Lomustine with or without reirradiation for first progression of glioblastoma, LEGATO, EORTC-2227-BTG: study protocol for a randomized phase III study.

BACKGROUND: Chemotherapy with lomustine is widely considered as standard treatment option for progressive glioblastoma. The value of adding radiotherapy to second-line chemotherapy is not known. METHODS: EORTC-2227-BTG (LEGATO, NCT05904119) is an investigator-initiated, pragmatic (PRECIS-2 score: 34 out of 45), randomized, multicenter phase III trial in patients with first progression of glioblastoma. A total of 411 patients will be randomized in a 1:1 ratio to lomustine (110 mg/m2 every 6 weeks) or lomustine (110 mg/m2 every 6weeks) plus radiotherapy (35 Gy in 10 fractions). Main eligibility criteria include histologic confirmation of glioblastoma, isocitrate dehydrogenase gene (IDH) wild-type per WHO 2021 classification, first progression at least 6 months after the end of prior radiotherapy, radiologically measurable disease according to RANO criteria with a maximum tumor diameter of 5 cm, and WHO performance status of 0-2. The primary efficacy endpoint is overall survival (OS) and secondary endpoints include progression-free survival, response rate, neurocognitive function, health-related quality of life, and health economic parameters. LEGATO is funded by the European Union's Horizon Europe Research program, was activated in March 2024 and will enroll patients in 43 sites in 11 countries across Europe with study completion projected in 2028. DISCUSSION: EORTC-2227-BTG (LEGATO) is a publicly funded pragmatic phase III trial designed to clarify the efficacy of adding reirradiation to chemotherapy with lomustine for the treatment of patients with first progression of glioblastoma. TRIAL REGISTRATION: ClinicalTrials.gov NCT05904119. Registered before start of inclusion, 23 May 2023.

A 'patient-industry complex'? Investigating the financial dependency of UK patient organisations on drug company funding.

We examined the minimum extent of dependency of UK patient organisations on pharmaceutical industry funding using drug company disclosure reports and patient organisation financial accounts from 2012 to 2016. We used linear regression to explain the overall share of industry funding ('general dependency') and top donor funding ('company-specific dependency') in organisations' income. Predictors included patient organisations' goal; having members and volunteers; geographical scope of activity; headquarter location; expenditure/income ratio; and disease area. The prevalent low levels of general dependency (IQR, 0.1%-6.0%) and company-specific dependency (IQR, 0.1%-4.3%) made a widespread capture of patient organisations unlikely, though only if one excludes the possibility of significant payment under-reporting. However, organisations with considerably higher dependency than others might be more prone to co-optation by industry. Of the 398 organisations, 18 (4.5%) and 8 (2.0%) had general and company-specific financial dependency over 50%, respectively. However, the shares of outliers exceeding the third quartile plus 1.5 times IQR were 51 (12.8%) and 56 (14.1%) for each dependency type. Certain characteristics including activity profile (advocacy) or indicating limited access to resources (remote location) made organisations vulnerable to developing financial dependency. Future research should examine both financial and non-financial links between the two sides and their impact on patient organisations' activity.

Implementation of evidence-based health policy in the field of integrated care: A Ritka Betegségek Nemzeti Eroforrás Központjának tervezési folyamata / Bizonyítékokon alapuló egészségpolitikai döntéshozatal az integrált ellátásban: A Ritka Betegségek Nemzeti Eroforrás Központjának tervezési folyamata

Összefoglaló. Bevezetés: A ritka betegséggel élok ellátásában fontos elorelépések történtek az elmúlt években. Egy következo lépés lehetne hazánkban a Ritka Betegségek Nemzeti Eroforrás (Uni-Versum) Központjának (a továbbiakban: Központ) létrehozása, amely az egészségügyi, szociális és köznevelési szolgáltatásokat összehangolva és kiegészítve személyközpontú ellátást nyújtana a betegek és támogatóik részére. Célkituzés: Célunk az volt, hogy egy nemzetközi tudományos módszertan alapján javaslatokat tegyünk arra, hogy milyen eszközökkel lehet feloldani a Központ megvalósításának lehetséges korlátozó tényezoit. Módszer: A Központ megvalósíthatóságának értékelésére interdiszciplináris szakmai egyeztetést szerveztünk különbözo érintett érdekcsoportok részvételével, a SELFIE H2020 kutatási projekt által kidolgozott módszertan alapján. Az elozetesen rangsorolt legfontosabb korlátozó tényezokre lehetséges megoldási javaslatokat tettünk. Eredmények: A lehetséges korlátozó tényezoket a résztvevok relevánsnak tartották a Központ létrehozásával kapcsolatban, és ezekre összesen 17 olyan konkrét javaslat született, amelyben a résztvevok között egyetértés alakult ki. A javaslatok kiterjedtek az ellátás tartalmára, az alkalmazott technológiák támogató szerepére, a humáneroforrás-korlátok megoldására, a hatékony vezetés és szervezés kialakítására, az összetett finanszírozási struktúra kialakítására és a kutatási lehetoségek megteremtésére is. Megbeszélés: A Központ megvalósítása esetén a ritka betegséggel élok ellátása az egészségügyi, szociális és köznevelési tevékenységeket integráló megközelítés felé mozdulna el. A kutatás során megfogalmazott javaslatok hozzájárulhatnak a Központ létrehozásához, amennyiben megvan az ehhez szükséges szakpolitikai támogatás is. Ezen túlmutatóan, a leírt munkamódszer más integrált ellátási modellek bevezethetoségének elemzéséhez is mintaként szolgálhat. Következtetés: Összefoglalva megállapíthatjuk, hogy a Központ létrehozásához számos, elozetesen is látható korlátozó tényezot kell feloldani. Az érdekcsoportok közös javaslatai alapján kialakítható egy olyan muködési forma, amely az ellátórendszerek kiegészítésével és összehangolásával jelentos társadalmi értéktöbbletet eredményezhet. Orv Hetil. 2021; 162(45): 1818-1825. INTRODUCTION: In Hungary, significant achievements have been made in the care of patients with rare diseases in recent years. A next step could be the establishment of the National Resource Centre for Rare Diseases (hereinafter: Centre) to facilitate patient-centered complex care by the integration and supplementation of existing health, social and educational services. OBJECTIVE: This research aimed to develop recommendations based on international scientific methodology to overcome potential implementation barriers of the aforementioned Centre. METHOD: To evaluate the feasibility of the implementation, we organized an interdisciplinary workshop with representatives of different stakeholder groups, adopting the methodology developed in the SELFIE H2020 research project. During the workshop, we discussed the previously ranked, most significant implementation barriers and made recommendations for potential solutions. RESULTS: The potential implementation barriers were considered relevant by the participants and, reflecting on these barriers, altogether 17 recommendations were developed by consensus. These recommendations were related to the content of service delivery, use of supportive technologies, overcoming workforce issues, establishing effective leadership, implementing a complex financing structure and creating research opportunities. DISCUSSION: Implementation of the Centre would shift the care of rare diseases towards personalized and integrated health, social and educational services. Our recommendations will contribute to the establishment of the Centre, subject to positive policy decision. Furthermore, our methodological approach could support the feasibility assessment of future integrated care solutions and programs. CONCLUSION: Several predictable barriers must be overcome to establish the Centre. Recommendations developed by representatives of relevant stakeholders could support successful implementation and societal value generation. Orv Hetil. 2021; 162(45): 1818-1825.

Early palliative care associated with lower costs for adults with advanced cancer: evidence from Hungary.

OBJECTIVE: Palliative Care Consult Service (PCCS) programme was established in Hungary to provide palliative care to hospitalised patients with complex needs and to coordinate integrated care across providers. The aim of this study was to measure the association of PCCS with healthcare costs from payer's perspective. METHODS: Study population consisted of patients with metastatic cancer, who were admitted to the Clinical Centre of the University of Pécs between 2014 and 2016. Patients who did not die within 180 days from enrolment were excluded. Patients receiving services from PCCS team (intervention patients) were compared to patients receiving usual care (controls). The two populations were matched using propensity scores. Data were obtained from electronic medical records linked to claims data. RESULTS: For patients who were involved in PCCS at least 60 days before their death, the costs of care outside the acute hospital were higher. However, this was offset by savings in hospital costs so that the total healthcare cost was significantly reduced (p = 0.034). The proportion of patients who died in the hospital was lower in the PCCS group compared to the usual care group (66% vs. 85%, p = 0.022). CONCLUSION: Timely initiation of palliative care for hospitalised patients is associated with cost savings for the healthcare system.

The effect of social distance measures on COVID-19 epidemics in Europe: an interrupted time series analysis.

Following the introduction of unprecedented "stay-at-home" national policies, the COVID-19 pandemic recently started declining in Europe. Our research aims were to characterize the changepoint in the flow of the COVID-19 epidemic in each European country and to evaluate the association of the level of social distancing with the observed decline in the national epidemics. Interrupted time series analyses were conducted in 28 European countries. Social distance index was calculated based on Google Community Mobility Reports. Changepoints were estimated by threshold regression, national findings were analyzed by Poisson regression, and the effect of social distancing in mixed effects Poisson regression model. Our findings identified the most probable changepoints in 28 European countries. Before changepoint, incidence of new COVID-19 cases grew by 24% per day on average. From the changepoint, this growth rate was reduced to 0.9%, 0.3% increase, and to 0.7% and 1.7% decrease by increasing social distancing quartiles. The beneficial effect of higher social distance quartiles (i.e., turning the increase into decline) was statistically significant for the fourth quartile. Notably, many countries in lower quartiles also achieved a flat epidemic curve. In these countries, other plausible COVID-19 containment measures could contribute to controlling the first wave of the disease. The association of social distance quartiles with viral spread could also be hindered by local bottlenecks in infection control. Our results allow for moderate optimism related to the gradual lifting of social distance measures in the general population, and call for specific attention to the protection of focal micro-societies enriching high-risk elderly subjects, including nursing homes and chronic care facilities.

Benefits Of Timely Care In Pancreatic Cancer: A Systematic Review To Navigate Through The Contradictory Evidence.

The evidence base of policies that improve the timeliness of cancer care is under ongoing debate. Pancreatic cancer is frequently diagnosed in a stage when curative therapy is not feasible; hence, it is an important target for timelier healthcare interventions. The objectives of our research were to identify all clinical studies on pancreatic cancer care delays via a systematic literature review, to assess the study methodologies for possible biases, to conclude on the available evidence, and to formulate research recommendations on evidence gaps. Nineteen studies were identified and eight reported multivariate analyses. Although many sources of bias shifted the results towards negative or paradoxical findings, a statistically significant association of shorter delays with better clinical outcomes was demonstrated in the majority of studies reporting multivariate analyses. Noninferiority analyses were not published. Further efforts to provide timely care for pancreatic cancer patients are encouraged, and studies on the associations of delay with patient experience and healthcare resource utilization are warranted.

Digital Health Transformation of Integrated Care in Europe: Overarching Analysis of 17 Integrated Care Programs.

BACKGROUND: Digital health tools comprise a wide range of technologies to support health processes. The potential of these technologies to effectively support health care transformation is widely accepted. However, wide scale implementation is uneven among countries and regions. Identification of common factors facilitating and hampering the implementation process may be useful for future policy recommendations. OBJECTIVE: The aim of this study was to analyze the implementation of digital health tools to support health care and social care services, as well as to facilitate the longitudinal assessment of these services, in 17 selected integrated chronic care (ICC) programs from 8 European countries. METHODS: A program analysis based on thick descriptions-including document examinations and semistructured interviews with relevant stakeholders-of ICC programs in Austria, Croatia, Germany, Hungary, the Netherlands, Norway, Spain, and the United Kingdom was performed. A total of 233 stakeholders (ie, professionals, providers, patients, carers, and policymakers) were interviewed from November 2014 to September 2016. The overarching analysis focused on the use of digital health tools and program assessment strategies. RESULTS: Supporting digital health tools are implemented in all countries, but different levels of maturity were observed among the programs. Only few ICC programs have well-established strategies for a comprehensive longitudinal assessment. There is a strong relationship between maturity of digital health and proper evaluation strategies of integrated care. CONCLUSIONS: Notwithstanding the heterogeneity of the results across countries, most programs aim to evolve toward a digital transformation of integrated care, including implementation of comprehensive assessment strategies. It is widely accepted that the evolution of digital health tools alongside clear policies toward their adoption will facilitate regional uptake and scale-up of services with embedded digital health tools.

Is there a fair allocation of healthcare research funds by the European Union?

BACKGROUND: This study aimed to investigate the distribution of European Union (EU) healthcare research grants across EU countries, and to study the effect of the potential influencing factors on grant allocation. METHODS: We analysed publicly available data on healthcare research grants from the 7th Framework Programme and the Horizon 2020 Programme allocated to beneficiaries between 2007 and 2016. Grant allocation was analysed at the beneficiary-, country-, and country group-level (EU-15 versus newer Member States, defined as EU-13). The investigated country-level explanatory variables included GDP per capita, population size, overall disease burden, and healthcare research excellence. Grant amounts per 100,000 inhabitants were used as an outcome variable in the regression analyses. RESULTS: Research funds were disproportionally allocated to EU-15 versus the EU-13, as 96.9% of total healthcare grants were assigned to EU-15 countries. At the beneficiary level, EU funding was positively influenced by participating in previous grants. The average grant amount per beneficiary was higher for EU-15 organizations. In the multiple regression analysis GDP per capita (p = 0.002) and research excellence (p<0.001) had a significant positive association with EU funding. Population size had an inverted U-shaped relationship with EU funding for healthcare research, having the largest per capita funding in second and the third quartiles (p = 0.03 and p = 0.02). CONCLUSION: The uneven allocation of healthcare research funds across EU countries was influenced by GDP per capita, medical research excellence and population size. Wealthier countries with an average population size and strong research excellence in healthcare had more EU funding for healthcare research. Higher disease burden apparently was not associated with more EU research funding. While our findings are in line with analyses on previous periods, they suggest that the EU did not implement any effective policy measures to improve the unfair allocation of research grants.

Strengthening the evidence-base of integrated care for people with multi-morbidity in Europe using Multi-Criteria Decision Analysis (MCDA).

BACKGROUND: Evaluation of integrated care programmes for individuals with multi-morbidity requires a broader evaluation framework and a broader definition of added value than is common in cost-utility analysis. This is possible through the use of Multi-Criteria Decision Analysis (MCDA). METHODS AND RESULTS: This paper presents the seven steps of an MCDA to evaluate 17 different integrated care programmes for individuals with multi-morbidity in 8 European countries participating in the 4-year, EU-funded SELFIE project. In step one, qualitative research was undertaken to better understand the decision-context of these programmes. The programmes faced decisions related to their sustainability in terms of reimbursement, continuation, extension, and/or wider implementation. In step two, a uniform set of decision criteria was defined in terms of outcomes measured across the 17 programmes: physical functioning, psychological well-being, social relationships and participation, enjoyment of life, resilience, person-centeredness, continuity of care, and total health and social care costs. These were supplemented by programme-type specific outcomes. Step three presents the quasi-experimental studies designed to measure the performance of the programmes on the decision criteria. Step four gives details of the methods (Discrete Choice Experiment, Swing Weighting) to determine the relative importance of the decision criteria among five stakeholder groups per country. An example in step five illustrates the value-based method of MCDA by which the performance of the programmes on each decision criterion is combined with the weight of the respective criterion to derive an overall value score. Step six describes how we deal with uncertainty and introduces the Conditional Multi-Attribute Acceptability Curve. Step seven addresses the interpretation of results in stakeholder workshops. DISCUSSION: By discussing our solutions to the challenges involved in creating a uniform MCDA approach for the evaluation of different programmes, this paper provides guidance to future evaluations and stimulates debate on how to evaluate integrated care for multi-morbidity.