TA/$${ TR}$$TR problem, which operates directly on a user’s histogram. Our experiments demonstrate that all algorithms are effective at preserving the distribution of locations in a histogram and the quality of location recommendation. They also demonstrate that the heuristic produces near-optimal solutions while being orders of magnitude faster than the optimal algorithm for $${ TA}$$TA/$${ TR}$$TR.
Functional Analysis of Sheep POU2F3 Isoforms
Authors: Ma Guang-Wei , Chu Yan-Kai , Yang Hua , Yan Xiao-Hong , Rong En-Guang , Li Hui , Wang Ning
Published: December 2019

POU domain class 2 transcription factor 3 (POU2F3) plays an important role in keratinocyte proliferation and differentiation. Our previous study identified four sheepPOU2F3transcript variants (POU2F3-1,POU2F3-2,POU2F3-3, andPOU2F3-4), encoding three POU2F3 protein isoforms (POU2F3-1, POU2F3-2, and POU2F3-3). However, the functional differences among the three POU2F3 isoforms remain unknown. The objective of this study was to determine the tissue expression pattern of the fourPOU2F3transcript variants in sheep and to investigate the functional differences in cell proliferation among the three POU2F3 isoforms. Quantitative RT-PCR analysis showed that the fourPOU2F3transcripts were ubiquitously expressed in all tested adult sheep tissues, andPOU2F3-1exhibited higher expression level than the other threePOU2F3transcript variants in skin (P < 0.05). Cell proliferation assay showed that overexpression of any one of the three POU2F3 isoforms significantly inhibited the proliferation of sheep fetal fibroblasts and HaCaT cells at 48 and 72 h after transfection (P < 0.05). POU2F3-3 had less inhibitory effect on cell proliferation than POU2F3-1 and POU2F3-2 (P < 0.05), and POU2F3-1 and POU2F3-2 had similar inhibitory effects (P > 0.05). Dual luciferase reporter assays demonstrated that overexpression of any one of the three POU2F3 isoforms significantly inhibited the promoter activities of keratin 14 (KRT14) and matrix metalloproteinase 19 (MMP19) genes (P < 0.05). POU2F3-3 had less inhibitory effect on the promoter activities ofKRT14andMMP19genes than POU2F3-1 and POU2F3-2 (P < 0.05), and POU2F3-1 and POU2F3-2 had similar inhibitory effects (P > 0.05). These results suggest three sheep POU2F3 isoforms have similar functional effects, but to a different extent.
Capacity of United States federal government and its partners to rapidly and accurately report the identity (taxonomy) of non-native organisms intercepted in early detection programs
Authors: Lyal Christopher H. C. , Miller Scott E.
Published: December 2019

The early detection of and rapid response to invasive species (EDRR) depends on accurate and rapid identification of non-native species. The2016–2018 National Invasive Species Council Management Plancalled for an assessment of US government (federal) capacity to report on the identity of non-native organisms intercepted through early detection programs. This paper serves as the response to that action item. Here we summarize survey-based findings and make recommendations for improving the federal government’s capacity to identify non-native species authoritatively in a timely manner. We conclude with recommendations to improve accurate identification within the context of EDRR by increasing coordination, maintaining taxonomic expertise, creating an identification tools clearinghouse, developing and using taxonomic standards for naming and identification protocols, expanding the content of DNA and DNA Barcode libraries, ensuring long-term sustainability of biological collections, and engaging and empowering citizens and citizen science groups.
Federal legal authorities: guidance for application to the early detection of and rapid response to invasive species
Authors: Burgos-Rodríguez Jhoset , Burgiel Stanley W.
Published: December 2019

Federal agency programs and associated actions are contingent on having the legal authority to act. There is no single authority established to direct the early detection of and rapid response to invasive species (EDRR). Rather, a patchwork of authorities unevenly addresses various aspects of the suite of EDRR measures. To support the development of national EDRR capacity, it is essential to delineate the federal legal statutes, regulations, and policies that enable or limit invasive species EDRR. Here we set forth general principles and a checklist of actions that agencies can refer to when they construct a more comprehensive EDRR legal and policy framework for addressing invasive species. This guidance is intended to complement the review and analysis of federal authorities contained elsewhere in this issue (Burgos-Rodríguez and Burgiel in Biol Invasions. 10.1007/s10530-019-02148-w, 2019, this issue).
Do you need a roadmap or can someone give you directions: When school‐focused possible identities change so do academic trajectories
Authors: Horowitz Eric , Oyserman Daphna , Dehghani Morteza , Sorensen Nicholas
Published: December 2019

Introduction

Despite the assumed importance of school‐focused possible identities for academic motivation and outcomes, interventions rarely assess the effect of intervention on possible identities. This may be due to difficulty coding open‐ended text at scale but leaves open a number of questions: 1) how do school‐focused possible identities change over the course of the school year, 2) whether these changes are associated with changes in school outcomes, and 3) whether a machine coding approach is viable.

Methods

In Study 1 (n = 247 Chicago 8th‐graders) we assess fall‐to‐spring change in school‐focused possible identities. We test whether change in school‐focused possible identities predicts 8th‐grade academic outcomes. We include robustness checks. Then we examine school context effects. In Study 2 (n = 1006 Chicago 8th‐graders) we address the problem of coding at scale, using a separate data set to train a machine‐learning algorithm.

Results

On average, school‐focused possible identities decline over the school year. But nearly a third of students have increasing school‐focused possible identity scores. Increase is associated with improved grades. School context influences whether linked strategies matter. Our machine‐learning algorithm accurately classifies school‐focused possible identities in our original sample and this school‐focused classification reliably predicts academic trajectories.

Conclusions

Change in school‐focused possible identities is normative over the course of the school year, interventions should take this into account. On average, students have fewer school‐focused possible identities by spring. This decline is associated with declining academic trajectories. However, when school‐focused possible identities increase, so do grades. Whether strategies matter is context dependent.
The European Court of Human Rights and Its Contribution to Judicial Fragmentation in International Human Rights Law
Authors: Abrusci Elena
Published: December 2019

Following the International Law Commission Report on Fragmentation in International Law (IL), scholars have started to question whether such fragmentation could also have affected its subbranches, and, especially, international human rights law (IHRL). Due to the proliferation of both IHRL norms and institutions, especially at the regional level, this appeared to be a real possibility.
Regional Human Rights Bodies as Instruments of International Law
Authors: Serrano Silvia
Published: December 2019

I will try to cover three different examples on issues in which the Inter-American and the European Courts have had different approaches, some substantive, some methodological, regarding the following issues:

1.

A substantive and radical difference in the approach of the right to appeal a criminal conviction;

2.

A substantive but slight difference in the approach of cases of involuntary or forced sterilization;

3.

An example of evolution from divergence to convergence in the subject of access to information; and

4.

A radical difference in the approach with respect to reparations.
Introductory Remarks by Saira Mohamed
Authors: Mohamed Saira
Published: December 2019

Welcome to this discussion on “Emerging Accountability Mechanisms: Innovative or Ineffective?” During this session, four expert panelists will examine the evolution and future of so-called “alternative” or “non-traditional” mechanisms that aim to secure accountability for serious violations of international human rights law and international humanitarian law. This category comprises mechanisms with a range of goals and forms, from investigative institutions that prepare evidence to be handed off to criminal courts, to transitional justice mechanisms that seek through non-criminal means to redress violations, prevent a relapse into violence, and facilitate reconciliation.
Remarks by Beth Stephens
Authors: Stephens Beth
Published: December 2019

Mechanisms to hold corporations liable for human rights abuses are usually grossly inadequate. All too often, local remedies are not available because the host government and legal system are inadequate or captured by corporate interests. The subsidiary directly responsible for the abuses may not have the funds to provide an adequate remedy, and the parent corporation may not be subject to the jurisdiction of local courts. As a result, victims and survivors of abuses have attempted to follow corporate actors to their home states, through human rights litigation in U.S. and European courts. Although such litigation flourished in U.S. courts for two decades, recent Supreme Court decisions have slashed the number of U.S. human rights cases.
Introductory Remarks by Judith Levine
Authors: Levine Judith
Published: December 2019

Less than twenty-four hours ago, the World Meteorological Organization (WMO) released its “State of the Climate Report,” which the UN secretary-general described as “yet another wake-up call for ambitious and urgent climate action.” The report shows climate change is making extreme weather events more frequent and severe and it sets out record highs in global temperatures, sea levels, and greenhouse gas concentrations. Secretary-General Guterres noted the report proves that climate change is moving faster than our efforts to address it, and called for a Climate Action summit in September, instructing leaders: “Don't come with a speech, come with a plan.”
Introductory Remarks by Sean D. Murphy
Authors: Murphy Sean D.
Published: December 2019

Welcome everyone. I am Sean Murphy, the President of the American Society of International Law, and I am delighted to have everyone here for what has become a signature event of our annual meeting.
Introductory Remarks by Ian Johnstone
Authors: Johnstone Ian
Published: December 2019

In 1945, world leaders gathered in San Francisco to sign the United Nations Charter, which laid the blueprint for today's international system. The institutional architecture that was built around the United Nations, including its specialized agencies (such as the World Bank and World Health Organization) and funds and programs (such as the United Nations Children's Fund (UNICEF) and the UN High Commissioner for Refugees (UNHCR)), survived the Cold War and seemed to have hit its stride in the immediate post-Cold War era. Yet the global distribution of power has changed, states are no longer the sole actors in international affairs, and the very idea of global governance is being called into question. Not surprisingly, there is much questioning of whether the institutional architecture that was built almost seventy-five years ago is still fit for purpose. Policymakers are rightly focused on reform of that architecture. Rather than tinkering at the margins, this panel was conceived with a more radical agenda. If the UN did not exist today, would we create it? If so, what would it look like?
Civil Society Representative
Authors: Baillie Lauren C.
Published: December 2019

In our increasingly globalized world, civilians feel most acutely the impact of conflicts and failures of interstate regulation. Modern conflict has been characterized by states and nonstate actors targeting civilians. One need only look to the offenses committed in Syria and South Sudan to understand the immense toll those conflicts have taken on civilian lives. In addition, failures in interstate regulation, particularly around business practices and climate change, disproportionately affect the world's most poor and vulnerable, as political and economic interests take precedence over the rights of civilians.
Socrates on the Parts of Virtue
Authors: Woodruff Paul
Published: December 2019

Plato represents Socrates as believing in the unity of the virtues, quarreling with those who, like Protagoras or Meno, wish to treat the virtues as distinct objects of inquiry (Protagoras 329c2ff., Meno 71e1ff.). On the other hand, there is good reason to deny that Plato's Socrates believed in the numerical identity of the virtues (cf. Meno 79a3-5). What Socrates did believe, I shall argue, is that the various virtues are one in essence. I shall show what this means and how it clears up prima facie inconsistencies among Plato's early dialogues.

If I am right, Socrates’ theory has startling consequences. Since essence is exactly what Socrates wants a definition to state, it follows that all virtues will have one and the same definition. And if this is so, no wonder the quest for separate definitions of virtues fails in every case! For example in the Laches the generals are baffled by Courage because Courage has no private essence and cannot be marked off from the other virtues by stating its essence. Its essence is Virtue entire. That is a radical view, but there are good reasons for attributing it to Socrates.
The Reception of Aristotle in the Middle Ages
Authors: Bosley Richard , Tweedale Martin
Published: December 2019

This collection of papers derives from a conference on the reception of Aristotle in the Middle Ages held at the University of Alberta in September, 1990, and organized by the editors. They conceived of the conference in the light of a general view of Aristotle and medieval thought, a statement of which may serve as an introduction to the papers which follow.

Within the Greek philosophical tradition Aristotle's works became the focus of commentary and discussion; they became, furthermore, the texts of instruction, particularly in logic. Some scholars, of a Neo-Platonist orientation, sought to harmonize the teachings of Plato and Aristotle and to deliver those teachings as a single science or body of knowledge.
OP19 Does The HST Represent A Best Practice Model For Ultra-Orphan HTA?
Authors: Macaulay Richard , Liu Lok Wan , Turkstra Erika
Published: December 2019

Introduction

Ultra-orphan therapies (prevalence: <1:50,000) can have trouble meeting Health Technology Assessment (HTA) clinical- and cost-effectiveness criteria, set by HTA bodies to inform reimbursement decision-making, due to low patient numbers limiting the supporting clinical evidence generated and high per-patient prices. Since 2013, National Institute of Health and Care Excellence (NICE) appraise Highly Specialised Technologies (HST) (“for use in the provision of services for rare and very rare conditions”) using a distinct appraisal framework. This research compares NICE HST appraisal outcomes with corresponding guidance by other HTA bodies.

Methods

All NICE HST technology guidance was screened (1 January 2013–6 November 2018) alongside corresponding guidance by Gemeinsamer Bundesausschuss (G-BA), Haute Autorité de Santé (HAS), Scottish Medicines Consortium (SMC), and National Centre for Pharmacoeconomics (NCPE).

Results

NICE have published eight HST guidances all with positive recommendations after a median of 21 months (range: 7–38) after European Marketing Authorization (MA). An additional eight HST have guidance in-development despite having European MA for a median of 12 months (range: 2–46) with 5/8 having draft guidance issued, all being “not recommended”. Of the 18 HSTs with NICE guidance published/in-development, 29 percent (2/7), and 33 percent (2/6) have been assessed with positive outcomes (definition: “recommended”/”accepted”/“conditional”/”restricted”) by SMC, and NCPE, respectively vs. 100 percent (9/9) by G-BA (definition: any additional benefit), and 50 percent (5/10) by HAS (definition: ASMR I-III). Median delays between European MA and positive appraisal outcomes were seven (G-BA), nine (HAS), 12 (NCPE), and 19.5 months (SMC).

Conclusions

Although all NICE HST final guidances to date have been positive, few technologies have completed this process after substantial delays from MA. Other cost/QALY HTA bodies (i.e. excluding the G-BA and HAS clinical-assessment HTAs) have shown low appraisal and recommendation rates for these technologies; therefore, ultra-orphan technologies may require a distinct appraisal process/framework but the HST may not (yet) represent best-practice.
OP20 Has The New HST Process Improved The Recommendation Chance In England?
Authors: Turkstra Erika , Liu Lok Wan , Mardiguian Silvy , Budhia Sangeeta
Published: December 2019

Introduction

The National Institute for Health and Care Excellence (NICE) in England has a separate appraisal process for drugs for very rare conditions, i.e. Highly Specialised Therapies (HST). In April 2017, the HST process has been changed to incorporate a quantitative approach: automatically fund treatments with incremental cost-effectiveness ratio (ICERs) up to GBP 100,000 (EUR 113,008 based on the 2018 average GBP / EUR exchange rate) per quality-adjusted life year (QALY). For treatments with an ICER above GBP 100,000 per QALY, NICE will consider treatments that offer a substantial magnitude of improvement, with additional QALY weighting. We investigated the impact of this more quantitative approach on the likelihood of a HST receiving a positive recommendation.

Methods

All HST appraisals and draft guidance documents were reviewed (up to November 2018) and data were extracted on ICERs, incremental QALY gain, budget impact, and recommendations. The extracted data from each HST were assessed based on the interim HST guidance.

Results

Eighteen products have been or are currently going through the NICE HST process. Of these, 8/18 (44%) have received a positive recommendation, while 5/18 (28%) have received a draft negative guidance, and for 5/18 (28%) products, no recommendations have been published. For the products with a positive outcome, 5/8 (63%) had incremental QALY gain of at least 10, qualifying these products for additional QALY weighting. For the products that received a draft negative recommendation, the negative decision was related to the cost-effectiveness estimates being higher than GBP 100,000 per QALY (5/5 reported) in all cases, while none of these products were eligible to receive a ‘QALY modifier’.

Conclusions

It has become more difficult for HSTs to get recommended by NICE under the new guidance, which requires cost-effectiveness analyses, whereas previously there was no official ICER threshold. The additional weighting of QALYs may be insufficient to meet an ICER threshold of GBP 100,000 per QALY for many products.
OP37 Impact On Uncertainty Of Disaggregating Cost Data
Authors: Teljeur Conor , Carty Paul , Ryan Máirín
Published: December 2019

Introduction

Economic models contain several parameters ordinarily subject to uncertainty. Unlike most other model parameters, costs can constitute numerous distinct components. For example, a surgical intervention can require a variety of disposables and reusable equipment. A micro-costing output may be disaggregated or presented as a total cost. Uncertainty could be applied to individual cost components or to total cost. We aimed to explore how disaggregation of cost data may impact on uncertainty using a case study.

Methods

A set of simulations using hypothetical scenarios were developed with uncertainty set at ± 20 percent. The simulations investigated the impact of number of cost components, balance between components, and correlation between them. A cost-utility model from an assessment of robot-assisted radical prostatectomy was analyzed; procedure cost was divided into 32 individual cost components or treated as a total cost.

Results

Based on five equal cost components, uncertainty reduces from ± 20 percent for correlated variables to ± 9 percent for uncorrelated variables. With increasing numbers of uncorrelated cost components, the uncertainty in the total cost decreases markedly. The uncertainty around total robot-assisted surgery procedure equipment costs was ± 19.7 percent when components were correlated and ± 9.4 percent when uncorrelated. The impact on uncertainty in the incremental cost effectiveness ratio (ICER) was negligible but the ranking of parameters in the univariate sensitivity analysis changed.

Conclusions

Analyzing uncertainty by aggregated or disaggregated costs can have implications for presenting uncertainty in costs to decision makers. Applying uncertainty to aggregated costs essentially implies that variation in the cost of individual components is perfectly correlated. By disaggregating cost components they are being treated as uncorrelated, which can substantially reduce uncertainty in the total cost. In this case study we found that although the reduction in uncertainty could be clearly seen in the cost parameter, it had a negligible impact on uncertainty in the ICER.
OP97 Cost-effectiveness Model Appraisal Guidelines For Health Technology Assessments In Ireland
Authors: Lamrock Felicity , O'Connor Joanne , Leahy Joy , Gorry Claire , Tilson Lesley , Barry Michael
Published: December 2019

Introduction

The National Centre for Pharmacoeconomics (NCPE) assesses the cost-effectiveness of new drugs for which reimbursement by the healthcare payer, the Health Service Executive (HSE), is sought in Ireland. This research aims to create a systematic approach for the NCPE review group (RG) to assess each of the cost-effectiveness models submitted by the applicant by creating cost-effectiveness model appraisal guidelines.

Methods

The RG consists of clinical, statistical and health economic expertise. In order to systematically appraise the HTA submission, which includes a cost-effectiveness model, clear guidelines on how each of the members of the RG can work together are required. The current members of the RG in the NCPE were given a draft of the guidelines created by the primary author, and additional feedback and testing was performed using the expert experience of the team. A version of the guidelines was tested for its usefulness.

Results

Three checklists were created. The purpose of the first checklist is to evaluate if the cost-effectiveness model works correctly. The second checklist ensures that each of the assumptions included in the HTA dossier are the same as those included in the cost-effectiveness model. The final checklist validates the assumptions used in the cost-effectiveness model to ensure they are reasonable and appropriate for decision making. The final version of the checklists were validated by choosing cost-effectiveness models with known errors and/or discrepancies and testing that the issues were captured by the checklists.

Conclusions

These guidelines are not an exhaustive list of checks that should be performed, but are presented as the minimum requirements for consideration to be included with each RG assessment of the corresponding HTA submission. The guidelines will be constantly updated as the process evolves over time. The cost-effectiveness models should follow the National Health Information and Quality Authority (HIQA) Guidelines for the Economic Evaluation of Health Technologies in Ireland.
OP106 The Xpert™ Clostridium difficile Kit Incorporation: Conducting a Local Clinical Study as Part of Hospital Health Technology Assessment
Authors: Roesch Eliane Würdig , Raabe Victorya , da Silva Alexandre , Ferreira Maria Angélica Pires
Published: December 2019

Introduction

The Xpert™ Clostridium difficile kit is a nucleic acid amplification test indicated after discrepant results from an enzymatic test; was submitted for incorporation in a teaching hospital in Brazil. In order to evaluate the potential for improvement with Xpert™ incorporation, the performance of the available technology (enzymatic test) was assessed using a real word evidence approach. Additionally, the association between enzymatic test results and the agreement to the Infectious Diseases Society of America (IDSA) recommendations for stool test submission (≥ 3 unformed stools in 24 hours without laxatives) for Clostridium difficile were evaluated.

Methods

This is a retrospective cohort study conducted at a tertiary teaching hospital. We included all consecutive tested patients that were submitted for enzyme immunoassay – glutamate dehydrogenase (GDH) plus toxin detection from 15 March to 8 May 2018. Data referent to episodes of unformed stools in 24 hours and use of laxatives were recorded. Statistical significance was tested by Fisher Exact test (α = 0.05).

Results

One hundred and thirty-eight consecutive patients were tested: 4 (2.9 percent) were positive for GDH and toxin (group III); 114 (82.6 percent) were negative for both (group I). Twenty (14.5 percent) cases were discrepant, all being positive to GDH and negative for toxin (group II). There were not negative GDH and positive toxin cases. The IDSA guidelines were followed in 33 (28.9%), 3 (15%) and 3(75%) test orders in groups I, II and III, respectively (p = 0.03).

Conclusions

Only a minority of patients had discrepant results in enzymatic tests and would be candidates for the Xpert™ test. The low adherence to IDSA guidelines could explain the low positivity rate of enzymatic tests at the hospital. Considering the uncertainty about the potential of the new test for changing infection control practices, Xpert™ was not recommended for incorporation. Using real world evidence data is important for contextualized health technology studies in hospitals.
PP08 Evaluation Of The Brazilian Health Technology Assessment Network
Authors: Farinasso Cecília Menezes , Gomes Dalila Fernandes , Leite Betânia Ferreira , Silva Roberta Borges , Rêgo Daniela Fortunato , de Lima Aurelina Aguiar , Gonçalves Lenilson Pereira , Simões Luciana , Leão Camara , Sachetti Camile Giaretta
Published: December 2019

Introduction

The Brazilian Network for Health Technology Assessment (REBRATS) is a network of collaborating centers and teaching and research institutions, focused on the generation and synthesis of scientific evidence in the field of health technology assessment. Currently, the network is composed of 119 member institutions and mobilizes approximately 1,094 researchers and 4,998 relations. The objective of this study was to evaluate the member institutions of REBRATS.

Methods

The evaluation process was developed in seven stages, including the identification of the objectives of the Network; identification of evaluation criteria; selection of performance indicators for each criterion; identification of the measures appropriate to each indicator; data collection and analysis; classification of the institutions and production of the final report.

Results

The evaluation of the member institutions of REBRATS mapped the capacity of these institutions to produce health technology assessment activities. The evaluation also provided information on the advances and challenges of health technology assessment in the country. In the long term, the initiative will contribute to the strengthening of the evaluation of health technology in Brazil, since the weaknesses of these institutions in the development of activities were mapped.

Conclusions

The production of this study will contribute to the dissemination of the evaluation methodology at the national and international level. This study is one of the few initiatives that exist in the world on the evaluation of networks and will contribute to the strengthening of the evaluation of health technology in Brazil.
PP39 Budget Projections And Health Impact Of PD-1/PD-L1 Inhibitors
Authors: Roediger Alexander , van Bavel Julie , Pellissier James , Lucherini Stefano , Davies Neil , Okhuoya Paul , Rachev Boris
Published: December 2019

Introduction

The rapid expansion of immuno-oncology treatment options has led to concerns around their long-term affordability. Evidence on the potential budget and health impact of these new treatment options is required to inform public health policy and ensure adequate allocation of budget for the future.

Methods

The Health Impact Projection model was developed to compare the economic impact and health outcomes observed with and without PD-1/PD-L1 inhibitors using traditional budget impact analysis. Seven types of high-incidence cancers were included: melanoma, first- and second-level non-small cell lung, bladder, head and neck, renal cell carcinoma, and triple negative breast. Inputs were based on publicly available data and literature, and over 10 key experts (oncologists, health economists) were involved in the model development. The model draws on five-year budget impact analysis.

Results

Using the experience of Belgium, Slovenia, Switzerland, and Italy, the model estimates budget and health impact of the PD-1/PD-L1 inhibitor class. It shows that for 2018-2022, the class will provide additional life years and avoid high-grade adverse events (AEs) with a manageable budget impact per year compared to the standard of care. The model also enables policy-makers to assess the adequacy of their budget for the near future and explore the implications of different policy decisions. Results for Belgium show that over the five-year period the PD-1/PD-L1 inhibitors will save 10,635 additional life years, avoid 7,597 AEs and have a budget impact of approximately EUR 260 million. Results for Slovenia show 1,468 additional life years gained and 869 AEs avoided with a budget impact of approximately EUR 116 million; for Switzerland, 6,775 life years gained, 6,953 AEs avoided, and EUR 106 million budget impact; and for Italy, 5,019 life years gained, 2,040 AEs avoided, and EUR 627 million budget impact.

Conclusions

Although limitations exist, the model informs planning by helping quantify the potential impact of immune-oncology treatments on health and budget in different scenarios.
PP142 Health Technology Assessment – A Major Bottleneck In Patient Access?
Authors: Wang George , Macaulay Richard
Published: December 2019

Introduction

Conditional marketing authorization (CMA) and accelerated assessment (AA) have been introduced to expedite the development of and access to therapies in Europe. However, to reach patients medicines must also be publicly reimbursed. This research evaluated the reimbursement of therapies which have received European CMA or underwent AA.

Methods

Medicines that received CMA or underwent AA between January 2012 and December 2017 were identified. Appraisals of these medicines conducted by major European payer bodies were obtained from relevant websites and key data were extracted.

Results

Out of the 38 medicines that received a CMA, 83 percent (19/23) were assessed by the National Institute for Health and Care Excellence (NICE) and received positive decisions, compared with 57 percent (16/26) by the Scottish Medicines Consortium (SMC) (defined as recommended/restricted), 74 percent (14/19) by Gemeinsamer Bundesausschuss (G-BA) (defined as any level of additional benefit), and 29 percent by Haute Autorité de Santé (HAS) (amélioration du service médical rendu I-III). The median delay between CMA approval and positive health technology assessment (HTA) outcome was 13 months for NICE, 11 months for SMC, 7 months for G-BA, and 5 months for HAS. Thirty-two medicines underwent AA. Of these, 68 percent (17/25) were appraised by G-BA and received positive outcomes, compared with 29 percent (7/24) by HAS, 90 percent (19/21) by SMC, and 86 percent (18/21) by NICE. The median delay between AA approval and positive HTA outcome was 7.4 months for G-BA, 7.9 months for HAS, 11.7 months for SMC, and 11.8 months for NICE.

Conclusions

CMA has expedited regulatory approval for products that address severe unmet needs. However, many of these products fail to gain public reimbursement, and even when they do there is a significant delay. AA provides market authorizations two months earlier than standard centralized assessment. Although high rates of positive payer outcomes have been achieved, the products typically experience substantial additional delays in securing public reimbursement. A parallel, cooperative approach among regulatory and HTA bodies across Europe is required to truly expedite patient access.
PP165 Content Instead Of Orders: Experiences Of Launching A Knowledge Base
Authors: Merész Gergő , Takács Bence
Published: December 2019

Introduction

In Hungary, the procedure for health technology assessment of innovative pharmaceutical products allows 13 assessors 43 calendar days to evaluate reimbursement submissions. These short timelines have created a need for smart capacity building, namely, streamlining the scientific evaluation process while making sure that the quality of the critical appraisals remain high. The objective of this study was to present and evaluate the implementation of an online knowledge base to distill community knowledge, and also for management purposes.

Methods

The scope and the content-, functional-, and technical specification was developed, and information technology security requirements were identified during the pre-implementation phase. An existing platform was chosen for adaptation, ensuring that descriptive follow-up data is available on uptake for monitoring purposes. Both the adaptation and maintenance were carried out internally by the Department of Health Technology Assessment at the National Institute of Pharmacy and Nutrition.

Results

The key requirements identified when developing the specification were searchability, low maintenance need, low operating costs and attractivity for users. An already existing open-source, flat file content management system was chosen for adaptation. In terms of content, a health technology assessment handbook, process documentation, a news bulletin section was created, and corporate identity elements were added. Since the start of the service in September 2018, the number of total daily page downloads to the knowledge base varied between four and 1,193 (average 205 per day), with the assessment handbook topping the overall page visit statistics.

Conclusions

The implementation of this knowledge base enables the Department of Technology Assessment to rely more on the formalized community knowledge when carrying out critical appraisal, while enabling better knowledge and quality management. Uptake remains an issue on the long run, indicating a need for continuous content development.
PP207 Evaluation On Effects Of Antimicrobial Stewardship In Tertiary Comprehensive Public Hospitals in Hainan, China
Authors: Zhou Hong
Published: December 2019

Introduction

The National Health Commission issued a special task force on antimicrobial stewardship (AMS). We assess the effects of AMS from 2012 to 2016 in four tertiary comprehensive hospitals in Hainan Province, China, to explore the achievement of AMS to facilitate rational use, to control antimicrobial resistance (AMR), to ensure safety and quality of care.

Methods

Data from Hospital Information System (HIS) of hospitals according to the criteria of AMS were analyzed. Microsoft Excel data entry and SAS version 9.3 was used for analysis.

Results

The indicators were general compliance to the national criteria from 2012 to 2016. The percentage of following results in hospitals were gradually reduced: the proportion of antibiotic use in outpatient care (11.09 to 3.25 percent); that in emergency departments (8.46 to 1.53 percent); antibiotics use rate of inpatient care (9.13 to 3.12 percent); antibiotics prophylactic use in type I surgical sites (24.19 to 3.38 percent); the proportion of drug cost (5.54 to 0.12 percent) and total cost of antibiotics (3.27 to 0.45 percent); total cost of antibiotics in outpatient care and emergency departments, which was below 10 percent. Pathogenic detection rate of antibiotics from 2013 to 2016 in three hospitals was increased from 38.75 to 59.6 percent. Hainan Provincial Antibiotics Resistance Monitoring Network conscientiously performs duties, several important and special detection rates of AMR close to the average national level, which have been effectively controlled.

Conclusions

It is needed to continue AMS and to enhance the capacity of rational use of antibiotics by medical professionals. Information systems need to be developed, coordinated and correlated to monitor the consumption of antibiotic use, surveillance of AMR and control of hospital infection.
VP06 HTA And Health Industry: Key Aspect Of Their Relationships
Authors: Toledo-Chávarri Ana , Pérez Lidia García , Perestelo-Perez Lilisbeth , del Mar Trujillo-Martin Maria , Alvarez-Perez Yolanda , Garcia-Lorenzo Borja , Castro-Campos José Luis , Imaz-Iglesia Inaki , Novella Blanca , Pego Yolanda Triñanes , Herrera-Ramos Estefania , Sarria-Santamera Antonio , Espallargues Mireia , Aguilar Pedro Serrano
Published: December 2019

Introduction

Conclusions and recommendations of health technology assessment (HTA) reports have an impact on all relevant actors involved in the health system (health authorities, administrators, health professionals, patients, citizens and industry). The involvement of all those relevant stakeholders in the HTA process facilitates making valid and informed decisions and an efficient allocation of resources. Improving communication, participation and transparency among all agents will lead to more efficient evaluation and decision-making processes.

Methods

To review key aspects of the relations between HTA agencies and health industries, two process were carried out: a narrative review of literature searched in Medline, PubMed, Embase, CINAHL and WOS (2007-2017) and a review of websites of international HTA agencies. References and webs with information on the framework, objectives, methodologies, impact or results of the relationships were included.

Results

A total of 1961 references were located and forty-five were selected. From the synthesis of the selected references the following key aspects of the relationships between HTA and industry were identified: (i) the importance of early dialogues with industry to align HTA objectives with the generation of evidence; (ii) challenges of the bias in the evidence produced by industry; (iii) difficulties in industry engagement in HTA processes; and (iv) industry interest in HTA. The review of six agency websites provided information on industry involvement in strategic activities, early dialogues, provision of documentation, management of industry clarifications, review of the report/allegations and other forms of relationship.

Conclusions

Both the review of the literature and the contents of the web pages of international agencies with experience in relations with industry show that the interest is in the creation of collaborative frameworks between regulatory authorities that decide on authorization and price and reimbursement and HTA agencies, while both try to maintain an early, transparent and systematic interaction with the healthcare industry.