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Objectives: X-linked retinitis pigmentosa (XLRP) is a rare inherited retinal disease with no available treatment. Gene therapies in clinical trials will pose challenges for health technology assessment (HTA) if found to be safe and effective. We evaluated 2 of these challenges, namely acceptability and difficulties in assessing value beyond short-term patient health and healthcare savings and discounting in economic evaluation., Methods: We conducted a narrative literature review on the socioeconomic burden of XLRP to identify relevant components of value for a hypothetical gene therapy from a societal perspective and to assess their relative importance. We compared the resulting value profile against the value frameworks of three European HTA agencies. We also reviewed their guidelines on discounting and potential discounting issues specific to XLRP., Results: Much of the societal value of an XLRP gene therapy is likely to originate from productivity effects, carer spillovers, and value elements related to patient uncertainty. The evidence on these effects, however, is often limited, making it difficult for HTA agencies to assess them. Cost-effectiveness results are likely to be highly sensitive to the discount rate, and discounting will compound the effects of omitting important sources of value., Conclusions: We have identified and detailed important components of societal value, key evidence gaps, and potential discounting issues for an XLRP gene therapy, which can inform future value assessments. Many of these may apply to gene therapies in other disease areas. Revisiting existing HTA approaches is recommended to ensure these are fit for purpose for such new classes of treatment., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: A health technology assessment (HTA) does not systematically account for the circumstances and needs of children and youth. To supplement HTA processes, we aimed to develop a child-tailored value assessment framework using a multicriteria decision analysis approach., Methods: We constructed a multicriteria-decision-analysis-based model in multiple phases to create the Comprehensive Assessment of Technologies for Child Health (CATCH) framework. Using a modified Delphi process with stakeholders having broad disciplinary and geographic variation (N = 23), we refined previously generated criteria and developed rank-based weights. We established a criterion-pertinent scoring rubric for assessing incremental benefits of new drugs. Three clinicians independently assessed comprehension by pilotscoring 9 drugs. We then validated CATCH for 2 childhood cancer therapies through structured deliberation with an expert panel (N = 10), obtaining individual scores, consensus scores, and verbal feedback. Analyses included descriptive statistics, thematic analysis, exploratory disagreement indices, and sensitivity analysis., Results: The modified Delphi process yielded 10 criteria, based on absolute importance/relevance and agreed importance (median disagreement indices = 0.34): Effectiveness, Child-specific Health-related Quality of Life, Disease Severity, Unmet Need, Therapeutic Safety, Equity, Family Impacts, Life-course Development, Rarity, and Fair Share of Life. Pilot scoring resulted in adjusted criteria definitions and more precise score-scaling guidelines. Validation panelists endorsed the framework's key modifiers of value. Modes of their individual prescores aligned closely with deliberative consensus scores., Conclusions: We iteratively developed a value assessment framework that captures dimensions of child-specific health and nonhealth gains. CATCH could improve the richness and relevance of HTA decision making for children in Canada and comparable health systems., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To comprehensively identify and map an exhaustive list of value criteria for the assessment of next-generation sequencing/comprehensive genomic profiling (NGS/CGP), to be used as an aid in decision making., Methods: We conducted a systematic review to identify existing value frameworks (VFs) applicable to any type of healthcare technology. VFs and criteria were mapped to a previously published Latin American (LA) VF to harmonize definitions and identify additional criteria and or subcriteria. Based on this analysis, we extracted a comprehensive, evidence-based list of criteria and subcriteria to be considered in the design of a NGS/CGP VF., Results: A total of 42 additional VFs were compared with the LA VF, 88% were developed in high-income countries, 30% targeted genomic testing, and 16% specifically targeted oncology. A total of 242 criteria and subcriteria were extracted; 227 (94%) were fully/partially included in the LA VF; and 15 (6%) were new. Clinical benefit and economic aspects were the most common criteria. VFs oriented to genomic testing showed significant overlap with other VFs. Considering all criteria and subcriteria, a total of 18 criteria and 36 individual subcriteria were identified., Conclusions: Our study provides an evidence-based set of criteria and subcriteria for healthcare decision making useful for NGS/CGP as well as other health technologies. The resulting list can be beneficial to inform decision making and will serve as a foundation to co-create a multistakeholder NGS/CGP VF that is aligned with the needs and values of health systems and could help to improve patient access to high-value technologies., Competing Interests: Author Disclosures Author disclosure forms can be accessed in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Background: Hypertension is responsible for 8.5 million deaths from stroke, ischemic heart disease and other vascular and kidney diseases. In Algeria, hypertension (HTN) is the most common chronic disease with an estimated prevalence of 23,6%., Methods: The PACT II study is a national, observational, descriptive, cross-sectional, multicenter and non-interventional study of therapeutic strategy, conducted in Algeria on hypertensive patients treated for at least 3 months, followed by 100 specialists or general practitioners. The primary objective is to describe the hypertension management in Algeria through the distribution of patients treated for HTN through predefined levels of arterial pressure (AP) reached under treatment., Results: 2000 eligible patients were recruited in the study. 63.5% and 36.4% of patients were female and male respectively. The average age was 62.4 years ± 10.7. The most affected age group (65.2%) was between 55 to 75 years old. Most of the patients had an elevated blood pressure (BP) with 49.30 % at level III AP (130 - 139 mmHg of SBP or 80 - 89 mmHg of DBP), with 49.6% for diabetic patients and 48.8% for non-diabetic patients, then followed by 20.35% at the level IV AP (140 - 159 mmHg of SBP or 90 - 99 mmHg of DBP) with 21.4% for diabetic and 18.3% for non-diabetic patients. Also, 47.32% were at AP level III in patients with Renal failure. Regarding the achievement of the BP target, it was 17.4% for the overall population with 18,3% for diabetic's patients and only 12.64% for Renal failure patients. Additionally, the risk of cardiovascular disease (CVD) was at very high level for most patients, corresponding to 38,4 % of the overall study population. At last, PACT II study data were collected on analysis of blood pressure levels in the overall population and in cardiovascular risk (CVR) population groups such as diabetes (65%), sedentary lifestyle (53%), dyslipidemia (50%), obesity (44%), and renal failure (11.3%)., Conclusion: PACT II has made it possible to update national data relating to hypertension in Algeria. It confirmed the low level of achievement of the BP target, even if the average arterial pressure level obtained was acceptable in 76% patients with a BP level which was lower than 140 mmHg for SBP and less than 90 mmHg for DBP. Many efforts must be made, according to WHO recommendations, to improve the management of hypertensive patients and BP control in Algeria., Competing Interests: Déclaration d'intérêt Pr.D.N. a reçu des honoraires personnels de Sanofi au cours de la réalisation de cette étude, et a reçu des honoraires de consultation, des honoraires, des frais de voyage et un soutien à la recherche de la part d'Amgen, AstraZeneca, Novo Nordisk et Sanofi en dehors de ce travail soumis. S.B., T.A., K.L et A.Z. sont des employés de Sanofi. Cette étude a été menée avec le soutien du laboratoire Sanofi : collecte des données, analyse et rédaction des résultats., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: The objective of this article is to show the relationship between socio-cultural factors and the state of health of hypertension subjects followed at the Regional Hospital Center of Sokodé -Togo., Materials and Methods: . Based on a prospective cross-sectional study carried out in 2021, with 84 hypertensive patients admitted to the Regional Hospital Center of Sokodé (Togo) during this period. Data were collected using a questionnaire and processed by SPSS software., Results: .The results highlight four main socio-cultural factors related to the state of health of hypertension subjects followed at the Regional Hospital Center of Sokodé (Togo): Loneliness, conflicting relationships, ignorance of hypertension risk factors and the feeling of lack of socio-economic support., Conclusion: Taking socio-cultural factors into account in therapeutic responses is essential to avoid decompensation in hypertension subjects at the Regional Hospital Center of Sokodé (Togo)., Competing Interests: Déclaration de liens d'intérêts Les auteurs déclarent ne pas avoir de liens d'intérêts., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objectives: The objective of this study was to evaluate the cost-utility of the Oxford, CoronaVac, and Janssen COVID-19 vaccines from the perspective of the Brazilian public health system., Methods: A total of 3 microsimulation models were constructed with individual data to evaluate the 3 vaccines. The simulation contains 7 transition states that are related to the natural history of the disease. The model with a daily cycle has a time horizon of 1 year and uses data from 289 days of the pandemic. The analysis was conducted from the perspective of the Brazilian public health system considering direct medical costs. For the model inputs, outpatient and hospital databases were used with information on treated patients stratified by age. Information on mortality was also stratified based on patients' age in the mortality database (SIM). The efficacy of vaccines to reduce the likelihood of patients becoming ill was evaluated independently for each vaccine. Information on the quality of life of patients in outpatient or hospital treatment and the sequelae resulting from the disease were extracted from the literature. The main outcome of the analysis was quality-adjusted life-years (QALYs)., Results: The vaccines showed incremental cost-utility ratios ranging from R$-23 161.3/QALY (Oxford) to R$17 757.85/QALY (CoronaVac). The older the population, the lower was the incremental cost-utility ratio. Given a willingness-to-pay threshold of R$17 586/QALY, all the vaccines were considered cost-effective in the probabilistic sensitivity analysis., Conclusions: The results of the analysis by age group can help in the preparation of a vaccination prioritization plan., (Copyright © 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Introduction: The incidence of foot fractures is increasing. These types of fractures represent the most expensive group of diagnoses in the emergency department. Next to this, the need for economic evaluation studies is growing fast. The aim of this article is to provide healthcare professionals with an introduction to economic evaluation studies in the field of foot fractures., Types of Economic Evaluation Studies: Four types of economic evaluation studies exist: cost-minimization analysis (CMA), cost-benefit analysis (CBA), cost-effectiveness analysis (CEA), and cost-utility analysis (CUA). An economic evaluation study can be either trial- or model-based., Cost Assessment: When assessing costs in an economic evaluation study, three steps need to be made: identification of costs, measurement of costs, and valuation of costs., Perspective of Analysis: Two main perspectives exist in economic evaluation studies. When using a healthcare perspective, only the potential costs and benefits of an intervention for the healthcare sector are included. The societal perspective includes all potential costs, including societal costs., Synthesis of Costs and Effects and Uncertainty Analysis: The level of cost-effectiveness can be objectively expressed using the incremental cost-effectiveness ratio (ICER). This measure can be plotted in a cost-effectiveness plane and can be compared with existing regional ceiling ratios., Conclusion: Although this article is not a guideline for economic evaluations, we do want to present five tips to consider when performing an economic evaluation. Firstly, when measuring resource use, consult the Database of Instruments for Resource Use Measurements (DIRUM) to find an appropriate instrument. Secondly, when measuring utility values, use the EuroQol questionnaire if possible. Thirdly, when setting up an economic evaluation study, consult the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) database for the appropriate pharmacoeconomic guidelines. Fourthly, consult international guidelines to decide which study design is most appropriate. Finally, when performing an economic evaluation, consult a heath technology assessment (HTA) specialist from the start to ensure methodological quality., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In Kazakhstan, cancer is the second leading cause of death with a major public health and economic burden. In the last decade, cancer care and cancer medicine costs have significantly increased. To improve the efficiency and efficacy of cancer care expenditure and planning, the Kazakhstan Ministry of Health requested assistance from the World Health Organization (WHO) and the European Society for Medical Oncology (ESMO) to review its systemic cancer treatment protocols and essential medicines list and identify high-impact, effective regimens., Materials and Methods: ESMO developed a four-phase approach to review Kazakhstan cancer treatment protocols: (i) perform a systematic analysis of the country's cancer medicines and treatment protocols; (ii) cross-reference the country's cancer protocols with the WHO Model List of Essential Medicines, the ESMO-Magnitude of Clinical Benefit Scale and the European Medicines Agency's medicine availability and indications database; (iii) extract treatment recommendations from the ESMO Clinical Practice Guidelines; (iv) expert review for all cancer medicines not on the WHO Model List of Essential Medicines and the country treatment protocols., Results: This ESMO four-phase approach led to the update of the Kazakhstan national essential cancer medicines list and the list of cancer treatment protocols. This review has led to the withdrawal of several low-value or non-evidence-based medicines and a budget increase for cancer care to include all essential and highly effective medicines and treatment options., Conclusion: When applied effectively, this four-phase approach can improve access to medicines, efficiency of expenditure and sustainability of cancer systems. The WHO-ESMO collaboration illustrated how, by sharing best practices, tools and resources, we can address access to cancer medicines and positively impact patient care., Competing Interests: Disclosure EGEdV declares institutional financial support for advisory board/consultancy from Sanofi, Daiichi, Sankyo, NSABP, Pfizer and Merck, and institutional support for clinical trials or contracted research from Amgen, Genentech, Crescendo, Roche, AstraZeneca, Synthon, Nordic Nanovector, G1 Therapeutics, Bayer, Chugai Pharma, CytomX Therapeutics, Servier and Radius Health. AI is a staff member of WHO and AI alone is responsible for the views expressed in this manuscript and they do not necessarily represent the decisions, policy or views of WHO. The remaining authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The prescribing process for children with cancer is complex, and errors can occur at any step. As a result, many interventions have been used to reduce errors. However, few of them have been designed based on an understanding of the prescriber behaviour that can lead to errors. In order to design effective behaviour change interventions, it is important first to understand the prescribing process and identify prescriber behaviours that could be targeted for change., Objectives: To describe the prescribing process in a paediatric oncology ward and to identify prescriber behaviours during prescription writing that could be targeted to reduce errors., Methods: This study employed two sequential phases. First, the prescribing process was observed and then described using the hierarchical task analysis (HTA) method. Second, prescriber tasks identified from the HTA were analysed using the behaviour change wheel (BCW) approach to identify promising behaviours for change. These identified behaviours were prioritised based on information collected from four focus groups with prescribers and chart review of errors made in the ward., Results: The prescribing process was complex and involved multiple tasks performed in varying orders. Applying the BCW identified thirty-two candidate behaviours for potentially reducing prescribing errors. However, after prioritization, only two emerged as promising candidate behaviours for intervention: writing drug indications at the time of prescribing and using a pre-written order when ordering medications through electronic prescribing., Conclusions: This research suggests that two behaviours could be promising in reducing errors. Having identified these behaviours, future work could explore what needs to change with respect to individuals and their work environments to achieve the desired change in these identified behaviours., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: Immunization programs in low-income and middle-income countries (LMICs) are faced with an ever-growing number of vaccines of public health importance recommended by the World Health Organization, while also financing a greater proportion of the program through domestic resources. More than ever, national immunization programs must be equipped to contextualize global guidance and make choices that are best suited to their setting. The CAPACITI decision-support tool has been developed in collaboration with national immunization program decision makers in LMICs to structure and document an evidence-based, context-specific process for prioritizing or selecting among multiple vaccination products, services, or strategies., Methods: The CAPACITI decision-support tool is based on multi-criteria decision analysis, as a structured way to incorporate multiple sources of evidence and stakeholder perspectives. The tool has been developed iteratively in consultation with 12 countries across Africa, Asia, and the Americas., Results: The tool is flexible to existing country processes and can follow any type of multi-criteria decision analysis or a hybrid approach. It is structured into 5 sections: decision question, criteria for decision making, evidence assessment, appraisal, and recommendation. The Excel-based tool guides the user through the steps and document discussions in a transparent manner, with an emphasis on stakeholder engagement and country ownership., Conclusions: Pilot countries valued the CAPACITI decision-support tool as a means to consider multiple criteria and stakeholder perspectives and to evaluate trade-offs and the impact of data quality. With use, it is expected that LMICs will tailor steps to their context and streamline the tool for decision making., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objectives: A recent debate in health economics and outcomes research community identified option value as one of the elements warranting consideration in the assessment of medical technologies. To conduct a scoping review of contributions on option value in the healthcare sector and identify relevant conceptual aspects and methods used to incorporate it in standard economic evaluations., Methods: A systematic search was conducted up to July 2020 to identify contributions from electronic bibliographic database and gray literature. Data on the proposed definitions of option value, theoretical implications of its use in economic evaluations, and methods used to estimate it were extracted and analyzed., Results: We found 57 eligible studies. Three different definitions emerged: insurance value, real option value, and option value of survival. Focusing on the latter (24 studies), we analyzed in depth 8 empirical applications across 7 therapeutic areas. The most relevant methodological challenges were on the perspective used in economic evaluations and how to robustly manage forecasting uncertainty, update cost-effectiveness thresholds, and avoid double-counting issues. For empirical studies assessing the total value of the technology, including option value, estimates ranged from +7% to +469% of its conventional value., Conclusions: This review synthesizes theoretical and empirical aspects on option value of healthcare technologies and proposes a terminology to distinguish 3 different concepts identified. Future work should focus primarily on agreeing on whether option value should be included in economic evaluations and, if so, on developing and validating reliable methods for its ex-ante estimation., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objectives: The availability of novel, more efficacious and expensive cancer therapies is increasing, resulting in significant treatment effect heterogeneity and complicated treatment and disease pathways. The aim of this study is to review the extent to which UK cancer technology appraisals (TAs) consider the impact of patient and treatment effect heterogeneity., Methods: A systematic search of National Institute for Health and Care Excellence TAs of colorectal, lung and ovarian cancer was undertaken for the period up to April 2020. For each TA, the pivotal clinical studies and economic evaluations were reviewed for considerations of patient and treatment effect heterogeneity. The study critically reviews the use of subgroup analysis and real-world translation in economic evaluations, alongside specific attributes of the economic modeling framework., Results: The search identified 49 TAs including 49 economic models. In total, 804 subgroup analyses were reported across 69 clinical studies. The most common stratification factors were age, gender, and Eastern Cooperative Oncology Group performance score, with 15% (119 of 804) of analyses demonstrating significantly different clinical outcomes to the main population; economic subgroup analyses were undertaken in only 17 TAs. All economic models were cohort-level with the majority described as partitioned survival models (39) or Markov/semi-Markov models. The impact of real-world heterogeneity on disease progression estimates was only explored in 2 models., Conclusion: The ability of current modeling approaches to capture patient and treatment effect heterogeneity is constrained by their limited flexibility and simplistic nature. This study highlights a need for the use of more sophisticated modeling methods that enable greater consideration of real-world heterogeneity., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Introduction: The medical treatment of preeclampsia is well structured in its acute phase but the required follow-up with patients in post-partum is discussed. However, preeclampsia is associated with an increased risk of cardiovascular morbi-mortality in the long term. In order to optimize the post-partum treatment, a care program has been developed for these patients in the city of Nantes, France. This includes a check-up of the cardiovascular risks at a day hospital. Our study presents the first results of this program., Methods: The study included 134 patients who were diagnosed with preeclampsia between October 2016 and January 2019 in the Nantes area, France, and took part in the program within the year following their childbirth. A descriptive analysis was first carried out and then a multivariate logistic regression model was used to investigate the risk factors for persistent high blood pressure after preeclampsia., Results: The study detected 28 cases of persistent hypertension (20.9%), 34 cases of obesity (25.3%) and 1 case of diabetes. Hypertension was predominantly diastolic, mild and sometimes masked (35.7%). In a third of the cases (32.1%), the hypertension was secondary. High blood pressure was found to be more frequent in older patients (OR: 2.26; 95% CI: 1.25-4.11, p=0.072), patients from sub-Saharan Africa (OR: 11.52; 95% CI: 2.67-49.86, p=0.01) and multiparous patients (OR: 7.82; 95% CI: 1.15-53.21, p=0.035)., Conclusion: The study confirmed that this care program enables an earlier detection and therefore treatment of the cardiovascular risk factors of these young women., (Copyright © 2021 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Objectives: This article provides updated GRADE guidance about how authors of systematic reviews and health technology assessments and guideline developers can rate the certainty of evidence (also known as quality of the evidence or confidence in the estimates) of a body of evidence addressing test accuracy (TA) on the domains imprecision, inconsistency, publication bias, and other domains. It also provides guidance for how to present synthesized information in evidence profiles and summary of findings tables., Study Design and Setting: We present guidance for rating certainty in TA in clinical and public health and review the presentation of results of a body of evidence regarding tests., Results: Supplemented by practical examples, we describe how raters of the evidence can apply the GRADE domains inconsistency, imprecision, and publication bias to a body of evidence of TA studies., Conclusion: Using GRADE in Cochrane and other reviews as well as World Health Organization and other guidelines helped refining the GRADE approach for rating the certainty of a body of evidence from TA studies. Although several of the GRADE domains (e.g., imprecision and magnitude of the association) require further methodological research to help operationalize them, judgments need to be made on the basis of what is known so far., (Copyright © 2020 Elsevier Inc. All rights reserved.)

There has been continuous development in the field of health technology assessment (HTA) owing to the added value of HTA in supporting healthcare reimbursement decisions. Collaboration and engagement among countries in Asia has been carried out to share experiences and learning on the barriers and factors facilitating the implementation and use of HTA in policy making. A symposium on the topic of Health Technology Assessment (HTA): Selecting the Highest Value Care was held on January 10, 2019 at the National University of Singapore, during which 3 major challenges confronting HTA development in Asia were identified. The symposium also offered possible ways to overcome the challenges., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Universal healthcare coverage in low- and middle-income countries requires challenging resource allocation decisions. Health technology assessment is one important tool to support such decision making. The International Decision Support Initiative worked with the Ghanaian Ministry of Health to strengthen health technology assessment capacity building, identifying hypertension as a priority topic area for a relevant case study., Methods: Based on guidance from a national technical working group of researchers and policy makers, an economic evaluation and budget impact analysis were undertaken for the main antihypertensive medicines used for uncomplicated, essential hypertension. The analysis aimed to address specific policy questions relevant to the National Health Insurance Scheme., Results: The evaluation found that first-line management of essential hypertension with diuretics has an incremental cost per disability-adjusted life-year avoided of GH¢ 276 ($179 in 2017, 4% of gross national income per capita) compared with no treatment. Calcium channel blockers were more effective than diuretics but at a higher incremental cost: GH¢ 11 061 per disability-adjusted life-year avoided ($7189 in 2017; 160% of gross national income per capita). Diuretics provide better health outcomes at a lower cost than angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers. Budget impact analysis highlighted the potential for cost saving through enhanced price negotiation and increased use of better-value drugs. We also illustrate how savings could be reinvested to improve population health., Conclusions: Economic evaluation enabled decision makers to assess hypertension medicines in a Ghanaian context and estimate the impact of using such evidence to change policy. This study contributes to addressing challenges associated with the drive for universal healthcare coverage in the context of constrained budgets., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: The relevance of studies focusing on patient satisfaction becomes imperative for patients with cancer, who often face major changes in their lifestyles. Their perceived uncertainty in illness and their personal experiences with the services received are crucial factors for a qualitatively adequate assistance., Objectives: To assess the determinants of patient satisfaction, using a sample of 306 Bulgarian oncology outpatients., Methods: The hypotheses tested concern the extent to which patient satisfaction depends on the uncertainty in illness; the patients' assessment of technical and interpersonal skills of nurses and medical staff; the information provision; and some organizational aspects. Patients were asked to answer a questionnaire composed of internationally validated scales assessing the determinants of patient satisfaction (measured through the European Organization for Research and Treatment of Cancer), uncertainty in illness (assessed through the Mishel Uncertainty in Illness Scale), and patients' health status (assessed through the EuroQol 5-dimensional questionnaire and the visual analogue scale). An ordered logit model was run, using the level of overall patient satisfaction as a dependent variable., Results: This is one of the first studies carried out in Bulgaria for oncology patient satisfaction of subjective factors related to the frailty of the oncology patient status such as age, self-assessed health-related quality of life, and uncertainty in illness. Nevertheless, other determinants, reflecting the quality of the care provided, also have an impact on patient satisfaction, namely, the assessment of the nonmedical personnel, the perception of medical technical skills, and the access to a medical center., Conclusions: Results stress the relevance of reducing uncertainty in illness in patients with cancer by implementing a satisfactory patient-physician relationship in the management of the disease., (Copyright © 2018 ISPOR–The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Economic models are used in health technology assessments (HTAs) to evaluate the cost-effectiveness of competing medical technologies and inform the efficient use of healthcare resources. Historically, these models have been developed with specialized commercial software (such as TreeAge) or more commonly with spreadsheet software (almost always Microsoft Excel). Although these tools may be sufficient for relatively simple analyses, they put unnecessary constraints on the analysis that may ultimately limit its credibility and relevance. In contrast, modern programming languages such as R, Python, Matlab, and Julia facilitate the development of models that are (i) clinically realistic, (ii) capable of quantifying decision uncertainty, (iii) transparent and reproducible, and (iv) reusable and adaptable. An HTA environment that encourages use of modern software can therefore help ensure that coverage and pricing decisions confer greatest possible benefit and capture all scientific uncertainty, thus enabling correct prioritization of future research., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Introduction: Singapore has a robust health care system that is well known for delivering good health outcomes. In the public health care sector, subsidies and financial assistance are provided for drugs listed on the Standard Drug List and Medication Assistance Fund. Additional financing mechanisms are also available to provide further support for patients in need. With new technologies entering the market at high costs, health technology assessment (HTA) is playing an increasingly important role to inform their relative value and determine how best to allocate finite health care resources to ensure long-term sustainability of the health care system., Role of Hta: National HTA efforts are currently focused on informing subsidy decision making and improving patient access to cost-effective drugs. The Agency for Care Effectiveness (ACE) was established in 2015 to support the Ministry of Health Drug Advisory Committee make evidence-based recommendations for the public funding of drugs. Standardized HTA methods and processes have been developed in line with international best practice to ensure that ACE's evaluations are conducted in a consistent and robust manner. Since ACE's establishment, subsidies are now provided earlier within a drug's life cycle, and value-based pricing has led to more cost-effective prices being negotiated with companies to improve affordability for patients and the public health care system., Conclusion: To achieve greater impact, Singapore needs to expand its HTA capacity beyond subsidy decision making and drive appropriate care in a sustainable manner for future generations., (Published by Elsevier Inc.)

Background: Proportional hazards (PH) is an assumption often made by researchers, despite evidence of nonproportionality in a significant proportion of clinical trials. In the presence of non-PH, the interpretation of hazard ratios, medians, and landmark survival as summary measures of treatment effect can become problematic. Several recent studies have recommended restricted mean survival time (RMST) as an alternative metric for survival analysis, particularly where non-PH may apply., Objectives: To determine the current approaches of health technology assessment (HTA) agencies to value assessment in the presence of non-PH, and the extent to which RMST is accepted as an alternative measure of treatment benefit., Methods: Methodological guidelines published by 10 HTA agencies were reviewed to establish recommended approaches for presenting survival benefit from clinical trials. Published HTA reports for 23 oncology agents approved by the US Food and Drug Administration and the European Medicines Agency since 2014 were reviewed to determine how guidelines are implemented in practice and identify instances where the PH assumption was tested and RMST analyses reported., Results: Testing for non-PH is not widely incorporated into HTA except by the UK National Institute for Health and Care Excellence. RMST is used infrequently but has been used in a number of countries, particularly by agencies that focus on cost effectiveness., Conclusions: HTA agencies vary in their approaches to non-PH. Most do not routinely check the PH assumption. RMST has played a role in assessing clinical benefit within HTA, although not consistently within countries (across drugs) or across countries (for the same drug)., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Mild cognitive impairment and Alzheimer's dementia involve a grey matter disease, quantifiable by 18 F-Fluorodeoxyglucose positron emission tomography (FDG-PET), but also white matter damage, evidenced by diffusion tensor magnetic resonance imaging (DTI), which may play an additional pathogenic role. This study aimed to determine whether such DTI and PET variations are also interrelated in a high-risk population of older hypertensive patients with only subjective memory complaints (SMC). Sixty older hypertensive patients (75 ± 5 years) with SMC were referred to DTI and FDG-PET brain imaging, executive and memory tests, as well as peripheral and central blood pressure (BP) measurements. Mean apparent diffusion coefficient (ADC mean ) was determined in overall white matter and correlated with the grey matter distribution of the metabolic rate of glucose (CMRGlc) using whole-brain voxel-based analyses of FDG-PET images. ADC mean was variable between individuals, ranging from 0.82 to 1.01.10 - 3  mm 2  sec - 1 , and mainly in relation with CMRGlc of areas involved in Alzheimer's disease such as internal temporal areas, posterior associative junctions, posterior cingulum but also insulo-opercular areas (global correlation coefficient: - 0.577, p  < 0.001). Both the ADC mean and CMRGlc of the interrelated grey matter areas were additionally and concordantly linked to the results of executive and memory tests and to systolic central BP (all p  < 0.05). Altogether, our findings show that cross-sectional variations in overall white brain matter are linked to the metabolism of Alzheimer-like cortical areas and to cognitive performance in older hypertensive patients with only subjective memory complaints. Additional relationships with central BP strengthen the hypothesis of a contributing pathogenic role of hypertension.

Slovak law sets clear rules and timelines in the process of approving the price and reimbursement of drugs. During the last decade, the Ministry of Health adopted several cost-containment measures in the price and reimbursement policy. The most effective measures were the implementation of the external referencing of drug prices in 2008 and the reimbursement law in 2011. The new act introduced several regulations such as making stricter rules for the referencing of prices, setting cost per quality-adjusted life-year threshold, and defining new rules for the setting of reimbursements. On one side, implementation of these measures helped to achieve visible cost savings, but, on the other side, cost-containment policies have had some unintended consequences. In recent years, Slovakia has been facing a decreased availability of drugs because of parallel exports. As a result of the government's effort, Slovakia is the only country in the European Union that implemented a legal ban on the re-export of medicines. During the decade before 2011, many innovative drugs were included in the reimbursement system. Because of stricter legal conditions introduced in 2011, there has been a gradual shift in reimbursing innovative drugs from the standard reimbursement system to reimbursement by way of exceptions of health insurance companies. Recently, there has been an ongoing discussion on possible changes to the reimbursement law., (Copyright © 2017. Published by Elsevier Inc.)

Off-patent pharmaceuticals (OPPs) represent more than 60% of the pharmaceutical market in many emerging countries, where they are frequently evaluated primarily on cost rather than with health technology assessment. OPPs are assumed to be identical to the originators. Branded and unbranded generic versions can, however, vary from the originator in active pharmaceutical ingredients, dosage, consistency formulation, excipients, manufacturing processes, and distribution, for example. These variables can alter the efficacy and safety of the product, negatively impacting both the anticipated cost savings and the population's health. In addition, many health care systems lack the resources or expertise to evaluate such products, and current assessment methods can be complex and difficult to adapt to a health system's needs. Multicriteria decision analysis (MCDA) simple scoring is an evidence-based health technology assessment methodology for evaluating OPPs, especially in emerging countries in which resources are limited but decision makers still must balance affordability with factors such as drug safety, level interchangeability, manufacturing site and active pharmaceutical ingredient quality, supply track record, and real-life outcomes. MCDA simple scoring can be applied to pharmaceutical pricing, reimbursement, formulary listing, and drug procurement. In November 2015, a workshop was held at the International Society for Pharmacoeconomics and Outcomes Research Annual Meeting in Milan to refine and prioritize criteria that can be used in MCDA simple scoring for OPPs, resulting in an example MCDA process and 22 prioritized criteria that health care systems in emerging countries can easily adapt to their own decision-making processes., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: China is investing considerably in health care reforms to address issues in its health care system. An example is access to innovative drugs, which remains challenging because it is largely dependent on patient self-pay. Recognizing this, the government has invested considerably in its basic medical insurance. As health care expenditure increases, there are growing concerns on budget control. Several health policy tools have been discussed recently such as health technology assessment, international reference pricing, and hospital budget control tools, which can be viewed as addressing the affordability concerns of the government budget. China has also listed her health outcomes goals in "Healthy China 2020" initiative., Objectives: This article aimed to discuss the "fit-for-purpose" of these tools to address budget concerns and support China in reaching her health outcomes goals., Methods: The findings are informed by a panel discussion at ISPOR Asia Pacific 2014, literature review, and authors' experience. This review looks at the current developments in China and the considerations and implications for using these tools by drawing experiences from countries where they are used., Results: These tools are generally used in countries with advanced health care systems. China's health care spending is still below that of countries with advanced health care systems and below World Health Organization recommendation., Conclusions: China has not yet reached the "critical mass" necessary for the effective use of these tools. As China continues its health care reforms, increase in health care spending to balance the health needs of the population would be key., (Copyright © 2015. Published by Elsevier Inc.)

Patient access to new cancer drugs in the EU involves centralised licensing decisions by regulators as well as reimbursement recommendations in the context of national healthcare systems. Differences in assessment criteria and evidence requirements may result in divergent decisions at central and national levels, ultimately compromising effective access to patients. Early access decisions are particularly challenging due to the limited clinical evidence available to conclude on the benefit-risk and relative (cost-) effectiveness of new high-priced cancer drugs. We describe mechanisms to accelerate approval of promising anticancer drugs that fulfil an unmet medical need, review the experience from the European Medicines Agency, compare timelines and outcomes of reimbursement decisions in major EU markets, and discuss shortcomings of the current system, ongoing initiatives, and future steps to facilitate effective early access., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Impaired renal function may occur following multimodal treatment of cancer in childhood. Renal late effects caused by chemotherapy, renal surgery and/or radiotherapy are now well described; but little is known about their prevalence and time of development. Herein, we provide a synthesis of the different renal complications that may occur with their physiopathology in relation with specific treatment exposures. This review summarized the literature that supported the recommendations issued by the long-term follow-up group of the "Société française des cancers de l'enfant (SFCE)" for childhood cancer survivors at risk for nephrotoxicity (www.sfce.org ; www.soc-nephrologie.org/SNP/index.htm). We developed these monitoring elements and the lifestyle recommendations for all asymptomatic survivors., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Unlabelled: Hypertension in focal segmental glomerulosclerosis is frequent and responsible for the progression of the disease. It could be a circumstance of the diagnosis of FSG or a complication of the nephrotic syndrome., Purpose: To determine the prevalence of hypertension among patients with FSG diagnosed in Tunisia and to describe the profile of patients with FSG having hypertension in contrast with who do not., Patients and Methods: It was a retrospective multicentric study based on 116 patient files having FSG located in 5 specialized centers in Tunisia., Results: The prevalence of hypertension among our patients was 41%, with a feminine predominance, their mean age was 36.34 ± 15.71 years. The systolic blood pressure among the patients with hypertension was 153.18 mmHg. The nephrotic syndrome was impure due to hypertension in 14.5% of the cases. The patients affected by hypertension were more obese. Proteinuria was higher among those not having hypertension than those with it, who score an average value of 5.67 ± 4.51 g/24h, with an insignificant difference. Serum creatinine at presentation was significantly higher among patients with hypertension. Vascular lesions were present at the renal biopsy among 39.45% of patients affected by hypertension, associated with renal failure in 58.50% of patients. The etiopathogenic treatment of FSG was essentially based on steroids full dose., Conclusion: Hypertension is often present in FSG and its' treatment must be as soon as possible in order to slow the progression of kidney chronic disease., (Copyright © 2015. Published by Elsevier SAS.)

Purpose: In systemic sclerosis, hypertension is feared because it is often heralding severe renal impairment. The objective of our study was to identify the frequency of arterial hypertension and clarify its etiologies in this condition., Patients/methods: Our study was prospective. From January 2008 to May 2012, we have included all patients over the age of 16 years which featured a systemic scleroderma meeting the criteria for classification of Leroy and Medsger modified. Blood pressure was systematic and hypertension was defined as a greater than 140/90 mmHg PAS/PAD., Results: We have collected 60 patients. It was 50 women and 10 men with an average age of 41.1 ans ± 13.03. Arterial hypertension was noted in sixteen patients (26.7%) with an average age of 48.8 years ± 13.21. It was nine diffuse cutaneous systemic scleroderma of six limited cutaneous scleroderma and one case of scleroderma sine scleroderma. Etiologic research hypertension had concluded to a renal cause in 12 patients. It was five scleroderma renal crisis (SRC), three vascular nephropathies, four chronic kidney failure (CKD) including three terminals and a moderate CKD. An 'essential' so-called HTA was observed in four patients. Hypertension was a major sign that reported five cases of SRC. These patients had received treatment anti hypertensive and renal extra cleansing., Discussion: Hypertension is common in systemic scleroderma. Our data approximates of literature when its frequency and severity., Conclusion: Hypertension is a major warning sign that under no circumstances should overlook it or novo or secondary aggravation. Its support must be very early under penalty to put at stake the life-threatening in particular during the CRS., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objectives: To compare processes and timings of regulatory and subsidized access systems for medicines across seven jurisdictions within the Asia-Pacific region., Methods: A questionnaire was developed focusing on regulatory and health technology assessment-based subsidized access processes and timings in each of the seven surveyant's jurisdictions., Results: Australia and Thailand are the only two jurisdictions that formally allow the subsidized access evaluation process to be conducted in parallel with the regulatory evaluation process. Australian, Japanese, Korean, New Zealand, and Taiwanese systems afford broad coverage, whereas Chinese and Thai systems provide limited coverage for medicines under patent. Subsidized access systems for all jurisdictions except Thailand have an associated patient co-payment for each medicine/prescription. The biggest disparity across the study group relates to time from regulatory submission to subsidized access of patented medicines-ranging from just over 1 year (Japan) to a minimum of 5 years (China)., Conclusions: There is consistency across the seven jurisdictions studied in relation to regulatory and subsidized patient access processes-that is, regulatory approval is required before subsidized access review; subsidized access coverage is broad; and the cost of medicine subsidization is offset, in part, by patient co-payments. Although local differences will always exist in relation to budget and pricing negotiation, there may be efficiencies that can be applied across systems to improve time to subsidized access. Closer understanding of regulatory and subsidized access systems can lead to best-practice sharing and, ultimately, timely access and better health outcomes for patients., (Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to compare the use of cost-effectiveness analysis and cost-utility analysis in health technology assessment in Poland., Methods: We analyzed all the submissions (155) made to the Polish Agency for Health Technology Assessment in the period 2007 to 2011, with 316 intervention-comparator comparisons reporting incremental cost-effectiveness ratios (ICERs) or incremental cost-utility ratios (ICURs). We compared ICERs and ICURs when both were reported (31%), determined factors associated with reporting one or the other, and tested the precision of their assessment., Results: In 13% of the cases, ICER and ICUR led to different decisions (were on opposite sides of the willingness-to-pay threshold). Cost-effectiveness analyses were more frequently performed in oncology, offering at the same time more favorable results. It was also more frequent for longer time-horizon models, although then ICER values were on average higher., Conclusions: In Poland, cost-utility analysis is a usual approach of increasing popularity. Interestingly, although assessing ICUR requires additional assumptions, it is estimated more precisely (reported ranges of values in sensitivity analyses are narrower), especially in oncology. ICER and ICUR disagree more often than previously shown in literature. There seem to be no clear signs of biases in submissions (selecting whether to present ICER or ICUR on the basis of their values), but the current study is limited because only the values presented by manufacturers in the submission are available., (Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

As part of the global trend to address the constrained resources for population health care coverage, the concepts of pharmacoeconomics (PE) and health technology assessment (HTA) have been introduced to Asia in the last decade. Medicines are just one of numerous types of innovative technologies developed to address unmet medical need. Many of these medicines receive a great deal of attention because of their potential impact on limited health care budgets. There are a few key challenges for using PE and HTA in making informed decisions regarding the value of a given new health care technology in an Asian country. These challenges include 1) recognizing the multidimensional aspects of PE and HTA, which can include both health care and political considerations; 2) involving stakeholders (with a focus on patients) in decision making; 3) balancing short- and long-term overall benefits of innovative medicines; and 4) giving consideration to specific local cultural and health care characteristics., (Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objectives: Health care decision making, assessment, and procurement of medicines is a complex, human resource-demanding, and time-consuming process. A thorough evaluation of all factors involved is necessary to optimize the process. The objective of this study was to describe and analyze the current stage of health technology assessment (HTA) in Cyprus., Methods: Literature research and private communication with all involved parties and competent authority. Moreover, data, decisions, and recommendations of the Drug's Committee were used., Results: Cyprus is a latecomer in this field. HTA has entered a growing phase after the 2007 reform. It has not reached its full potential, and the current state is applicable only to the public sector, because of the nonexistence of a national health system. Therefore, this poses both a great challenge and a great barrier considering maximization of the value of money spent and health access equity., Conclusions: There is definitely enough space and clear necessity for further dissemination, and early successes indicate that steps should be taken toward the introduction of an HTA procedure that will cover both private and public sectors. The introduction of a national health system will further enhance the uptake of HTA, optimize the process, and use the common knowledge strategy for evidence-based decision making., (Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.)

Objectives: In 2012, the National Institute for Health and Care Excellence assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment of chronic phase chronic myelogenous leukemia (CML). Licensing of these alternative treatments was based on randomized controlled trials assessing complete cytogenetic response (CCyR) and major molecular response (MMR) at 12 months as primary end points. We use this case study to illustrate the validation of CCyR and MMR as surrogate outcomes for overall survival in CML and how this evidence was used to inform National Institute for Health and Care Excellence's recommendation on the public funding of these first-line treatments for CML., Methods: We undertook a systematic review and meta-analysis to quantify the association between CCyR and MMR at 12 months and overall survival in patients with chronic phase CML. We estimated life expectancy by extrapolating long-term survival from the weighted overall survival stratified according to the achievement of CCyR and MMR., Results: Five studies provided data on the observational association between CCyR or MMR and overall survival. Based on the pooled association between CCyR and MMR and overall survival, our modeling showed comparable predicted mean duration of survival (21-23 years) following first-line treatment with imatinib, dasatinib, or nilotinib., Conclusions: This case study illustrates the consideration of surrogate outcome evidence in health technology assessment. Although it is often recommended that the acceptance of surrogate outcomes be based on randomized controlled trial data demonstrating an association between the treatment effect on both the surrogate outcome and the final outcome, this case study shows that policymakers may be willing to accept a lower level of evidence (i.e., observational association)., (Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.)