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Background Spinal muscular atrophy (SMA) is a rare and devastating condition for which new disease-modifying treatments have recently been approved. Given the increasing importance of economic considerations in healthcare decision-making, this review summarizes the studies assessing the cost of SMA and economic evaluations of treatments. A systematic review of the literature in PubMed and Scopus up to 15 September 2020 was conducted according to PRISMA guidelines. Results Nine studies reporting the annual cost of care of patients with SMA and six evaluations of the cost-effectiveness of SMA treatments were identified. The average annual cost of SMA1, the most frequent and severe form in which symptoms appear before the age of 6 months were similar according to the different studies, ranged from $75,047 to $196,429 per year. The yearly costs for the forms of the later-onset form, called SMA2, SMA3, and SMA4, which were usually pooled in estimates of healthcare costs, were more variable, ranging from $27,157 to $82,474. The evaluations of cost-effectiveness of treatment compared nusinersen treatment against standard of care (n = 3), two treatments (nusinersen and onasemnogene abeparvovec) against each other and no drug treatment (n = 1), nusinersen versus onasemnogene abeparvovec (n = 1), and standard of care versus nusinersen with and without newborn screening (n = 1). The incremental cost-effectiveness ratio (ICER) of nusinersen compared to standard of care in SMA1 ranged from $210,095 to $1,150,455 per quality-adjusted life years (QALY) gained and that for onasemnogene abeparvovec ranged from $32,464 to $251,403. For pre-symptomatic patients, the ICER value ranged from $206,409 to $735,519. The ICERs for later-onset forms of SMA (2, 3 and 4) were more diverse ranging from $275,943 to $8,438,049. Conclusion This review confirms the substantial cost burden of standard of care for SMA patients and the high cost-effectiveness ratios of the approved drugs at the current price when delivered in post-symptomatic patients. Since few studies have been conducted so far, there is a need for further prospective and independent economic studies in pre- and post-symptomatic patients.

Osteoporosis care has evolved markedly over the last 50 years, such that there are now an established clinical definition, validated methods of fracture risk assessment and a range of effective pharmacological agents. Currently, bone-forming (anabolic) agents, in many countries, are used in those patients who have continued to lose bone mineral density (BMD), patients with multiple subsequent fractures or those who have fractured despite treatment with antiresorptive agents. However, head-to-head data suggest that anabolic agents have greater rapidity and efficacy for fracture risk reduction than do antiresorptive therapies. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) convened an expert working group to discuss the tools available to identify patients at high risk of fracture, review the evidence for the use of anabolic agents as the initial intervention in patients at highest risk of fracture and consider the sequence of therapy following their use. This position paper sets out the findings of the group and the consequent recommendations. The key conclusion is that the current evidence base supports an “anabolic first” approach in patients found to be at very high risk of fracture, followed by maintenance therapy using an antiresorptive agent, and with the subsequent need for antiosteoporosis therapy addressed over a lifetime horizon.

Background Although the economic burden of multiple sclerosis (MS) in high-income countries (HICs) has been extensively studied, information on the costs of MS in low- and middle‐income countries (LMICs) remains scarce. Moreover, no review synthesizing and assessing the costs of MS in LMICs has yet been undertaken. Objective Our objective was to systematically identify and review the cost of illness (COI) of MS in LMICs to critically appraise the methodologies used, compare cost estimates across countries and by level of disease severity, and examine cost drivers. Methods We conducted a systematic literature search for original studies in English, French, and Dutch containing prevalence or incidence-based cost data of MS in LMICs. The search was conducted in MEDLINE (Ovid), PubMed, Embase (Ovid), Cochrane Library, National Health Service Economic Evaluation Database (NHS EED), Econlit, and CINAHL (EBSCO) on July 2020 without restrictions on publication date. Recommended and validated methods were used for data extraction and analysis to make the results of the COI studies comparable. Costs were adjusted to $US, year 2019 values, using the World Bank purchasing power parity and inflated using the consumer price index. Results A total of 14 studies were identified, all of which were conducted in upper-middle-income economies. Eight studies used a bottom-up approach for costing, and six used a top-down approach. Four studies used a societal perspective. The total annual cost per patient ranged between $US463 and 58,616. Costs varied across studies and countries, mainly because of differences regarding the inclusion of costs of disease-modifying therapies (DMTs), the range of cost items included, the methodological choices such as approaches used to estimate healthcare resource consumption, and the inclusion of informal care and productivity losses. Characteristics and methodologies of the included studies varied considerably, especially regarding the perspective adopted, cost data specification, and reporting of costs per severity levels. The total costs increased with greater disease severity. The cost ratios between different levels of MS severity within studies were relatively stable; costs were around 1–1.5 times higher for moderate versus mild MS and about two times higher for severe versus mild MS. MS drug costs were the main cost driver for less severe MS, whereas the proportion of direct non-medical costs and indirect costs increased with greater disease severity. Conclusion MS places a huge economic burden on healthcare systems and societies in LMICs. Methodological differences and substantial variations in terms of absolute costs were found between studies, which made comparison of studies challenging. However, the cost ratios across different levels of MS severity were similar, making comparisons between studies by disease severity feasible. Cost drivers were mainly DMTs and relapse treatments, and this was consistent across studies. Yet, the distribution of cost components varied with disease severity.

Background Considering the heavy economic burden of osteoporotic fractures, the limits of healthcare resources, and the recent availability of new anti-osteoporosis drugs, there is continuing interest in economic evaluation studies of osteoporosis management strategies. Objectives This study aims to (1) systematically review recent economic evaluations of drugs for osteoporosis and (2) to apply an osteoporosis-specific guideline to critically appraise them. Methods A literature search was undertaken using PubMed, EMBASE, National Health Service Economic Evaluation database, and the Cost-Effectiveness Analysis Registry to identify original articles containing economic evaluations of anti-osteoporosis drugs, published between 1 July, 2013 and 31 December, 2019. A recent European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases-International Osteoporosis Foundation (ESCEO-IOF) guideline for the conduct and reporting of economic evaluations in osteoporosis was used to assess the quality of included articles. Results The database search retrieved 3860 records, of which 27 studies fulfilled the inclusion criteria. These studies were conducted in 15 countries; 12 active drugs were assessed, including various traditional pharmacological treatments such as bisphosphonates, raloxifene, strontium ranelate, denosumab, and teriparatide, and new agents such as abaloparatide, romosozumab, and gastro-resistant risedronate. Eight out of 12 studies that compared traditional oral bisphosphonates to other active interventions (denosumab, zoledronic acid, gastro-resistant risedronate, and teriparatide) suggested that the other active agents were generally cost-effective or dominant. Additionally, the cost-effectiveness of sequential therapy has recently been assessed and indications are that it can lead to extra health benefits (larger gains in quality-adjusted life-year). The key drivers of cost effectiveness included baseline fracture risk, drug effect on the risk of fractures, drug cost, and medication adherence/persistence. The current average score for quality assessment was 17 out of 25 (range 2–15); room for improvement was observed for most studies, which could potentially be explained by the fact that most studies were published prior to the osteoporosis-specific guideline. Greater adherence to guideline recommendations was expected for future studies. The quality of reporting was also suboptimal, especially with regard to treatment side effects, treatment effect after discontinuation, and medication adherence. Conclusions This updated review provides an overview of recently published cost-effectiveness analyses. In comparison with a previous review, recent economic evaluations of anti-osteoporosis drugs were conducted in more countries and included more active drugs and sequential therapy as interventions/comparators. The updated economic evidence could help decision makers prioritize health interventions and the unmet/unreported quality issues indicated by the osteoporosis-specific guideline could be useful in improving the transparency, quality, and comparability of future economic evaluations in osteoporosis.

Three new therapies for spinal muscular atrophy (SMA) have been approved by the United States Food and Drug Administration and the European Medicines Agency since 2016. Although these new therapies improve the quality of life of patients who are symptomatic at first treatment, administration before the onset of symptoms is significantly more effective. As a consequence, newborn screening programs have been initiated in several countries. In 2018, we launched a 3-year pilot program to screen newborns for SMA in the Belgian region of Liège. This program was rapidly expanding to all of Southern Belgium, a region of approximately 55,000 births annually. During the pilot program, 136,339 neonates were tested for deletion of exon 7 of SMN1 , the most common cause of SMA. Nine SMA cases with homozygous deletion were identified through this screen. Another patient was identified after presenting with symptoms and was shown to be heterozygous for the SMN1 exon 7 deletion and a point mutation on the opposite allele. These ten patients were treated. The pilot program has now successfully transitioned into the official neonatal screening program in Southern Belgium. The lessons learned during implementation of this pilot program are reported.

This study aims to assess stakeholder perceptions on the challenges and value of real-world evidence (RWE) post approval, the differences in regulatory and health technology assessment (HTA) real-world data (RWD) collection requirements under the German regulation for more safety in drug supply (GSAV), and future alignment opportunities to create a complementary framework for postapproval RWE requirements. Eleven semistructured interviews were conducted purposively with pharmaceutical industry experts, regulatory authorities, health technology assessment bodies (HTAbs), and academia. The interview questions focused on the role of RWE post approval, the added value and challenges of RWE, the most important requirements for RWD collection, experience with registries as a source of RWD, perceptions on the GSAV law, RWE requirements in other countries, and the differences between regulatory and HTA requirements and alignment opportunities. The interviews were recorded, transcribed, and translated for coding in Nvivo to summarize the findings. All experts agree that RWE could close evidence gaps by showing the actual value of medicines in patients under real-world conditions. However, experts acknowledged certain challenges such as: (i) heterogeneous perspectives and differences in outcome measures for RWE generation and (ii) missing practical experience with RWD collected through mandatory registries within the German benefit assessment due to an unclear implementation of the GSAV. This study revealed that all stakeholder groups recognize the added value of RWE but experience conflicting demands for RWD collection. Harmonizing requirements can be achieved through common postlicensing evidence generation (PLEG) plans and joint scientific advice to address uncertainties regarding evidence needs and to optimize drug development.

The COVID-19 pandemic, particularly the period when safe and protective vaccines became available, presented an excellent opportunity to investigate public preferences regarding how to ration a scarce, life-saving resource. It is important to understand which distributive strategies are preferred but, as this is an inherently normative matter, also to which extent different socio-demographic groups hold different opinions. This study assesses the impact of socio-demographic characteristics on preferences for vaccine prioritization during the early stages of the COVID-19 pandemic at the moment when vaccines were not available yet. A representative sample of 2060 Belgians were asked to rank eight prioritization strategies. Based on the rankings, we clustered the eight strategies into five overarching groups. Then, we estimated the potential impact of respondents' socio-demographic characteristics on their preferences towards these five strategies. The ranking exercise shows that the vulnerability strategy (i.e. chronically ill and elderly) is preferred most often (N = 1815) and the market strategy (i.e. individuals who come first or pay the most) by the fewest respondents (N = 116). Preferences for vaccine distribution vary among population subgroups. Women, older or retired individuals, residents of Flanders, those with a positive attitude towards vaccination efforts and/or high vaccination willingness, and those who prefer the government or scientists to decide upon prioritization were more likely to prefer a designated priority strategy (i.e. vulnerability strategy, workers strategy or spreaders). Furthermore, younger respondents, residents of Wallonia, and those previously infected by COVID-19 tended to favour a risk-independent prioritization strategy (i.e. lottery or market strategy) more than others. This study validates the appropriateness of the implemented rationing approaches, by supporting a phased approach in which first vulnerables were vaccinated. However, it also demonstrates that different subgroups had substantially different preferences and the population was in disagreement about what constitutes a fair rationing policy for a scarce, potentially lifesaving resource. •Preferences regarding vaccine distribution differ among population subgroups.•Most respondents prefer designated priority strategies over risk-independent ones.•Our study supports a phased vaccination approach if another pandemic emerges.•A lottery system is considered acceptable to distribute the remaining vaccines.•Lottery preferences vary with respondents' education level and region of residence.

The aim of this study was to deliver insights from multiple stakeholders into actual and future collaboration for health technology assessment (HTA) in general and in oncology in particular. Eighteen semi-structured interviews were conducted with experts from European HTA bodies (HTAbs), former board members of the European Network for Health Technology Assessment (EUnetHTA), and representatives from the pharmaceutical industry, a regulatory agency, academia, and patient organizations. The stakeholders were asked about their support of the EUnetHTA's intent, about the general strengths and challenges of the EUnetHTA and its Joint Action 3 (JA 3), the strengths and challenges of the clinically oriented HTA collaboration in oncology during JA 3 across the technology life cycle, about future challenges to HTA in oncology with consequences for collaboration, and about collaboration in the economic domains of HTA. The transcribed interviews were analyzed qualitatively. The participants perceived the intention and work quality of the EUnetHTA as positive. The experts described methodological, procedural, and capacity challenges in early dialogues (EDs) and rapid relative effectiveness assessments (REAs) meant to analyze clinical effectiveness in oncology. The majority attached increasing importance to collaboration in the future to cope with the uncertainty of HTA. Several stakeholders also proposed the incorporation of joint postlaunch evidence generation (PLEG) activities. Some gave sporadic suggestions for voluntary nonclinical collaboration as well. Stakeholders' continued readiness to discuss the remaining challenges to and sufficient resources for implementing HTA regulation, as well as further cooperative expansion along the technology life cycle, are necessary for improved HTA collaboration in Europe.

Objectives This research aims to (1) replicate published health economic models, (2) compare reproduced results with original results, (3) identify facilitators and hurdles to model replicability and determine reproduction success, and (4) suggest model replication reporting standards to enhance model reproducibility, in the context of health economic obesity models. Methods Four health economic obesity models simulating an adult UK population were identified, selected for replication, and evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Reproduction results were compared to original results, focusing on cost-effectiveness outcomes, and the resulting reproduction success was assessed by published criteria. Replication facilitators and hurdles were identified and transferred into related reporting standards. Results All four case studies were state-transition models simulating costs and quality-adjusted life-years (QALYs). Comparing original versus reproduction outcomes, the following deviation ranges were observed: costs − 3.9 to 16.1% (mean over all model simulations 3.78%), QALYs − 3.7 to 2.1% (mean − 0.11%), and average cost-utility ratios − 3.0 to 17.9% (mean 4.28%). Applying different published criteria, an overall reproduction success was observed for three of four models. Key replication facilitators were input data tables and model diagrams, while missing standard deviations and missing formulas for equations were considered as key hurdles. Conclusions This study confirms the feasibility of rebuilding health economic obesity models, but minor to major assumptions were needed to fill reporting gaps. Model replications can help to assess the quality of health economic model documentation and can be used to validate current model reporting practices. Simple changes to actual CHEERS reporting criteria may solve identified replication hurdles.

Background Different criteria regarding outcome measures in smoking research are used, which can lead to confusion about study results. Consensus in outcome criteria may enhance the comparability of future studies. This study aims (1) to provide an overview of tobacco researchers’ considered preferences regarding outcome criteria in randomized controlled smoking cessation trials, and (2) to identify the extent to which researchers can reach consensus on the importance of these outcome criteria. Methods A three-round online Delphi study was conducted among smoking cessation experts. In the first round, the most important smoking cessation outcome measures were collected by means of open-ended questions, which were categorized around self-reported and biochemical validation measures. Experts ( n  = 17) were asked to name the outcome measures (as well as their assessment method and ideal follow-up period) that they thought were important when assessing smoking-related outcomes. In the second ( n  = 48) and third rounds ( n  = 37), a list of outcome measures—identified in the first round—was presented to experts. Asking them to rate the importance of each measure on a seven-point scale. Results Experts reached consensus on several items. For self-reports, experts agreed that prolonged abstinence (6 or/and 12 months), point prevalence abstinence (7 days), continuous abstinence (6 months), and the number of cigarettes smoked (7 days) are important outcome measures. Experts reached consensus that biochemical validation methods should not always be used. The preferred biochemical validation methods were carbon monoxide (expired air) and cotinine (saliva). Preferred follow-ups included 6 and/or 12 months, with or without intermediate measurements. Conclusions Findings suggest only partial compliance with the Russell standard and that more outcome measures may be important (including seven-day point-prevalence abstinence, number of cigarettes smoked, and cotinine when using biochemical validation). This study showed where there is and is not consensus, reflecting the need to develop a more comprehensive standard. For these purposes we provided suggestions for the Russell 2.0 standard.