bluuebunny/crossref_metadata_2025_split huggingface dataset:
VP49 Brazilian Consumer Willingness To Pay For Dengue Vaccine (CYD-TDV)
Authors: Godói Isabella , Santos André , Reis Edna , de Lemos Livia Pires , Brandão Cristina , Alvares Juliana , Acurcio Francisco , Bennie Marion , Godman Brian , Guerra Augusto 
Published: January 2018

INTRODUCTION:Dengue virus is a serious global health problem with an estimated 3.97 billion people at risk for infection worldwide. In December 2015, the first vaccine (CYD-TDV) for dengue prevention was approved in Brazil, developed by Sanofi Pasteur (1). However, given that the vaccine will potentially be paid via the public health system, information is needed regarding consumers willingness to pay for the dengue vaccine in the country, as well as discussions related to the possible inclusion of this vaccine into the public health system at prices suggested by the manufacturer. This was the objective of this research.METHODS:We conducted a cross-sectional study with residents of Greater Belo Horizonte, Minas Gerais, about their willingness to pay for the CYD-TDV vaccine. Respondents had to be over 18 years and not currently have the disease although they may have had dengue in the past (2,3).RESULTS:Five-hundred and seven individuals were interviewed, who were mostly female (62.4 percent), had completed high school (62.2 percent), were working (74.4 percent), had private health insurance (64.5 percent) and did not have dengue (67.4 percent). The maximum median value of consumers willingness to pay for the CYD-TDV vaccine, assuming vaccine efficacy against virologically-confirmed symptomatic dengue illness of approximately 60 percent, is USD33.61 (BRL120.00) for the complete 3-course schedule and USD11.20 (BRL40.00) per dose. At the price currently being assessed by the Brazil's regulatory chamber of pharmaceutical products market (CMED) for Dengvaxia® for three doses, only 17 percent of the population expressed a willingness to pay for the vaccine at this price.CONCLUSIONS:Brazil is currently one of the largest markets for dengue vaccine in the world and the price established is a key issue. The manufacturer should asses the possibility of lowering its price in Brazil to reach a larger audience among the Brazilian population, especially as other public health activities to control the disease will continue.
VP74 Russian System Of Medicines Provision: Status And Future Aspects
Authors: Babiy Vladimir , Yagudina Roza , Kulikov Andrey 
Published: January 2018

INTRODUCTION:Russian system of medicines provision is one of the biggest in the world. It covers 85 regions, around 17.1 million square kilometers and 146.5 million people; therefore the organizing of a stable and effective system is a challenge for decision makers. In this paper we make an effort to clarify main principles and aspects.METHODS:To systemize all the information concerning Russian medicines provision system, we review legislation, literature and made interview of experts.RESULTS:By 2015 more than 3,230 International Non-proprietary Names and 26,239 Trade names were registered in the Russian Federation. The pharmaceutical market consists of the commercial drug sector, drug reimbursement and hospital sector: 8 percent, 22 percent and 70 percent in monetary values and 1 percent, 19 percent and 80 percent in volume terms, respectively. Medicines provision through compulsory health insurance is divided into in-patient health services (first health and sanitary treatment, special health treatment and palliative treatment) and emergency services. Three drug lists form the reimbursement system: “list of vital and essential medicines”, “7 disease areas” and “Medicines provision population”. The “List of vital and essential medicines” is a basis for all other drug lists and fixes the maximum sale price for drugs. The “7 disease areas” detach high-priced drugs that are used in treatment of particular diseases and optimize the financing of treatment of people with high-cost diseases. The “Medicines provision for population” states the list of drugs that are reimbursed by the federal budget. Federal and regional budgets divides medicines into fully and partly reimbursed medicines.CONCLUSIONS:At the present time, the Russian system of medicines provision is rather complicated. Nevertheless, the system still develops: in 2016 Russian Ministry of Health began the development of the concept of medicines insurance system.
VP107 Pharmaceutical Industry's Experiences with the German Health Technology Assessment Scientific Advice
Authors: Dintsios Charalabos-Markos , Schlenkrich Sara 
Published: January 2018

INTRODUCTION:The early benefit assessment of drugs was introduced in Germany with the ‘Act to Reorganize the Pharmaceuticals’ Market in the SHI’ (AMNOG) in 2011. Before submitting the manufacturer's dossier, optional scientific advice is offered by the Federal Joint Committee (G-BA). The objective was to elicit manufacturers experience with the scientific advice offered by the Federal Joint Committee.METHODS:To prepare the survey, several manufacturers were interviewed on their experience with the scientific advice offered by the Federal Joint Committee. Subsequently, a questionnaire was developed to collect information for this purpose, comprising eight items on different topics aimed at understanding the perceived quality of the scientific advice provided.RESULTS:The qualitative part comprised seven manufacturers who had received between one and ten advisories before the end of 2012. With regard to the quantitative elicitation part, a total of sixty-one completed questionnaires from nineteen manufacturers were included until the beginning of 2015 (corresponding to almost 25 percent of the overall implemented scientific advice). Fourteen cases were about so called “early” scientific advice in terms of relating to evidence before commencing phase-III trials, forty-four cases concerned “late” scientific advice (pivotal trials were just conducted or already terminated), another two concerned repeated scientific advice and finally, four referred to miscellaneous contents (multiple answers possible). Both, the preceding qualitative and the following quantitative part of the elicitation, highlighted points about the process as well as the content shortcomings from an industry's point of view: inconsistencies, lacking expertise with conducting clinical trials, partially incomplete answers and a low readiness to engage in dialogue were criticized. On the other hand, the majority of respondents showed a positive attitude concerning unambiguousness, completeness, traceability, atmosphere and the protocol of the advice. Over the course of time, propositions on study design, agreement with the determined appropriate comparative therapy and subgroup definitions improved significantly.CONCLUSIONS:A more active involvement of further stakeholders and the incorporation of procedural elements from other health are systems with longer experience could improve the scientific advice provided.
VP109 Identifying Priorities For A National Health Research Funder
Authors: Turner Sheila , Ollerhead Liz , Cook Andrew 
Published: January 2018

INTRODUCTION:It is vitally important that research questions posed are important and that funded research meets a research need or a gap in evidence; these needs may be observed at a local, national or international level. Identifying such research priorities for a national research funder can be challenging, particularly for complex health problems such as health inequalities, where there is a need to consult a large number of experts with a range of expertise. Many methods are used in the identification of such research priorities, however, these can be resource intensive, costly, and logistically challenging particularly where large numbers of people are required and geographical distances are great.METHODS:This study investigated the use of Delphi type survey methods in identifying important research priorities related to health inequalities. Public health professionals with an interest in health inequalities were asked to identify research priorities, these research priorities were subsequently compared to those identified using different methods.RESULTS:Fifty-two public health professionals agreed to take part, the response rates were high, (69 percent, 50 percent and 40 percent) across three survey rounds; which indicated that participants were receptive to the methodology and motivated to respond. The themes identified as encompassing the most important research priorities were: mental health, environmental issues and health behaviours. Within these themes, topic areas which emerged most strongly included: community interventions for prevention of mental health problems, and the food and alcohol environment.CONCLUSIONS:Delphi type survey methods are effective as a means of obtaining opinions from a wide number of relevant experts identifying potential priority topic areas where there is a need for research evidence. Opinions may be sought at local and national levels in order to inform national research priorities.
VP120 A United Kingdom Research Commissioning Framework For Devices And Diagnostics
Authors: White Judith , Kimpton Christine , Cole Helen , Carolan-Rees Grace , Peirce Susan 
Published: January 2018

INTRODUCTION:Generation of high-quality evidence on medical devices through clinical trials can be challenging. The United Kingdom's National Institute for Health and Care Excellence (NICE) has developed a research commissioning framework for producing clinical evidence where gaps in the literature prevent definitive recommendations in their medical technology guidance and diagnostics guidance. The research commissioning framework involves NICE's external assessment centers collaborating with clinical researchers to secure funding and to design, conduct, and publish a study to address research recommendations within 3 years of guidance publications. We aimed to describe the early results of the framework.METHODS:Publically available information and results from an informal survey of NICE's external assessment centers were reviewed.RESULTS:As of December 2016, NICE has published a total of thirty medical technology guidance topics and twenty-four diagnostics guidance topics, five and twenty of which have research recommendations, respectively. A total of fourteen research commissioning framework-facilitated projects have been initiated. Two research projects have successfully secured external funding for a clinical trial: (i) non-contact low frequency ultrasound therapy for wound healing; and (ii) Parafricta bootees for pressure ulcer prevention. Further projects have produced published outputs without external funding. Four projects have been completed and undergone guidance review; one guidance topic was withdrawn and three have been transferred to the “static list”. Early experiences of NICE's research commissioning framework suggest that securing financial support from manufacturers or funding bodies for interventional clinical trials to answer single technology research questions within a short time frame is challenging but possible. The value of early feasibility studies to assess the likelihood of obtaining funding and of addressing NICE's research recommendations was recognised.CONCLUSIONS:NICE can facilitate independent research through its research commissioning framework initiative. Securing funding has proved challenging but recent successes have shown that approach is possible. Outputs which fill the evidence gap to an extent where a definitive guidance update is possible have been rare.
VP175 Validating Outcome Assessments For Health Technology Assessment In Ceroid Lipofuscinosis Neuronal 2 (CLN2), An Ultra-Rare Disease
Authors: Ballinger Rachel , Llewellyn Samuel , Macey Jake , Eliasson Lina , Butt Thomas , Jain Mohit , Olaye Andrew , West Andrea 
Published: January 2018

INTRODUCTION:Ceroid lipofuscinosis neuronal 2 (CLN2) disease, a form of Batten disease, is a rare, degenerative neurometabolic disorder. Disease onset around 2–4 years is followed by rapid decline in motor and neurologic function and mortality in early teenage years (1). Disease burden is best captured using observer-reported outcomes. However, validation is challenging in ultra-orphan diseases, requiring flexible methods and reasonable acceptance of limitations related to participant access.The study aim was to assess content validation of clinical trial measures (i) CLN2 Disease Based Quality of Life Assessment (Sponsor-developed), (ii) EQ-5D-5L, (iii) Pediatric Quality of Life Inventory (PedsQL); and (iv) PedsQL Family Impact Module.METHODS:The Batten Disease Family Association recruited United Kingdom caregivers of a child with CLN2 disease (aged 3–7 years, non-participants in any CLN2 trial), to:
1.Focus groups with symptom elicitation2.Cognitive interviews to assess measures.RESULTS:The Focus group comprised eleven caregivers (eight female, three male) from six families. Three families were current caregivers and remainders bereaved. Symptom and disease impact elicited showed the majority of measures domains were relevant.The interview sample comprised sixteen current caregivers (twelve female, four male) from ten families (caring for eleven children). Overall measures were relevant, easy to understand and answer. However several items were difficult to apply to children with advanced disease (for example, Euroqol, EQ-5D-5L “overall health”), when ability is lost (for example, PedsQL walking), with misinterpretation of “no difficulties” with eating where child feeds using gastrostomy (CLN2 QoL). Caregivers found it difficult to know how their uncommunicative child was feeling (PedsQL worrying, EQ-5D-5L depression). Some symptoms and impacts were missing (for example, constipation, working life).CONCLUSIONS:The mixed-methods approach enabled content validity assessment of multiple measures. While these measures were largely relevant, adjustments could strengthen these for use in this fatal pediatric condition population and increase their acceptance within health technology assessment (HTA).
VP181 From National To European Assessment - The German Case
Authors: Panni Tommaso , Eberle Karolin , Seiler Nina , Brüderl Monika , Burkert-Kautzsch Cornelia , Carls Alexandra , Thiele Alexandra , Schleibner Stefan , Jänel Gerlinde 
Published: January 2018

INTRODUCTION:Health Technology Assessment (HTA) processes have become a fundamental part in the lifecycle of new medicines. However, their deep relation with national legislation creates ambiguous and controversial results between the European countries. Can they be standardized across Europe?METHODS:Sources of national differences have been identified in timelines, documents, methods, data interpretation, and conclusions. In order to harmonize and standardize HTA cooperation across Europe the European Network for HTA (EUnetHTA) was established. We analyzed guidelines, requirements, and output of EUnetHTA and noted the differences between those guidelines and the German G-BA (Federal Joint Committee, Gemeinsamer Bundesausschuss) standard and IQWiG (Institute for Quality and Efficiency in Health Care, Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen) methods.RESULTS:The comparison between German and European HTAs highlights that although both procedures follow the rules of Evidence-Based Medicine, differences in Body of Evidence, Comparator, Surrogate Endpoints, Subgroups, and Evidence Synthesis may lead to diverging HTA outcomes. The European HTA framework facilitates the appropriate depiction of clinical reality through comprehensive inclusion of the existing evidence with context specific statistical methods. It might become a worldwide platform for HTA evaluation and discussion.CONCLUSIONS:Only the involvement of both, pharmaceutical companies and HTA bodies within a unified European framework can lead to a mature and transparent procedure with a reliable outcome independent of legal requirements.
VP208 Informing An Economic Model For Hyperhidrosis: A Clinical Survey
Authors: Stoniute Julija , Moloney Eoin , Rice Stephen , Levell Nick , Craig Dawn 
Published: January 2018

INTRODUCTION:Hyperhidrosis is characterized by uncontrollable excessive sweating, which occurs at rest, regardless of temperature. As part of a wider study exploring the clinical and cost effectiveness of alternative treatments for primary hyperhidrosis, a survey of United Kingdom (UK) dermatologists was conducted to gain a better understanding of current clinical practice in the area and inform economic model inputs.METHODS:The survey was conducted by means of an online survey tool, “Qualtrics”. It was circulated to members of the British Association of Dermatologists. Topics covered included treatments typically administered, medication dosages prescribed, effectiveness of treatments, adverse events related to treatments and resource use associated with individual treatments.RESULTS:Forty-five respondents from forty-two different dermatology units completed the survey. The majority of clinicians (83 percent) prescribed more than one medication - most commonly oxybutynin and propantheline bromide. The next most commonly reported treatments were: iontophoresis, botulinum toxin and curettage.Respondents were asked to indicate dosage, frequency and details about follow-up visits related to medication use. Doses prescribed were largely consistent with British National Formulary (BNF) recommendations. For other treatments, dermatologists were asked to indicate duration of the procedure, job title of the treatment provider and details about monitoring visits. Results were similar to the findings from the literature and previously conducted interviews with clinicians.Respondents were asked to indicate the dropout rates for each type of treatment due to lack of effectiveness and adverse events. Dropout rates were relatively high for both reasons.CONCLUSIONS:The results highlight the wide range of treatments for hyperhidrosis currently administered by dermatologists across the UK, and the variation in current clinical practice. This variation highlights the lack of evidence-based guidance underpinning practice and the importance of clinical surveys as a complement to usual data collection methods.
VP216 Health Technology Assessment's Balance Between Additional Data, Adoption, And Patient Access
Authors: Patel Parashar , Cangelosi Michael , McIntyre Mark 
Published: January 2018

INTRODUCTION:Historically, many Health Technology Assessment (HTA) bodies were developed with a focus on addressing rapidly rising drug costs and the unique need to evaluate each drug as a de novo entity. The degree to which the unique needs for evaluating technologies vis a vis drugs are reflected in distinct HTA methods and activity is to date understudied.METHODS:We examined HTA's reviews of two technologies: WATCHMAN™, a device to reduce the risk of stroke in certain patients and Alair™, a procedure-based treatment for severe asthma. Both technologies have been extensively reviewed by HTA bodies and payers in many countries. These HTA reviews are compared to a convenience sample of these HTA's bodies reviews of drugs and qualitative differentiators between these two categories explored.RESULTS:The differences and similarities (for example, in rigor and necessity of evidence) between US Section 510(k) clearances, US premarket approval (PMA), and US new drug application (NDA) regulatory pathways have not been clearly understood by HTA or reflected in their methodologies employed. Additionally, emergent methodologies such as Bayesian statistical analyses may encounter challenges within technologies reviews. HTA bodies may not be cognizant of development timelines or the timelines of comparators. Finally, HTA bodies may overestimate device adoption rates.CONCLUSIONS:The differences in evidence requirements for regulatory approval between US 510(k), US PMA, and US NDA pathways have not been reflected in different methodological approaches within HTA bodies reviews. Opportunities and novel methods are needed for HTA bodies to derive imputed comparisons between technologies that may have inherently incongruent timelines. Finally, HTA bodies could benefit from methods to more accurately estimate projected adoption curves. Challenges exist using frameworks, paradigms, and methodologies initially established for, and commonly used for, pharmaceuticals on device evaluations; leaders of HTA methods can improve the situation by providing guidance and recommendations for more appropriate HTA methods to evaluate devices.
DNA methylation profile is associated with the osteogenic potential of three distinct human odontogenic stem cells
Authors: Ai Tingting , Zhang Jieni , Wang Xuedong , Zheng Xiaowen , Qin Xueyan , Zhang Qian , Li Weiran , Hu Wei , Lin Jiuxiang , Chen Feng 
Published: January 2018

AbstractAmong the various sources of human autologous stem cells, stem cells isolated from dental tissues exhibit excellent properties in tissue engineering and regenerative medicine. However, the distinct potential of these odontogenic cell lines remains unclear. In this study, we analyzed DNA methylation patterns to determine whether specific differences existed among three different odontogenic cell types. Using the HumanMethylation450 Beadchip, the whole genomes of human dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and dental follicle progenitor cells (DFPCs) were compared. Then, the osteogenic potential of these cells was evaluated both in vitro and in vivo, and the methylation levels of certain genes related to bone formation differed among the three cell lines. P values less than 0.05 were considered to indicate statistical significance. The three cell types showed highly similar DNA methylation patterns, although specific differences were identified. Gene ontology analysis revealed that one of the most significantly different gene categories was related to bone formation. Thus, expression of cell surface epitopes and osteogenic-related transcription factors as well as the bone formation capacity were compared. The results showed that compared with DFPCs and DPSCs, PDLSCs had higher transcription levels of osteogenic-related factors, a higher in vitro osteogenic potential, and an increased new bone formation capacity in vivo. In conclusion, the results of this study suggested that the differential DNA methylation profiles could be related to the osteogenic potential of these human odontogenic cell populations. Additionally, the increased osteogenic potential of PDLSCs might aid researchers or clinicians in making better choices regarding tissue regeneration and clinical therapies.