bluuebunny/crossref_metadata_2025 huggingface dataset:
PP042 Rapid Health Technology Assessment - No Flare Reaction With Synolis V-A In Knee Osteoarthritis
Authors: Pwee Keng Ho
Published: January 2018

INTRODUCTION:

The Changi General Hospital (CGH) carries out viscosupplementation for patients with knee osteoarthritis through intra-articular hyaluronic acid injections, using Synvisc or Synvisc-One (containing hylan G-F 20). Some patients on Synvisc are susceptible to flare or pseudoseptic reaction on repeated therapy. It was proposed to procure Synolis V-A intra-articular injection as an alternative for these patients.

METHODS:

A rapid health technology assessment was carried out on the following PICO elements: Population - Patients with knee osteoarthritis, Intervention - Synolis V-A, Comparator - Synvisc, Outcomes - Risk of flare reaction/pseudoseptic arthritis.

Based on a preliminary scan of the literature, a simple search was conducted for all publications on Synolis V-A, and for reviews on the risk of flare/pseudoseptic reaction with Synvisc.

RESULTS:

No publications reporting on flare/pseudoseptic reactions with Synolis V-A were found. There are limited case series of patients treated with Synolis V-A, with most evidence coming from a prospective post-marketing surveillance case series, which showed reduced pain and functional impairment at 6 months. Adverse reactions were rare. CGH's own small trial of Synolis V-A did not show any flare reactions.

In contrast, flare/pseudoseptic reactions with Synvisc are an established phenomenon. A systematic review of randomized controlled trials documented one flare reaction among 381 patients (0.26 percent) in Synvisc compared to none in patients receiving other hyaluronan products. Small case series of patients on Synvisc showed incidences of flare reaction of 21 percent (in repeat treatment) to 27 percent. CGH's own experience is that flare occurs in 4.7 percent of patients on Synvisc.

CONCLUSIONS:

It is reasonable for the hospital to stock an alternative for patients who show repeated flare reactions to Synvisc. The limited evidence base is not a barrier to using Synolis V-A as an alternative, given the local experience.
PP048 Quality Of Health Care Through Integration: Experience Of Cochlear Implantation
Authors: Kosherbayeva Lyazzat , Medeulova Aigul , Alzhanov Abdulla
Published: January 2018

INTRODUCTION:

The State Program for Health Development of the Republic of Kazakhstan (RK) “Densaulyk” for 2016–2019 initiated the modernization of primary health care with the introduction of family practice in order to ensure the availability, completeness and quality of health services on the basis of an integrated healthcare system focused on the needs of the population. The aim of this study was to determine the effectiveness of the cochlear implantation (CI) programs.

METHODS:

A literature search was conducted for all clinical trials, randomized controlled trials, and reviews in the PubMed, Cochrane, and Center for Reviews and Dissemination databases. Two reviewers independently evaluated all publications for selection. The analysis included the cost-effectiveness and benefit from the CI program.

RESULTS:

We analyzed the effectiveness of the services for CI in the RK and other countries (1). In our analysis, we identified that there is no research on Quality-adjusted Life Years (QALYs) and Cost-Utility Analysis (CUA) in RK. We found that, in general, the cost of CI and pre-surgical procedures are comparable with other countries. The length of stay in Kazakhstan was much higher (an average of 8 days) compared with other countries (3 days). Also in RK, there were significantly lower prices per hospital day and cost of various consultations. Postoperative costs of other countries consisted of one-third to two-thirds of the total costs for preoperative and implantation stages (2, 3). There was a little information on the effectiveness of rehabilitation programs in RK.

CONCLUSIONS:

Economic research like QALYs and CUA are new directions in the healthcare system in the RK. Lack of integration between primary care, rehabilitation and other services leads to difficulties in assessing the effectiveness of CI programs (for example, in our case, there was the restriction of assessment in only postoperative costs).
PP068 Stakeholder Views On Peer Review Of National Institute for Health Research Grant Applications
Authors: Turner Sheila , Lathlean Judith , Chinnery Fay , Moran Rebecca , Guegan Eleanor , Wyatt Jeremy
Published: January 2018

INTRODUCTION:

It takes on average 17 years to translate a promising laboratory development into better patient treatments or services. About 10 years of this innovation process lies within the National Institute for Health Research (NIHR) research pathway. Innovations developed through research have both national and global impact, so selecting the most promising studies to fund is crucial. Peer review of applications is part of the NIHR research funding process, but requires considerable resources. The NIHR is committed to improving efficiency and proportionality of this process. This study is part of a wider piece of work being undertaken by NIHR (1) to reduce the complexity of the funding pathway and thus make a real difference to patients lives.

METHODS:

This study elicited the views of various stakeholders concerning current and possible future methods for peer review of applications for research funding. Stakeholder groups included: members of boards with responsibility for making funding decisions; applicants (both successful and unsuccessful); peer reviewers and NIHR staff. Qualitative interviews were conducted with stakeholders selected from each group, and results were analyzed and integrated using a thematic template analytical method. The results were used to inform a larger online opinion survey which will be reported separately.

RESULTS:

The views and insights of thirty stakeholders across the four groups about the peer review process of applications for funding will be presented. Findings generalizable to other funding programs outside the NIHR will be emphasized. The key themes which emerged included: strengths and weaknesses of applications, feedback, targeting and acknowledgement of peer reviewers.

CONCLUSIONS:

The results of our study of peer review processes carried out by one national research funder has relevance for other funding organizations, both within our country and internationally.
PP081 Relation Between Pain And Treatment/Activity Based On Mobile App Data
Authors: Takeshima Tomomi , Iwasaki Kosuke , Inoue Hideki , Hiki Takeru
Published: January 2018

INTRODUCTION:

Recently, a number of mobile apps to record symptoms and medication by patients themselves have been developed. These apps are expected to improve the patients' symptoms through self-management, and to enable a smooth decision making through effective communication between doctors and patients. “Itami Renrakucho” (Pain Diary, Welby Inc.) is one of these apps that records body pain, medication, physical conditions, and activity in life. We examined the relationship between pain and medication/activity based on its data.

METHODS:

Data between 25 December 2015 and 9 December 2016 were used. Medication and degree of pain (0-10, low < high) were recorded at morning, daytime, evening, and bedtime. Of ninteen activities, up to three were recorded about whether they could or could not do them. We compared the degree of pain among different frequency/timing of medication, or activities that they could or could not do.

RESULTS:

Data included 708 individuals. Among 561 individuals who answered about pain, the mean (Standard Deviation, SD) degree was 5.0 (2.3). The mean degree in individuals taking 0, 1, 2, 3, and 4 times medication a day were 4.6, 5.0, 5.4, 5.5, and 6.2, respectively. Regarding medication timing and degree of pain in two consecutive time points (t0, t1), regression towards the mean occurred for individuals without medication in both time points. The degree changed more for individuals taking medicine only at t0, but not for those taking at both time points. Weaker pain was reported when they could do hanging laundry and rising early than when they could not, but they could do shopping, strolling and light exercise even having stronger pain.

CONCLUSIONS:

We showed a tendency of relationship between pain and medication/activity based on the data from the app. More data and connecting to claims will help us to show characteristics of patients and diseases, select a treatment, and evaluate a medicine.
PP084 Diabetic Macular Edema: A Comparison Between Treatment Options
Authors: Ferrario Lucrezia , Foglia Emanuela , Bandello Francesco , Ferri Camilla , Figini Innocente , Franzin Michela , Gambaro Gianpiera , Introini Ugo , Medaglia Massimo , Staurenghi Giovanni , Tadini Patrizia , Zuppini Teresa , Tessari Roberto , Scarpa Giuseppe , Urban Franscesca , Beltramini Sabrina , Tobaldi Rita Francesca , Nicolò Massimo , Ancona Chiara , Croce Davide
Published: January 2018

INTRODUCTION:

Health Technology Assessment (HTA) aims at providing decision makers with relevant data, matching different perspectives, with an evidence-based approach. The most common framework used is the European Network for Health Technology Assessment (EUnetHTA) Core Model (1): HTA may be further supported by a Multi-Criteria Decision Analysis (MCDA) (2,3), leading to a final quantitative synthesis, facilitating the appraisal phase.

This project presents a multi-dimensional comparison of the technologies available for the treatment of diabetic macular edema (Ranibizumab, Aflibercept, Dexamethasone implant and off-label Bevacizumab), comparing three Italian Regions: Lombardy, Liguria and Veneto.

METHODS:

The nine EUnetHTA dimensions were first prioritized by seventeen multidisciplinary evaluators. Thereafter a further nine professionals attributed a 3-level rating score (from “1” not performant, to “3” most performant) to each dimension and sub-dimension, after carefully assessing the three HTA reports. In conclusion, the investigation of statistically significant differences between the attributed scores of the evaluators was conducted, using a multi-variate analysis.

RESULTS:

No statistically significant differences were reported in the prioritization of each dimension, except for the equity (more important in Liguria and in Lombardy) and the economic financial dimensions (more relevant in Veneto and in Lombardy).

Notwithstanding the evaluators’ different professional titles, job roles, center size, and various Regional contexts, they attributed similar scores to the HTA dimensions during the appraisal phase (even though conducted in different years, in 2015 and 2016). This finding demonstrates the robustness of both the evaluations and the final MCDA results: i) no statistically inter-regional significant differences emerged regarding Ranibizumab and Aflibercept (p-value >.05); ii) no statistically significant inter-regional differences emerged regarding Dexamethasone, except for the assessments in the clinical dimensions (p-value = .026), since in Lombardy Region the evaluation was carried out earlier in the technology's life-cycle.

CONCLUSIONS:

Dexamethasone was consistently attributed a higher total score, considering the final normalised weight derived from the MCDA approach (p-value =.001).
PP108 Health Technology Assessment Educational Programs In The Russian Federation
Authors: Yagudina Roza , Kulikov Andrey , Ugrekhelidze Dzhumber
Published: January 2018

INTRODUCTION:

Health Technology Assessment (HTA) processes are extensively used during making decisions on the inclusion of medicinal products in Essential medicines lists. There is a high interest in HTA among specialists in the healthcare sphere and decision makers in Russia. According to a survey of chief physicians 62 percent of them would like to attend HTA educational programs. One of the steps necessary to disseminate HTA in Russia is the exploration of experience and best practices.

METHODS:

Information retrieval using websites of medical institutions in Russia were observed.

RESULTS:

As a result, it was found that educational program “Modern requirements for conducting health technology assessment” for decision makers in the area of health care is held in Department of organization of medicinal provision and pharmacoeconomics of the I.M. Sechenov First Moscow State Medical University. During this course basic methods of pharmacoeconomic analysis and their practical application, modern schemes of treatment and peculiarities of the conduct of pharmacoeconomic studies in different diseases, issues of HTA at different levels of the health system are covered. More than 1,900 specialists from 12 subjects of Russia (Samara, Nizhny Novgorod, Rostov, Orenburg, Bryansk, Astrakhan regions, Khanty-Mansi Autonomous Okrug, Altai, Krasnoyarsk, Stavropol and Perm territories, the Republic of Tatarstan) attended seminars including heads of regional health authorities, chief specialists of the ministries, chief physicians of hospitals, and heads of pharmacies.

CONCLUSIONS:

During the educational process the results of pharmacoeconomic analysis and their interpretation at the regional level, legislative changes in the sphere of health technologies circulation, the data requirements for inclusion of a medicinal product in the state lists, the rules of state procurement, and the interchangeability of medicines are highlighted. During educational process the results of pharmacoeconomic analysis and their interpretation at the regional level, legislative changes in the sphere of health technologies circulation, the data requirements for inclusion of a medicinal product in the state Lists, the rules of state procurement, and the interchangeability of medicines are highlighted.
PP110 Economic Impact Of Therapeutic Regime Reduction In The Hepatitis C Virus Infection
Authors: Barila Diego Antonio , Bianco Alessandra , Bordignon Susanna , Cattel Francesco , Valinotti Giulia
Published: January 2018

INTRODUCTION:

Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. The goal of HCV therapy is to eradicate the infection, which results in eliminating detectable circulating HCV after cessation of treatment, to prevent complications.

METHODS:

A prospective analysis was undertaken in the primary referral center in Turin. Throughout the use of questionnaries submitted to healthcare professionals, clinical and economic data from three different care pathways of HCV treatment were collected and processed. Costs were measured up to 8, 12, and 24-weeks treatment and based on time-driven activity-based costing (ABC) of the two main HCV treatments, Sovaldi and Harvoni. For the ABC analysis, three types of care pathways were considered, based on patient's clinical history resources used: patients treated for 8, 12, and 24 weeks. Gastroenterologists, pharmacists, administrative personel, and storemen were involved in the project. The aim of the analysis was to evaluate the organizational impact of the three different strategies for the treatment of HCV infection with Harvoni or Sovaldi and to estimate the differential cost.

RESULTS:

The data indicates that shortening treatment from 24 to 12 weeks and from 24 to 8 weeks leads to a saving of EUR192 and EUR766 for both treatment strategies. When drug costs are also taken into account, the reduction of treatment with shortening treatment from 12 to 8 weeks leads to a saving of EUR15,252.77, a reduction of EUR60,691.07 from 24 to 8 weeks for Harvoni treatment. The reduction of treatment with shortening from 24 to 12 weeks for Sovaldi leads to a saving of EUR37,668.30. The paths of 8 and 12 weeks are those associated with fewer resources in terms of professional's time, costs relating to laboratory tests, and cost of drugs.

CONCLUSIONS:

The reduction of the amount of time spent by healthcare professionals in the 12 weeks and in the 8 weeks strategies allows a reallocation of the resources employed.
VP35 Economic Consequences Of A Restricted Dutch Sexually Transmitted Infection-Testing Policy
Authors: Suijkerbuijk Anita , Over Eelco , Aar Fleur , Götz Hannelore , Benthem Birgit , Lugnér Anna
Published: January 2018

INTRODUCTION:

Due to the rising costs caused by an increasing demand for Sexually Transmitted Infection (STI) care, the Dutch government changed the funding of STI-clinics (1). A more restrictive testing policy introduced in 2015 no longer required syphilis and human immunodeficiency virus (HIV) tests for younger, heterosexual clients. A less extensive testing policy could be detrimental to the aim of finding and treating STIs (2,3). Infections that remain undetected could possibly lead to an increase in both the total and individual burden of disease, due to transmission and the need for more intensive treatment resulting in higher healthcare costs in the long term. In this study, we evaluated the new Dutch testing policy with respect to intended savings and missed syphilis and/or HIV infections. Moreover, we explored the efficiency of alternative test policies.

METHODS:

Using national surveillance data from 2011 to 2013 with still comprehensive testing for all, we estimated the effects of restrictive testing on test costs, number of infections missed, costs per missed infection, costs per Quality Adjusted Life Year (QALY) lost, and calculated the net monetary benefit.

RESULTS:

The 2015-policy led to estimated savings of EUR1.1 million, while missing approximately three of ten HIV infections and seven of twenty syphilis infections among all younger heterosexual clients (in total 143,612 consultations) per year. Savings were EUR435,000 per QALY lost. Standard testing second-generation immigrants for syphilis and HIV saved EUR525,000/QALY lost. Offering an HIV test when diagnosed with chlamydia or gonorrhoea resulted in savings of EUR568,000/ QALY lost.

CONCLUSIONS:

The 2015-testing policy resulted in substantial savings as few missed HIV and syphilis infections caused QALY losses. Additional standard syphilis and HIV tests for second-generation immigrants and an additional HIV test in case of positive chlamydia or gonorrhoea diagnosis could reduce missed infections in a cost-effective way.
VP90 Uniform Assessment Methods To Assess New Genomic Tests
Authors: Scheibler Fueloep , Fleer Daniel , Angelescu Konstanze , Rodenhäuser Lina , Markes Martina , Rutjes Anne
Published: January 2018

INTRODUCTION:

With the possibility to analyze gene expression a plethora of new genomic tests are surging into the medical market. The assessment of these new technologies in Health Technology Assessment (HTA) reports is challenging and we need international consensus on uniform criteria to support HTA, but also to establish clear and standardized requirements for clinical studies.

METHODS:

The German Institute for Quality and Efficiency in Health Care (IQWiG) has been commissioned to assess the benefits and harms of biomarkers to predict which women would benefit from chemotherapy treatment after surgery of primary breast cancer. The final report was published in October, 2016 (1).

RESULTS:

Only eight studies complied with the inclusion criteria of the systematic review. No prognostic study fulfilled the inclusion criteria. Only two randomized controlled trials (RCTs) delivered information utilizable for benefit assessment. Based mainly on 5-year results from the MINDACT trial, the report concluded that there currently is not enough information to support a positive decision on biomarkers in this specific indication. Ongoing randomized controlled trials like TailorX, PlanB, RxPONDER, ADAPT or OPTIMA are expected to provide some additional evidence in the near future. After publication of the IQWiG report an extensive debate on several methodological characteristics of this report was fuelled. In addition, some other HTA agencies, such as the National Institute for Health and Care Excellence (NICE) made slightly different conclusions.

CONCLUSIONS:

The presentation will give a résumé of the main arguments and focus on differences between the IQWiG report and other HTA reports. Questions, like the required study type, study characteristics (for example, attrition rate, follow up, outcomes), data quality, cut-offs or patient preferences in diagnostic information will be provided. The aim of the presentation and discussion is to get a step forward in defining key characteristics and elements of benefit assessment and primary studies for these new technologies. A consensus among HTA reviewers in these approaches seems to be essential in the near future.
VP94 Framework Of High-Quality Value Assessment Criteria In Health Care
Authors: Raycheva Ralitsa , Stefanov Rumen
Published: January 2018

INTRODUCTION:

No single assessment can evaluate the wide spectrum of health technologies pending access to healthcare systems. It is important to envision a complex systematic framework, in which different instruments are used for different purposes - all criteria should be used to ensure the transparency of the process, and should model good assessment and implementation practices (1,2).

METHODS:

A cross-sectional web-based survey was conducted from September 2013 to May 2015 which was designed to gain information about the present status of Health Technology Assessment (HTA) activities; to examine its institutional contexts and the kind of application of its principles, logic, assessment methods, tools and best practices.

RESULTS:

A total number of 161 questionnaires from 39 countries on 6 continents were received representing a 41.7 percent response rate. Based on analysis of the results, a complex systematic framework for value assessment was designed. Five major features define the framework that can fully measure the common and support the evaluation of more complex health technologies: (i) implementation of higher-order evaluation approaches that support complex multi-criteria assessment, rather than emphasizing only the use of basic evaluation procedures; (ii) precise evaluation of critical criteria, that measure technologies directly as they will be used in actual practical settings; (iii) assessment approaches, based on international best HTA practices that are accurate, in terms of the content and context of the evaluated technology, as well as the expected performance; (iv) high-fidelity priority-setting elements that are evaluation sensitive; and (v) assessments that are sound, unbiased, and transparent – in order to be truly valid for a wide range of technologies, assessments should evaluate them accurately and do so reliably across technology content and context. They should be unbiased and accessible and used in ways that support superior outcomes and higher quality for healthcare systems.

CONCLUSIONS:

The healthcare systems that decide to use this framework should evaluate the set of assessments they select and develop them against the standards required, and should use them in ways for which they have been appropriately validated and in contexts that ensure a transparent evaluation process (3).
VP110 Building Capacity In Health Technology Assessment Through Plain Language
Authors: Globerman Kinneret
Published: January 2018

INTRODUCTION:

Health Technology Assessments (HTAs) and policy papers are generally written in academic style using industry jargon — pharmaceutical, medical, or scientific terminology — with a generous use of abbreviations. Transforming technical or biomedical data into easily understandable text is a necessity and a challenge for all of us if our goal is to facilitate HTA collaboration beyond borders and integrate HTA into healthcare practice. Many countries have legislated for plain language (PL), and organizations globally are beginning to recognize how it helps in the uptake of information, whether geared to healthcare professionals and all those interested in HTA, or the lay public.

METHODS:

A preliminary, informal online search for legislative and supporting guidance on PL was conducted, and a query sent out to forty-eight International Network of Agencies for Health Technology Assessment (INAHTA) members.

RESULTS:

•

The United States Plain Writing Act of 2010 has legislated that federal agencies use “clear Government communication that the public can understand and use” (1). Of the twenty-one respondents from INAHTA Listserv, seven use plain language in either their knowledge transfer tools (such as executive and research summaries, booklets and fact sheets, and patient or lay material).

•

The Government of Canada promotes plain language in all of its communications (2).

•

McMaster University's 2014 Health Forum on strengthening public and patient engagement in HTA in Ontario supported “clarity and consistency in the use of public- and patient-engagement terminology” in HTAs.

•

A growing number of international health-related and HTA organizations promote PL in their reports and HTAs to help with their health literacy.

•

Many pharmaceutical companies encourage PL communication in their writing (3).

•

Of the eighteen INAHTA responses received, eight reported that they use PL in their report summaries, knowledge transfer materials, and/or patient education tools.

CONCLUSIONS:

Adopting the practice of clear, straightforward writing and editing in all biomedical communication — including HTAs and journal articles — encourages interaction and engagement among patient, public, and healthcare stakeholders invested in HTAs, and their desire to have measured decision making based on comprehensive, informed, and easily understandable information. However, it remains to be seen if PL will be embraced by organizations worldwide. This preliminary, informal inquiry as to its use suggests that the adoption of PL by governments, HTA organizations, and the scientific community worldwide has not yet been fully embraced.
VP124 The End Of A French Medical Dogma For Hepatitis B And C Diagnosis
Authors: Lafarge Jean-Charles , David Denis-Jean , Morin-Surroca Michèle
Published: January 2018

INTRODUCTION:

Since the 1990s in France, based on contemporary French consensus conferences, for Hepatitis B (HBV) or Hepatitis C (HCV), diagnosis is acknowledged when detection of Hepatitis B surface antigen or anti-HCV antibody is positive on a 1st test line and further replicated on an independent blood sample.

The replication was introduced to alleviate the low performance of immunoassay and avoid false positive results.

Currently, the Haute Autorité de santé (HAS) is managing an update of diagnostic tests reimbursed for HBV and HCV to fully cover diagnostic needs.

Our aim is to assess the clinical relevance of this repetition.

METHODS:

The assessment involves a critical analysis of national and international guidelines identified by a systematic literature search, and stakeholders’ views (professionals and public authorities).

RESULTS:

Since the 1990s, new tools were introduced (that is, polymerase chain reaction (PCR) for diagnosis and follow-up), and performances were improved for both enzyme immunoassay tests and PCR. Despite those change, replications are still performed nowadays in France.

Neither guidelines nor stakeholders’ contributions mentioned any replication tests’ clinical relevance.The Ministry of Health confirms that replications have not any legal basis contrary to HIV diagnosis procedures. Also the French National agency for health products safety confirms there are neither technological pitfalls nor reagent vigilance signals involving HBV or HCV in vitro diagnostic tests. Furthermore, after 1st line positive results, a second blood sample is always collected to test other markers such as HBV DNA or HCV RNA which represent the best 2nd proof of infection.

CONCLUSIONS:

This work has enlightened a lack of clinical relevance for the replication of the same serological makers’ detection. It may obliterate soon this French medical dogma. This work has illustrated that short assessment based on critical guideline analysis linked with stakeholders’ views allows a rapid answer without assessment quality reduction. This HAS work will contribute to medical practice rationalization and cost reduction.
VP157 What Is The Response To Immuno-Oncology By Health Technology Assessment Agencies?
Authors: Rubinstein Judith , Adler Boaz , Blumenthal Jake , Chang Ruth , Ho S. Yin , Jaksa Ashley , Lurie Briana , Pontynen Anson , Rubinstein Emily , Sliman Rachel
Published: January 2018

INTRODUCTION:

Immunotherapies are a relatively new innovative class of drug that have garnered excitement in the fight against cancer. In 2011, the immunotherapy drug, ipilimumab, was approved. Since then, four additional drugs have gained approval. This analysis evaluates the initial reception of immunotherapies by Health Technology Assessment (HTA) agencies.

METHODS:

The Context Matters Data Model was used to evaluate the regulatory and HTA agency decisions surrounding the five approved immunotherapies through November 2016: atezolizumab, elotuzumab, ipilimumab, nivolumab, and pembrolizumab. Thirty-three labels from Australia, Canada, Europe, and the United States, and ninety-two assessments from Agenzia Italiana del Farmaco (AIFA), Gemeinsamer Bundesausschuss (Federal Joint Committee; G-BA), Haute Autorité de Santé (French National Authority for Health; HAS), Institute for Clinical and Economic Review (ICER), Institute for Quality and Efficiency in Health Care (IQWiG), National Institute for Health and Care Excellence (NICE), Pharmaceutical Benefits Advisory Committee (PBAC), pan-Canadian Oncology Drug Review (pCODR), and Scottish Medicines Consortium (SMC) were found. Using a sample t-test and a chi-squared test, reimbursement agencies’ decisions were evaluated, and the clinical and economic factors that went into these decisions were examined.

RESULTS:

Of the evaluated reviews: sixty-four were for melanoma indications, fourteen were for non-small-cell lung cancer (NSCLC) indications, and seven were for kidney cancer indications. Many of the reviews did not reach any decision, but 75 percent of HTA decisions (n = 72; p = .0000) reached were positive. Elotuzumab, approved for multiple myeloma, received a positive decision from G-BA and a negative one from SMC. There was an association between different disease conditions or drugs and the rate of positive decisions.

For reviews that had clinical reasons for their decisions, 72.9 percent (n = 59; p = .0000) had positive clinical rationales that were associated with positive decisions (p = .000). Economic rationales for decisions were more mixed, with only 48.4 percent (n = 31; p = .0000) receiving positive decisions. Positive economic evaluations were also associated with positive decisions (p = .000). Atezolizumab, approved only in the United States at the time of this writing, has yet to be reviewed by any of the HTA agencies.

CONCLUSIONS:

Immunotherapies are promising new options for the treatment of cancer. Thus far, reception by HTA agencies has generally been positive.
VP161 Identification Of Needs Of Pigmented Villonodular Synovitis Patients Using Online Bulletin Board
Authors: Cook Nigel , Landskroner Kyle , Walda Susann , Weiss Olivia , Pallapotu Vikrant
Published: January 2018

INTRODUCTION:

Pigmented villonodular synovitis (PVNS) is a very rare, benign proliferative tumor affecting the inner lining of synovial joints and tendon sheets. Information on treatment needs of PVNS patients to inform drug development is currently scarce, hence we conducted qualitative research with patients using an online bulletin board (OBB) methodology to generate insights on objective and emotional aspects related to the medical journey and living with this disease.

METHODS:

OBB is an asynchronous, online qualitative market research tool that allows participants to comprehensively answer pre-defined questions in a comprehensive manner. Patients were recruited via physician referral and underwent screening questions to ensure eligibility for the study and willingness to participate. The discussion was moderated, structured, and allowed open answers and in response to other participants posts. Analysis was conducted using a combination of different qualitative analytical tools.

RESULTS:

The patient OBB ran for 4 days with eleven participants (n = 3 Canada, n = 4 United Kingdom, n = 4 United States of America) aged 28–57 years, suffering from PVNS for 2–27 years. The key patient insights were: (i) pain is the primary factor, constituting a significant emotional and psychological burden; (ii) surgery (arthroscopy) does not get rid of PVNS, relapse rate was high in these patients; and (iii) PVNS has a big financial impact on patients, their families, and the healthcare system, due in particular to time off work/lost wages (patient & caretaker), for healthcare system it is repeat costs for surgeries/hospital stays plus other medical expenses. We also identified orthopedic specialists/surgeons are the physicians who predominantly manage PVNS at this point, as surgery is the only option.

CONCLUSIONS:

This study shows the suitability of the OBB for uncovering qualitative patient insights to inform decision making and strategy in early pharmaceutical drug development. OBB lends itself very well to uncovering patient insights which might not be revealed in focus group or telephone interviews, particularly in a rare disease like this. PVNS patients are in need of a medical drug treatment which can reduce pain, relapses and provide an alternative to surgery, the current standard of care.
VP180 Effect Of Two-Invoice System On Drug Distribution And Price In China
Authors: Ye Yingfeng , Ying XiaoHua
Published: January 2018

INTRODUCTION:

Drug prices are mainly determined by production costs, commercial circulation and use in medical institutions. In 2015, total sales of the Chinese drug distribution industry was CNY1,613.3 billion (USD248.6 billion at 31 December 2015 exchange rate), with CNY28.3 billion (USD4.4 billion) profit and an average cost rate of 5.4 percent due to high logistics costs (1). Under Multi-invoice Systems in China, drugs are delivered through national, provincial, local agents, with invoiced and prices going up each time (2). The Two-invoice System, which comes up in April 2016, is China's first drug distribution policy aiming to compress circulation, and reduce unrealistically high prices. There will be only two invoices, one from production enterprises to distributors, the other from distributors to medical institutions. The objective of this study is to evaluate the effect of the Two-invoice System on drug distribution and price in China.

METHODS:

We conducted a literature review of relevant articles and policies in five provinces on China National Knowledge Infrastructure (CNKI), Wanfang, PubMed and government websites. We conducted in-depth individual interviews for qualitative research on policy mechanisms with two government officials and four drug production and distribution enterprise managers. The quantitative study on policy effect measured indicators, namely, number of distributors, concentration ratio index (CR), net sales ratio, and ex-factory price. We compared the pilot province before and after the policy, with national level and other provinces. We considered related drug policies to eliminate confounding. Focus group discussion on conclusions and suggestions will be conducted.

RESULTS:

There are no peer review articles, only news media on this topic. In Fujian Province, the number of distributors droped from 246 to 62. In 2015, the Top 3 drug wholesalers reached a market share of 36 percent (CR3), and Top 10 for 86 percent (CR10). Compared to the whole country, CR3 is 26 percent and CR100 is 86 percent. Net sales in the drug wholesale market in Fujian accounted for 75.6 percent, with an increase of 4.3 percent. While at the national level, it is only 57.2 percent with an increase of 0.3 percent (3).

CONCLUSIONS:

The Two-invoice System in China reduces intermediate circulation, and increases industrial concentration. Net sales directly to hospitals are encouraged, whichaffects distribution and production areas. Production enterprises tend to invoice with higher prices instead of offering reserve prices to agents.
Evaluation of ELISA and haemagglutination inhibition as screening tests in serosurveillance for H5/H7 avian influenza in commercial chicken flocks
Authors: Arnold M. E. , Slomka M. J. , Breed A. C. , Hjulsager C. K. , Pritz-Verschuren S. , Venema-Kemper S. , Bouwstra R. J. , Trebbien R. , Zohari S. , Ceeraz V. , Larsen L. E. , Manvell R. J. , Koch G. , Brown I. H.
Published: January 2018

Avian influenza virus (AIV) subtypes H5 and H7 can infect poultry causing low pathogenicity (LP) AI, but these LPAIVs may mutate to highly pathogenic AIV in chickens or turkeys causing high mortality, hence H5/H7 subtypes demand statutory intervention. Serological surveillance in the European Union provides evidence of H5/H7 AIV exposure in apparently healthy poultry. To identify the most sensitive screening method as the first step in an algorithm to provide evidence of H5/H7 AIV infection, the standard approach of H5/H7 antibody testing by haemagglutination inhibition (HI) was compared with an ELISA, which detects antibodies to all subtypes. Sera (n = 1055) from 74 commercial chicken flocks were tested by both methods. A Bayesian approach served to estimate diagnostic test sensitivities and specificities, without assuming any ‘gold standard’. Sensitivity and specificity of the ELISA was 97% and 99.8%, and for H5/H7 HI 43% and 99.8%, respectively, although H5/H7 HI sensitivity varied considerably between infected flocks. ELISA therefore provides superior sensitivity for the screening of chicken flocks as part of an algorithm, which subsequently utilises H5/H7 HI to identify infection by these two subtypes. With the calculated sensitivity and specificity, testing nine sera per flock is sufficient to detect a flock seroprevalence of 30% with 95% probability.
Immune loss as a driver of coexistence during host-phage coevolution
Authors: Weissman J L , Holmes Rayshawn , Barrangou Rodolphe , Moineau Sylvain , Fagan William F , Levin Bruce , Johnson Philip L F
Published: January 2018

Bacteria and their viral pathogens face constant pressure for augmented immune and infective capabilities, respectively. Under this reciprocally imposed selective regime, we expect to see a runaway evolutionary arms race, ultimately leading to the extinction of one species. Despite this prediction, in many systems host and pathogen coexist with minimal coevolution even when well-mixed. Previous work explained this puzzling phenomenon by invoking fitness tradeoffs, which can diminish an arms race dynamic. Here we propose that the regular loss of immunity by the bacterial host can also produce host-phage coexistence. We pair a general model of immunity with an experimental and theoretical case study of the CRISPR-Cas immune system to contrast the behavior of tradeoff and loss mechanisms in well-mixed systems. We find that, while both mechanisms can produce stable coexistence, only immune loss does so robustly within realistic parameter ranges.
Pathogenesis of bone disease in multiple myeloma: from bench to bedside
Authors: Terpos Evangelos , Ntanasis-Stathopoulos Ioannis , Gavriatopoulou Maria , Dimopoulos Meletios A.
Published: January 2018

Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and mortality. The basis of the pathogenesis of myeloma-related bone disease is the uncoupling of the bone-remodeling process. The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and suppression of osteoblasts, resulting in bone loss. Several intracellular and intercellular signaling cascades, including RANK/RANKL/OPG, Notch, Wnt, and numerous chemokines and interleukins are implicated in this complex process. During the last years, osteocytes have emerged as key regulators of bone loss in myeloma through direct interactions with the myeloma cells. The myeloma-induced crosstalk among the molecular pathways establishes a positive feedback that sustains myeloma cell survival and continuous bone destruction, even when a plateau phase of the disease has been achieved. Targeted therapies, based on the better knowledge of the biology, constitute a promising approach in the management of myeloma-related bone disease and several novel agents are currently under investigation. Herein, we provide an insight into the underlying pathogenesis of bone disease and discuss possible directions for future studies.
Speciation of common Gram-negative pathogens using a highly multiplexed high resolution melt curve assay
Authors: Edwards Thomas , Sasaki Shugo , Williams Christopher , Hobbs Glyn , Feasey Nicholas A. , Evans Katie , Adams Emily R.
Published: January 2018

The identification of the bacterial species responsible for an infection remains an important step for the selection of antimicrobial therapy. Gram-negative bacteria are an important source of hospital and community acquired infections and frequently antimicrobial resistant. Speciation of bacteria is typically carried out by biochemical profiling of organisms isolated from clinical specimens, which is time consuming and delays the initiation of tailored treatment. Whilst molecular methods such as PCR have been used, they often struggle with the challenge of detecting and discriminating a wide range of targets. High resolution melt analysis is an end-point qPCR detection method that provides greater multiplexing capability than probe based methods. Here we report the design of a high resolution melt analysis assay for the identification of six common Gram-negative pathogens; Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, Salmonella Sp, and Acinetobacter baumannii, and a generic Gram-negative specific 16S rRNA control. The assay was evaluated using a well characterised collection of 113 clinically isolated Gram-negative bacteria. The agreement between the HRM assay and the reference test of PCR and sequencing was 98.2% (Kappa 0.96); the overall sensitivity and specificity of the assay was 97.1% (95% CI: 90.1–99.7%) and 100% (95% CI: 91.78–100%) respectively.
Cytokine-mediated changes in K+ channel activity promotes an adaptive Ca2+ response that sustains β-cell insulin secretion during inflammation
Authors: Dickerson Matthew T. , Bogart Avery M. , Altman Molly K. , Milian Sarah C. , Jordan Kelli L. , Dadi Prasanna K. , Jacobson David A.
Published: January 2018

Cytokines present during low-grade inflammation contribute to β-cell dysfunction and diabetes. Cytokine signaling disrupts β-cell glucose-stimulated Ca2+ influx (GSCI) and endoplasmic reticulum (ER) Ca2+ ([Ca2+]ER) handling, leading to diminished glucose-stimulated insulin secretion (GSIS). However, cytokine-mediated changes in ion channel activity that alter β-cell Ca2+ handling remain unknown. Here we investigated the role of K+ currents in cytokine-mediated β-cell dysfunction. Kslow currents, which control the termination of intracellular Ca2+ ([Ca2+]i) oscillations, were reduced following cytokine exposure. As a consequence, [Ca2+]i and electrical oscillations were accelerated. Cytokine exposure also increased basal islet [Ca2+]i and decreased GSCI. The effect of cytokines on TALK-1 K+ currents were also examined as TALK-1 mediates Kslow by facilitating [Ca2+]ER release. Cytokine exposure decreased KCNK16 transcript abundance and associated TALK-1 protein expression, increasing [Ca2+]ER storage while maintaining 2nd phase GSCI and GSIS. This adaptive Ca2+ response was absent in TALK-1 KO islets, which exhibited decreased 2nd phase GSCI and diminished GSIS. These findings suggest that Kslow and TALK-1 currents play important roles in altered β-cell Ca2+ handling and electrical activity during low-grade inflammation. These results also reveal that a cytokine-mediated reduction in TALK-1 serves an acute protective role in β-cells by facilitating increased Ca2+ content to maintain GSIS.
Precisely controlled synthesis of α-/β-MnO2 materials by adding Zn(acac)2 as a phase transformation-inducing agent
Authors: Zhang Ningqiang , Li Lingcong , Zhao Jinsheng , Yang Tingting , Zhang Guizhen , He Hong , Sun Shaorui
Published: January 2018

The ratio of the Zn species present in single-atomic dispersions and nanoclusters dominates the generation of α-MnO2 and β-MnO2.
1,4-Additions of tricyclic 1,4-diphosphinines – a novel system to study σ-bond activation and π–π dispersion interactions
Authors: Koner Abhishek , Kelemen Zsolt , Schnakenburg Gregor , Nyulászi László , Streubel Rainer
Published: January 2018

The reactivity of the aromatic π-system in 1,4-diphosphinineIwas explored towards [4+2]-cycloaddition reactions along with activation of organo dichalcogenides under thermal conditions.
Photochemical transformation of lipoic acid-based ligands: probing the effects of solvent, ligand structure, oxygen and pH
Authors: Mishra Dinesh , Wang Sisi , Michel Serge , Palui Goutam , Zhan Naiqian , Perng Woody , Jin Zhicheng , Mattoussi Hedi
Published: January 2018

We have combined optical absorption with the Ellman's test to identify the parameters that affect the transformation of the 5-membered dithiolanes to thiols in lipoic acid (LA) and its derivatives during UV-irradiation.
Mesoporous lipid-silica nanohybrids for folate-targeted drug-resistant ovarian cancer
Authors: Samanta Sayan , Pradhan Lina , Bahadur D.
Published: January 2018

A novel folate conjugated lipid coated mesoporous silica nanoparticle was synthesized to enhance cellular uptake and cytotoxicity and reduce multidrug resistance (MDR) in cancer.
Facile synthesis of electrostatically anchored Nd(OH)3 nanorods onto graphene nanosheets as a high capacitance electrode material for supercapacitors
Authors: Arunachalam Subasri , Kirubasankar Balakrishnan , Murugadoss Vignesh , Vellasamy Devadoss , Angaiah Subramania
Published: January 2018

Nd(OH)3/G hybrid is prepared by a solvothermal reduction process and used as an electrode material for asymmetric supercapacitors.
A multi-component synthesis of N-substituted 2-amino-3-cyano pyrroles via ring-opening of nitroepoxides
Authors: Liu Xingyu , Nie Zhuang , Shao Jiaan , Chen Wenteng , Yu Yongping
Published: January 2018

A multi-component synthesis of N-substituted 2-amino-3-cyano pyrroles from nitroepoxides, amines and malononitrile has been demonstrated.
Accuracy of a Screening Tool for Early Identification of Language Impairment
Authors: Uilenburg Noëlle , Wiefferink Karin , Verkerk Paul , van Denderen Margot , van Schie Carla , Oudesluys-Murphy Anne-Marie
Published: January 2018

Purpose

A screening tool called the
VTO Language Screening Instrument
(VTO-LSI) was developed to enable more uniform and earlier detection of language impairment. This report, consisting of 2 retrospective studies, focuses on the effects of using the VTO-LSI compared to regular detection procedures.

Method

Study 1 retrospectively compared VTO-LSI with regular detection procedures. Outcome measure was the detection rate of language impairment among 24-month-old children. Data were retrieved from medical records of children attending a youth health care center. Study 2 retrospectively compared the effects of VTO-LSI and regular detection procedures on the age at referral for diagnostic investigations and the influence of sex. Data were retrieved from medical records from the speech and hearing center and analyzed with multivariate analysis of variance.

Results

With the VTO-LSI, significantly more cases with language impairment were identified compared with the regular detection procedure (2.4% vs. 0.4%). In regions where the VTO-LSI was used, girls were almost 2 years younger, and boys were 1 year younger when referred to diagnostic investigations than in regions with regular detection procedures.

Conclusion

The VTO-LSI was more effective than regular detection procedures.