bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transgressing the Division of Powers: The Case of the James Bay and Northern Quebec Agreement
Authors: Scholtz Christa , Polataiko Maryna 
Published: December 2019

AbstractIn 1975, the Bourassa government received legal advice that the James Bay Northern Quebec Agreement exceeded provincial jurisdiction. Legal counsel advised the constitutionality of the Agreement be secured through formal constitutional amendment. No such amendment was sought. Based on authorized access to Premier Bourassa’s archived dossier on the Agreement’s negotiation, this article sets out the following: 1) why the provincial government sought to encroach on federal jurisdiction; 2) the strategic means employed to insulate the Agreement from s. 91(24) litigation; and 3) provincial negotiators’ views on how judges would approach the Agreement going forward. This article confirms theoretical expectations about when governments might coordinate to transgress federalism’s division of powers: a high probability that courts would find a transgression occurred, and a high political cost should governments not coordinate on a transgression strategy.
OP34 One-Way Sensitivity Analysis For Cost Effectiveness Analysis
Authors: McCabe Christopher , Awotwe Isaac , Paulden Mike , Sutton Andrew , Hall Peter 
Published: December 2019

IntroductionAlthough stochastic analysis has become the accepted standard for decision analytic cost effectiveness models, deterministic one-way sensitivity analysis continues to be used to meet the needs of decision makers to understand the impact that changing the value taken by one specific parameter has on the results of the analysis. However, there are a number of problems with this approach.MethodsWe review the reasons why deterministic one-way sensitivity analysis will provide decision makers with biased and incomplete information. We then describe a new method - stochastic one-way sensitivity analysis (SOWSA), and apply this to a previously published cost effectiveness analysis, to produce a stochastic tornado diagram and conditional incremental net benefit curve. We then discuss how these outputs should be interpreted and the potential barriers to the implementation of SOWSA.ResultsThe results illustrate the shortcomings of the current approaches to deterministic one-way sensitivity analysis. For SOWSA, the expected costs and outcomes are captured, along with the sampled value of the parameter and these are linked to the probability that the parameter takes that value – which can be read off the probability distribution for the parameter used in the stochastic analysis. From these results it is possible to gain insights into probability that a parameter will take a value that will change a decision.ConclusionsAlthough a well-used technique, one-way deterministic sensitivity analysis has a number of shortcomings that may contribute to incorrect conclusions being drawn about the importance of certain parameter values on model results. By providing fuller information on uncertainty in model results, it is hoped that the methods here will lead to more informed decision making. Although, as with all developments in the presentation of analytic results to decision makers, care will be required to ensure that the decision makers understand the information provided to them.
OP48 Nursing Requirements In Long-Term Care: A Health Technology Assessment
Authors: Corabian Paula , Yan Charles , Armijo-Olivo Susan , Guo Bing 
Published: December 2019

IntroductionThe objectives of this study were to systematically review published research on the relationship between nursing staff coverage, care hours, and quality of care (QoC) in long-term care (LTC) facilities; and to conduct a real world evidence (RWE) analysis using Alberta real world data (RWD) to inform policy makers on whether any amendments could be made to current regulations.MethodsA systematic review (SR) of research evidence published between January 2000 and May 2018 on the relationship between nursing staff coverage, care hours, and QoC in LTC facilities was conducted. Panel data regressions using available RWD from Alberta, Canada, were performed to assess associations between nursing care hours and LTC outcomes. Outcomes of interest included quality indicators related to resident outcomes, hospital admissions, emergency room visits and family satisfaction. Nursing care hours considered in SR and RWE analysis included those provided by registered nurses (RNs) and licensed practical nurses (LPNs).ResultsThe SR found inconsistent and poor quality evidence relevant to the questions of interest, indicating a great uncertainty about the association between nursing staff time and type of coverage and QoC. Although some positive indications were suggested, major weaknesses of reviewed studies limited interpretation of SR results. RWE analysis found that impact of care hours on LTC outcomes was heterogeneous, dependent on outcome measurements. There was evidence that total staff, RN, and LPN hours had positive effects on some resident outcomes and magnitude of effect differed for different nursing staff.ConclusionsNo definitive conclusion could be drawn on whether changing nursing staff time or nursing staff coverage models would affect residents’ outcomes based on the research evidence gathered in the SR. RWE analysis helped to fill a gap in the available published literature and allowed policy makers to better understand the impact of revising current regulations based on actual outcomes.
OP50 IQWiG And GRADE – An Exemplary Comparison Of Methods
Authors: Schell Lisa , Sauerland Stefan , Thomas Stefanie , Kaiser Thomas , Luhnen Miriam , Lietz Martina , Skipka Guido 
Published: December 2019

IntroductionEfforts to harmonize health technology assessment (HTA) processes and methods across Europe are currently intensified. In this context, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach has been proposed as a “common ground” in joint HTAs. However, GRADE has been primarily developed to support authors of clinical guidelines. Therefore, it is unclear whether HTA reports based on GRADE are compatible with the methods currently applied by European HTA organizations.MethodsWe contrasted IQWiG's methods paper and publications by the GRADE Working Group with regard to the following domains: 1) risk of bias (RoB) assessment 2) prerequisites for “greater benefit” (assuming that IQWiG's “greater benefit” corresponds to a GRADE assessment of at least low certainty and a small important effect) and 3) consideration of non-randomized studies (NRS). We present illustrative differences and highlight similarities.ResultsOverall, RoB assessments are very similar under both approaches. However, we identified several important differences. In case of very severe publication bias, IQWiG methods preclude drawing a conclusion, whereas GRADE requires only downgrading the certainty of evidence while still allowing for a conclusion on effect sizes. Secondly, IQWiG generally requires a statistically significant effect for a “greater benefit”, while GRADE does not (statistically non-significant effects would only necessitate downgrading the certainty of results for imprecision). Another difference is that in general, NRS are not included in IQWiG assessments when randomized studies (RS) are available and thus possible. In contrast, preliminary GRADE guidance recommends considering NRS in addition to RS when the RS evidence is of low or very low certainty.ConclusionsWhile GRADE and IQWiG's method share some similarities, our exemplary analysis shows that there are some notable differences. Therefore, GRADE should not be used “out of the box” for European HTAs. To foster further discussion, more research (including a comprehensive comparison of methods and an analysis of resources for adaptation) is needed.
OP69 Initiatives To Improve The Timeliness Of Cancer Diagnosis
Authors: Pollock Michelle , Craig Rodger , Chojecki Dagmara , Guo Bing 
Published: December 2019

IntroductionConventional wisdom suggests that accelerating the speed of cancer diagnosis should improve health outcomes. However, cancer diagnosis requires complex coordination and effective communication between care providers working across many areas of the healthcare system. Since 2000, several nations and jurisdictions have aimed to improve timeliness of cancer diagnosis by integrating and coordinating cancer diagnostic services for patients. The objective of this study was to describe the impact of these existing initiatives.MethodsWe conducted an environmental scan consisting of a literature review (published academic and grey literature) and key informant consultations (online surveys and telephone interviews with experts who have knowledge of existing initiatives). We searched for initiatives in the United Kingdom, the Nordic countries, Canada, Australia, and New Zealand. For each initiative, we extracted data on their development and implementation, structure and functioning, intended outcomes and effectiveness, costs and cost savings, and enablers and barriers.ResultsEighty-nine relevant documents and 20 key informants contributed to this study. We identified 21 relevant initiatives, including seven national initiatives targeting multiple types of cancer. The literature review found that most initiatives accelerated the diagnostic phase of cancer care by several days or weeks. These wait time reductions were often associated with improved patient experience, but not less advanced cancer stage or increased long-term survival. Insights from key informants improved our understanding of the costs, enablers, and barriers associated with program implementation and maintenance.ConclusionsThese results can be used as a first step to inform the development, evaluation, and improvement of international cancer diagnostic pathways. Stakeholders wishing to accelerate cancer diagnosis should consider the feasibility of achieving their intended program outcomes based on the existing research evidence, desired type of initiative, and jurisdiction's unique contextual factors.
OP105 Factors Affecting Horizon Scanning For Hospital-Based Health Technology Assessment
Authors: Chalkidou Anastasia , Erskine Jamie , Macmillan Thomas , Keevil Stephen 
Published: December 2019

IntroductionThe strategic MedTech investment for the expansion of a central London paediatric hospital must sustain its ambitions to remain a state-of-the-art hospital, whilst implementing recent and future MedTech innovations and taking into account spatial and financial limitations. Horizon scanning (HS) is an important health technology assessment (HTA) tool to achieve these goals. To this end, we developed a methodology to help decide the suitability of investing in the following imaging-based MedTech: a hybrid theatre incorporating a biplane, intra-operative MRI (iMRI), multi-detector computed tomography (CT) scanners, and an EOS imaging system and predict the complementary technologies required for the decade to come. These technologies not only require adequate spatial resources but a significant upfront capital investment.MethodsThree sources of information were used: i) a literature search, selected journals and other horizon scanning resources that examined current efficiency, safety, and cost-effectiveness for the proposed technologies, ii) expert elicitation in the form of user-group meetings and one-to-one discussions with clinical and service management teams and iii) hospital data consisting of audit and information from capital equipment bids.ResultsWith the exception of limited comparative data on iMRI (mainly including adults), little evidence exists to support investment in the proposed technologies. However, the decision of whether to adopt these technologies was influenced not only by existing evidence on the proposed technologies and associated cost but other factors such as local disease burdens, hospital staff requirements (training, expertise), space requirements for the new MedTech, and its impact on organizing healthcare services and hospital workflows. Complementary technologies associated with radiation monitoring image visualization and control were identified.ConclusionsStrategic MedTech investment requires a holistic approach that assigns equal weight to information arising by expert elicitation and hospital audit data with existing literature evidence. The decision for adoption is heavily influenced by the clinical expertise and hospital workflows.
OP127 Sugar And Spice And All Things NICE - Managed Access Agreements
Authors: Hall Adam , Liu Lok Wan , Macaulay Richard , Walsh Sean 
Published: December 2019

IntroductionThe National Institute for Health and Care Excellence (NICE) has increasingly agreed to reimburse innovative products with high levels of uncertainty as part of managed access agreements (MAAs) while additional data are collected, through the new Cancer Drugs Fund (CDF) or highly specialized technology (HST) pathways. This research aimed to review the data collection stipulations of current MAAs.MethodsWe reviewed all current MAAs entered into between NHS England and manufacturers as of 29 October 2018 and key data were extracted.ResultsTwenty-two MAAs were identified (19 through the CDF; three through HST). All MAAs involved an observational data collection component. The source of observational data collection was existing NHS databases (19/22 MAAs: 86.5 percent), existing independent registries (one MAA: 4.5 percent [ataluren]); bespoke MAA registry maintained by manufacturer (1/22 MAA: 4.5 percent [asfotase alfa]), and registries developed as a part of regulatory approval and maintained by the manufacturer (1/22 MAA: 4.5 percent [elosulfase alfa]). Only eight MAAs (asfotase alfa, ataluren, elosulfase alfa, brentuximab vedotin, venetoclax, ibrutinib, daratumumab, and pembrolizumab) had observational data collection as the primary method of data collection. Additionally, 17/22 MAAs (77 percent; all from the CDF) also required ongoing data collection from clinical trials as a key component of the data collection arrangement.ConclusionsThis research identified observational data collection as a requirement in all MAAs, which is primarily through existing registries (except ataluren, which required development of a bespoke registry), while ongoing trial data collection was limited to the CDF. The relatively low cost of using existing registries to fulfil data requirements, with the ability to achieve reimbursement whilst still collecting data from ongoing RCTs, make MAAs an attractive proposition for manufacturers. NICE reportedly plan to increase use of MAAs, with ongoing NICE consultation for changes in the appraisal process potentially allowing expansion to include all indications, which would mean increased opportunities to explore innovative MAAs to support access in the future.
OP135 CAR T-cell Therapy HTA Informs Australian Policy
Authors: Fennessy Paul , Clements Vanessa 
Published: December 2019

IntroductionChimeric antigen receptor (CAR) T-cell therapy is offered as a once-only treatment for patients with certain cancers that are not responsive to standard treatment. While clinicians, patients and their families increasingly seek access to CAR T-cell therapy, there is no revenue stream to support access through public or private health systems.MethodsThe New South Wales (NSW) Ministry of Health and Victorian Department of Health and Human Services oversighted a health technology assessment (HTA) to explore the status and geography of regulatory frameworks supporting delivery of CAR T-cell therapy, evidence for the safety, efficacy and cost, clinical trials conducted or underway and manufacturing aspects.ResultsCAR T-cell therapies are approved in the European Union and United States of America, and being considered in Australia, Canada, China and Japan. Efficacy, safety and cost-effectiveness is limited by the size and single-arm design of early stage trials and variation between them. While overall response ranges from 36–93 percent, early results for some cancers are less favorable. Durability of treatment effect is unknown, adverse events are common and can be life-threatening and risk of delayed onset toxicity remains unknown. Treatment requires access to approved manufacturing facilities (none in Australia) and specialist clinical staff.ConclusionsCAR T-cell therapy is promising and demand is increasing, but the limited safety profile and evidence base should mitigate policy and investment decisions. Broader consideration should be given to developing, or identifying access to, manufacturing and clinical workforce capability and capacity to meet national demand. Australia is likely to encounter similar issues in other jurisdictions, such as limited evidence base and complex safety issues. Factors to be considered on a local and national basis for assessment and implementation include: (i) Regulatory support for industry; (ii) Strategies to manage uncertainties in long-term risks, benefits and costs; (iii) Access to accredited manufacturing facilities; (iv) Developing clinical and manufacturing workforce capability and capacity.
PP94 Clinical Effectiveness Of Regorafenib For Metastatic Colorectal Cancer
Authors: Absattarova Karlygash , Almadiyeva Alima , Sultanov Marat , Almatova Venera 
Published: December 2019

IntroductionColorectal cancer (CRC) is the third most common malignant neoplasm among men and the second most common among women. According to the World Cancer Report, the number of people suffering from this disease is growing steadily. In 2012, there were more than 1.36 million new cases of CRC, and approximately 694,000 people died from this disease worldwide.MethodsA sensitive literature search identified 12 relevant publications, including: a CORRECT phase III study assessing the effect of regorafenib in patients with metastatic CRC that continued to progress despite using all standard treatment methods; a CONCUR Phase III study evaluating the clinical effect of regorafenib in Asian patients with metastatic CRC; a CONSIGN study conducted after the CORRECT and CONCUR studies that assessed the safety profile of regorafenib prior to market entry; and various systematic reviews evaluating the safety of regorafenib.ResultsThe efficacy and safety of regorafenib for treating patients with metastatic CRC was evaluated in two major clinical studies: CORRECT and CONCUR. Although the studies were randomized, double-blind, and placebo-controlled, they were conducted in different patient populations. Before treatment with regorafenib, patients received, depending on the country, fluoropyrimidines, oxaliplatin, irinotecan, or bevacizumab, and patients with the wild-type KRAS gene also received cetuximab and panitumumab. Results from both studies indicated that regorafenib had a clinically significant positive effect on rates of progression-free survival and overall survival in patients with treatment-resistant metastatic CRC.ConclusionsRegorafenib can be recommended as a monotherapy for resistant metastatic CRC when there are no contraindications to use. Considering the safety profile of regorafenib, further research is needed to determine the best dosage of regorafenib and the most appropriate clinical and molecular biomarkers for determining which patients would benefit most from this treatment.
PP139 Adapting Health Technology Assessment And Procurement To Tackle Antimicrobial Resistance
Authors: Neri Margherita , Towse Adrian , Hampson Grace , Henshall Christopher 
Published: December 2019

IntroductionThe rise of antimicrobial resistance (AMR) as an international public health threat calls urgently for improved stewardship of antibiotics and for the development of new antibiotics to tackle AMR. There is growing agreement that changes are needed to existing systems for health technology assessment (HTA) and procurement if antibiotics are to be used appropriately, and manufacturers are to receive rewards that incentivize research and development. However, there has been little discussion of what changes might actually be made.MethodsWe conducted a literature review of recent proposals to modify HTA and contracting for antibiotics, and interviewed HTA experts from England, France, Germany, Italy, Japan, and Sweden to explore the attractiveness of these and other proposals in their countries. A forum (held in February 2019) with government and health system representatives from these countries, as well as from industry, will promote face-to-face discussions on practical ways to modify approaches in these countries to recognize the full value of antibiotics and promote responsible stewardship.ResultsThe focus of the main proposal is to define value attributes that reflect the societal impact of antibiotics, model the dynamics of infection transmission and resistance development, and conceptualize payment models that delink volumes sold from final revenues. However, HTA experts perceived a number of issues with these proposals, including a lack of data to demonstrate societal value, complex modeling techniques that require advanced capabilities, uncertain value estimates, and lack of alignment with current approaches. At present, it appears that only England and Sweden have started to actively address HTA and contracting for antibiotics as a priority.ConclusionsPreliminary findings suggested that efforts and progress on modifying HTA and contracting of antibiotics have been heterogeneous so far. The forum will shed further light on possible ways forward within the two value assessment approaches of clinical added benefit and quality-adjusted life years.
PP151 Establishing Health Technology Assessment Impact Evaluation With Stakeholder Input From Day One
Authors: Poole Ruth Louise , Hughes Sophie , Elston Lauren , Myles Susan 
Published: December 2019

IntroductionHealth Technology Wales (HTW) is a relatively new Health Technology Assessment (HTA) agency which focuses on non-medicines. In common with other HTA organizations, it identifies and appraises a range of technologies. However, HTW is also looking beyond the publication of guidance, to assess the adoption of advice and its eventual impact.MethodsHTW commissioned development of an Evaluation Plan from independent experts (Matter of Focus). A literature review was carried out to inform an options appraisal of methods for assessing impact. The selected approach was Contribution Analysis, which estimates the counterfactual through engagement of stakeholders.ResultsWhilst it is too early to report the full impact of HTW's guidance, a number of activities have taken place to prepare for evaluation. The core HTW team developed a series of logic models to describe the anticipated impact, the mechanisms by which it would be achieved, and key assumptions. Stakeholders were consulted for insight from a range of perspectives, and to manage expectations. This was achieved through individual interviews, presentation and discussion at committee meetings, and the sharing of written materials for feedback. This information was collated to populate bespoke software (OutNav). The collection of data relating to processes, outputs and outcomes is already an ongoing routine task of researchers and support staff.ConclusionsHTW has an opportunity to build impact evaluation into its culture from the beginning. This will facilitate the future reporting of HTW's influence using a well-designed, evidence-based approach. Furthermore, this pioneering work will clearly demonstrate the value of HTA to funders, commissioners, governments, and other decision-making bodies.