European Public Research Articles

HPR138 How Are Patient Experience Data Reported in Regulatory Evaluation of Medicinal Products? A Document Analysis of European Public Assessment Reports

HPR138 How Are Patient Experience Data Reported in Regulatory Evaluation of Medicinal Products? A Document Analysis of European Public Assessment Reports

“European Public Sector Accounting” (2nd edition)

“European Public Sector Accounting” (2nd edition)

Preclinical Pharmacokinetic/Pharmacodynamic Studies and Clinical Trials in the Drug Development Process of EMA-Approved Antifungal Agents: A Review.

Antifungal drug development is essential as invasive fungal disease is still associated with a very high mortality rate and the emergence of resistant species in the last decade. In Europe, the European Medical Agency (EMA) approves antifungals and publishes the European Public Assessment Report (EPAR) including the information leading up to the authorisation. We looked at EMA-approved antifungals and their reports within the last 23 years. We focused primarily on the role of pharmacokinetic/pharmacodynamic indices in antifungal development and the level of information depicted in their corresponding report. Furthermore, we investigated guidelines applicable to the development process at the time and compared the content with a focus on pharmacokinetic/pharmacodynamic studies and preclinical requirements. Since 2000, six new antifungal substances have been authorised. Most were authorised for treatment of Candida infections or Aspergillus infections but also included rarer pathogens. Pharmacokinetic/pharmacodynamic indices were scarcely investigated and/or mentioned in the report. Current antifungal EMA guidelines started emphasising investigating pharmacokinetic/pharmacodynamic indices in 2010 and then again in 2016. It remains to be seen how this translates into the authorisation process for new antifungals.

Understanding the Needs and Lived Experiences of Patients With Graft-Versus-Host Disease: Real-World European Public Social Media Listening Study.

Graft-versus-host disease (GVHD) is the major cause of short- and long-term morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Treatment options beyond corticosteroid therapy remain limited, and prolonged treatment often leads to impaired quality of life (QoL). A better understanding of the needs and experiences of patients with GVHD is required to improve patient care. The aim of this study is to explore different social media (SM) channels for gathering and analyzing the needs and experiences of patients and other stakeholders across 14 European countries. We conducted a retrospective analysis of SM data from the public domain. The Talkwalker social analytics tool collected data from open-access forums, blogs, and various social networking sites using predefined search strings. The raw data set derived from the aggregator tool was automatically screened for the relevancy of posts, generating the curated data set that was manually reviewed to identify posts that fell within the predefined inclusion and exclusion criteria. This final data set was then used for the deep-dive analysis. A total of 9016 posts relating to GVHD were identified between April 2019 and April 2021. Deduplication and relevancy checks resulted in 325 insightful posts, with Twitter contributing 250 (77%) posts; blogs, 49 (15%) posts; forums, 13 (4%) posts; Facebook, 7 (2%) posts; and Instagram and YouTube, 4 (1%) posts. Patients with GVHD were the primary stakeholders, contributing 63% of all SM posts. In 234 posts, treatment was the most discussed stage of the patient journey (68%), followed by symptoms (33%), and diagnosis and tests (21%). Among treatment-related posts (n=159), steroid therapy was most frequently reported (54/159, 34%). Posts relating to treatment features (n=110) identified efficacy (45/110, 41%), side effects (38/110, 35%), and frequency and dosage (32/110, 29%), as the most frequently discussed features. Symptoms associated with GVHD were described in 24% (77/325) of posts, including skin-related conditions (49/77, 64%), dry eyes or vision change (13/77, 17%), pain and cramps (16/77, 21%), and fatigue or muscle weakness (12/77, 16%). The impacts of GVHD on QoL were discussed in 51% (165/325) of all posts, with the emotional, physical and functional, social, and financial impacts mentioned in 69% (114/165), 50% (82/165), 5% (8/165), and 2% (3/165) of these posts, respectively. Unmet needs were reported by patients or caregivers in 24% (77/325) of analyzed conversations, with treatment-related side effects being the most common (35/77, 45%) among these posts. SM listening is a useful tool to identify medical needs. Treatment of GVHD, including treatment-related side effects, as well as its emotional and physical impact on QoL, are the major topics that GVHD stakeholders mention on SM. We encourage a structured discussion of these topics in interactions between health care providers and patients with GVHD. Not applicable.

Concordance between expectations and preferences of patients and evaluation criteria of the European Medicines Agency

ObjectiveThe European Medicines Agency's marketing authorisation criteria for drugs are reflected in the European Public Assessment Reports. The objective is to describe the expectations and preferences of our onco-hematological outpatients with respect to their oral treatments, and to evaluate the concordance with the results of European Public Assessment Reports. MethodA survey of onco-hematological patients’ expectations and preferences about overall survival and quality of life was developed, with three items: expectations on treatment, preferences of benefit and willingness to receive novel treatments with non-definitive results. European Public Assessment Reports of the indicated drugs were reviewed. Kappa index (κ) was used to assess the agreement between patients’ expectations and preferences respect to the benefit in overall survival and quality of life described in the corresponding European Public Assessment Report. Concordance between willingness of patients to receive novel treatments and European Public Assessment Reports results was evaluated by absolute agreement (Ao). ResultsThere were 29 participants, and 19 different European Public Assessment Reports were consulted. Patients’ expectations about their treatment: 82.1% expected improvement in overall survival and quality of life; the κ value between expectations and results of European Public Assessment Reports was 0.091 (confidence interval 95%: -0.025 to 0.207). Patients’ preferences about benefit of their treatment: 92.6% preferred quality of life; the κ value was 0.016 (confidence interval 95%: -0.127 to 0.160). Willingness to receive novel treatments: 82.1% participants demanded benefit in overall survival or quality of life; exigences were met in Ao = 53.6% of patients. ConclusionsLittle agreement was observed between expectations and preferences of our onco-hematological patients and European Public Assessment Reports, according to overall survival and quality of life. Most patients preferred an improvement in quality of life, but also expected an increase in overall survival with their treatment. Almost half of patients would not meet their requirements to receive their drug when it was authorized.

A European Public Sphere United by Football: A Comparative Quantitative Text Analysis of German, Norwegian, Polish and Spanish Football Media

AbstractThe ability of the European community to respond to the multiple crises threatening the European Union and Europe depends in part on citizens' shared European identity giving legitimacy and support to communal action. Men's elite European club football is an example of a cultural practice that is highly Europeanised, reaches diverse audiences and is a known carrier of collective identities. This article examines the emergence of a European public football sphere through the convergence of football coverage across national media spaces, serving as a foundation for European identity constructions. It connects the concept of a European public sphere to the Europeanisation and mediatisation of football and its potential effects on European identity formation. Results indicate a convergence of football coverage around high‐profile and high‐status aspects of European football, creating a strongly aligned, homogenous but exclusive European public football sphere that leaves many parts of Europe on the sidelines.

Parents’ knowledge towards prevention of unintentional injuries in children aged up to 14 years

Abstract The CHILD Vigilance project is a European study supported by the Injury Prevention & Safety Promotion Section of the European Public Health Association (EUPHA INJ) and aims at assessing parenting knowledge and attitudes that are relevant to supervision and risk taking in children. The study aims contribute to the epidemiological knowledge of injuries and accidents in Greece and Portugal, through the study of the knowledge of the perceptions of parents and caregivers of children and adolescents between 0 and 14 years old. A descriptive, observational, cross-sectional study was developed in these countries during the period from february till april 2023, under the CHILD Vigilance project. In this study was obtained a total of 577 valid responses, involving 890 children (53,1% male; 46,8% female), with an average age of 8,9 years old. In both countries the mother was the main child carer (60,3% in Greece vs 60,1% in Portugal). In majority of the cases parents had two children (30,1% in Greece vs 44,9% in Portugal). The results revealed that almost all the parents knew about unintentional injuries (82,4 % in Greece vs 92,3% in Portugal), considered that have a big impact on children (89,8% in Greece vs 66,9% in Portugal) and injuries are preventable (63,2% in Greece vs 88,4% in Portugal). Considering data from both countries, the analysis of the association of parents’ knowledge with their occupation showed that civile servant were those who most considered that injuries have a big impact on children (86,5% - mother; 83,2% - father) and that injuries can be preventable (87,9% - mother; 84,9% - father), these differences were statistically significant (p < 0,01). The results may inform the design, implementation and evaluation of interventions to promote safety and prevent accidents in these both countries. Key messages • The lack of data regarding to parents’ knowledge on injury prevention involving children highlight the need to conduct this type of studies. • Education injuries prevention programs addressed to parents should be design considering demographic variables.

8.I. Skills building seminar: Improving your elevator pitch: convincing a policymaker in a matter of seconds

Abstract Many public health researchers aspire their scientific findings to contribute to evidence-informed policies. However, realising this translation of evidence into policy is often experienced as a challenge. This is no surprise, as typical researchers’ activities - from data collection and analysis to publishing scientific articles - is a totally different ballgame than getting your messages across to policymakers. Additional skills are required by public health researchers in order to let their research findings make their way into health policies. One of those skills is to be able to pitch your work when meeting a policymaker e.g. in an elevator. In this skills building seminar high scoring abstract submitters will be invited to present their work in maximum 60 seconds to a panel of policymakers and politicians. Following the learning by doing approach, this hands on session will not only be a learning experience for the presenting researchers, also the audience will learn, as each pitch will receive feedback on the spot from the panel of real policymakers and politicians. Are they interested? Do they remember the key message? And if all goes well, do you get an invitation to come back and present more of your work? Since a number of years the European Public Health Association (EUPHA) has been organising skills building seminars on the elevator pitch. Building forward on those previous four successful and well-attended workshops, the current workshop will follow up on this series and take forward where the previous editions ended. Lessons learned at the previous elevator pitch workshops: - Have a clear ask (keep it simple) and show enthusiasm. - Appeal to the policymaker's own interests and priorities. - Spell out how action will be beneficial for the policymaker. - Be aware of upcoming elections. - Build a relationship with the assistants of politicians. - Consider the ‘policy window’. - Make the comparison with the policy plan. - Propose an action the politician should undertake. - Identify the relevant stakeholders and groups affected by the problem. For this fifth edition we take the elevator pitch to the next level. Whereas previous editions allowed pitches up to 2 minutes, the current seminar will set the timer at 60 seconds. The previous editions showed that keeping the pitch very short was more successful. The session will be wrapped up by a key note with reflections on the pitches exercise and linking this to what the literature says about influencing healthy policy making. Key messages • The elevator pitch is a useful skill to have for public health researchers to facilitate the outcomes of their research feed into health policies. • There are numerous tools available to effectively communicate public health messages to policymakers and promote evidence-informed policy making.

10.M. Workshop: Community Health Practice and Research in Europe: Up front and centre!

Abstract Community Health (CH) is one of the most undervalued and poorly funded domains of action of health systems. Although evidence is strong on its contribution to population health, well-being and equity, national and regional health systems, and to some extent public health institutions, tend to pay little attention to its contribution. Community health encompasses the application of health promotion principles and strategies at the local level to improve equity and resilience of a community. It does so through three fundamental means: cross-sectoral collaborations, community involvement/engagement, and community health workers (CHW). It engages and works with communities in a culturally appropriate manner in order to implement effective strategies. In community health, capacity building is essential. The aim of this workshop is three-fold: 1) to generate a discussion among participants on the state of practice and research, 2) to reflect on strategies to strengthen and improve community health in Europe and, 3) to enhance the visibility of this domain within the ranks of the European Public Health Association (EUPHA). The workshop will provide a space for reflections and discussions. Each of our speakers, who are researchers from 5 different countries (Belgium, Czech Republic, Germany, Spain, and UK), will have 5 minutes to provide some elements of answers to the two following questions: • What is the state of community health practice and research in your country? • What difference does it make for health systems to implement community health strategies? Eric Breton (France) will briefly introduce the workshop providing a conceptual framework for community health and an overview of the different perspectives that drive practices and policies. Manfred Cassens (Germany) and Caroline Masquillier (Belgium) will discuss how the COVID-19 pandemic has enhanced the shortfalls of health systems and lead their countries to experiment community health strategies. Camila Picchio (Spain) will demonstrate how CHWs are essential in reaching out marginalised communities as will Ekaterina Volevach (Czech Republic) drawing lessons from a programme targeting the Roma population. Both will highlight the difficulties health systems face in answering the need of vulnerable population. Catherine Jenkins (United Kingdom), will describe a city-region intervention for galvanising community-level innovation to reduce gambling-related harms. Luis Saboga-Nunes, President of the EUPHA Health Promotion Section and Goof Buijs, Manager of the UNESCO Chair Global Health & Education will conclude the session. We trust that this very interactive workshop will help attendees of the EUPHA conference in Dublin working in community health to find each other and facilitate the development of partnerships. Key messages • Community Health strategies are essential in improving populations’ health and well-being. Yet, this contribution is hardly reflected in national health policies and in the resources invested locally. • The COVID-19 pandemic cast a harsh light on the limits of health systems under-investing in community engagement, community health workers and in the mobilisation of local stakeholders.

Evaluation of the impact of the complex intervention ‘10,000 Steps Duesseldorf’: Replication study

Abstract Background The World Health Organization (WHO) recommends 150-300 minutes of moderate physical activity (PA) per week (approximately 7,000-10,000 steps/day). In Germany, fewer than half of all adults achieve this goal. This highlights the need for population-based intervention approaches to promote regular daily PA. The aims of this replication study are to adapt, implement and evaluate a community-based complex PA intervention originally developed and successfully implemented in Belgium. The following research questions are investigated: 1. Is the intervention ‘10,000 Steps Ghent’ adaptable and transferrable to the German context? 2. Is the intervention ‘10,000 Steps Duesseldorf’ effective for the promotion of PA among residents of city districts selected for the study compared to city districts of a control city? Methods The intervention includes components at different intervention levels (i.e., individual level: website; organizational level: promotion of PA e.g., in companies, senior citizens’ associations; community level: media campaign, environmental changes, e.g., signage in parks). To investigate the effects of the intervention, PA-levels were assessed via telephone interviews and pedometers in two representative samples of adults aged 25-75 years in the cities of Duesseldorf (intervention) and Wuppertal (control) at baseline (April 2021 - March 2022). The one-year follow-up will start in May 2023. Results 376 participants in the intervention and 253 in the control city districts completed baseline (60% female, 32% wore accelerometers in addition to the pedometers). First study results will be presented at the annual European Public Health Conference after the trial is completed. Conclusions To our knowledge, this study is the first research project aiming to replicate the effects of a complex PA intervention successfully implemented in another European country. Key messages • Results regarding the adaptation and transferability of a complex PA intervention originally developed and implemented in Belgium will be presented. • Results regarding the impact of the community-based complex intervention ‘10,000 Steps Duesseldorf’ on residents’ PA levels will be shown.

In the Shadows of the Commonwealth: Catholicism, Religious Tolerance, and Nineteenth-Century Polish Independence

Polish intellectuals in the first half of the nineteenth century defended Polish independence in the European public sphere through the conscious invention of a tradition of religious tolerance. Because defenses of Polish independence in this period were often designed for a European public, the multi-religious heritage of Poland-Lithuania’s past provided resources to shape Polish politics for a variety of audiences and their differing political and religious values. European and Polish publics saw the Russian empire as religiously intolerant, and therefore Poles crafted histories of Poland that offered an explicit counterpoint to this perception of Russia: a Polish tradition of religious co-existence. As long as these international geopolitical appeals remained a dominant part of their political imaginations, Polish intellectuals conceived of Poland in a multi-confessional manner. Polish intellectuals in the first half of the nineteenth century did not conflate Polish national identity with Roman Catholicism but framed their ideas against the multi-religious legacy of the Polish-Lithuanian Commonwealth. However, by tying the question of Polish independence so strongly to the religious sphere, the figures in this article laid the groundwork for future developments in Polish nationalism in later (and more confessionally rigid) periods.

Precision medicine in regulatory decision making: Biomarkers used for patient selection in European Public Assessment Reports from 2018 to 2020.

Biomarkers can guide precision medicine in clinical trials and practice. They can increase clinical trials' efficiency through selection of study populations more likely to benefit from treatment, thus increasing statistical power and reducing sample size requirements or study duration. We performed a narrative synthesis to explore biomarker utilization for patient selection to guide precision medicine trials in marketing authorization dossiers of centrally approved medicines in Europe between 2018 and 2020 and analyzed in-depth those that eventually included biomarkers in the medicines' indications. From 119 eligible products, 26 included a biomarker in the indication, of which most were oncology products (n = 15). Included biomarkers were often known from literature or from previously approved products in the European Union or the United States. Additionally, 52 dossiers mentioned one or more biomarkers for patient selection in their clinical efficacy and safety information. Although these were not always included in the medicines' indication, they were often implicitly embedded in condition definitions adopted from clinical guidelines or practice. In 15 out of the 26 medicines with a biomarker-guided indication, only biomarker-positive populations were included in the main clinical studies supporting the marketing authorization. These studies were mostly randomized controlled trials or single-arm trials; only two products were studied for multiple indications in an innovative basket trial. Definitions of biomarkers could be subject of debate and needed adaptation after post hoc analyses requested by the assessment committee in four cases, stressing the importance of thorough justification of these definitions to include the right population for an optimal benefit-risk balance, enabling precise medicine.

Do the Outcomes of Clinical Efficacy Trials Matter in Regulatory Decision-Making for Biosimilars?

There is an increasing body of evidence supporting a more flexible approach in clinical data requirements for the approval of more complex biosimilar substances such as monoclonal antibodies (mAbs). The aim of this paper is to further analyse the role of quality/chemistry, manufacturing and controls (CMC) and clinical data for the conclusion on biosimilarity and the decision on marketing authorisation (MA). In the present study, we analysed the MA applications (MAAs) of all 33 mAbs and three fusion proteins evaluated by the European Medicines Agency (EMA) between July 2012 and November 2022 with special emphasis on all submitted rituximab (four products) and trastuzumab (seven products) biosimilar candidates, including withdrawn applications. For the two withdrawn applications, the comparative efficacy trials suggested biosimilarity, but the quality/CMC package was not accepted by EMA. We therefore investigated whether a negative MAA outcome could have been predicted based on the evidence generated in the quality/CMC packages, regardless of clinical trial data. For this purpose, we reviewed the respective European Public Assessment Reports (EPARs) or withdrawal assessment reports, and the first regulatory assessments for all these 36 MAAs (i.e. day 120 of the centralized procedure), which are not publicly available. During EMA review, where significant issues are identified which would preclude a marketing authorisation, these issues are raised as questions to the applicant and are classified as major objections (MO). In 67% of cases, the outcome of the quality and clinical assessment was the same, i.e. both the quality and clinical assessments either supported approval or did not support approval. In 11% of cases, MO were identified in the quality part of the submission but not in the clinical data. In 22% of cases, MO were raised on the clinical data package but not on the quality data. However, we found no instance where seemingly negative clinical data, including failed efficacy trials, led to a negative overall decision. In each instance, the failure to confirm similar clinical performance in all investigated aspects was eventually viewed as not being related to the biosimilar per se but as being due to imbalances in the trial arms, immaturity of secondary endpoint results, change in the reference product, or even chance findings. Furthermore, when performing an in-depth analysis of the quality and clinical packages of trastuzumab and rituximab biosimilars, we found that in no case were clinical trial data necessary to resolve residual uncertainties regarding the quality part. The results further support the argument that sufficient evidence for biosimilarity can be obtained from a combination of analytical and functional testing and pharmacokinetic studies which may also generate immunogenicity data. This calls into question the usefulness of comparative efficacy studies for the purposes of regulatory decision-making when approving biosimilar mAbs and fusion proteins.

European Public Health News.

European Public Health News.

Field Epidemiology: Fit for the future.

In recent years, field epidemiologists have embraced rapidly evolving digital tools, data sources and technologies, and collaborated with an ever-growing field of scientific specialisms. The COVID-19 pandemic put field epidemiology under unprecedented demand and scrutiny. As the COVID-19 emergency recedes, it is timely to reflect on the core values of our profession and the unique challenges and opportunities that lie ahead. In November 2022, alumni of the European Programme for Intervention Epidemiology Training (EPIET) and the European Public Health Microbiology (EUPHEM) training programme celebrated 25 years of EPIET, and the present and future of field epidemiology was discussed. The output was recorded and qualitatively analysed. This Perspective reflects the authors' interpretation of the discussion. We should reaffirm our commitment to field epidemiology's core strengths: competence and rigour in epidemiology, surveillance, outbreak investigation and applied research, leading to timely and actionable evidence for public health. Our future success will be defined by an ability to adapt, collaborate, harness innovation, communicate and, ultimately, by our tangible impact on protecting and improving health.

Field Epidemiology and Public Health Microbiology training: capturing the alumni perspectives of the training's impact.

We present the findings from the European Programme for Intervention Epidemiology Training (EPIET) Alumni Network (EAN) Member Survey conducted in October to December 2021. The EAN consists of field epidemiologists (EPIET) and public health microbiologists (European Public Health Microbiology Training Programme (EUPHEM)) who stay connected after their 2-year fellowship. This active alumni network provides opportunities for career development, mentorship, knowledge exchange and sharing of best practices for community members, affiliated professionals and public health organisations in Europe. Overall, 281 of 732 members participated in the survey. Of the 192 European fellowship alumni respondents, 173 (90%) indicated that skills and competencies acquired during their fellowship improved performance in their role compared with their abilities before the fellowship. Reported skills and competencies that could be further strengthened included data management/analysis, communication, mathematical modelling and leadership/team management. The EAN Member Survey provides valuable feedback to the EAN, as well as the fellowship programme offices at the European Centre for Disease Prevention and Control (ECDC) and affiliated field epidemiology programmes. The COVID-19 pandemic was a stark reminder of how essential cross-border collaborations are for continued European health security. Maintaining and increasing the professional, well-trained workforce remains crucial for optimal response to infectious diseases and protection of public health.

Duration of Effectiveness Evaluation of Additional Risk Minimisation Measures for Centrally Authorised Medicinal Products in the EU Between 2012 and 2021.

In studies evaluating the effectiveness of additional risk minimisation measures (aRMMs), the need for speed must be properly balanced with the quality of the study. We assessed the duration of aRMM effectiveness evaluations, using additional pharmacovigilance activities, for centrally authorised medicinal products in the European Union. We established a cohort of medicinal products with aRMMs at marketing authorisation (MA) that were centrally authorised from July 2012-December 2021 using the European Public Assessment Reports. Evaluation studies were identified from the Risk Management Plans at the time of MA. Subsequently, we retrieved protocols, final study reports, Pharmacovigilance Risk Assessment Committee (PRAC) assessment reports, and PRAC minutes. We calculated the probability of completing an effectiveness evaluation within 60 months after MA using time-to-event analyses. Besides, we compared the planned final report with the actual final report date. We identified 134 medicinal products authorised with aRMMs, of which almost half (n = 63, 47.0%) had an effectiveness evaluation study. The probability of an evaluation for a medicinal product being completed within 60 months after MA was 20.7% (95% CI 6.8-32.6). Regarding study design, the probability of completing a study was higher for cross-sectional studies when compared to cohort studies (p = 0.002). Moreover, 81.0% of studies were delayed when compared to their planned final report date. The probability of completing an aRMM effectiveness evaluation at time for renewal of the MA was only one in five. Furthermore, estimates of the duration of studies around MA are too optimistic, with the majority being delayed.

The Assessment of Patient-Reported Outcomes for the Authorisation of Medicines in Europe: A Review of European Public Assessment Reports from 2017 to 2022.

Health regulators have progressively increased their attention and focus on patient-reported outcomes (PROs), driven by the diffusion of a patient-centred approach to the drug development process. This study investigates the consideration of PROs and their measures (PROMs) in the authorisation of medicines in Europe. All medicines for human use authorised or refused by the European Medicines Agency (EMA) in the period 2017-2022 were identified, and corresponding European Public Assessment Reports (EPARs) were downloaded for review. Medicine and PROs/PROM characteristics were systematically recorded. A multivariate logistic regression was performed to identify variables associated with the use of patient-reported evidence in EPARs. Overall, 497 EPARs of authorised medicines and 19 EPARs of refused medicines were analysed; of these, 240 (48.3%) and 10 (52.6%), respectively, reported any use of PROs/PROMs (p = 0.710). For authorised medicines, the likelihood of using PROs/PROMs was negatively affected by generic (OR = 0.01, p < 0.001) and biosimilar status (OR = 0.46, p = 0.013) and positively affected by orphan status (OR = 1.41, p = 0.177). The use of PROMs (50.6% in 2017 vs 47.9% in 2022) did not show a clear pattern over the 6-year period considered (p = 0.758) and was particularly uncommon in some therapeutic areas (e.g., 15.2% in infectious diseases). A total of 816 dyads of PROs/PROMs were identified. On average each EPAR considered 1.6 (range: 0-14) instruments. Patient-reported outcomes were typically secondary (53.3%) and exploratory endpoints (18.8%); in one-third of cases (32.5%), they assessed generic quality of life. Among the PROMs, 227 (27.8%) targeted general population; EQ-5D (11.0%), SF-36/SF-12 (5.9%) and EORTC QLQ-C30 (5.6%) were the instruments most frequently used. This study suggests PROs/PROMs are considered in less than half of total medicine assessments and even more rarely in some disease areas. The adoption of PROs is key in EMA strategy to 2025 and would be facilitated by consensus development on their measures and optimisation of data collection.

How can patient preferences be used and communicated in the regulatory evaluation of medicinal products? Findings and recommendations from IMI PREFER and call to action.

Objective: Patients have unique insights and are (in-)directly affected by each decision taken throughout the life cycle of medicinal products. Patient preference studies (PPS) assess what matters most to patients, how much, and what trade-offs patients are willing to make. IMI PREFER was a six-year European public-private partnership under the Innovative Medicines Initiative that developed recommendations on how to assess and use PPS in medical product decision-making, including in the regulatory evaluation of medicinal products. This paper aims to summarize findings and recommendations from IMI PREFER regarding i) PPS applications in regulatory evaluation, ii) when and how to consult with regulators on PPS, iii) how to reflect PPS in regulatory communication and iv) barriers and open questions for PPS in regulatory decision-making. Methods: PREFER performed six literature reviews, 143 interviews and eight focus group discussions with regulators, patient representatives, industry representatives, Health Technology Assessment bodies, payers, academics, and clincians between October 2016 and May 2022. Results: i) With respect to PPS applications, prior to the conduct of clinical trials of medicinal products, PPS could inform regulators' understanding of patients' unmet needs and relevant endpoints during horizon scanning activities and scientific advice. During the evaluation of a marketing authorization application, PPS could inform: a) the assessment of whether a product meets an unmet need, b) whether patient-relevant clinical trial endpoints and outcomes were studied, c) the understanding of patient-relevant effect sizes and acceptable trade-offs, and d) the identification of key (un-)favorable effects and uncertainties. ii) With respect to consulting with regulators on PPS, PPS researchers should ideally have early discussions with regulators (e.g., during scientific advice) on the PPS design and research questions. iii) Regarding external PPS communication, PPS could be reflected in the assessment report and product information (e.g., the European Public Assessment Report and the Summary of Product Characteristics). iv) Barriers relevant to the use of PPS in regulatory evaluation include a lack of PPS use cases and demonstrated impact on regulatory decision-making, and need for (financial) incentives, guidance and quality criteria for implementing PPS results in regulatory decision-making. Open questions concerning regulatory PPS use include: a) should a product independent broad approach to the design of PPS be taken and/or a product-specific one, b) who should optimally be financing, designing, conducting, and coordinating PPS, c) when (within and/or outside clinical trials) to perform PPS, and d) how can PPS use best be operationalized in regulatory decisions. Conclusion: PPS have high potential to inform regulators on key unmet needs, endpoints, benefits, and risks that matter most to patients and their acceptable trade-offs. Regulatory guidelines, templates and checklists, together with incentives are needed to foster structural and transparent PPS submission and evaluation in regulatory decision-making. More PPS case studies should be conducted and submitted for regulatory assessment to enable regulatory discussion and increase regulators' experience with PPS implementation and communication in regulatory evaluations.

Radca prawny w postępowaniach prowadzonych przez „nowy” OLAF i EPPO

Attorney-at-law in the proceedings conducted by the new OLAF and EPPO The article extensively discusses the issue of combating broadly understood white-collar crime and crimes affecting the interests of the European Union, per the PIF Directive, as well as the new police and investigative powers of the European Anti-Fraud Office (OLAF) and the European Public Prosecutor’s Office (EPPO). The author not only discusses OLAF’s policing and investigating powers but also points to the role of an attorney-at-law as a person who serves both advice and ensures that procedural guarantees are observed. By presenting in detail the catalogue of procedural guarantees and the role of the Controller of Procedural Guarantees, the author indicates the mechanisms of ensuring the protection of the person who is subject to EU investigation as well as presenting the necessity for a support of a professional legal representative. The detailed description of procedural guarantees is followed by postulates of strengthening the independence and expansion of the system of protection of procedural guarantees by providing it with an independent back office and establishing Controllers of Procedural Guarantees in countries where OLAF will be the leading institution of European investigations (Poland, Hungary, Sweden, Ireland and Denmark).