bluuebunny/crossref_metadata_2025_split huggingface dataset:
OP64 Implementation Of Whole Exome Sequencing For Rare Diseases
Authors: Fennessy Paul , Griffin Marianne 
Published: December 2019

IntroductionThe Victorian Department of Health and Human Services provided AUD 25 million (i.e. USD 17.3 million) over four years to determine the place of whole exome sequencing (WES) for patients attending public genetics clinics. Comparative analysis of WES and ‘usual care’ determined that WES increased diagnosis rate (from 14 to 58 percent), changed clinical management in one third of patients and identified relatives and couples at high risk of recurrence in future pregnancies. Translating this into routine care requires co-design with clinical and laboratory stakeholders.MethodsVictoria's clinical and laboratory genetics service system uses a ‘hub and spoke’ model. Representatives from these were invited to join a ‘Clinical Adoption Group’ (CAG) to oversight implementation of new government funding (AUD 2 million (i.e. USD 1.4 million) per year) to ensure statewide access to, and funding of, WES for children with rare undiagnosed genetic conditions. The CAG developed terms of reference, ‘traffic light’ evidence-based eligibility criteria, a pricing model and reporting mechanism, and recommended funding for sequencing, curation, curator training and multidisciplinary team (MDT) meetings to support implementation.ResultsFunding was distributed across hub and spoke sites reflecting clinical and laboratory demand and workforce requirements. All cases demonstrated clinical utility and were reviewed at MDT meetings. To date, 37 percent of patients have received a diagnosis changing management, with equity of access between metropolitan and regional areas demonstrated. Eligibility criteria are reviewed as new evidence is published to ensure new evidence is incorporated, although curation capacity limits turn-around-times.ConclusionsCo-designing a statewide and evidence-based clinical model has resulted in sector (i.e. clinician and laboratory) buy-in and supported broad access to funded WES. In addition, the sector has developed a better understanding of how evidence informs policy and funding decisions, which has resulted in delivering equitable WES that provides early diagnosis leading to changed clinical management and cessation of unnecessary interventions.
OP65 Pharmacoeconomic Evaluation Of Orphan Drugs: Impact Of Extra Criteria?
Authors: Maguire Orla , McCullagh Laura , Usher Cara , Barry Michael 
Published: December 2019

IntroductionThere is ongoing debate as to whether conventional pharmacoeconomic evaluation (PE) methods are appropriate for orphan medicinal products (OMPs). The National Centre for Pharmacoeconomics (NCPE) in Ireland has a well-defined process for conducting pharmacoeconomic evaluations of pharmaceuticals, which is the same for OMPs and non-OMPs. The objective of this study was to identify whether supplementary criteria considered in the pharmacoeconomic evaluation of OMPs would affect final reimbursement recommendations.MethodsA literature search was conducted to identify criteria. Orphan drug pharmacoeconomic evaluations completed by the NCPE between January 2015 and December 2017 were identified and supplementary criteria, where feasible, were applied.ResultsFourteen pharmacoeconomic evaluations were included in the study. Three criteria that could feasibly be applied to the NCPE evaluation process were identified, all three of which essentially broadened the economic perspective of the pharmacoeconomic evaluation. Higher cost-effectiveness threshold: Despite being arbitrarily raised from EUR 45,000/QALY to EUR 100,000/QALY, only one orphan drug demonstrated cost-effectiveness at this higher threshold. Weighted QALY gain: here, a weighted gain of between one and three is applied to drugs demonstrating QALY gains between 10 and 30, respectively. No OMPs included in the study showed a QALY gain of more than 10. Thirteen demonstrated QALY gains less than 10 and one could not be evaluated. Societal perspective: six submissions incorporated societal perspective as a scenario analysis. Despite incremental cost-effectiveness ratios (ICERs) being reduced between 4 percent and 58 percent, only two OMPs demonstrated cost-effectiveness at the higher threshold (EUR 100,000/QALY).ConclusionsApplication of supplementary criteria to the pharmacoeconomic evaluation of OMPs had a minor effect on three products assessed. However, for the majority, the final cost-effectiveness outcomes remained the same. The study highlights that other criteria are being considered in the decision to reimburse.
OP68 Value-Engineered Translation: An Example for Bladder Cancer Diagnosis
Authors: Sutton Andrew , Lamont John , Evans R. , Williamson Kate , O'Rourke Declan , Duggan Brian , Sagoo Gurdeep , Reid Cherith , Ruddock Mark 
Published: December 2019

IntroductionThe Institute of Health Economics offers a suite of analyses that provide developers an understanding of the expected commercial viability of an early stage health technology. In combination, these analyses form the Value-Engineered Translation framework. These methods incorporate innovative methods to manage uncertainty in early economic evaluations, in particular, moving beyond current stochastic assessments of headroom to account for inter-market variability in value hurdles, as well as incorporating social value premia considerations. An illustration of these methods is demonstrated using the example of a non-invasive diagnostic test (called DCRSHP) at an early stage of development, compared to current practice of cystoscopy in the diagnosis of bladder cancer.MethodsCompeting technologies were identified to inform the headroom assessment based on price and effectiveness. Then, a model-based cost-effectiveness analysis was undertaken incorporating headroom analysis, stochastic one-way sensitivity analysis, and value of information analysis using data from secondary sources.ResultsCurrently there are a number of non-invasive tests available, but none have sufficient test accuracy to be suitable for bladder cancer diagnosis alone. From the headroom analysis, DCRSHP can be priced at up to CAD 790 (i.e. USD 588) and still be cost-effective compared to the current practice of cystoscopy. Interestingly this price can be increased for patient groups that have lower levels of bladder cancer prevalence.ConclusionsThe requirements of economic evaluations depend on the stage of technology development, and analysis approaches must reflect this. The results here indicate that DCRSHP clears the value hurdle in terms of being cost-effective, and thus provides the opportunity to make a commercial return on future investment. Future analysis of DCRSHP could consider the cost drivers for development of the technology, including the regulatory pathways, costs associated with the intellectual asset management for the technology, and alternative manufacturing costs. All of which contribute to the research-to-practice continuum.
OP72 HTA Beyond 2020 In China： HB-HTA Rising Up In Tertiary Hospitals
Authors: Lin Xia , Bai Fei , Lv Lanting , Qin Xiaoxiao 
Published: December 2019

IntroductionHealth technology assessment (HTA) was introduced into China more than 20 years ago and has developed rapidly recently. While only recently has the concept of hospital-based health technology assessment (HB-HTA) attracted attention in China. The purpose of this study is to investigate the views of government officials, decision makers and relevant stakeholders in the management and application of medical technologies in hospitals, within the environment of Health System Reform in China. We analysed the current situation and identified obstacles and prospects of HB-HTA in Chinese tertiary hospitals.MethodsWe conducted semi-structured interviews in 8 provinces in Eastern, Central and Western China; in 2 to 4 tertiary public hospitals in each province. We interviewed doctors, nurses, and Chiefs in hospitals, and key informants in the National Center for Medical Service Administration.ResultsA total of 98 people participated in the panel discussions and interviews. We found that:
1.China's tertiary public hospitals have embraced HB-HTA, and various hospitals have performed different forms of HB-HTA (including ambassador model, Mini-HTA model, and internal committee model). However, the assessment process, standards, and methods are yet to be standardized.2.The promotion of HB-HTA in China's tertiary public hospitals has remarkable external incentives and internal advantages.3.The lack of HB-HTA professionals, improvements in cognition level, and evidence-based decision-making models and management culture hinders the development of HB-HTA in China.ConclusionsHB-HTA is in high demand in China, especially in tertiary hospitals. It will continue to develop rapidly over the next decade along with the development of China's HTA. HB-HTA will complement the national HTA to jointly extend the Chinese HTA system.
OP88 Digital Approaches For Randomized Controlled Trial Recruitment Or Retention: A Systematic Map
Authors: Frampton Geoff , Shepherd Jonathan , Pickett Karen , Griffiths Gareth , Wyatt Jeremy 
Published: December 2019

IntroductionRecruitment and retention of participants in randomized controlled trials (RCTs) is challenging, and is why many RCTs fail or are not completed on time. Digital approaches such as social media, data mining, email or text messaging could improve recruitment and/or retention, but how well they match these purposes is unclear. We used systematic methods to map the digital approaches that have been investigated during the past 10 years.MethodsWe searched Medline, Embase, other databases and relevant web sites in July 2018 to identify comparative studies of digital approaches for recruiting and/or retaining participants in clinical or health RCTs. Two reviewers screened references against protocol-specified eligibility criteria. Studies included were coded by one reviewer (with 20 percent checked by a second reviewer) using pre-defined keywords to describe characteristics of the studies, populations and digital approaches evaluated.ResultsWe identified 9,133 potentially relevant references, of which 100, reporting 101 unique studies, met the criteria for inclusion in the map. Among these, 95 percent of studies investigated recruitment but only 11 percent investigated retention. Study areas included health promotion and public health (36 percent), cancer (17 percent), circulatory system disorders (13 percent) and mental health (10 percent). Most study designs were observational (89 percent). The most frequent digital approaches for recruitment were internet sites (53 percent of recruitment studies), social media (42 percent), television or radio (31 percent) and/or email (31 percent). For retention these were email (63 percent of retention studies) or text messaging (38 percent). Time and costs of recruitment were reported in 17 percent and 30 percent of recruitment studies respectively, whilst costs were reported in 19 percent of retention studies.ConclusionsA wide range of digital approaches has been studied, in many combinations. Evidence gaps include lack of experimental studies; studies on retention; and studies for specific populations (e.g. children or older people) and outcomes (e.g. user satisfaction). More robust experimental studies, perhaps conducted as studies-within-a-trial (SWAT), are needed to address knowledge gaps and ensure that estimates of digital tool effectiveness and efficiency are reliable.
OP89 Conference Abstract Searching In National Institute For Health And Care Excellence Health Technology Appraisals
Authors: Wong Ruth 
Published: December 2019

IntroductionThe National Institute for Health and Care Excellence (NICE) guidelines manual recommend that MEDLINE, Embase and Cochrane Central Register of Controlled Trials should be prioritized for searching for reviews of the effectiveness of pharmacological interventions. Additionally, searching trial registries and conference abstracts are recommended to identify ongoing or unpublished research. However, the approaches to searching conference abstracts have not been previously studied. The aim is to analyze searches of conference abstracts reported in NICE Technology Appraisal (TA) company submissions for cancer interventions from 2013 until September 2018.MethodsThe company submissions were searched and obtained via the NICE technology appraisal guidance website. The sources used to find conference abstracts were identified from the company clinical effectiveness review search methods and appendices. Conference abstract searching in both database and website sources were compared.ResultsOf all 394 TAs, 124 (31 percent) were cancer TAs. Between 2013 and 2018, 91 TAs were completed or updated, which covered 18 cancer categories and 52 different named technologies. Technologies to treat non-small-cell lung cancer was the most frequently appraised in the last five years. Nivolumab was the most frequently appraised technology. Searches for conference abstracts were reported in 70 (77 percent) out of 91 company submissions. Supplementary searching was reported in 59 (84 percent), compared with 11 (16 percent) searching either/both Embase and the Web of Science Conference Proceeding Index (WoS-CPCI). A total of 54 supplementary website sources were searched which ranged from one to 11 per TA (average four sources). The American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology were the most frequently searched sources.ConclusionsWhilst the WoS-CPCI has better coverage of cancer conference abstracts than Embase, searching databases alone are inadequate. Supplementary conference websites should be searched for reasons such as access to the most recent abstracts and incomplete indexing of titles within databases. A wide range of cancer specific sites exists although the impact of broad (e.g. ASCO) versus condition specific sites is unclear.
OP123 A Cost-Effectiveness Registry For Prioritization In Emerging Markets
Authors: Ollendorf Daniel , D'Cruz Brittany , Emerson Joanna , Bacon Rachel , Cohen Joshua , Neumann Peter 
Published: December 2019

IntroductionDecision-makers in low- and middle-income countries (LMICs) often must prioritize health spending without quantitative benchmarks for the value of their purchases. The Tufts Global Health Cost-Effectiveness Analysis (GH CEA) Registry (healtheconomicevaluation.org/GHCEARegistry/) is a freely-available, curated and standardized dataset designed to address this need.MethodsAll indexed English-language articles published between 1995 and 2017 are currently included in the GH CEA Registry. Studies are limited to those reporting cost-effectiveness in terms of cost per disability-adjusted life years (DALYs) averted, a commonly-employed metric in global health. Abstracted data include intervention type, comparator(s), country, funding source, study characteristics (e.g., perspective, time horizon), primary study findings, sensitivity analyses, and disaggregated data on costs and DALYs. Study quality is assessed using a numerical scoring system (from 1-7, higher scores indicating better quality) based on accuracy of findings and comprehensive reporting of methods and results.ResultsTo date, 620 articles have been included in the GH CEA Registry. Among LMICs, studies have been conducted primarily in Sub-Saharan Africa (41 percent) or South Asia (34 percent), have focused on communicable diseases (67 percent), and have involved immunization, educational, or pharmaceutical interventions (67 percent). As a priority-setting example, seven percent of interventions from higher-quality studies (ratings of 5 or higher) were reported to be cost-saving (i.e., lower costs and greater DALYs than standard care), two-thirds of which involved primary disease prevention (e.g., immunization, educational or behavioral interventions).ConclusionsThe GH CEA Registry is a new tool for decision-makers in LMICs, particularly those without a formal health technology assessment infrastructure but with a remit for providing access to essential, cost-effective health interventions. New functions are under development, including league tables for priority ranking, a repository for shared models, and tools for enhancing transferability between settings.
PP12 Cost-Utility Analysis Of Dolutegravir For HIV-1 Infection In Thailand
Authors: Yoopetch Panida , Khemvaranan Chalida 
Published: December 2019

IntroductionHIV drug resistance (HIVDR) has significantly increased in Thailand. However, a new generation integrase inhibitor, dolutegravir, has not yet been included in the country's National List of Essential Medicines (NLEM). Since these drugs are high in costs, an economic evaluation is needed to support the decision. This study aims to assess the cost-utility analysis of dolutegravir for HIV-1 infection in Thailand.MethodsA Markov model was developed to evaluate the cost-utility as follows: (i) the current practice of darunavir/ritonavir (DRV/r) + tenofovir (TDF) + lamivudine (3TC); (ii) DRV/r + etravirine (ETR) + TDF + 3TC; (iii) DRV/r + raltegravir (RAL) + TDF + 3TC; (iv) DRV/r + RAL + ETR; and (v) DRV/r + RAL + maraviroc (MVC); (vi) DRV/r + dolutegravir (DTG) + MVC; (vii) DRV/r + DTG + ETR; (viii) DRV/r + DTG + TDF + 3TC. The model incorporated cost data adjusted for 2017 using the consumer price index, and effectiveness data from a review of published studies. Outcomes were measured in life years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), and future costs and outcomes were discounted at 3 percent per annum. Finally, a probabilistic sensitivity analysis was conducted to deal with uncertainties around the parameters.ResultsAll alternative treatment regimens for HIV patients resistant to first- and second-line antiretroviral therapies (ARTs) in Thailand were found to be not cost-effective at the willingness-to-pay (WTP) of THB 160,000/QALY (USD 5,197/QALY). However, the eighth regimen of DRV/r + DTG + TDF + 3TC had the lowest lifetime cost at THB 5.3 million (USD 172,145) while increasing QALY by approximately 14 QALYs.ConclusionsAt a societal WTP of THB 160,000 per QALY gained (USD 5,197 per QALY gained), dolutegravir for HIV patients resistant to first- and second-line ARTs in Thailand was found to be not cost-effective.
PP50 How Do Target Population Sizes In Health Technology Assessments Impact Drug Price Changes?
Authors: Liden Daniel , Jao Rachel , Lockwood Cameron , Reinaud Floriane 
Published: December 2019

IntroductionThe relationship between heath technology assessment (HTA) recommendations and drug prices has received little attention in the published literature. We consider whether target population sizes estimated as part of positive HTA decisions impact future price changes. We hypothesize that larger target populations may result in larger drug price reductions, as overall budget impact is an important component of price negotiations.MethodsHTA and pricing data were obtained from the Context Matters Market Access Platform (MAP) and IHS Markit's PharmOnline International (POLI) pricing database, respectively. We analyzed 55 HTA decisions from the Gemeinsame Bundesausschuss (G-BA; Germany) and the Haute Autorité de Santé (HAS; France) for oncology products receiving European Medicines Agency approval between 2011 and the end of 2014. Pricing and HTA histories were tracked from the beginning of 2012 until October 2018. Using multiple regression to control for HTA agency, country-specific scores (Improvement in Actual Benefit and Additional Benefit scores), pack size, and initial price, we examined the relationship between a drug's price change in the year following an HTA review and the increase in target population resulting from the HTA decision.ResultsWe found that larger increases in target population were related to larger reductions in drug prices (p = 0.014). The magnitude of the effect size was low.ConclusionsFor the sample evaluated, we found a small but statistically significant association between target population size increases (as estimated by HTA bodies) and price reductions, supporting our hypothesis that target population plays a role in price negotiations. Confidential discounts and managed-access agreements likely account, in part, for the low magnitude of the observed association. Future work on this topic will involve larger samples covering a greater number of HTA agencies to improve the power and generalizability of the analysis.
PP81 Real World Data: The Early Access To Medicines Scheme Catches The Worm
Authors: Hall Adam , Liu Lok Wan , Macaulay Richard , Walsh Sean 
Published: December 2019

IntroductionThe Early Access to Medicines Scheme (EAMS) aims to provide access to medicines prior to market authorization for patients with severe, life-threatening diseases who do not have adequate treatment options. An EAMS designation enables the potential collection of United Kingdom-specific real world evidence (RWE) prior to health technology assessment (HTA) by the National Institute for Health and Care Excellence (NICE). This research evaluates whether RWE is being gathered through the EAMS and utilized to support HTA submissions.MethodsAll EAMS designations as of 7 November 2018 were identified from the Medicines and Healthcare products Regulatory Agency website. For products with final NICE guidance, all publicly-available NICE documentation was reviewed.ResultsSixteen product and indication pairings with an EAMS designation were identified, with 12 having received final NICE guidance (11 were recommended, 3 were recommended for temporary reimbursement via the Cancer Drugs Fund, and 2 were not recommended). Of the 11 recommended products, seven had references to the number of patients or sites with product access through the EAMS, but only one (dupilumab for atopic dermatitis) had detailed data collected during the EAMS period. The manufacturer of dupilumab reported baseline demographics and disease characteristics from a cohort of 35 patients treated under the EAMS to inform the generalizability of trial populations for clinical practice. Follow-up results from this cohort demonstrated that real-world data on dupilumab effectiveness was comparable with the clinical trial data, despite a higher proportion of patients in the real-world cohort receiving immunosuppressant therapy, which makes improvements in efficacy harder to achieve. The committee also noted that the RWE presented supported the understanding of dupilumab's long-term clinical effectiveness and informed assumptions for the economic model.ConclusionsTo date, the majority of products receiving an EAMS designation have not presented RWE at NICE reappraisal. The case of dupilumab illustrated how RWE collected through the EAMS can be used to reduce uncertainty around how clinical trial data can be translated into clinical practice. In the future, RWE may increasingly be used to help inform NICE decisions.