'How shall we handle this situation?' Social workers' discussions about risks during the COVID-19 pandemic in Swedish elder care

Within a context where New Public Management [NPM] has become increasingly influential in shaping everyday working practices, social workers often handle risks in their everyday work using formalised bureaucratic procedures, among other strategies. As the COVID-19 pandemic progressed, rapid changes occurred in Swedish elder care that social workers were required to address in their everyday work. Intra-professional case conferences amongst social workers provide one opportunity to discuss individual viewpoints and obtain suggestions from colleagues on how to proceed with a case. These discussions have so far received little scholarly attention. In this study we used a data set consisting of 39 audio-recorded case conferences to analyse social workers' intra-professional discussions about risks during the COVID-19 pandemic. In the case conferences, social workers discussed the risks that were accentuated by the pandemic, such as the risk of spreading COVID-19 to clients, the risk of unmet care needs amongst clients, risks related to accountability, and the risks pertaining to blurred boundaries between different organisations. The collegial discussions in case conferences included opportunities for social workers to use their collective professional experience and competency to establish creative solutions 'on the go' and to discuss various ways of handling and balancing different risks while continuing to carry out their work in the changing and unknown situation. Our findings highlight the importance of collegial support in social work in dealing with accentuated risks during the pandemic.Copyright © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Barriers to health care services among US-based undocumented Latinx immigrants within the sociopolitical climate under the Trump administration: A comparative analysis between client experiences and provider perceptions

As President Biden's administration works towards a 'fair and humane' immigration overhaul, it becomes critical to examine the implications of immigration policies/laws under the Trump administration on the well-being of undocumented residents to inform equitable reformations. We investigate challenges faced by undocumented Latinx immigrants in accessing health care services in the sociopolitical climate under the Trump administration. This study, which follows a similar study among frontline service providers, presents key findings from 23 in-depth interviews with Latinx individuals. Understanding their experiences is necessary to advance access to health-promoting services and uphold the human right to health. Our study participants' narratives document multiple barriers to health care services, many notably exacerbated by increasingly restrictive immigration policies/laws and heightened punitive interior enforcement practices under the Trump administration. As the nation awaits equitable immigration reform, health care organizations should immediately incorporate, amplify, or alter programs/practices to facilitate access among their undocumented clients. Focused organizational changes have the potential to reduce unmet health needs, minimize financial burdens for families, and curtail potential public health threats, the latter a particularly imperative goal within the current COVID-19 pandemic. We also distill conclusions drawn from our interviews with clients and their convergence with and divergence from conclusions drawn from our related research with providers. While providers recognize the negative impact of sociopolitical factors on their clients' access to health care services, client experiences illuminate potential gaps in their understanding. Bridging understanding between providers and clients can improve access, utilization, and retention in health care services.Copyright © 2022 The Authors

HTA189 Implications of the French Temporary Authorisation for Use Reform for the Pharma Industry

Objectives: In July 2021, the temporary authorisation for use (Autorisation Temporaire d'Utilisation, ATU) system was the subject of a major reform, initially published within the 2021 healthcare plan in December 2020. The presumption of innovation for the products compared with the most clinically relevant comparator was introduced among other evaluation criteria. What are the implications of this reform and what does this mean for the pharma industry? Methods: This study scrutinizes the application of all non-COVID related medications submitted for an Autorisation d'acces precoce (AAP, which includes the previous cohort ATU) between July 2021 and July 2022. The three evaluation criteria of the presumption of innovation (i.e. new treatment approach with an appropriate development plan and that addresses an unmet medical need) were analysed and linked to the decision outcomes of the Haute Autorite de Sante (HAS) for each product. Result(s): This study shows that most products assessed post-ATU reform met all three evaluation criteria and were granted AAP approval. In their evaluation, consideration of unmet medical need was particularly important for oncology products for HAS. The HAS showed to accept the absence of comparative data in the case of concurrent development of comparative studies vs. standard of care and with additional input from external experts. However, the absence of novel mode of action or treatment approach and / or the lack evidence of comparative clinical efficacy data without appropriate clinical development plans were key factors leading to product rejection. Conclusion(s): This study shows that the majority of non-COVID related products were granted AAP approval in the first months post-reform. Although this remains an initial observation, this research suggests that the reforms to the French early access programme, whilst more restrictive, have not significantly impacted patient access. Copyright © 2022

A scoping review on the impact of austerity on healthcare access in the European Union: rethinking austerity for the most vulnerable.

BACKGROUND: There is consensus that the 2008 financial and economic crisis and related austerity measures adversely impacted access to healthcare. In light of the growing debt caused by the COVID-19 crisis, it is uncertain whether a period of austerity will return. OBJECTIVE: This study aims to provide a structured overview of the impact of austerity policies in the EU-28 zone, applied in response to the Great Recession, on access to health care for the adult population, using the five access dimensions by Levesque et al. (2013). METHODS: This study followed the PRISMA extension for Scoping Reviews guideline. Medline (PubMed) and Web of Science were searched between February 2021 and June 2021. Primary studies in the English language published after the 1st of January 2008 reporting on the possible change in access to the healthcare system for the adult population induced by austerity in an EU28 country were included. RESULTS: The final search strategy resulted in 525 articles, of which 75 studies were reviewed for full-text analysis, and a total of 21 studies were included. Results revealed that austerity policy has been primarily associated with a reduction in access to healthcare, described through four main categories: i) Increase in rates of reported unmet needs (86%); ii) Affordability (38%); iii) Appropriateness (38%); iv) and Availability and Accommodation (19%). Vulnerable populations were more affected by austerity measures than the general population when specific safeguards were not in place. The main affected adult vulnerable population groups were: patients with chronic diseases, elderly people, (undocumented) migrants, unemployed, economically inactive people and individuals with lower levels of education or socioeconomic status. CONCLUSION: Austerity measures have led to a deterioration in access to healthcare in the vast majority of the countries studied in the EU-28 zone. Findings should prompt policymakers to rethink the fiscal agenda across all policies in times of economic crisis and focus on the needs of the most vulnerable populations from the health perspective.

How Can the EU Beating Cancer Plan Help in Tackling Lung Cancer, Colorectal Cancer, Breast Cancer and Melanoma?

Cancer is the second leading cause of mortality in EU countries, and the needs to tackle cancer are obvious. New scientific understanding, techniques and methodologies are opening up horizons for significant improvements in diagnosis and care. However, take-up is uneven, research needs and potential outstrip currently available resources, manifestly beneficial practices-such as population-level screening for lung cancer-are still not generalised, and the quality of life of patients and survivors is only beginning to be given attention it merits. This paper, mainly based on a series of multistakeholder expert workshops organised by the European Alliance for Personalised Medicine (EAPM), looks at some of those specifics in the interest of planning a way forward. Part of this exercise also involves taking account of the specific nature of Europe and its constituent countries, where the complexities of planning a way forward are redoubled by the wide variations in national and regional approaches to cancer, local epidemiology and the wide disparities in health systems. Despite all the differences between cancers and national and regional resources and approaches to cancer care, there is a common objective in pursuing broader and more equal access to the best available care for all European citizens.

Regulatory Science Challenges - Encouraging Innovation Through an Adaptive Regulatory System

ATMPs - a new era A boy from Hungary, Zente, was one and a half years old when the crowd-funding campaign to finance his life-saving medicine Zolgensma concluded with a happy end. He was the third European patient that received the new gene therapy, which replaces the function of the missing or nonworking survival motor neuron 1 (SMN1) gene with a new, working copy of a human SMN gene that helps motor neuron cells work properly and survive. From a European perspective, it has been almost 15 years by now since regulatory framework for advanced therapy medicinal products (ATMPs) had been established to ensure the free movement of these medicines within the European Union, to facilitate their access to the EU market, and to foster the competitiveness of European pharmaceutical companies in the field. Zolgensma has been approved in the EU in May 2020. The FDA expects it will be reviewing and approving up to 20 cell and gene therapies each year until 2025. Rapid development of technology and better understanding of the manufacturing challenges are not the only prerequisites of the growth. Assessment of products like Zolgensma requires very specific knowledge and often an adaptive approach from regulators. They have to gain enough experience and need to be able to summarize knowledge in guidelines that would help developers of products that are substantially different from traditional medicines. FDA issued seven new guidelines in January 2020, in which, for example, they highlight the importance of long-term follow-up for gene therapies that offer one-time fix for inherited diseases and where pre-market studies may have limited value. 2. Regulatory tools These examples may already show that rapid change in technology leads to new kinds of medicines that require a properly adapted regulatory system. Patients would expect state-of-the-art medicines within the shortest possible time frame, however, authorities are traditionally more cautious. Still, there are several various initiatives from the EMA and the FDA to foster early access to medicines. Some of these have been available for a longer time. EMA's accelerated assessment reduces the timeframe for review of innovative applications of medicines with major public health interest. Conditional marketing authorisation grants authorization before a complete dataset is available, and compassionate use allows the use of an unauthorized medicine for patients with an unmet medical need. A more recent regulatory tool of EMA is the priority medicines scheme (PRIME) that aims to enhance support for the development of medicines that are expected to make a real difference to patients. Early dialogue between EMA and the developers is a crucial part of the tool, together with accelerated assessment and continuous scientific advice and protocol assistance. Up to now, 282 applications for PRIME eligibility have been assessed by the CHMP of which 95 have received a green light. Most of the applicants are small and medium size enterprises, and the major therapeutic area is oncology. FDA has similar programs, such as the Fast Track, Breakthrough Therapy and Priority Review designations, and is also aiming to facilitate and accelerate development and marketing authorization of key medicines. By 2018, about 70% of new drug approvals by the FDA were expedited, compared to about 50% in 2010. The result is a growing pro-portion of medicines authorized with less premarket evidence, a trade-off, that most patients with fatal or debilitating disease would likely accept. Nevertheless, conditional approval requires a strong post-marketing attention from regulators, and lack of enough evidence sometimes leads to difficult decisions. In April 2019 a fast-tracked cancer drug, Lartruvo was withdrawn because a large study was not able to prove a favourable benefit-risk profile, which was established previously on a smaller patient population. The regulators approach is not expected to be changed, but experience from such cases would gradually be built into the decision-making process. In addition to this real world evidence (RWE) and patient recorded outcomes may also help in decision making. 3. Digital revolution The rapid development of biotechnology is not the only area where an adaptive regulatory approach is needed. Digital medicine is a new field, as smartphones and sensors open up new ways of generating data. For example, collecting and analysing RWE seems to be a good solution for single arm studies where randomized trials are not feasible. FDA has approved easy-to-use devices that are able to track several physiological systems of our body, which in turn can give a boost to developments in this field. In addition to these simpler devices, digital revolution in terms of artificial intelligence (AI) and cognitive machine learning is another challenge that our regulatory systems should tackle. It has been recently announced that a new drug candidate, a long-acting and potent serotonin 5-HT1A receptor agonist, which was created using an artificial intelligence platform, will enter into clinical study. There are also numerous radiological applications based on AI, including computer aideddetection and diagnosis software, where images are analysed, and clinically relevant findings suggested to aid diagnostic decisions. Many of these new developments require a tailored approach from regulators to find a way for authorization within the existing regulatory framework. The fact, that many of these new developments are carried out by academic research groups or small companies without extensive regulatory experience, adds an extra layer of difficulty. To meet this challenge, EMA and the Heads of Medicines Agencies have established the EU-Innovation Network, to support medicine innovation and early development. As a milestone of its function, beginning in 1 February 2020 a pilot for simultaneous scientific advice is starting, where the applicants will receive a consolidated advice from the participating agencies. Innovative products often require specific expertise;therefore this new form of advice is also extremely beneficial for regulators as they are able to learn from each other and broaden their knowledge. 4. Conclusions The rapid development of pharmaceutical and digital technology requires a concerted action from all stakeholders. Or, as we all experience, a global pandemic can be an important driving force of the evolution of regulatory policies. Appropriate usage of currently available regulatory tools and a continuous discussion between academia, industry and regulators would be the only way to ensure quick access to state-of-the-art, safe and efficacious medicines, and medical devices. It is clearly shown currently by the concerted action of various stakeholders and series of rolling reviews which led to the expedited authorization of COVID-19 vaccines.

ASCIMINIB PROVIDES DURABLE MOLECULAR RESPONSES IN PATIENTS (PTS) WITH CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE (CML-CP) WITH THE T315I MUTATION: UPDATED EFFICACY AND SAFETY DATA FROM A PHASE I TRIAL

Background: In pts with CML, the BCR::ABL1 T315I mutation is associated with poor clinical outcomes and confers resistance to previously approved ATP-competitive tyrosine kinase inhibitors (TKIs). Until recently, ponatinib (PON) was the only TKI available for these pts, but its use may be limited by associated cardiovascular events. In the primary analysis of the phase I trial X2101, asciminib-the 1st BCR::ABL1 inhibitor to Specifically Target the ABL Myristoyl Pocket (STAMP)-demonstrated efficacy and a favorable safety profile in heavily pretreated pts with CML with T315I. These results supported the FDA approval of asciminib as a new treatment option for pts with CML-CP with T315I (NCCN 2021). We report updated efficacy and safety data in these pts (data cutoff: January 6, 2021). Aims: Provide updated safety and efficacy data for pts with CML-CP with T315I treated with asciminib monotherapy 200 mg twice daily (BID) after added exposure. Methods: Pts with CML-CP with T315I were enrolled if treated with ≥1 prior TKI and no other effective therapy was available, provided informed consent, and received asciminib 200 mg BID. Results: 48 pts with T315I were included;2 (4.2%) pts had additional BCR::ABL1 mutations at baseline. Eight (16.7%), 15 (31.3%) and 25 (52.1%) pts received 1,2, and ≥3 prior TKIs, respectively. At data cutoff, treatment was ongoing in more than half (27 [56.3%]) of pts;the predominant reason for treatment discontinuation was physician's decision (11 [22.9%]), mainly due to lack of efficacy. Of the 48 pts, 45 were evaluable (BCR::ABL1IS >0.1% at baseline) for major molecular response (MMR);3 were excluded for BCR::ABL1 atypical transcripts. Among evaluable pts, 19 (42.2%) achieved MMR by wk 24 and 22 (48.9%) by wk 96;19 were still in MMR at the cutoff date. Evaluable pts included 26 PON-pretreated and 19 PONnaive pts;34.6% and 68.4%, respectively, achieved MMR by the cutoff date (Table). The probability of pts maintaining MMR for ≥96 wks was 84% (95% CI, 68.1-100.0). Thirteen (28.9%) and 11 (24.4%) pts achieved MR4 and MR4.5, respectively. Twenty (54.1%) and 23 (62.2%) of 37 pts with BCR::ABL1IS >1% at baseline achieved BCR::ABL1IS ≤1% by wk 48 and 96, respectively. The median duration of exposure was 2.08 (range, 0.04-4.13) yrs with more than half (27 [56.3%]) of pts receiving treatment for ≥96 wks;the median daily dose intensity was 398.3 (range, 179-400) mg/day. The safety/tolerability profile of asciminib remained favorable after ≈9 months of added follow-up (Table). The most common (≥5%) grade ≥3 adverse events (AEs) were lipase increase (18.8%, all asymptomatic elevations), thrombocytopenia (14.6%), and vomiting, ALT increase, abdominal pain, hypertension, anemia, neutropenia, and neutrophil count decrease (6.3% each). Arterial occlusive events occurred in 4 (8.3%) pts;none led to dose adjustment/interruption/discontinuation. AEs leading to discontinuation were reported in 2 new pts since the previous data cutoff;both pts discontinued and died due to COVID-19. These were the only study deaths reported in this pt population. Image: Summary/Conclusion: Asciminib monotherapy 200 mg BID exhibited a sustained, favorable safety profile after added exposure with no new safety signals in pts with CML-CP with T315I-a population with high unmet medical need. The clinical efficacy of asciminib is demonstrated by the high proportion of pts achieving durable MMR and BCR::ABL1IS ≤ 1%. The updated analysis confirms asciminib as a treatment option for pts with CML-CP with T315I, including those for whom treatment with PON has failed.

Towards Better Pharmaceutical Provision in Europe-Who Decides the Future?

Significant progress has been achieved in human health in the European Union in recent years. New medicines, vaccines, and treatments have been developed to tackle some of the leading causes of disease and life-threatening illnesses. It is clear that investment in research and development (R&D) for innovative medicines and treatments is essential for making progress in preventing and treating diseases. Ahead of the legislative process, which should begin by the end of 2022, discussions focus on how Europe can best promote the huge potential benefits of new science and technology within the regulatory framework. The challenges in European healthcare were spelled out by the panellists at the roundtable organised by European Alliance for Personalised Medicine (EAPM). Outcomes from panellists' discussions have been summarized and re-arranged in this paper under five headings: innovation, unmet medical need, access, security of supply, adapting to progress, and efficiency. Some of the conclusions that emerged from the panel are a call for a better overall holistic vision of the future of pharmaceuticals and health in Europe and a collaborative effort among all stakeholders, seeing the delivery of medicines as part of a broader picture of healthcare.

Meeting the Need for a Discussion of Unmet Medical Need.

As Europe and the world continue to battle against COVID, the customary complacency of society over future threats is clearly on display. Just 30 months ago, such a massive disruption to global lives, livelihoods and quality of life seemed unimaginable. Some remedial European Union action is now emerging, and more is proposed, including in relation to tackling "unmet medical need" (UMN). This initiative-directing attention to the future of treating disease and contemplating incentives to stimulate research and development-is welcome in principle. But the current approach being considered by EU officials merits further discussion, because it may prove counter-productive, impeding rather than promoting innovation. This paper aims to feed into these ongoing policy discussions, and rather than presenting research in the classical sense, it discusses the key elements from a multistakeholder perspective. Its central concern is over the risk that the envisaged support will fail to generate valuable new treatments if the legislation is phrased in a rigidly linear manner that does not reflect the serpentine realities of the innovation process, or if the definition placed on unmet medical need is too restrictive. It cautions that such an approach presumes that "unmet need" can be precisely and comprehensively defined in advance on the basis of the past. It cautions that such an approach can reinforce the comfortable delusion that the future is totally predictable-the delusion that left the world as easy prey to COVID. Instead, the paper urges reflection on how the legislation that will shortly enter the pipeline can be phrased so as to allow for the flourishing of a culture capable of rapid adaptation to the unexpected.

Clinical studies and monitoring activities in Sant Pau Hospital before and during the pandemic period

Objective: We aim to describe the evolution in the number of clinical studies sponsored by Institut d'Investigació Biomèdica Sant Pau (IIBSP) before and during the COVID-19 pandemic period (2019-2021). Besides, we aim to quantify the monitoring activities carried out by Sant Pau Clinical Trials Unit (SP-CTU) and by external clinical research organizations (CRO) in the same period. Material and/or methods: A database was designed to record and follow-up all independent studies sponsored by IIBSP and monitored by SP-CTU. In the same way, the Documentation and Archive Management Area of Sant Pau (AGDAC) registered the monitoring activities carried out by external CROs. A descriptive analysis of the number and types of clinical studies, and monitoring activities was made. Results: The evolution in the number of clinical studies sponsored by IIBSP was 91 in 2019, 121 in 2020 and 93 in 2021. Clinical trials represented the 11%, 13.2% and 10.7%, whereas observational studies supposed 57.1%, 54.6% and 57%, and biomedical research projects 31.9%, 32.2% and 32.3% respectively, during the evaluated years. Regarding the number of monitoring visits, in 2019 was 82 for SP-CTU and 1919 for external CROs;whereas in 2020 the number of monitoring visits was 50 for SP-CTU and 1431 for external CROs. Finally, in 2021, the number of monitoring visits was: 92 for SP-CTU and 1731 for external CROs. Conclusions: The number of clinical studies sponsored by IIBSP was higher during the first year of COVID-19 pandemic compared to the year before and the year after, probably due to the unmet medical need for COVID-19 knowledge base and therapies. Conversely, a clear reduction of monitoring activities for both independent sponsored and pharmaceutical industries sponsored studies was observed during the first year of the pandemic period, with an important recovery the following year. These data support the need to encourage remote monitoring.

POSC274 Does Conditional Marketing Authorisation Speed Up Patient Access?

Objectives: Conditional marketing authorisation (CMA) facilitates early approval for medicines intended for seriously debilitating or life-threatening diseases whose benefit of immediate availability outweighs the risk of less mature clinical data. While CMA has the potential to accelerate patient access, the perceived value at the regulatory level may not translate to value at the health technology assessment (HTA) level. This research explores whether CMA can accelerate time to patient access while maintaining optimal reimbursement outcomes. Methods: HTA outcomes of medicines with CMA from 2018-2020 were analysed, followed by 30-minute, qualitative, in-depth interviews with payer advisors from France and Germany to predict the evolution of HTA frameworks to accommodate future CMA candidates. Results: 22 medicines received CMA from the European Medicines Agency (EMA) from 2018-2020. Despite substantial unmet medical need across indications, CMA translated to poor HTA outcomes. Of 18 available HTAs in France, 8 medicines received a negative reimbursement recommendation of SMR ‘Insufficient’ (in primary indication or subgroup), while the remaining outcomes were split between ‘Important’, ‘Moderate’ and ‘Low’. Most of the reimbursed medicines demonstrated poor quality of evidence, and received ASMR V. Of 13 available HTAs in Germany, only one medicine achieved an added benefit rating, while most demonstrated ‘no’ or ‘non-quantifiable’ added benefit. Payers expect future CMA candidates will face similar reimbursement hurdles if market-specific HTA requirements are not met. Conclusions: While CMA accelerates regulatory approval, limited data packages create huge uncertainty in the appraisal of medicines. This leads to significant risk of unfavourable reimbursement outcomes and delays in patient access. While HTA frameworks continue to evolve over time, they are unlikely to reward immature data submissions particularly as payer bodies face ever-increasing funding constraints likely exacerbated by the COVID-19 pandemic. Manufacturers should ensure their drug development programs meet both regulatory and payer requirements to support accelerated patient access.

POSC254 The Impact of COVID-19 on European HTA Decisions

Objectives: To investigate the impact of the COVID-19 pandemic on the drug technology assessment (TA) process of European HTA agencies. This study explored changes to routine practice and assessment in response to the pandemic, and assessed the impact of these changes on the number and type of assessments published during this time. Methods: Adaptations to current assessment practices were established for each HTA agency, including timelines where available. TAs published by the National Institute for Health and Care Excellence (NICE), Scottish Medicines Consortium (SMC), Haute Autorité de Santé (HAS) and Gemeinsame Bundesausschuss (G-BA) during the last 2 years were identified and compared. Results: Initial meeting suspension resulted in the absence of SMC assessments between May and July 2020, with a subsequent phased approach including scope for ‘fast-track to advice’. As part of the phased approach, medicines with the potential to deliver the greatest benefit to patients were prioritised for assessment, although the number of cancer-related assessments remained consistent. NICE published only one assessment per month in March and April 2020, with minimal notable impact on the number of subsequent assessments. Work related to addressing COVID-19 diagnostic or therapeutic interventions and medicines deemed ‘therapeutically critical’ was prioritised, and a higher proportion of assessments pertaining to cancer were published following the emergence of COVID-19. HAS initially assigned priority to drugs intended to manage COVID-19 in addition to new TAs or extension of indication assessments in oncology, paediatrics and in serious illnesses with an unmet medical need;the number of oncology assessments remained consistent following COVID-19 emergence. The reported impact on Germany was minimal;G-BA meetings were held virtually to minimise delays in assessments or pricing negotiations. Conclusions: Despite the individualised approach in response to the challenges of COVID-19, European HTA agencies demonstrated minimal long-term impact and a return to normal drug TA output.

Unmet Medical Need as a Driver for Pharmaceutical Sciences - A Survey Among Scientists.

Historical antecedents of pharmaceutical sciences are sound on product orientation based on (analytical) chemistry, drug delivery and basic pharmacology. Over the last decades we have seen a transition towards a stronger disease orientation. This raises questions on whether, how and to what extent unmet medical need (UMN) is important in priority setting, funding and impact in pharmaceutical sciences. An online survey in 2020 collected perspectives of internationally recognised pharmaceutical scientists (N = 92), mainly from academia and industry, on drivers and influencing factors in pharmaceutical sciences. The study offers a unique global perspective, demonstrating a solid command of the global needs in pharmaceutical sciences. The survey revealed that UMN is currently seen as one of the three most important drivers, also in addition to emerging trends in science and opportunities driven by collaboration. There are expectations that UMN's impact becomes more influential. This was consistent for both industry and academic respondents. The majority of respondents also indicated that anticipated lessons learned from COVID-19 will strengthen the impact of UMN on science and leadership. This is important as prioritisation of research towards UMN can address the clinical needs where needed the most.