The Legal Landscape for Opioid Treatment Agreements.

Policy Points Opioid treatment agreements (OTAs) are controversial because of the lack of evidence that their use reduces opioid-related harms and the potential risks they pose of stigmatizing patients and undermining the clinician-patient relationship. Even so, their use is now required in most jurisdictions, and their use is influencing the outcomes of civil and criminal lawsuits. More research is needed to evaluate how OTAs are implemented given existing requirements. If additional research does not resolve the current level of uncertainty regarding OTA benefits, then policymakers in jurisdictions where they are required should consider eliminating OTA mandates or providing flexibility in the legal requirements to make room for clinicians and health care institutions to implement best practices. CONTEXT: Opioid treatment agreements (OTAs) are documents that clinicians present to patients when prescribing opioids that describe the risks of opioids and specify requirements that patients must meet to receive their medication. Notwithstanding a lack of evidence that OTAs effectively mitigate opioids' risks, professional organizations recommend that they be implemented, and jurisdictions increasingly require them. We sought to identify the jurisdictions that require OTAs, how OTAs might affect the outcomes of lawsuits that arise when things go wrong, and instances in which the law permits flexibility for clinicians and health care institutions to adopt best practices. METHODS: We surveyed the laws and regulations of all 50 states and the District of Columbia to identify which jurisdictions require the use of OTAs, the circumstances in which OTA use is mandatory, and the terms OTAs must include (if any). We also surveyed criminal and civil judicial decisions in which OTAs were discussed as evidence on which a court relied to make its decision to determine how OTA use influences litigation outcomes. FINDINGS: Results show that a slight majority (27) of jurisdictions now require OTAs. With one exception, the jurisdictions' requirements for OTA use are triggered at least in part by long-term prescribing. There is otherwise substantial variation and flexibility within OTA requirements. Results also show that even in jurisdictions where OTA use is not required by statute or regulation, OTA use can inform courts' reasoning in lawsuits involving patients or clinicians. Sometimes, but not always, OTA use legally protects clinicians from liability. CONCLUSIONS: Our results show that OTA use is entwined with legal obligations in various ways. Clinicians and health care institutions should identify ways for OTAs to enhance clinician-patient relationships and patient care within the bounds of relevant legal requirements and risks.

Financial Characteristics of Outcomes-Based Agreements: What Do Canadian Public Payers and Pharmaceutical Manufacturers Prefer?

OBJECTIVES: This study sought to gain insight into the financial characteristics of outcomes-based agreements (OBAs) considered most suitable to Canadian public payers and pharmaceutical manufacturers, and the rationale for their preferences. METHODS: A total of 17 public payers and pharmaceutical manufacturers participated in semistructured qualitative interviews, which assessed their knowledge of OBAs and their preferred financial characteristics. RESULTS: Payers identified 5 OBA financial models that they considered both acceptable and feasible, in no preferential order: (1) discontinuation of therapy, (2) rebates for nonresponders, (3) free trial period, (4) adjustable pricing, and (5) blended rebate. Payers had a clear preference for short-term OBAs (<1 year), whereas both payers and manufacturers agreed OBAs with longer durations (up to 5 years) would be manageable if appropriately designed. Six key success factors to design suitable and acceptable OBA financial models were identified, including the areas of interim reporting, easily measurable health outcomes, trusted data sources, engaging unbiased third-party data experts, harmonizing OBA billing methods, and the inclusion of budget caps. CONCLUSIONS: Manufacturers and payers showed high level of interest in OBAs and a robust understanding of their potential role in supporting timely market access for patients in need, with the caveat that they need to be carefully designed to provide value. Further opportunities for discussion and engagement between public payers and manufacturers are needed to establish how to implement OBAs at a pan-Canadian level and how individual provinces and territories can incorporate them within their existing governance infrastructures.

Market Entry Agreements for Innovative Pharmaceuticals Subject to Indication Broadening: A Case Study for Pembrolizumab in The Netherlands.

OBJECTIVES: Managed entry agreements and especially financial-based agreements are commonly used in European countries for innovative cancer pharmaceuticals. These agreements facilitate access to innovative treatments while mitigating financial risks for payers. This study focuses on the confidential price agreement made by the Dutch government for the reimbursement of pembrolizumab, the implications of broadening indications on cost-effectiveness, and the viability or desirability of said agreement. METHODS: We selected 5 indications in which pembrolizumab was deemed effective and developed portioned survival models for each indication. Survival and progression-free survival data from the published trials were utilized to recreate individual patient data, and we extrapolated-using parametric models-to a time horizon of 30 years. Inputs for both quality of life and costs were derived from the available literature and were indexed. RESULTS: The incremental cost-effectiveness ratios ranged between €35 313 and €322 349 per quality-adjusted life-year, depending on the indication. Only 1 indication fell under the €80 000 (or €100 000) cost-effectiveness threshold. When applying the average reported discount on intramural pharmaceuticals in The Netherlands, incremental cost-effectiveness ratios ranged between €20 881 and €252 934 per quality-adjusted life-year gained, and the €80 000 (or €100 000) threshold was met in 3 indications out of 5. CONCLUSIONS: Our results show that pembrolizumab could be cost-effective in some indications, depending on the confidential price agreement established. However, the possibility of reimbursing not cost-effective care when the price is anchored in 1 indication remains possible. Indication-based pricing could help align value and price for innovative pharmaceuticals that are subject to indication broadening.

Uncertainty in Long-Term Relative Effectiveness of Medicines in Health Technology Assessment.

OBJECTIVES: Uncertainty regarding the long-term relative effectiveness is an important factor in health technology assessment (HTA) of medicines. This study investigated how different HTA bodies address this uncertainty in their assessments. METHODS: A total of 49 HTA reports from 6 national HTA bodies, assessing 9 medicines for spinal muscular atrophy, cystic fibrosis, and hypercholesterolemia, were included. In these reports, 81 relative effectiveness assessments and 45 cost-effectiveness assessments were performed on an indication level. We collected information on included trials, assessment outcomes, uncertainty regarding the long-term effectiveness, proposed managed entry agreements, and reassessments. RESULTS: Uncertainty regarding the long-term effectiveness was an important consideration in almost all cost-effectiveness assessments (91%) and three-quarters of relative effectiveness assessments (74%), despite differences in methodologies among HTA bodies. There were considerable differences in the amount and type of long-term effectiveness data included by HTA bodies due to timing and inclusion criteria. In total 23 managed entry agreements were proposed of which 14 were linked to uncertainty regarding the long-term effectiveness. In addition, 13 reassessments were performed of which 4 led to an increase in patient access because of more available long-term effectiveness data. CONCLUSIONS: Uncertainty regarding the long-term effectiveness is an important challenge for HTA bodies. There are large differences in the acceptance of evidence among HTA bodies, which leads to heterogeneity in the inclusion of available long-term effectiveness data for decision making. In cases with large uncertainty regarding the long-term effectiveness, outcome-based agreements and reassessments are used by HTA bodies, but differently between HTA bodies and indications.

Linking Reimbursement to Patient Benefits for Advanced Therapy Medicinal Products and Other High-Cost Innovations: Policy Recommendations for Outcomes-Based Agreements in Europe.

OBJECTIVES: Health technology assessment (HTA) of advanced therapy medicinal products (ATMPs), such as high-cost and one-time cell and gene therapies, is particularly challenging. Outcomes-based agreements (OBAs) are a potential solution to mitigate the risks while providing access to patients but are not widely used across Europe. This study aimed to develop policy recommendations to support the acceptability and implementation of OBAs in Europe. METHODS: A policy sandbox approach was used to engage with stakeholders and explore how HTA organizations can support reimbursement decisions regarding OBAs for ATMPs. A panel of 38 experts from across the European region was convened in 2 workshops, representing payers, HTA organizations, patients, registries, and an industry trade body. RESULTS: Policy recommendations were developed to support the appropriate consideration of OBAs for reimbursing highly uncertain technologies, such as ATMPs. If a positive HTA recommendation cannot be made at the proposed price, then a simple price discount reflecting the uncertainty is preferred over complex solutions such as OBAs. If an OBA is pursued, it should be designed collaboratively with all stakeholders to understand data collection feasibility and minimize burden to patients and providers. Payers are encouraged to approach OBAs as a tool for informed decision making, including a readiness to make negative reimbursement decisions based on unfavorable evidence. CONCLUSIONS: The study presents a policy framework for using OBAs in reimbursement decisions. OBAs must be carefully designed, focusing on appropriateness and the burden of implementation. The relevant authorities should be committed to making decisions in light of the resulting evidence.

Illustrating the Financial Consequences of Outcome-Based Payment Models From a Payers Perspective: The Case of Autologous Gene Therapy Atidarsagene Autotemcel (Libmeldy®).

OBJECTIVES: To illustrate the financial consequences of implementing different managed entry agreements (managed entry agreements for the Dutch healthcare system for autologous gene therapy atidarsagene autotemcel [Libmeldy]), while also providing a first systematic guidance on how to construct managed entry agreements to aid future reimbursement decision making and create patient access to high-cost, one-off potentially curative therapies. METHODS: Three payment models were compared: (1) an arbitrary 60% price discount, (2) an outcome-based spread payment with discounts, and (3) an outcome-based spread payment linked to a willingness to pay model with discounts. Financial consequences were estimated for full responders (A), patients responding according to the predicted clinical pathway presented in health technology assessment reports (B), and unstable responders (C). The associated costs for an average patient during the time frame of the payment agreement, the total budget impact, and associated benefits expressed in quality-adjusted life-years of the patient population were calculated. RESULTS: When patients responded according to the predicted clinical pathway presented in health technology assessment reports (scenario B), implementing outcome-based reimbursement models (models 2 and 3) had lower associated budget impacts while gaining similar benefits compared with the discount (scenario 1, €8.9 million to €6.6 million vs €9.2 million). In the case of unstable responders (scenario C), costs for payers are lower in the outcome-based scenarios (€4.1 million and €3.0 million, scenario 2C and 3C, respectively) compared with implementing the discount (€9.2 million, scenario 1C). CONCLUSIONS: Outcome-based models can mitigate the financial risk of reimbursing atidarsagene autotemcel. This can be considerably beneficial over simple discounts when clinical performance was similar to or worse than predicted.

A practical approach to meeting national obligations for sustainable trade under CITES.

Reconciling conservation goals with sustainable resource use requires adaptive management strategies. The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) regulates global trade for species listed on Appendix II, partly by requiring member countries (parties) to ensure exports do not damage wild populations (called making positive "nondetriment findings" [NDFs]). Unfortunately, when parties find NDFs difficult, they often suspend legal trade, imposing economic costs and driving trade underground. To make it easier for parties to examine the detrimental nature of exports, we devised a spatial approach and applied it to seahorses (Hippocampus spp.) in Tamil Nadu, India, as an example. Our approach involves mapping answers to 5 key questions on species distribution (QA), pressures (QB), management measures (QC), management implementation (QD), and species' population status (QE). We gathered data from fisher interviews and published literature. Seahorse abundance was greatest in southern Palk Bay and the northern Gulf of Mannar, primarily in seagrasses and coral reefs (QA). Fishing pressure was highest in Palk Bay, primarily from bottom trawlers and dragnetters operating in shallow seahorse habitats near the coastline (QB). Management measures including a marine protected area (MPA), bottom trawl exclusion zone, and closed season were theoretically in place (QC), but their implementation was poor (QD). Fishers reported seahorse catches in 85% of the area covered by the MPA and the exclusion zone; bottom trawlers were responsible for most violations. Seahorses were also captured in Sri Lankan waters, where bottom trawling is banned. Fisher reports indicated declining seahorse catches and reduced body sizes (QE), highlighting unsustainable exploitation. Our results highlight the need for better implementation of existing management measures before a positive NDF can be made and suggest mitigation beyond bans. Such pragmatic spatial analyses can help regulate exports at sustainable levels, supporting CITES implementation for its vast range of species.

Un enfoque práctico para cumplir las obligaciones nacionales para el mercado sustentable bajo CITES Resumen Conciliar los objetivos de conservación con el uso sostenible de los recursos exige estrategias de gestión adaptativa. La Convención sobre el Comercio Internacional de Especies Amenazadas de Fauna y Flora Silvestres (CITES) regula el comercio mundial de las especies incluidas en el Apéndice II, en parte exigiendo a los países miembros (partes) que garanticen que las exportaciones no perjudiquen a las poblaciones silvestres (lo que se conoce como dictámenes de extracción no perjudicial [DENP] positivos). Desgraciadamente, cuando las partes encuentran dificultades para formular DENP, a menudo suspenden el comercio legal, lo que impone costos económicos y lleva al comercio a la clandestinidad. Para facilitar a las partes el examen del carácter perjudicial de las exportaciones, ideamos un enfoque espacial y lo aplicamos a los caballitos de mar (Hippocampus spp.) en Tamil Nadu, India, como un ejemplo. Nuestro planteamiento consiste en responder cinco preguntas clave sobre la distribución de las especies (PA), las presiones (PB), las medidas de gestión (PC), la aplicación de la gestión (PD) y el estado de la población de las especies (PE). Se recopilaron datos de entrevistas con pescadores y de la bibliografía publicada. La abundancia de caballitos de mar era mayor en el sur de la bahía Palk y el norte del Golfo de Mannar, principalmente en las praderas marinas y los arrecifes de coral (QA). La presión pesquera era mayor en la bahía Palk, principalmente por parte de redes de arrastre de fondo y redes de arrastre que operaban en hábitats poco profundos de caballitos de mar cerca de la costa (QB). En teoría existían medidas de gestión, como un área marina protegida (AMP), una zona de exclusión para las redes de arrastre de fondo y una temporada de veda (QC), pero su aplicación era deficiente (QD). Los pescadores reportaron capturas de caballitos de mar en el 85% del área cubierta por el AMP y la zona de exclusión; las redes de arrastre de fondo fueron responsables de la mayoría de las infracciones. También se capturaron hipocampos en aguas de Sri Lanka, donde está prohibida la pesca de arrastre de fondo. Los informes de los pescadores indicaron una disminución de las capturas de caballitos de mar y una reducción del tamaño corporal (QE), lo que expone una explotación insostenible. Nuestros resultados resaltan la necesidad de aplicar mejor las medidas de gestión existentes antes de poder hacer un DENP positivo y sugieren medidas de mitigación más allá de las prohibiciones. Estos análisis espaciales pragmáticos pueden ayudar a regular las exportaciones a niveles sostenibles, apoyando la aplicación para la amplia gama de especies de la CITES.

Values, challenges, and responses associated with high-priced potential cures: perspectives of diverse stakeholders in South Korea.

BACKGROUND: The emergence of high-priced potential cures has sparked significant health policy discussions in South Korea, where the healthcare system is funded through a single-payer National Health Insurance model. We conducted focus group interviews (FGIs) and accompanying surveys with diverse stakeholders to comprehensively understand related issues and find better solutions to the challenges brought by these technologies. METHODS: From October to November 2022, 11 FGIs were conducted with stakeholders from various sectors, including government payers, policy and clinical experts, civic and patient organisations, and the pharmaceutical industry, involving a total of 25 participants. These qualitative discussions were supplemented by online surveys to effectively capture and synthesise stakeholder perspectives. RESULTS: Affordability was identified as a critical concern by 84% of stakeholders, followed by clinical uncertainty (76%) and limited value for money (72%). Stakeholders expressed a preference for both financial-based controls and outcome-based pricing strategies to mitigate these challenges. Despite the support for outcome-based refunds, payers raised concerns about the feasibility of instalment payment models, whether linked to outcomes or not, due to the specific challenges of the Korean reimbursement system and the potential risk of 'cumulative liabilities' from ongoing payments for previously administered treatments. In addition, the FGIs highlighted the need for clear budgetary limits for drugs with high uncertainties, with mixed opinions on the creation of special silo funds (64.0% agreement). Less than half (48%) endorsed the use of external reference pricing, currently applied to such essential drugs in South Korea. A significant majority (84%), predominantly non-pharma stakeholders, advocated for addressing cost-effectiveness uncertainty through re-assessment once long-term clinical data become available. CONCLUSIONS: This study uncovers a broad agreement among stakeholders on the need for more effective value assessment methodologies for high-priced potential cures, stressing the importance of more robust and comprehensive re-assessment supported by long-term data collection, rather than primarily relying on external reference pricing. Each type of stakeholders exhibited a cautious approach to their specific uncertainties, suggesting that new funding strategies should accommodate these uncertainties with predefined guidelines and agreements prior to the initiation of managed entry agreements.

Sexual Agreement Discussions Among Adolescent Sexual Minority Men in the USA.

Nearly two-thirds of new HIV infections are attributed to primary partners, necessitating a greater understanding of relationship context of HIV transmission among sexual minority men. Sexual agreements, which are the explicit decisions couples make about sexual behaviors allowed inside and outside of their relationship, have been primarily studied among adult sexual minority men. Little work has sought to understand how adolescent sexual minority men utilize and navigate sexual agreement conversations. In this qualitative study, we explored adolescent sexual minority men's motivations for having these conversations, how they define different types of agreements (e.g., monogamous, non-monogamous), and the topics most commonly discussed in their conversations. We conducted thematic analysis of in-depth interviews with 30 partnered, HIV-negative, adolescent sexual minority men ages 15-19 years. Participants reported similar reasons, definitions, and desires for creating sexual agreements as those reported in the adult literature. Novel to this population was the influence of stigma and heterosexism on the participants' choice of sexual agreement type. Like adult sexual minority men, participants used sexual agreement conversations to respond to life events; however, the adolescents in our sample, when talking with their partners, led with the context of developmentally specific events such as leaving for college or attending a school dance. Those with more relationship experience often described having intentional, explicit sexual agreement conversations. Study findings suggest that content focused on sexual agreements is important for HIV prevention interventions designed with adolescent sexual minority men, especially young men who have less relationship experiences.

The potential impact of the Comprehensive and Progressive Agreement for Prans-Pacific Partnership on Thailand's hepatitis C treatment program.

BACKGROUND: Thailand has expressed interest in joining the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP), a twelve-country plurilateral trade agreement whose original incarnation included the United States of America (USA). When the USA withdrew from this agreement, key intellectual property clauses relevant to pharmaceuticals were suspended. These could be reinstated should the CPTPP Parties decide to do so. METHODS: This study uses two scenarios to cost the impact the CPTPP would have had on Thailand's 2020 hepatitis C treatment regime if Thailand joined the CPTPP and suspended clauses were reinstated. RESULTS: Joining the CPTPP could have increased the cost more than tenfold if suspended CPTPP clauses were reinstated and Thailand was not willing or able to issue compulsory licenses. Based on the 2020 budget, the price for this possible scenario could have reduced hepatitis C treatment coverage by 90%. CONCLUSIONS: Acceding to trade agreements such as the CPTPP that require increasing intellectual property protection, could compromise Thailand's hepatitis C program and other national treatment programs reliant on affordable generic medicines. The CPTPP could also prevent Thailand from relying on its own pharmaceutical capabilities to manufacture medicines needed to sustain its treatment programs.

Experiences of central child health services teams regarding a special governmental investment in child health services.

BACKGROUND: Historically marked by a high infant mortality rate, Sweden's healthcare reforms have successively led to a robust, decentralized universal child health system covering over 97% of the population 0-5 years. However, inequities in health have become an increasing problem and the public health law explicitly states that health inequities should be reduced, resulting in various government initiatives. This study examines the experiences of Central Child Health Services (CCHS) teams during the implementation of the Child Health Services Accessibility Agreement between the State and the regions starting in 2017. The agreement aimed to enhance child health service accessibility, especially in socio-economically disadvantaged areas, but broadly stated guidelines and the short-term nature of funding have raised questions about its effectiveness. The aim of this study was to understand the experiences of CCHC teams in implementing the Child Health Services Accessibility Agreement, focusing on investment decisions, implementation efforts, as well as facilitators and barriers to using the funds effectively. METHODS: CCHC teams were purposefully sampled and invited via email for interviews, with follow-ups for non-respondents. Conducted from January to October 2023, the interviews were held digitally and recorded with individuals familiar with the agreement's implementation within these teams. Both authors analyzed the transcripts thematically, applying Braun and Clarke's framework. Participants represented a cross-section of Sweden's varied healthcare regions. RESULTS: Three main themes emerged from the thematic analysis: "Easy come, easy go," highlighting funding uncertainties; "What are we supposed to do?" expressing dilemmas over project prioritization and partner collaboration; and "Building castles on sand," focusing on the challenges of staff retention and foundational program stability. Respective subthemes addressed issues like fund allocation timing, strategic decision-making, and the practical difficulties of implementing extended home visiting programs, particularly in collaboration with social services. CONCLUSIONS: This study uncovered the challenges faced in implementing the Child Health Services Accessibility Agreement across different regions in Sweden. These obstacles underline the need for precise guidelines regarding the use of funds, stable financing for long-term project sustainability, and strong foundational support to ensure effective interprofessional collaboration and infrastructure development for equitable service delivery in child health services.

National polarization and international agreements.

The network of international environmental agreements (IEAs) has been characterized as a complex adaptive system (CAS) in which the uncoordinated responses of nation states to changes in the conditions addressed by particular agreements may generate seemingly coordinated patterns of behavior at the level of the system. Unfortunately, since the rules governing national responses are ill understood, it is not currently possible to implement a CAS approach. Polarization of both political parties and the electorate has been implicated in a secular decline in national commitment to some IEAs, but the causal mechanisms are not clear. In this paper, we explore the impact of polarization on the rules underpinning national responses. We identify the degree to which responsibility for national decisions is shared across political parties and calculate the electoral cost of party positions as national obligations under an agreement change. We find that polarization typically affects the degree but not the direction of national responses. Whether national commitment to IEAs strengthens or weakens as national obligations increase depends more on the change in national obligations than on polarization per se. Where the rules governing national responses are conditioned by the current political environment, so are the dynamic consequences both for the agreement itself and for the network to which it belongs. Any CAS analysis requires an understanding of such conditioning effects on the rules governing national responses.

Evaluation of the Clinical Efficacy and Trust in AI-Assisted Embryo Ranking: Survey-Based Prospective Study.

BACKGROUND: Current embryo assessment methods for in vitro fertilization depend on subjective morphological assessments. Recently, artificial intelligence (AI) has emerged as a promising tool for embryo assessment; however, its clinical efficacy and trustworthiness remain unproven. Simulation studies may provide additional evidence, provided that they are meticulously designed to mitigate bias and variance. OBJECTIVE: The primary objective of this study was to evaluate the benefits of an AI model for predicting clinical pregnancy through well-designed simulations. The secondary objective was to identify the characteristics of and potential bias in the subgroups of embryologists with varying degrees of experience. METHODS: This simulation study involved a questionnaire-based survey conducted on 61 embryologists with varying levels of experience from 12 in vitro fertilization clinics. The survey was conducted via Google Forms (Google Inc) in three phases: (1) phase 1, an initial assessment (December 23, 2022, to January 22, 2023); (2) phase 2, a validation assessment (March 6, 2023, to April 5, 2023); and (3) phase 3 an AI-guided assessment (March 6, 2023, to April 5, 2023). Inter- and intraobserver assessments and the accuracy of embryo selection from 360 day-5 embryos before and after AI guidance were analyzed for all embryologists and subgroups of senior and junior embryologists. RESULTS: With AI guidance, the interobserver agreement increased from 0.355 to 0.527 and from 0.440 to 0.524 for junior and senior embryologists, respectively, thus reaching similar levels of agreement. In a test of accurate embryo selection with 90 questions, the numbers of correct responses by the embryologists only, embryologists with AI guidance, and AI only were 34 (38%), 45 (50%), and 59 (66%), respectively. Without AI, the average score (accuracy) of the junior group was 33.516 (37%), while that of the senior group was 35.967 (40%), with P<.001 in the t test. With AI guidance, the average score (accuracy) of the junior group increased to 46.581 (52%), reaching a level similar to that of the senior embryologists of 44.833 (50%), with P=.34. Junior embryologists had a higher level of trust in the AI score. CONCLUSIONS: This study demonstrates the potential benefits of AI in selecting embryos with high chances of pregnancy, particularly for embryologists with 5 years or less of experience, possibly due to their trust in AI. Thus, using AI as an auxiliary tool in clinical practice has the potential to improve embryo assessment and increase the probability of a successful pregnancy.

Inter-regional patient mobility in decentralised Spain: Explaining regional budget imbalances.

Inter-regional patient mobility represents both a resource and a challenge for the organization and financing of health systems, particularly in decentralised countries. We use cross-sectional time series regression analysis to test the determinants of imbalances in regional funds to finance inter-regional patient mobility for the 17 Spanish regions for the period 2014-2020. The findings indicate that highly specialised health centres and bilateral agreements partly explain the budget imbalance from inter-regional patient referrals, while local tourism partly explains the budget imbalance from non-referred patient mobility. Developing effective national schemes to compensate net patient recipient regions would be fundamental to addressing territorial imbalances.

How to facilitate the introduction of value-based payment models?

Value-based payment (VBP) models are designed and implemented to improve outcomes at the same or lower costs. Their adoption requires significant changes in the way healthcare organisations and insurance companies operate. Usually, before VBP models are widely implemented, pilot projects are conducted. Payers need to have a comprehensive set of requirements to enter into agreements with healthcare organisations on these pilots. In this short communication, we outline key elements reported in the literature, inside and outside healthcare organisations, as well as within the contract, that need to be considered in a pilot VBP model. Discussions regarding the introduction of VBP models may be strongly affected by external contextual factors, including regulations, which are outside the control of healthcare organisations. It requires collaboration between organisations, including primary care organisations and hospitals, while within organisations, it frequently requires creating multidisciplinary teams. The focus is on ensuring transparency, collaboration, and shared decision-making, realised by standardising communication processes and regular meetings. Additionally, effective leadership is needed, in which leaders set goals and priorities, as well as manage change. In the contractual agreements between payers and healthcare organisations, outcome measures need to be adequately defined and measured, including individual patient outcomes and composite scores, as well as absolute and relative performance measures. These measures should be tested periodically and catered to the organisations adopting the model. Also, incentives should have adequate size and frequency and be intrinsic and extrinsic. The consideration of these sets of key elements by the payers is essential when implementing VBP model pilot projects.

Unraveling the impact of environmental provisions in preferential trade agreements on green total factor energy efficiency.

Environmental provisions in Preferential Trade Agreements (PTAs) have increased in recent years, however, their impact on green total factor energy efficiency (GTFEE) remains underexplored. Utilizing comprehensive data on countries' engagement with PTAs' environmental provisions, along with environmental legislative information and green trade data, this study employs various quantitative and qualitative research methods to investigate heterogeneity influence, mechanism, nonlinear relationship, and combined effect of PTAs' environmental provisions on GTFEE. The empirical results indicate that: (1) Environmental provisions within PTAs significantly enhance the GTFEE of participating countries, which is more pronounced in North-South PTAs, particularly when these provisions are closely tied to trade issues. (2) Environmental provisions in PTAs improve the GTFEE by promoting environmental legislation, facilitating green goods trade, and fostering cleaner energy structures in participating countries. (3) As the number of PTAs' environmental provisions increases in participating countries, their effect on GTFEE follows a pattern of initial inhibition, followed by promotion, and ultimately insignificance. (4) The combined effect of different types of environmental provisions in PTAs reveals three primary pathways contributing to improved GTFEE: the "environment", the "environment-trade synergy", and the "trade-safeguard synergy".

Evaluating the impact of private land conservation with synthetic control design.

Programs to protect biodiversity on private land are increasingly being used worldwide. To understand the efficacy of such programs, it is important to determine their impact: the difference between the program's outcome and what would have happened without the program. Typically, these programs are evaluated by estimating the average program-level impact, which readily allows comparisons between programs or regions, but masks important heterogeneity in impact across the individual conservation interventions. We used synthetic control design, statistical matching, and time-series data to estimate the impact of individual protected areas over time and combined individual-level impacts to estimate program-level impact with a meta-analytic approach. We applied the method to private protected areas governed by conservation covenants (legally binding on-title agreements to protect biodiversity) in the Goldfields region of Victoria, Australia using woody vegetation cover as our outcome variable. We compared our results with traditional approaches to estimating program-level impact based on a subset of covenants that were the same age. Our results showed an overall program-level impact of a 0.3-0.8% increase in woody vegetation cover per year. However, there was significant heterogeneity in the temporal pattern of impact for individual covenants, ranging from -4 to +7% change in woody vegetation cover per year. Results of our approach were consistent with results based on traditional approaches to estimating program-level impact. Our study provides a transparent and robust workflow to estimate individual and program-level impacts of private protected areas.

Evaluación del impacto del suelo privado de conservación con diseño de control sintético Resumen Los programas de protección de la biodiversidad en suelo privado se utilizan cada vez más en todo el mundo. Para entender la eficacia de estos programas, es importante determinar la diferencia entre el resultado del programa y lo que habría ocurrido sin él. Normalmente, estos programas se evalúan estimando el impacto medio a nivel de programa, lo que permite fácilmente las comparaciones entre programas o regiones, pero oculta una importante heterogeneidad en el impacto entre las intervenciones individuales de conservación. Utilizamos un diseño de control sintético, un emparejamiento estadístico y datos de series temporales para estimar el impacto de las áreas protegidas individuales a lo largo del tiempo y combinamos los impactos a nivel individual para estimar el impacto a nivel de programa con un enfoque meta-analítico. Aplicamos el método a áreas protegidas privadas regidas por acuerdos de conservación (acuerdos con vínculos jurídicos sobre la titularidad para proteger la biodiversidad) destinados a mejorar la cubierta vegetal leñosa en la región de Goldfields de Victoria, Australia. Comparamos nuestros resultados con los métodos tradicionales de estimación del impacto a nivel de programa basados en un subconjunto de pactos de la misma antigüedad. Nuestros resultados mostraron un impacto global a nivel de programa de un aumento del 0.3-0.8% de la cubierta vegetal leñosa al año. Sin embargo, hubo una heterogeneidad significativa en el patrón temporal del impacto para los pactos individuales, que osciló entre −4 y +7% de cambio en la cubierta vegetal leñosa por año. Los resultados de nuestra estrategia fueron consecuentes con los resultados basados en las estrategias tradicionales usadas para estimar el impacto a nivel de programa. Nuestro estudio proporciona un flujo de trabajo transparente y sólido para estimar el impacto individual a nivel de programa de las áreas protegidas privadas.

Public health advocacy strategies to influence policy agendas: lessons from a narrative review of success in trade policy.

BACKGROUND: Despite accumulating evidence of the implications of trade policy for public health, trade and health sectors continue to operate largely in silos. Numerous barriers to advancing health have been identified, including the dominance of a neoliberal paradigm, powerful private sector interests, and constraints associated with policymaking processes. Scholars and policy actors have recommended improved governance practices for trade policy, including: greater transparency and accountability; intersectoral collaboration; the use of health impact assessments; South-South networking; and mechanisms for civil society participation. These policy prescriptions have been generated from specific cases, such as the World Trade Organization's Doha Declaration on TRIPS and Public Health or specific instances of trade-related policymaking at the national level. There has not yet been a comprehensive analysis of what enables the elevation of health goals on trade policy agendas. This narrative review seeks to address this gap by collating and analysing known studies across different levels of policymaking and different health issues. RESULTS: Sixty-five studies met the inclusion criteria and were included in the review. Health issues that received attention on trade policy agendas included: access to medicines, food nutrition and food security, tobacco control, non-communicable diseases, access to knowledge, and asbestos harm. This has occurred in instances of domestic and regional policymaking, and in bilateral, regional and global trade negotiations, as well as in trade disputes and challenges. We identified four enabling conditions for elevation of health in trade-related policymaking: favourable media attention; leadership by trade and health ministers; public support; and political party support. We identified six strategies successfully used by advocates to influence these conditions: using and translating multiple forms of evidence, acting in coalitions, strategic framing, leveraging exogenous factors, legal strategy, and shifting forums. CONCLUSION: The analysis demonstrates that while technical evidence is important, political strategy is necessary for elevating health on trade agendas. The analysis provides lessons that can be explored in the wider commercial determinants of health where economic and health interests often collide.

How are health technology assessment bodies responding to the assessment challenges posed by cell and gene therapy?

BACKGROUND: The aims of this research were to provide a better understanding of the specific evidence needs for assessment of clinical and cost-effectiveness of cell and gene therapies, and to explore the extent that the relevant categories of evidence are considered in health technology assessment (HTA) processes. METHODS: A targeted literature review was conducted to identify the specific categories of evidence relevant to the assessment of these therapies. Forty-six HTA reports for 9 products in 10 cell and gene therapy indications across 8 jurisdictions were analysed to determine the extent to which various items of evidence were considered. RESULTS: The items to which the HTA bodies reacted positively were: treatment was for a rare disease or serious condition, lack of alternative therapies, evidence indicating substantial health gains, and when alternative payment models could be agreed. The items to which they reacted negatively were: use of unvalidated surrogate endpoints, single arm trials without an adequately matched alternative therapy, inadequate reporting of adverse consequences and risks, short length of follow-up in clinical trials, extrapolating to long-term outcomes, and uncertainty around the economic estimates. CONCLUSIONS: The consideration by HTA bodies of evidence relating to the particular features of cell and gene therapies is variable. Several suggestions are made for addressing the assessment challenges posed by these therapies. Jurisdictions conducting HTAs of these therapies can consider whether these suggestions could be incorporated within their existing approach through strengthening deliberative decision-making or performing additional analyses.

Uptake and availability of new outpatient cancer medicines in 2010-2021 in Nordic countries - survey of competent authorities.

BACKGROUND: Nordic countries excel in cancer care, but studies on uptake, costs, or managed entry agreements of cancer medicines have not been conducted recently. The aim of this study was to examine the uptake and availability of orally administered new cancer medicines in Nordic countries. Orally administered cancer medicines enable and are used in the community as part of outpatient care. Firstly, we studied the distribution, costs and adoption of managed entry agreements of these medicines, and secondly, uptake of and managed entry agreements for cancer medicines used in outpatient care that were granted marketing authorization in Europe in 2010-2021. METHODS: An E-mail survey of competent authorities, meaning pharmaceutical service organizers, payers or other government or non-government actors developing pharmaceutical service operations, in Denmark, Finland, Iceland, Norway, and Sweden in April-June 2022. The data were analysed using frequencies and percentages for descriptive analysis. RESULTS: The distribution of cancer medicines has similarities in Finland, Iceland, Norway, and Sweden, where cancer medicines can be distributed both via hospitals or hospital pharmacies for inpatient use, and via community pharmacies for outpatient use. In Denmark, cancer medicines are predominantly distributed via publicly funded hospitals. In all countries that provided data on the costs, the costs of cancer medicines had notably gone up from 2010 to 2021. The number of reimbursable medicines out of new cancer medicines varied from 36 products in Denmark and Iceland to 51 products in Sweden, out of 67 studied products. Managed entry agreements, often with confidential discounts, were in use in all Nordic countries. The number of agreements and the cancer types for which agreements were most often made varied from three agreements made in Iceland to 35 agreements made in Finland, out of 67 studied products. Average days from authorization to reimbursement of new cancer medicines varied from an average of 416 to 895 days. CONCLUSIONS: Nordic countries share similar characteristics but also differ in terms of the details in distribution, adopted managed entry agreements, market entry, and availability of new orally administered cancer medicines used in the outpatient care. The costs of cancer medicines have increased in all Nordic countries during the last decade. Due to differences in health care and because orally administered cancer medicines can be dispensed at community and hospital pharmacies in all studied countries other than Denmark, the number of reimbursable medicines and managed entry agreements vary between countries. However, Nordic countries show good agreement for 2010 to 2021 in entry and reimbursement decisions of novel cancer medicines.