Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Cost-effectiveness of a multicomponent-adherence intervention in fracture liaison services.

BACKGROUND: This study aims to assess the lifetime cost-effectiveness of a multi-component adherence intervention (MCAI), including a patient decision aid and motivational interviewing, compared to usual care in patients with a recent fracture attending fracture liaison services (FLS) and eligible for anti-osteoporosis medication (AOM). RESEARCH DESIGN AND METHODS: Data on AOM initiation and one-year persistence were collected from a quasi-experimental study conducted between 2019 and 2023 in two Dutch FLS centers. An individual level, state-transition Markov model was used to simulate lifetime costs and quality-adjusted life years (QALYs) with a societal perspective of MCAI vs usual care. One-way and probabilistic sensitivity analyses were conducted including variation in additional FLS and MCAI costs (no MCAI cost in baseline). RESULTS: MCAI was associated with gain in QALYs (0.0012) and reduction in costs (-€16) and is therefore dominant. At the Dutch willingness-to-pay threshold of €50,000/QALY, MCAI remained cost-effective when increasing costs of the FLS visit or the yearly maintenance cost for MCAI up to +€60. Probabilistic sensitivity analysis demonstrated MCAI to be dominant in 54% of the simulations and cost-effective in 87% with a threshold of €50,000/QALY. CONCLUSIONS: A MCAI implemented in FLS centers may lead to cost-effective allocation of resources in FLS care, depending on extra costs.

Preferences of people with diabetes for diabetes care in Germany: a discrete choice experiment.

OBJECTIVES: The objective of this study is to elicit health care preferences of people with diabetes and identify classes of people with different preferences. METHODS: A discrete choice experiment was conducted among people with diabetes in Germany comprising attributes of role division in daily diabetes care planning, type of lifestyle education, support for correct medication intake, consultation frequency, emotional support, and time spent on self-management. A conditional logit model and a latent class model were used to elicit preferences toward diabetes care and analyze preference heterogeneity. RESULTS: A total of 76 people with diabetes, recruited in two specialized diabetes care centers in Germany (mean age 51.9 years, 37.3% women, 49.1% type 2 diabetes mellitus, 50.9% type 1 diabetes mellitus), completed the discrete choice experiment. The most important attributes were consultation frequency, division in daily diabetes care planning, and correct medication intake. The latent class model detected preference heterogeneity by identifying two latent classes which differ mainly with respect to lifestyle education and medication intake. CONCLUSION: While the majority of people with diabetes showed preferences in line with current health care provision in Germany, a relevant subgroup wished to strengthen lifestyle education and medication intake support with an aid or website.

Treatment Preference Research in Atopic Dermatitis: A Systematic Review of Quantitative Studies.

BACKGROUND: Treatment preference research can support shared and informed decision making for currently available atopic dermatitis (AD) treatments, and simultaneously guide research and development for future therapies. In this systematic literature review, we aimed to provide an overview of preferences for AD treatments. METHODS: This systematic literature review was conducted in the Medline and Embase (via Ovid) databases, supplemented by manual searching. Quantitative research published from 2010 to September 2023 that investigated preferences for AD treatments were included. Quality assessment was conducted by using the purpose, respondents, explanation, findings, significance checklist, and a checklist developed by the Professional Society for Health Economics and Outcomes Research. RESULTS: In total, 207 references were screened after removing duplicates and 15 studies were included. Most studies were conducted in the US, followed by European countries. On average, people directly or indirectly affected by AD rate efficacy and treatment-related risk as the most important criteria when choosing an AD therapy. Participants are willing to increase risks in order to have a higher chance of achieving a certain benefit, e.g. reduction in itch or clearer skin. Participants have preferences for different modes of administration. On average, 68% (all full-text studies) and 87% (only discrete choice experiments [DCEs]) of quality criteria per reference were rated as fulfilled. DCEs received generally higher quality assessment scores than non-DCEs. CONCLUSIONS: This review revealed that AD treatment preference research is limited. Diverse study designs hampered comparison and synthesis of the results. We recommend conducting more DCEs in this field to increase the likelihood of AD patients receiving the therapy that best fits their individual needs and preferences. CLINICAL TRIALS REGISTRATION: This protocol was published in PROSPERO (ID: CRD42023468757).

The impacts of undetected nonadherence in phase II, III and post-marketing clinical trials: An overview.

AIMS: This research aims to provide an overview of the consequences of undiagnosed nonadherence (noninitiation, suboptimal implementation, nonpersistence) in randomized clinical trials (RCTs). METHODS: This research was conducted by combining a literature review and qualitative semistructured interviews with key opinion leaders. Based on this groundwork, the consequences of undiagnosed nonadherence in RCTs were summarized and reported in a figure. This study focused on phases II, III and post-marketing in ambulatory settings across a variety of therapeutic areas and indications. RESULTS: Various consequences of nonadherence in RCTs were investigated. In phase II, drug efficacy may be underestimated, variability in the outcomes may be high and a distorted picture of side effects could be reported, resulting in an uncertain impression of the investigational product's profile and complicating decision-making. The sponsor may need to increase the sample size of the upcoming phase III study to improve its power, representing additional costs, or even terminate the study. In phase III, similar phenomena may be observed, making demonstration of efficacy to the regulatory bodies more difficult. Lastly, after commercialization, a distortion in pharmacometrics may occur: the drug may underperform, prescriptions may be refilled less often than expected or extra expenses may be incurred by the payers. This can result in post-marketing dose reduction, new competitors coming into the market and, eventually, product withdrawal. CONCLUSIONS: This research highlighted the many potential adverse consequences of undiagnosed nonadherence in RCTs, including additional costs. Collecting accurate data appeared to be crucial for decision-making throughout the drug development process.

Societal costs before and up to 1 year after the first fracture liaison service visit in patients requiring anti-osteoporosis treatments.

This study aimed to estimate societal and healthcare costs incurred before and 1 year after the first fracture liaison services (FLS) visit and to explore differences in fracture type. All costs after 1 year significantly decreased compared to costs preceding the first visit. Fracture type did not significantly affect costs. INTRODUCTION: Limited literature is available on resource utilization and costs of patients visiting fracture liaison services (FLS). This study aimed to estimate the societal and healthcare costs incurred by patients with a recent fracture requiring anti-osteoporosis medication before and 1 year after the first FLS visit and to explore differences according to fracture type. METHODS: Resource utilization was collected through a self-reported questionnaire with a 4-month recall on health resource utilization and productivity losses immediately following the first FLS visit, and 4 and 12 months later. Unit costs derived from the national Dutch guideline for economic evaluations were used to compute societal and healthcare costs. Linear mixed-effect models, adjusted for confounders, were used to analyze societal and healthcare costs over time as well as the effect of fracture type on societal and healthcare costs. RESULTS: A total of 126 patients from two Dutch FLS centers were included, of whom 72 sustained a major fracture (hip, vertebral, humerus, or radius). Societal costs in the 4 months prior to the first visit (€2911) were significantly higher compared to societal costs 4 months (€711, p-value = 0.009) and 12 months later (€581, p-value = 0.001). Fracture type did not have a significant effect on total societal or healthcare costs. All costs 12 months after the initial visit were numerically lower for major fractures compared to others. CONCLUSION: Societal and healthcare costs in the year following the first FLS visit significantly decreased compared to those costs preceding the first visit.

The role and impact of health economics in the optimization of patient care in osteoarthritis: insights from a practical example.

Osteoarthritis (OA) is a degenerative joint disease with a substantial global burden, causing chronic pain and reduced quality of life. Managing OA efficiently while maximizing healthcare resources is crucial. Health economics and health technology assessment (HTA) are central tools providing a framework to evaluate the clinical, economic, and ethical aspects of healthcare technologies and interventions. This article presents some insights into the role of health economics and the HTA process in OA management. It also illustrates an example of cost-effectiveness analysis in a specific healthcare context, on the basis of a recent clinical trial involving hyaluronic acid treatment for knee OA. While HTA offers valuable insights, it faces challenges like data availability and resource constraints. Integrating health economics into decision-making can enhance patient care and allocate resources effectively in OA and other healthcare domains.

Health-related quality of life and utilities among Lebanese patients with Multiple Sclerosis: A cross-sectional study.

OBJECTIVE: This study assessed the Health-Related Quality of Life (HRQoL) and utilities of Multiple Sclerosis (MS) patients in Lebanon using generic and MS-specific QoL instruments, categorized by disease severity, and explored factors associated with HRQoL. METHODS: This was a cross-sectional, retrospective HRQoL study collecting data through face-to-face interviews using the EQ-5D-5 L and the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaires. We enrolled Lebanese patients aged ≥18 years, diagnosed with MS for >6 months. Patients were categorized by disease severity using the expanded disability status scale (EDSS) scores: 0-3 (mild MS), 4-6.5 (moderate MS), and 7-9 (severe MS). Bivariate and linear regression analyses were performed to study factors associated with HRQoL. RESULTS: A total of 210 patients (mean age: 43.3 years; 65.7 % females) were included. The mean EQ-5D-5 L utility score was 0.74. This score decreased significantly with disease severity (p < 0.001 for the trend): 0.93, 0.60, and 0.32 for mild, moderate, and severe MS, respectively. The mean MusiQoL global index score was 71.33 and was significantly lower for severe MS (58.68), than for moderate (65.23) and mild (77.80), (p < 0.001 for the trend). Higher educational level, lower EDSS scores, and longer disease duration were associated significantly with a higher EQ-5D-5 L utility (R2 = 0.67), while employment, lower EDSS scores, and decrease in cognitive difficulties were associated with better MusiQoL utility (R2 = 0.46). CONCLUSIONS: This study reveals a significant and gradual deterioration in HRQoL as MS progresses, resulting in low utility scores for patients with severe MS.

HTA community perspectives on the use of patient preference information: lessons learned from a survey with members of HTA bodies.

This research sought to assess whether and how patient preference (PP) data are currently used within health technology assessment (HTA) bodies and affiliated organizations involved in technology/drug appraisals and assessments. An exploratory survey was developed by the PP Project Subcommittee of the HTA International Patient and Citizen Involvement Interest Group to gain insight into the use, impact, and role of PP data in HTA, as well as the perceived barriers to its incorporation. Forty members of HTA bodies and affiliated organizations from twelve countries completed the online survey. PP data were reported to be formally considered as part of the HTA evidence review process by 82.5 percent of the respondents, while 39.4 percent reported that most of the appraisals and assessments within their organization in the past year had submitted PP data. The leading reason for why PP data were not submitted in most assessments was time/resource constraints followed by lack of clarity on PP data impact. Participants reported that PP data had a moderate level of influence on the deliberative process and outcome of the decision, but a higher level of influence on the decision's quality. Most (81.8 percent) felt patient advocacy groups should be primarily responsible for generating and submitting this type of evidence. Insights from the survey confirm the use of PP data in HTA but reveal barriers to its broader and more meaningful integration. Encouragingly, participants believe obstacles can be overcome, paving the way for a second phase of research involving in-depth collaborative workshops with HTA representatives.

Evidence-Based Guideline for the management of osteoporosis in men.

Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.

Prospective health care costs and lost work days associated with diabetes-related distress and depression symptoms among 1488 individuals with diabetes.

The aim of this study was to investigating the impact of major depression symptoms and diabetes-related distress on future health care costs and lost workdays in individuals with diabetes. We linked survey data from a random sample of a German statutory health insurance (SHI) with diabetes (n = 1488, 63.0% male, mean age 66.9 years) with their SHI data one year after the survey. Within the survey data we identified major depression symptoms (Patient Health Questionnaire-9) and diabetes-related distress (Problem Areas in Diabetes Scale). We retrieved health care costs and lost workdays from SHI data. To assess the impact of major depression symptoms and diabetes-related distress on health care costs and lost workdays, we adjusted regression models for age, sex, education, employment status, and diabetes duration, type, and severity. Major depression symptoms were associated with significantly higher costs (by a factor of 1.49; 95% CI: 1.18-1.88). Lost workdays were also more likely for respondents with depression symptoms (RR1.34; 0.97-1.86). Health care costs (by a factor of 0.81; 0.66-1.01) and the risk of lost workdays (RR 0.86; 0.62-1.18) may be lower among respondents with high diabetes-related distress. While major depression and diabetes-related distress have overlapping indicators, our results indicate different impacts on health care costs.

FLOW: Flow dysfunction of hemodialysis vascular access: A randomized controlled trial on the effectiveness of surveillance of arteriovenous fistulas and grafts.

INTRODUCTION: It is assumed that identification and correction of asymptomatic stenoses in the vascular access circuit will prevent thrombosis that would require urgent intervention to continue hemodialysis treatment. However, the evidence base for this assumption is limited. Recent international clinical practice guidelines reach different conclusions on the use of surveillance for vascular access flow dysfunction and recommend further research to inform clinical practice. METHODS: The FLOW trial is a double-blind, multicenter, randomized controlled trial with a 1:1 individual participant treatment allocation ratio over two study arms. In the intervention group, only symptomatic vascular access stenoses detected by clinical monitoring are treated, whereas in the comparison group asymptomatic stenoses detected by surveillance using monthly dilution flow measurements are treated as well. Hemodialysis patients with a functional arteriovenous vascular access are enrolled. The primary outcome is the access-related intervention rate that will be analyzed using a general linear model with Poisson distribution. Secondary outcomes include patient satisfaction, access-related serious adverse events, and quality of the surveillance process. A cost effectiveness analysis and budget impact analysis will also be conducted. The study requires 828 patient-years of follow-up in 417 participants to detect a difference of 0.25 access-related interventions per year between study groups. DISCUSSION: As one of the largest randomized controlled trials assessing the clinical impact of vascular access surveillance using a strong double-blinded study design, we believe the FLOW trial will provide much-needed evidence to improve vascular access care for hemodialysis patients.

Pediatric Market Access: A Qualitative Study.

OBJECTIVES: This qualitative study aims to analyze current PM regulation and market access requirements and proposes potential solutions to mitigate current challenges. METHODS: Twenty-two semi-structured interviews were conducted with experts from pharmaceutical industry, regulatory authorities, national health technology assessment (HTA) bodies, pediatricians, and academia from the Netherlands (NL), Germany (DE), the United Kingdom (UK), and France (FR) to get insight into the pediatric research, the regulatory and reimbursement processes, challenges, and solutions. Themes for further testing were developed on how to facilitate pediatric market access. Atlas.ti 9 was used to analyze the findings. RESULTS: Heterogeneity in requirements for the European Medicines Agency (EMA) and HTA approvals are noted. By example, DE grants direct reimbursement after regulatory approval, the other countries require additional reimbursement which generate delays and challenges in patient access after marketing authorization. Key components in facilitating PM market access include multi-stakeholder collaboration, transparency, patient representatives, informed consent guidance, real-world evidence, and appropriate clinical trial designs. Pricing models based on the economic capabilities of individual countries could further reduce delays and challenges in market access. The additional specific pediatric incentives should be taken as best practice to encourage innovation in pediatric conditions. CONCLUSION: This study highlights differences in requirements for regulatory and reimbursement approval, along with international differences in pricing and reimbursement procedures for pediatric market access.

Comparison of the cost-effectiveness of sequential treatment with abaloparatide in US men and women at very high risk of fractures.

BACKGROUND: Osteoporotic-related fractures represent an increasing burden to patients, health care systems and society. AIMS: This study estimated cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) compared to relevant alternative strategies in US men and women aged 50 to 80 years at very high fracture risk (bone mineral density T-score ≤ - 2.5 and a recent fracture). METHODS: A lifetime Markov-based microsimulation model was used to estimate healthcare costs and quality-adjusted life years (QALYs). Comparators were sequential treatment with unbranded teriparatide (TPTD)/ALN, generic ALN monotherapy, and no treatment. Analyses were conducted based on initial fracture site (hip, vertebral, or any fracture) and treatment efficacy data (derived from clinical trials or a recent network meta-analysis). RESULTS: From all analyses completed, sequential ABL/ALN demonstrated more QALYs for lower healthcare costs versus unbranded TPTD/ALN. No treatment was dominated (higher costs for less QALYs) versus ALN monotherapy. Sequential ABL/ALN resulted in favorable cost-effectiveness (at US threshold of $150,000/QALY) versus generic ALN monotherapy in men aged ≥ 50 years with any fracture type, women aged ≥ 65 years with any fracture type, and women aged ≥ 55 years having a hip or vertebral fracture. DISCUSSION: Similar cost-effectiveness of sequential ABL/ALN versus unbranded TPTD/ALN, ALN monotherapy, and no treatment was observed in both US men and women at very high fracture risk, with a moderate improvement in cost-effectiveness in men versus women and in patients with a hip or vertebral fracture. CONCLUSIONS: Sequential therapy with ABL/ALN was cost-effective in US men and women at very high risk of fractures.

Preferences of people living with HIV for injectable and oral antiretroviral treatment in the Netherlands: a discrete choice experiment.

ABSTRACTInjectable antiretroviral treatment (ART) represents a new effective and potentially more convenient alternative to oral ART for people living with HIV (PLWH). This study assessed preferences of PLWH for long-acting injectable compared with oral ART in the Netherlands. A labelled discrete choice experiment presented 12 choice sets of long-acting injectable and oral ART. PLWH were asked to select their preferred ART, described by six attributes: location of administration, dosing frequency, risk of short-term side effects, drug-drug interaction, forgivability, and food and mealtime restrictions. Random parameters logit and latent class models were used to estimate preferences of PLWH. 98.6% of 76 respondents were experienced oral ART users that had taken ART for a median of 12 years (Q1-Q3: 7.0-20.0). 30 (39.5%) respondents chose long-acting injectable ART in all choice tasks and 22 (28.9%) always chose oral ART. The random parameter model showed that, on average, respondents significantly favoured long-acting injectable ART over oral ART, preferred administration of the long-acting injectable ART at home, and a less frequent regimen. The latent class model confirmed one class strongly preferring long-acting injectable ART and one class slightly preferring oral ART. This study highlights the value for both long-acting injectable and oral ART.

Developing the Lebanese health economic evaluation guideline.

OBJECTIVE: To report on the process of developing the Lebanese Economic Evaluation Guideline (LEEG), and to provide relevant material that could assist guideline developers in the future. METHODS: The development of the LEEG closely followed the process proposed by the World Health Organization, i.e. to set up a Guideline Development Group (composed of three Lebanese experts), to establish the rationale for developing the guideline in Lebanon, to identify its scope, to search and retrieve evidence through two systematic reviews, to assess and present the evidence, to translate the evidence into guidelines and recommendations through a deliberative process, and to consult international experts. The deliberative process included a survey, an in-person interview, and a consensus workshop with 16 Lebanese key stakeholders. Data was collected and quantitative analysis was conducted using SPSS software. International experts from Maastricht University - The Netherlands were consulted for issuing the LEEG. Supported by the Lebanese Ministry of Public Health (MoPH), the LEEG will be available for public consultation on the MoPH's webpage, and a final version will be made available thereafter. CONCLUSION: Clear and transparent reporting of the guideline development process should support international organizations as well as other developers in establishing their guidelines within their national context.

Patients' preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study.

The RICO study indicated that most patients would like to receive information regarding their fracture risk but that only a small majority have actually received it. Patients globally preferred a visual presentation of fracture risk and were interested in an online tool showing the risk. PURPOSE: The aim of the Risk Communication in Osteoporosis (RICO) study was to assess patients' preferences regarding fracture risk communication. METHODS: To assess patients' preferences for fracture risk communication, structured interviews with women with osteoporosis or who were at risk for fracture were conducted in 11 sites around the world, namely in Argentina, Belgium, Canada at Hamilton and with participants from the Osteoporosis Canada Canadian Osteoporosis Patient Network (COPN), Japan, Mexico, Spain, the Netherlands, the UK, and the USA in California and Washington state. The interviews used to collect data were designed on the basis of a systematic review and a qualitative pilot study involving 26 participants at risk of fracture. RESULTS: A total of 332 women (mean age 67.5 ± 8.0 years, 48% with a history of fracture) were included in the study. Although the participants considered it important to receive information about their fracture risk (mean importance of 6.2 ± 1.4 on a 7-point Likert scale), only 56% (i.e. 185/332) had already received such information. Globally, participants preferred a visual presentation with a traffic-light type of coloured graph of their FRAX® fracture risk probability, compared to a verbal or written presentation. Almost all participants considered it important to discuss their fracture risk and the consequences of fractures with their healthcare professionals in addition to receiving information in a printed format or access to an online website showing their fracture risk. CONCLUSIONS: There is a significant communication gap between healthcare professionals and patients when discussing osteoporosis fracture risk. The RICO study provides insight into preferred approaches to rectify this communication gap.

Systematic Review of Outcomes for Assessment of Medication Adherence Enhancing Interventions: An ISPOR Special Interest Group Report.

OBJECTIVES: The lack of universal guidance on outcome measures for evaluating medication adherence enhancing interventions (MAEIs) poses a challenge for assessing their effectiveness. This literature review aimed to provide a systematic overview of outcome measures currently used for the value assessment of MAEIs. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched MEDLINE, PsycINFO, Scopus, CINAHL, and Academic Search Complete for randomized and nonrandomized clinical trials, prospective cohort studies, model-based economic evaluations, and value frameworks published in English between January 2010 and September 2020. Two independent reviewers screened all titles and abstracts, followed by a full-text review. Due to the large number of relevant studies, data extraction was limited to articles published between January 2018 and September 2020. We collected data on the general characteristics of the study, the type of intervention, and the outcomes measured. RESULTS: We screened 14 685 records and identified 308 articles for data extraction. Behavioral interventions were the most common (n = 143), followed by educational interventions (n = 110) and mixed-method interventions (n = 73). Outcomes were clustered into 7 categories with medication adherence (n = 286) being the most frequently measured, followed by clinical outcomes (n = 155), health-related quality of life (n = 57), resource use (n = 43), patient satisfaction (n = 31), economic outcomes (n = 18), and other outcomes (n = 76). CONCLUSIONS: Various outcomes measures have been used to evaluate MAEIs, with only a small number of studies exploring economic and patient-reported outcomes. Future research is warranted to develop a consensus-based set of criteria for assessing MAEIs to facilitate the comparison of interventions and enable informed decision making.