Health Economics Research Research Articles

PNS356 PAYERS RELATED ISSUES ARISING FROM THE DEVELOPMENT OF PHARMACEUTICAL PRODUCTS AT PRE-LAUNCH

Pre-launch stage of pharmaceutical product development consists of 3 components; Target Product Profile (TPP), Product Development Plan (PDP) and Design of Clinical Trials (DOCT). Involving payers at this stage is now a requirement by some Health Technology Assessment (HTA) bodies, sponsors and policy-makers. The study investigated payer’s related issues arising from involving payers at early stage of pharmaceutical product development. Questionnaire was administered at two different settings: Market Access (MA) and Health Economics and Outcomes Research (HEOR) Conference ISPOR 2015 and MA educational course European Market Access University Diploma (EMAUD) held in Paris. They were asked payers’ related issues arising from TPP, PDP and DOCT. Participants responded under four domains: evidence requirements, manufacturer’s related issues, payer’s related issues and unmet needs. Thematic analysis used to investigate payers’ related issues arising from involving payers at this level, 50 professionals participated in this study. At DOCT level, it showed that the main issue experienced by payers was evidence requirements making 72% (31) other issues experienced were; unmet needs 14% (6); payers related issues 12% (5). Manufacturers’ related issues had least percentage with only 2% (1). At TPP level, the main issue experienced was unmet needs 36% (16), followed by payers’ issues 34% (15) and evidence generation 25% (11). Just like DOCT level, manufacturer’s related issues was 5% (2) not a major issue at TPP. At PDP level, payers’ related issue was the major issue 53% (18), while evidence requirements and manufacturers related issues had the same response with 18% (6). Stakeholders are to work on evidence generation requirements at DOCT level, and should focus on payers’ issues at PDP level and at TPP level. Attention are to be paid to unmet needs and payers’ issues. This may help payers to be involved in early pharmaceutical products development effectively.

Reflections on the ISPOR Special Task Force on U.S. Value Frameworks: Implications of a Health Economics Approach for Managed Care Pharmacy.

In 2016, The Professional Society for Health Economics and Outcomes Research (ISPOR) formed a special task force (STF) to review approaches and methods to support the definition and use of high-quality U.S. value frameworks. As the leadership group of that initiative, we present our perspective, focusing on implications for the managed care pharmacy community. Our reflections are organized by 9 key observations and conclude with a summary recommendation. We begin by emphasizing the importance of distinguishing among "perspectives" and "decision contexts." Possible perspectives include patient, payer, provider, health care sector, and societal. Decision contexts range from formulary inclusion to guideline development to clinical shared decision making, and multiple perspectives can be taken on each of these decisions. The STF focused on value in the context of including a new medicine in a formulary and, thus, health plan, using a health economics approach that compares marginal benefit (gross value) and marginal (opportunity) cost, yielding the net value. Health care is unique compared with other markets. While economists often use market purchases as indicators of value, they also recognize that this does not work well in health care, since most patent-protected drugs are covered by insurance. To assess the likely health and economic impact, health economists often employ cost-effectiveness analysis, using the quality-adjusted life-year (QALY), a metric that combines mortality and morbidity into a single preference-based index. We strongly endorse the STF's recommendation that payers should use the cost-per-QALY metric as a starting point. However, like the STF, and many of those stakeholders who provided input, we recognize that this metric has some limitations in theory and in practice. Nonetheless, the cost-per-QALY metric is a pragmatic tool that can be augmented to address some of its limitations by integrating other elements of value, particularly those related to uncertainty, such as financial risk protection, health risk protection, the value of hope, real option value, and the value of knowing. The resulting adjusted ratio can be compared with a willingness-to-pay threshold or combined in a measure of net monetary benefit. Alternatively, the array of elements can be valued using multi-criteria decision analysis. We end with the key recommendation that further development and testing of these promising approaches is needed to improve the deliberative process of health technology assessment. DISCLOSURES: No outside funding supported the writing of this article. The authors are leaders of the ISPOR Special Task Force on U.S. Value Frameworks. Willke is employed by ISPOR. Garrison and Neumann have nothing to disclose. The opinions expressed in this article should be considered as belonging only to the authors.

Developing an intervention around referral and admissions to intensive care: a mixed-methods study

BackgroundIntensive care treatment can be life-saving, but it is invasive and distressing for patients receiving it and it is not always successful. Deciding whether or not a patient will benefit from intensive care is a difficult clinical and ethical challenge.ObjectivesTo explore the decision-making process for referral and admission to the intensive care unit and to develop and test an intervention to improve it.MethodsA mixed-methods study comprising (1) two systematic reviews investigating the factors associated with decisions to admit patients to the intensive care unit and the experiences of clinicians, patients and families; (2) observation of decisions and interviews with intensive care unit doctors, referring doctors, and patients and families in six NHS trusts in the Midlands, UK; (3) a choice experiment survey distributed to UK intensive care unit consultants and critical care outreach nurses, eliciting their preferences for factors used in decision-making for intensive care unit admission; (4) development of a decision-support intervention informed by the previous work streams, including an ethical framework for decision-making and supporting referral and decision-support forms and patient and family information leaflets. Implementation feasibility was tested in three NHS trusts; (5) development and testing of a tool to evaluate the ethical quality of decision-making related to intensive care unit admission, based on the assessment of patient records. The tool was tested for inter-rater and intersite reliability in 120 patient records.ResultsInfluences on decision-making identified in the systematic review and ethnographic study included age, presence of chronic illness, functional status, presence of a do not attempt cardiopulmonary resuscitation order, referring specialty, referrer seniority and intensive care unit bed availability. Intensive care unit doctors used a gestalt assessment of the patient when making decisions. The choice experiment showed that age was the most important factor in consultants’ and critical care outreach nurses’ preferences for admission. The ethnographic study illuminated the complexity of the decision-making process, and the importance of interprofessional relationships and good communication between teams and with patients and families. Doctors found it difficult to articulate and balance the benefits and burdens of intensive care unit treatment for a patient. There was low uptake of the decision-support intervention, although doctors who used it noted that it improved articulation of reasons for decisions and communication with patients.LimitationsLimitations existed in each of the component studies; for example, we had difficulty recruiting patients and families in our qualitative work. However, the project benefited from a mixed-method approach that mitigated the potential limitations of the component studies.ConclusionsDecision-making surrounding referral and admission to the intensive care unit is complex. This study has provided evidence and resources to help clinicians and organisations aiming to improve the decision-making for and, ultimately, the care of critically ill patients.Future workFurther research is needed into decision-making practices, particularly in how best to engage with patients and families during the decision process. The development and evaluation of training for clinicians involved in these decisions should be a priority for future work.Study registrationThe systematic reviews of this study are registered as PROSPERO CRD42016039054, CRD42015019711 and CRD42015019714.FundingThe National Institute for Health Research Health Services and Delivery Research programme. The University of Aberdeen and the Chief Scientist Office of the Scottish Government Health and Social Care Directorates fund the Health Economics Research Unit.

Changes in health inequality for diabetes among middle-aged and older people aged 45 years and older in China from 2011 to 2015: a systematic analysis

BackgroundSocioeconomic factors have important roles in the prevalence of diabetes. However, there is insufficient evidence to confirm trends in income-related inequality in diabetes and their determinants. This study aimed to measure income-related health inequality among middle-aged and older patients with diabetes in China from 2011 to 2015, and to determine its causes. MethodsThe data for this study were obtained from the China Health and Retirement Longitudinal Study. A total of 48 519 Chinese patients aged 45 years and older were included (15 457 in 2011, 16 576 in 2013, and 16 486 in 2015). A principal component analysis was performed to measure asset-based economic status. The concentration index was used to measure income-related inequality in patients with diabetes. In addition, we decomposed the concentration index to identify factors that explained wealth-related inequality in patients with diabetes. FindingsThe prevalence of self-reported diabetes was 5·61% (867 of 15 457) in 2011, 7·49% (1241 of 16 576) in 2013, and 8·99% (1482 of 16 486) in 2015. The concentration indices for diabetes were 0·1359 (95% CI 0·0525–0·0597) in 2011, 0·1207 (0·0709–0·0789) in 2013, and 0.1021 (0·0855–0·0942) in 2015, indicative that diabetes affects the rich more than the poor. Decomposition of the concentration index showed that urban area (39·38%), body-mass index (31·16%), education (7·28%), and geographical region (6·09%) were factors that affected health inequality for diabetes in 2015. However, this health inequality decreased with higher age (−29·93%) in 2015. InterpretationThere are health inequities in diabetes in which the disease affects the rich more than the poor. Policies associated with health equity should be facilitated. FundingThis study was funded by the NHC Key Laboratory of Health Economics and Policy Research (Shandong University, Jinan, China) and the National Natural Science Foundation of China (81402761).

1095P - RUBIH2 - Use of NGS in haematological malignancies: From real world data to national recommendations, an innovative program to evaluate the impact of healthcare technology on patient care

BackgroundKnowledge of molecular abnormalities in haematological malignancies led to better understanding of their role in disease development, progression and resistance to treatments. However, effective impact of NGS analyses need to be evaluated. RuBIH2 programme aims to determine appropriate prescription, clinical utility and validity, cost and territorial organisation of NGS under a governmental funded “Programme de Recherche Médico-Economique” (Health Economics Research Program). MethodsWe considered 5 haematological malignancies: myelodysplasia, acute lymphoid leukaemia, acute myeloid leukaemia, lymphoma and lymphoproliferative disorders and myeloproliferative disorders. 26 French biomolecular platforms are involved. The program is split into 4 work packages (WP). WP1: micro-costing, WP2: appropriate prescribing guidelines, WP3: evaluation of clinical validity, WP4: recommendations on national organization. ResultsWP1: is a micro-costing of NGS on 5 biomolecular platforms to assess production cost depending on the volume of analyses performed, type of pathology and panel size. Based on a bottom-up approach and onsite observations, we calculated an average mean cost. WP2: is to define recommended diagnostic tests according to pathologies and patients’ characteristics. National key opinion leaders (clinicians and biologists) defined a NGS minimal panel depending on therapeutic possibilities. Biological analyses performed at diagnosis, relapse or during follow-up will be classified as mandatory, recommended, under evaluation or obsolete. WP3: is a real-world data study of NGS analyses carried out by 26 biomolecular platforms. Biological and clinical information are collected in an eCRF. Analysis will describe the impact of NGS on patients’ pathways. WP4: will integrate data collected during WP 1-3 to define an optimal national organization and bundled payment scheme. ConclusionsFinal objective is to improve patient care and access to NGS based on better stratification and definition of analyses to perform at each stage of patient’s care pathways: diagnostic, relapse and follow-up. Clinical trial identificationNCT03750994. Legal entity responsible for the studyAssistance Publique Hôpitaux de Paris. FundingDirection Générale de l’Offre de Soins (DGOS) - French Ministry of Health. DisclosureAll authors have declared no conflicts of interest.

Endoscopic ultrasound staging in patients with gastro-oesophageal cancers: a systematic review of economic evidence

BackgroundThe sensitivity of endoscopic ultrasound (EUS) in staging gastro-oesophageal cancers (GOCs) has been widely studied. However, the economic evidence of EUS staging in the management of patients with GOCs is scarce. This review aimed to examine all economic evidence (not limited to randomised controlled trials) of the use of EUS staging in the management of GOCs patients, and to offer a review of economic evidence on the costs, benefits (in terms of GOCs patients’ health-related quality of life), and economic implications of the use of EUS in staging GOCs patients.MethodsThe protocol was registered prospectively with PROSPERO (CRD42016043700; http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42016043700). MEDLINE (ovid), EMBASE (ovid), The Cochrane Collaboration Register and Library (including the British National Health Service Economic Evaluation Database), CINAHL (EBSCOhost) and Web of Science (Core Collection) as well as reference lists were systematically searched for studies conducted between 1996 and 2018 (search update 28/04/2018). Two authors independently screened the identified articles, assessed study quality, and extracted data. Study characteristics of the included articles, including incremental cost-effectiveness ratios, when available, were summarised narratively.ResultsOf the 197 articles retrieved, six studies met the inclusion criteria: three economic studies and three economic modelling studies. Of the three economic studies, one was a cost-effectiveness analysis and two were cost analyses. Of the three economic modelling studies, one was a cost-effectiveness analysis and two were cost-minimisation analyses. Both of the cost-effectiveness analyses reported that use of EUS as an additional staging technique provided, on average, more QALYs (0.0019–0.1969 more QALYs) and saved costs (by £1969–£3364 per patient, 2017 price year) compared to staging strategy without EUS. Of the six studies, only one included GOCs participants and the other five included oesophageal cancer participants.ConclusionsThe data available suggest use of EUS as a complementary staging technique to other staging techniques for GOCs appears to be cost saving and offers greater QALYs. Nevertheless, future studies are necessary because the economic evidence around this EUS staging intervention for GOCs is far from robust. More health economic research and good quality data are needed to judge the economic benefits of EUS staging for GOCs.PROSPERO Registration NumberCRD42016043700.

Psychometric Design of a Questionnaire for the Prevention of Induced Demand for Medicine Prescription

Background: Unnecessary demand for healthcare services for patients is a major concern in health economics research, and social science researchers primarily use questionnaires. The present study aimed to evaluate the reliability and validity of the questionnaire of the prevention of induced demand for medicine prescription. Methods: This descriptive study was conducted after designing the primary questionnaire (63 items). The reliability and validity of the questionnaire were assessed by determining the face validity, content validity, construct validity, and reliability. Results: Initially, no items were eliminated in the qualitative assessment of face validity. To determine the content validity, six items were integrated due to overlapping, and 34 items remained. Principal component analysis revealed a three-factor solution to provide the best fit. Intraclass correlation and Cronbach's alpha for each component of the questionnaire confirmed its reliability. Conclusion: In order for valid and reliable questionnaires, the views of the target group and experts must be considered and all the psychometric stages should be accomplished. Due to the differences in various studies, a single questionnaire cannot be used in every research.

Role of Health Economics Research in Implementing Saudi Arabia’s Health Sector Transformation Strategy Under Vision-2030

Health economics analyses play a crucial role in providing health policy makers and planners with the relevant information required to maximize the use of available resources. Health system reforms introduced in Saudi Arabia have recognized the application of health economic theories in making policy decisions and many of the health system strategies proposed under the Saudi vision-2030 have health economic ramifications. Since the health system has undergone a rapid transition leading to new set of health problems related to non-communicable diseases and life style disorders, the country needs more cost-effective strategies to improve maximum health gains and reduce future financial burden of the government. The paper highlights some reflections on the role and relevance of health economics and health economic research in implementing various strategies proposed under the vision. The paper also provides implications of developing health economics knowledge among physicians and how such knowledge can be applied to evidence based decision making on the use of health resources. It recommends the need for creation of opportunities for development of health economics and integration of health economics discipline into medical education curriculum in Saudi Arabia. Keywords: health economics, health resources, Saudi vision-2030, transformation strategy DOI : 10.7176/JESD/10-18-12 Publication date :September 30 th 2019

Measuring, valuing and including forgone childhood education and leisure time costs in economic evaluation: Methods, challenges and the way forward

Economic evaluations carried out to inform the allocation of finite public funds ought to take into account all relevant costs and benefits. When such evaluations adopt a societal perspective, it is important that they include ‘time-related’ costs arising from productivity and leisure time losses due to receipt of care, ill health or both. For programmes that relate to children, similar costs arise from forgone time, though there is a distinct lack of insights into how such costs should be identified, measured and valued. We set out to explore how forgone time—including absence from formal education and childhood leisure time—can be estimated and incorporated into economic evaluations. To do so, we look at theories and approaches to time valuation proposed in different disciplines and we discuss their suitability for use in health economics research. We find that, while there is a sizeable literature on time valuation methods in education, labour and transportation economics, much of this is not directly applicable to economic evaluation of health care interventions for children. We identify gaps in existing methods and practice, we outline challenges in moving forwards and we provide a list of considerations aiming to assist researchers in deciding whether, and how, to include foregone time-related costs in economic evaluation.

Usability of existing alcohol survey data in South Africa: a qualitative analysis

ObjectiveThis paper assesses the usability of existing alcohol survey data in South Africa (SA) by documenting the type of data available, identifying what possible analyses could be done using these...

The Finnish psychiatric birth cohort consortium (PSYCOHORTS) – content, plans and perspectives

Background: Psychiatric disorders tend to be developmental, and longitudinal settings are required to examine predictors of psychiatric phenomena. Replicating and combining data and results from different birth cohorts, which are a source of reliable data, can make research even more valuable. The Finnish Psychiatric Birth Cohort Consortium (PSYCOHORTS) project combines birth cohorts in Finland.Aim: The aim of this paper is to introduce content, plans and perspectives of the PSYCOHORTS project that brings together researchers from Finland. In addition, we illustrate an example of data harmonization using available data on causes of death.Content: PSYCOHORTS includes eight Finnish birth cohorts. The project has several plans: to harmonize different data from birth cohorts, to incorporate biobanks into psychiatric birth cohort research, to apply multigenerational perspectives, to integrate longitudinal patterns of marginalization and inequality in mental health, and to utilize data in health economics research. Data on causes of death, originally obtained from Finnish Cause of Death register, were harmonized across the six birth cohorts using SAS macro facility.Results: Harmonization of the cause of death data resulted in a total of 21,993 observations from 1965 to 2015. For example, the percentage of deaths due to suicide and the sequelae of intentional self-harm was 14% and alcohol-related diseases, including accidental poisoning by alcohol, was 13%.Conclusions: PSYCOHORTS lays the foundation for complex examinations of psychiatric disorders that is based on compatible datasets, use of biobanks and multigenerational approach to risk factors, and extensive data on marginalization and inequality.

Consensus document for invasive coronary physiologic assessment in Asia-Pacific countries

Currently, invasive physiologic assessment such as fractional flow reserve is widely used worldwide with different adoption rates around the globe. Patient characteristics and physician preferences often differ in the Asia-Pacific (APAC) region with respect to treatment strategy, techniques, lesion complexity, access to coronary physiology and imaging devices, as well as patient management. Thus, there is a need to construct a consensus document on recommendations for use of physiology-guided percutaneous coronary intervention (PCI) in APAC populations. This document serves as an overview of recommendations describing the best practices for APAC populations to achieve more consistent and optimal clinical outcomes. A comprehensive multiple-choice questionnaire was provided to 20 interven- tional cardiologists from 10 countries in the APAC region. Clinical evidence, tips and techniques, and clinical situations for the use of physiology-guided PCI in APAC were reviewed and used to propose key recommendations. There are suggestions to continue to develop evidence for lesion and patient types that will benefit from physiology, develop directions for future research in health economics and local data, develop appropriate use criteria in different countries, and emphasize the importance of education of all stakeholders. A consensus recommendation to enhance the penetration of invasive physiology-based therapy was to adopt the 5E approach: Evidence, Education, Expand hardware, Economics and Expert consensus. This consensus document and recommendations support interventional fellows and cardiologists, hospital administrators, patients, and medical device companies to build confidence and encourage wider implementation of invasive coronary physiology-guided therapy in the APAC region.

1269-P: Assessing the Performance of the UKPDS 82 Risk Equations to Predict Cardiovascular Events in the DECLARE-TIMI 58 Trial Population

Risk equations (RE) from the UK Prospective Diabetes Study (UKPDS) remain the most commonly used within economic models of type 2 diabetes mellitus (T2DM). However, clinical practice has evolved since UKPDS reported and the applicability of these RE to contemporary T2DM patients is uncertain. The Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial assessed cardiovascular (CV) outcomes in a broad T2DM population treated with dapagliflozin (DAPA) versus placebo (PLA). This study aimed to assess the performance of the UKPDS 82 RE in the DECLARE-TIMI 58 population. RE for myocardial infarction (MI), heart failure (HF) and stroke were applied to baseline characteristics and 12-month effects of DAPA versus PLA on HbA1c, weight and blood pressure from DECLARE-TIMI 58. Predicted annual probabilities were converted to event rates per 1,000-person years and associated relative risks (RR) for DAPA versus PLA derived for comparison to trial outcomes. Due to misalignment of the UKPDS and DECLARE-TIMI 58 endpoints, predictions of congestive heart failure were compared to observed incidence of hospitalization for HF and stroke to ischemic stroke, respectively. Predicted (study reported) rates per 1,000 person years for MI, HF and stroke were 8.15 (11.7), 2.47 (6.20) and 3.28 (6.90) for DAPA, and 8.53 (13.2), 2.59 (8.50) and 3.46 (6.80) for PLA. Predicted RR of MI, HF and stroke for DAPA versus PLA were 0.96, 0.95, 0.95, respectively, compared to reported hazard ratios of 0.89 (95% CI: 0.77, 1.01), 0.73 (0.61, 0.88) and 1.01 (0.84, 1.21) in DECLARE-TIMI 58. UKPDS 82 RE did not predict the reduction in CV events demonstrated for DAPA versus PLA based on risk factor improvements observed in DECLARE-TIMI 58. These findings add to a growing body of evidence that suggests the CV effects of sodium-glucose co-transporter inhibitors such as DAPA cannot be fully described via treatment-induced changes in conventional prognostic factors. Disclosure P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. V. Foos: Employee; Self; Health Economics and Outcomes Research Ltd., IQVIA. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. B. Kartman: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. C. Edmonds: Employee; Self; AstraZeneca. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. Funding AstraZeneca

1213-P: Assessing the Performance of Cardiovascular Risk Equations in the DECLARE-TIMI 58 Population

Sodium-glucose co-transporter inhibitors have demonstrated reduced incidence of cardiovascular (CV) events, which cannot be fully explained by effects on HbA1c, body weight or blood pressure. Type 2 diabetes mellitus (T2DM) economic models link treatment-related changes in risk factor levels to long-term incidence of CV events via risk equations (RE). This study assessed the performance of commonly used CV RE in T2DM to the CV outcomes trial DECLARE-TIMI 58. Ten sets of RE were coded in MS-Excel (ADVANCE, ARIC, BRAVO, Framingham, Fremantle, New Zealand CVD, QRisk3, Swedish NDR, UKPDS 68 and 82) to predict annual probabilities of CV events and applied to baseline characteristics and 1-year treatment effects (HbA1c, weight and blood pressure) for dapagliflozin (DAPA) versus placebo (PLA) from DECLARE-TIMI 58. Predicted event rates for myocardial infarction (MI), heart failure (HF) and stroke and the relative risks (RR) associated with DAPA versus PLA were estimated and compared to the closest reported trial outcome. Of the ten sets of RE, seven predicted composite CV outcomes, demanding assumptions to predict risk of individual events; only UKPDS and BRAVO predicted all three events. When comparing trial observations against predictions averaged across RE, correlation was greater for absolute event rates (R2: 0.92) than RRs (R2: 0.42). ARIC, Fremantle and New Zealand RE considerably overpredicted risk of MI and stroke compared to the trial. RE typically underpredicted the effect of DAPA on HF (average predicted RR: 0.89 versus reported hazard ratio 0.73, CI: 0.61 to 0.88) and MI (average predicted RR: 0.93 versus reported hazard ratio 0.89, CI: 0.77 to 1.01). Existing methods of CV risk prediction evaluated in this study did not accurately predict the treatment benefits observed in DECLARE-TIMI 58. The development of DECLARE-TIMI 58-specific risk equations may be required to robustly evaluate the long-term clinical and economic impact of DAPA in T2DM. Disclosure P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. V. Foos: Employee; Self; Health Economics and Outcomes Research Ltd., IQVIA. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. B. Kartman: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. C. Edmonds: Employee; Self; AstraZeneca. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. Funding AstraZeneca

15-OR: Renal Outcomes from the DECLARE-TIMI 58 Trial: Quantifying the Health-Care Implications

Chronic kidney disease (CKD) and end stage renal disease (ESRD) pose a significant global health burden. Approximately 40% of people with type 2 diabetes develop CKD. The Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial showed a reduced rate of the composite endpoint of sustained decrease of ≥40% in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73m2, ESRD, or renal death when comparing dapagliflozin (DAPA) to placebo (PBO) (hazard ratio 0.53; 95% CI 0.43, 0.66). This study aimed to quantify the implications of renal outcomes from DECLARE-TIMI 58, in terms of direct healthcare costs and resource use. DECLARE-TIMI 58 event rates were used to characterize expected numbers of patients experiencing sustained decrease of ≥40% in eGFR to <60 mL/min/1.73m2 (‘CKD progression’) or ESRD, per 1,000 patients over a 4-year time horizon. Renal replacement therapy (RRT) was assumed following the incidence of ESRD events only and the distribution of RRT modalities based on U.S. Renal Data. Published annual U.S. costs (2017 $) of ESRD and excess healthcare associated with CKD stage 3 versus CKD stage 2 were applied and discounted at 3% annually. Per 1,000 patients, PBO was associated with 25.6 CKD progression events and 2.4 ESRD events over four years, while DAPA was associated with 11.8 (-46%) and 1.6 (-67%) fewer events, respectively. Consequently, over 4 years DAPA was estimated to avoid 1,126 days of RRT per 1,000 patients, of which over 70% relate to a need for dialysis. The estimated cost of CKD progression and ESRD associated with PBO was $460,277 per 1,000 patients over 4 years, while costs associated with DAPA were an estimated $285,444 lower (-62% versus PBO). Economic modelling utilizing renal outcomes data from DECLARE-TIMI 58 indicate that treatment with DAPA may translate into renal cost savings within a short-term horizon. Potential delays to ESRD may have a more profound impact on patients’ quality of life, cost savings, and service delivery over the longer-term. Disclosure P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. B. Kartman: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. C. Edmonds: Employee; Self; AstraZeneca. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. Funding AstraZeneca

2355-PUB: Discontinuation of Dapagliflozin in DEPICT-1 and DEPICT-2 Led to Clinically Meaningful Increases in HbA1c and Body Weight

Concerns about hypoglycaemia and weight gain are barriers to treatment adherence, and consequently glucose control, in type 1 diabetes (T1D). In adults inadequately controlled by insulin alone, DEPICT-1 and DEPICT-2 phase 3 trials showed statistically significant decreases in HbA1c, glycaemic variability and body weight for adjunct dapagliflozin (DAPA), along with moderate reduction in insulin requirements. As adherence to T1D treatment can be a daily challenge, understanding the implications of discontinuation is important. This study evaluated changes in HbA1c, weight and insulin dose following discontinuation of DAPA in the DEPICT trials. Data were analyzed from patients discontinuing DAPA (5 mg or 10 mg, added to insulin) at any point in DEPICT-1 or DEPICT-2 (unplanned or end of study). Annualized rates of change in HbA1c (%) and weight (kg) following discontinuation of DAPA were estimated via linear regression and trajectories derived from mean rates of change. Insulin doses were summarized before and after discontinuation and correlated to analyzes of weight and HbA1c. The main reasons for unplanned discontinuation of DAPA were adverse events and patient withdrawal of consent. Following DAPA discontinuation, annualized changes in HbA1c and weight were +0.99% (95% CI: 0.39, 1.59) and +3.75Kg (1.65, 5.86), respectively (N=91). Mean insulin dose two weeks post-discontinuation was higher than two weeks prior to discontinuation (5mg: +4.0 IU, 10mg: +4.4 IU). These estimates directly contrast to observed reductions in HbA1c, weight and insulin dose associated with DAPA treatment. Discontinuation of DAPA led to significant increases in HbA1c and weight, in addition to higher insulin doses soon after discontinuation. Enabling ongoing DAPA treatment may benefit patients due to the detrimental impact of poor glycaemic control and weight gain on retinopathy, nephropathy and cardiovascular disease shown in long-term T1D studies, such as DCCT and EDIC. Disclosure J. Gordon: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, GlaxoSmithKline plc., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Takeda Canada, Takeda Pharmaceutical Company Limited. T. Danne: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis. Speaker's Bureau; Self; Dexcom, Inc. L.M. Beresford-Hulme: None. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. A. Tank: Employee; Self; AstraZeneca. C. Edmonds: Employee; Self; AstraZeneca. F.A. Thoren: Employee; Self; AstraZeneca. M.F. Scheerer: Employee; Self; AstraZeneca. P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd.

2356-PUB: The Relationship between Hypoglycaemia, Weight, and Quality of Life among Patients with Type 1 Diabetes: Observations from the DEPICT-2 Trial

Insulin-treatment in type 1 diabetes mellitus (T1DM) is associated with elevated risk of hypoglycaemia and weight gain, which may act as a barrier to achieving optimal glycaemic control. For patients inadequately controlled by insulin alone, adjunct dapagliflozin can reduce body weight and improve glycaemic control without increased risk of hypoglycaemia. This study aimed to empirically quantify the inter-relationships between hypoglycaemia, body mass index (BMI) and quality of life using DEPICT-2 trial data. A two-stage linear regression framework evaluated (1) the relationship between hypoglycaemic fear score (HFS) and the occurrence of severe hypoglycaemia, the number of documented symptomatic events and patient age, and (2) the relationship between health-related utility (EQ-5D) and prognostic factors for utility, including HFS and BMI. Model selection was based on clinically-relevant factors. A linked evidence approach correlated the relationship between treatment, hypoglycaemia incidence and HbA1c over 52-weeks, to the relationships captured within the regression models. HFS increased as a function of incidence of severe hypoglycaemia (coefficient estimate (CE): 14.62, p=0.004) and frequency of symptomatic events (log transposed, CE: 1.32, p=0.0026). In turn, increased HFS and increased BMI were both independently associated with a significant reduction in utility (CE 0.0024, p<0.001 and 0.0026, p=0.0016 respectively). In DAPA-treated patients, attainment of target glycaemic control was not associated with an increased rate of hypoglycaemic events. This study demonstrates that fear of hypoglycaemia, driven by increased incidence of hypoglycaemia, and BMI are significant determinants of quality of life for people with T1DM. These findings support the role of dapagliflozin in T1DM management, which was associated with achievement of glycaemic control targets and weight loss, without increased hypoglycaemia. Disclosure J. Gordon: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, GlaxoSmithKline plc., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Takeda Canada, Takeda Pharmaceutical Company Limited. L.M. Beresford-Hulme: None. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. A. Tank: Employee; Self; AstraZeneca. C. Edmonds: Employee; Self; AstraZeneca. P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd.

A chronological map of 308 physical and mental health conditions from 4 million individuals in the English National Health Service

SummaryBackgroundTo effectively prevent, detect, and treat health conditions that affect people during their lifecourse, health-care professionals and researchers need to know which sections of the population are susceptible to which health conditions and at which ages. Hence, we aimed to map the course of human health by identifying the 50 most common health conditions in each decade of life and estimating the median age at first diagnosis.MethodsWe developed phenotyping algorithms and codelists for physical and mental health conditions that involve intensive use of health-care resources. Individuals older than 1 year were included in the study if their primary-care and hospital-admission records met research standards set by the Clinical Practice Research Datalink and they had been registered in a general practice in England contributing up-to-standard data for at least 1 year during the study period. We used linked records of individuals from the CALIBER platform to calculate the sex-standardised cumulative incidence for these conditions by 10-year age groups between April 1, 2010, and March 31, 2015. We also derived the median age at diagnosis and prevalence estimates stratified by age, sex, and ethnicity (black, white, south Asian) over the study period from the primary-care and secondary-care records of patients.FindingsWe developed case definitions for 308 disease phenotypes. We used records of 2 784 138 patients for the calculation of cumulative incidence and of 3 872 451 patients for the calculation of period prevalence and median age at diagnosis of these conditions. Conditions that first gained prominence at key stages of life were: atopic conditions and infections that led to hospital admission in children (<10 years); acne and menstrual disorders in the teenage years (10–19 years); mental health conditions, obesity, and migraine in individuals aged 20–29 years; soft-tissue disorders and gastro-oesophageal reflux disease in individuals aged 30–39 years; dyslipidaemia, hypertension, and erectile dysfunction in individuals aged 40–59 years; cancer, osteoarthritis, benign prostatic hyperplasia, cataract, diverticular disease, type 2 diabetes, and deafness in individuals aged 60–79 years; and atrial fibrillation, dementia, acute and chronic kidney disease, heart failure, ischaemic heart disease, anaemia, and osteoporosis in individuals aged 80 years or older. Black or south-Asian individuals were diagnosed earlier than white individuals for 258 (84%) of the 308 conditions. Bone fractures and atopic conditions were recorded earlier in male individuals, whereas female individuals were diagnosed at younger ages with nutritional anaemias, tubulointerstitial nephritis, and urinary disorders.InterpretationWe have produced the first chronological map of human health with cumulative-incidence and period-prevalence estimates for multiple morbidities in parallel from birth to advanced age. This can guide clinicians, policy makers, and researchers on how to formulate differential diagnoses, allocate resources, and target research priorities on the basis of the knowledge of who gets which diseases when. We have published our phenotyping algorithms on the CALIBER open-access Portal which will facilitate future research by providing a curated list of reusable case definitions.FundingWellcome Trust, National Institute for Health Research, Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Department of Health and Social Care (England), Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), Economic and Social Research Council, Engineering and Physical Sciences Research Council, National Institute for Social Care and Health Research, and The Alan Turing Institute.

Advanced Data Visualisation in Health Economics and Outcomes Research: Opportunities and Challenges.

Data visualisation techniques are valuable tools for exploring, synthesising and communicating the results of research studies. Advanced data visualisation techniques, including dynamic and interactive visualisations, are just beginning to be used in health economics and outcome research (HEOR). In HEOR, there is the potential to use these techniques both to explore methodological challenges that are central to the design and interpretation of the findings of pharmacoeconomic and outcomes research studies, but also to communicate research findings to various stakeholders. In this manuscript, we discuss opportunities and methodological challenges for data visualisation specific to HEOR, describe external barriers that may impact the use of data visualisation methods, and discuss future applications of this technology in HEOR. While there are a number of obvious applications within the data-heavy field of HEOR, caution is required to ensure that visualisations, particularly advanced ones, accurately and fairly reflect the underlying data. However, researchers will benefit from adopting these increasingly sophisticated techniques to help ensure that decisionmakers and other stakeholders can understand, digest and communicate the data-which is critical for achieving the ultimate goal of improving patient outcomes.

PNS12 WHY ADVANCING DATA VISUALIZATION DOGMA IS OUR BEST TOOL IN DISAMBIGUATING RESEARCH FINDINGS

A well-done data visualization (DV) can be worth more than a thousand words, and suboptimal visualizations can confuse or mislead viewers. Despite much published research on DV principles, defiance persists in the health economics and medical communities. This study curated principles of DV and assessed adherence to these tenants in recently published and highly circulated medical literature. DV experts were selected based on frequency of references to their works, regularity of contributions, and the publication of books or manuscripts on the topic. Tenants of DV repeated across experts comprised a master list: “The Dogma.” Literature published in 2017 by four top medical research journals (Nature, New England Journal of Medicine (NEJM), The Journal of the American Medical Association (JAMA), and The Lancet) were reviewed based on Altmetric (a measure of dissemination and influence) ranking by two researchers. DV techniques used in these articles were cross-checked with The Dogma. Modifications were developed for a sample of visualizations that were nonadherent. DV experts included Scott Berinato, Alberto Cairo, Stephen Few, Matthew Kay, Andy Kirk, Robert Kosara, Elijah Meeks, Cole Nussbaumer, Naomi Robbins, and Edward Tufte. The Dogma was structured into four categories: clarity, engagement, integrity, and messaging. Key concepts within these classifications included clutter, variety, color choice, scaling, chart selection, and annotation. Most manuscripts within the top 50 ranked by Altmetric had limited data visualizations, critical DV flaws, or no visualizations. Four manuscripts with similar but contrarily executed DV techniques were selected to evaluate in depth. Widely disseminated research is currently lacking an emphasis on DV. Adherence to DV techniques could improve the communication and exploration of relevant facts and new findings in medical research. The Dogma is not exhaustive, visualizing data – like health economics research – is a subjective art, and we did not incorporate methods of causal inference.