Why engagement remains fragile: A qualitative comparison of principal investigators’ and patient organisations’ perspectives in Italy

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Despite this, engagement often remains fragile and inconsistently embedded in routine trial practices, especially where shared operational standards are limited. This study examines why engagement remains difficult to institutionalise in Italy by comparing perspectives from principal investigators and patient organisation representatives. Methods: We conducted semi-structured remote interviews with principal investigators involved in oncological clinical research and representatives of patient organisations engaged in advocacy and research-related activities. Interviews were audio-recorded with consent, transcribed verbatim, and analysed using an iterative qualitative process focused on barriers to meaningful engagement. Coding and thematic clustering were performed to identify recurring patterns and areas of convergence and divergence across the two stakeholder groups. In a subsequent interpretive step, the resulting barrier themes were organised into four cross-cutting dimensions—cultural, organisational, operational, and institutional—to support comparison and reporting. Results: Participants in both groups described a shared set of interrelated barriers but interpreted and prioritised them differently. Cultural barriers centred on tensions around expertise, authority, and the perceived legitimacy of experiential knowledge in trial design. Organisational barriers included fragmentation within the patient organisation landscape and misalignment of priorities between scientific endpoints and patient-relevant concerns. Operational barriers reflected workload pressure, limited integration of engagement into trial workflows, and asymmetries in language and expertise that constrained informed participation. Institutional barriers included discontinuity, limited feedback to patients and organisations, and the absence of clear guidance on when and how to engage patients consistently. Together, these factors contributed to engagement being late, episodic, and dependent on individual initiative rather than routine practice. Conclusions: PE and PPI in Italian oncology research remain fragile because multiple barriers intersect across culture, organisation, operations, and institutions, while stakeholders often hold different assumptions about roles and value. Strengthening engagement requires more explicit operational guidance, dedicated resources, and shared capacity-building to support earlier, more consistent, and more sustainable collaboration. patient organisations patient and public involvement patient engagement principal investigators clinical trials research involvement oncology Figures Figure 1 Plain English Summary Patients and patient organisations are increasingly encouraged to contribute to clinical research so that studies better reflect real-life needs and are easier, fairer, and more relevant for those taking part. This is especially important in cancer research, where treatments and clinical trials can be long, complex, and disruptive to everyday life. However, in Italy, patient involvement is still not routine in research and often depends on individual researchers' willingness. In this study, we explored why this happens by interviewing two groups: principal investigators, who design and lead clinical studies, and representatives of patient organisations, who support patients and often interact with research teams. We asked about their experiences and about the main difficulties that make patient involvement hard to achieve in practice. Both groups recognised many of the same problems, but often understood them differently. Some barriers are linked to culture and professional roles, including uncertainty about who should influence research decisions and how much value should be given to patients’ lived experience. Others are organisational and practical, such as fragmented collaboration, lack of time, heavy workloads, and limited resources. Communication is another challenge, especially when research is presented in highly technical language that non-specialists find difficult to understand. There are also broader system-level problems, including a lack of continuity, limited feedback to patients and organisations, and no clear shared guidance on how involvement should happen. Overall, patient involvement remains fragile because these barriers interact with one another. Clearer guidance, dedicated support, and shared training could help make involvement earlier, more consistent, and more meaningful. Introduction Over the past decade, the involvement of patients and patients' organisations has become increasingly prominent in clinical research ( 1 – 3 ). Patient Engagement (PE) and Patient and Public Involvement (PPI) are related but distinct: PE refers to individuals’ participation in their own care (e.g., self-management, shared decision-making), whereas PPI concerns the involvement of patients, caregivers, and the public in shaping health research (e.g., design, conduct, governance, and dissemination) ( 1 , 4 – 12 ). Accordingly, PE operates mainly at the micro level of care delivery, while PPI functions at meso- and macro-levels by influencing research processes and, indirectly, health system governance ( 13 ). A growing body of literature shows the benefits of both PE ( 4 , 14 – 24 ) and PPI ( 13 , 25 – 27 ), including greater recognition and inclusion for patients and the introduction of perspectives that can challenge established assumptions and enrich researchers’ decision-making ( 5 , 18 , 21 , 28 – 30 ). In this sense, PE is increasingly framed not only as an ethical commitment but also as a pragmatic strategy to improve research effectiveness ( 21 , 31 ). The relevance of PE is particularly evident in oncology, where clinical trials are often long and complex, involve multiple treatment phases, and entail substantial side effects with profound implications for patients’ Quality of Life (QoL) ( 1 , 32 – 34 ). Moreover, oncology is characterised by a high volume of clinical trials aimed at evaluating innovative therapies, making it crucial that patients’ perspectives are adequately considered when defining research questions, endpoints, and acceptable trade-offs between treatment efficacy and QoL ( 1 , 15 , 34 , 35 ). Compared with other therapeutic areas, oncology has also developed a relatively strong tradition of collaboration between researchers and patient organisations, making it a particularly informative setting for exploring both the potential and the limitations of PE. Despite its growing endorsement, PPI remains difficult to implement in practice. While numerous frameworks, recommendations, and policy initiatives promote greater patient involvement, operational guidance is often limited, and engagement activities risk becoming tokenistic or poorly embedded within research processes ( 8 , 17 , 36 – 42 ). Moreover, many existing approaches insufficiently account for the complexity of PPI, which can take different forms across research phases and typically involves a broader constellation of actors beyond clinicians and patients alone ( 43 , 44 ). This gap between normative aspirations and everyday practice raises pressing questions about what constrains effective PE, its implications for PPI, and under what conditions it can be realised in a meaningful, non-tokenistic way. This paper focuses on Italy, where PE and PPI are increasingly visible in policy agendas and scholarly debate. Within this context, the study investigates barriers to engagement and involvement in clinical research that impede the attainment of its anticipated benefits. To develop a more comprehensive account, we draw on two complementary qualitative analyses of stakeholder groups central to oncology clinical trials: principal investigators (PIs), who design and conduct studies, and patient organisations (POs), which represent patients’ interests and often mediate between patients and the research community. PIs and POs occupy distinct yet interdependent positions in the research ecosystem. PIs typically prioritise methodological rigour and clinical effectiveness, with a strong emphasis on scientific and regulatory requirements ( 45 ). POs, by contrast, are closely attuned to patients’ lived experience and may provide psychological, logistical, or financial support, while also advocating for patients’ needs within institutional arenas ( 46 , 47 ). Considering these perspectives together is essential to understanding how engagement can be both evidence-informed and experience-grounded, feasible within operational constraints, and sustainable through clearer roles and capabilities across actors. Accordingly, we compare and integrate PIs’ and POs’ views to identify convergent and divergent understandings of engagement barriers and to surface organisational, cultural, relational, and systemic challenges. In doing so, the study contributes to ongoing debates on how PPI can move beyond rhetorical commitment toward more structured, durable, and consequential practices in clinical research. Methods This study adopts a qualitative research design, drawing on 34 semi-structured interviews ( 48 ) to investigate barriers to PPI in oncology clinical research from the perspectives of two key stakeholder groups: POs ( n = 13) and PIs ( n = 21) (Tables 1 and 2 ). Table 1 Patient organisations interviewees PO ID Geographical area Target pathology PO1 Southern Italy Cancer (generic) PO2 Italy and Europe Prostate cancer PO3 Italy Cancer associated with genetic mutations PO4 Southern Italy Cancer (generic) PO5 Northern Italy Breast cancer, Onco-haematology PO6 Northern Italy Bladder cancer PO7 Italy Laryngeal cancer PO8 Nothern Italy Gynaecological cancer PO9 Southern Italy Gynaecological cancer PO10 Northern Italy End-stage cancer PO11 Italy Cancer (generic) PO12 Italy Breast cancer PO13 Northern Italy Long-term patients and cancer survivors Table 2 Principal investigators interviewees PI ID Geographical area Target pathology PI1 Milan Lung cancer PI2 Reggio Emilia Psyco-oncology PI3 Rome Sarcoma and rare cancers PI4 Rome Solid cancers PI5 Verona Lung and urological cancers PI6 Verona Breast and gynaecological cancers PI7 Milan Melanoma and solid cancers PI8 Forlì Urogenital cancers PI9 Rome Parkinson and neurodegenerative diseases PI10 Rome Neurology PI11 Rome Breast cancer PI12 Forlì Hematology and biostatistics PI13 Forlì Hepatobiliary and pancreatic cancers PI14 Forlì Data scientist PI15 Milan Experimental immunology PI16 Verona Radiotherapy oncology PI17 Reggio Emilia Palliative care PI18 Milan Genomics of cancer PI19 Rome Neurology PI20 Forlì Clinical nursing PI21 Milan Breast cancer PIs were recruited from Italian research institutes active in oncology and related clinical fields. POs were identified with the support of the Italian association of patient organisations in support of cancer patients and their families (Federazione delle Associazioni di Volontariato in Oncologia, FAVO), which facilitated access to organisations involved in patient advocacy and research-related activities thanks to its role as an interlocutor with political, cultural and labour institutions ( 49 ). Patient organisation representatives participated in this study as interviewees providing their perspectives on engagement practices in oncology research. They were not involved in the design, analysis, or interpretation of the study and therefore were not included as co-authors. This reflects the study design, which aimed to analyse patient and public involvement as an object of inquiry rather than to conduct the research through a co-production approach. All interviews were conducted remotely, audio-recorded with participants’ informed consent, and transcribed verbatim. The interview guide explored participants’ prior experiences with patient involvement, perceived barriers and facilitators, organisational and procedural conditions, and suggestions for improving engagement practices across different stages of the clinical research process. Data analysis followed a two-stage qualitative approach that combined inductive and deductive logics. In the first stage, participants’ experiences of patient organisations' involvement were analysed using an existing framework derived from the literature ( 50 ) that conceptualises engagement across the phases of clinical research and distinguishes levels of engagement intensity and effectiveness. This initial stage was primarily aimed at systematically describing how PPI had been implemented in practice, based on the interviewees' experience, and at gathering information about the actual context in Italy, regardless of theoretical notions. In the second stage, interview transcripts were analysed to identify barriers to PPI directly from participants’ accounts. Instead of applying a predefined framework, the analysis followed the structure of the interviews and proceeded through iterative coding and comparison. Reported difficulties, tensions, and critical situations were progressively grouped into recurring thematic clusters across interviews, leading to the identification of the main categories of barriers presented in the Results section. This inductive process resulted in six clusters of barriers. In a subsequent interpretative step, these were organised into four cross-cutting dimensions, cultural, organisational, operational, and institutional, which provided a coherent lens for structuring and presenting the findings. While additional aspects emerged during the analysis, this article focuses specifically on the barriers, as other elements primarily served to deepen the understanding of the Italian context beyond the scope of the present paper. Ethical approval was obtained from the ethics committee of [hidden]. All participants provided informed consent before participation, and all data were anonymised to ensure confidentiality and compliance with applicable privacy regulations. This research was supported by the [hidden], a national programme funded by [hidden]. The programme aims to develop an integrated, federated platform for the collection, sharing, and analysis of scientific and clinical data across 51 Scientific Institute for Research, Hospitalisation and Healthcare (Istituti di Ricovero e Cura a Carattere Scientifico, IRCCS). These institutions combine clinical care with biomedical and health services research, making them key partners in advancing patient engagement and involvement in oncology research and care ( 49 ). Results This section presents the main barriers to PPI identified through the interviews with PIs and PO representatives. While both groups recognised these barriers, they were often interpreted differently, reflecting their distinct roles and perspectives within the research ecosystem. Table 3 summarises how the identified barriers are organised across four analytical dimensions that guide the presentation of the results. Table 3 Classification of patient involvement barriers across cultural, organisational, operational, and institutional dimensions Results subsection Cultural Organisational Operational Institutional Cultural resistance and professional identity in negotiating expertise and authority in study design X Fragmentation and representativeness of patient organisations X Fragmentation of priorities in the research ecosystem X PPI as a marginal activity under operational overload and limited organisational integration X Asymmetries in language and expertise limiting informed and active participation X Limited continuity and feedback in a fragile engagement ecosystem X Cultural resistance and professional identity in negotiating expertise and authority in study design POs identify a deep cultural tension stemming from researchers’ perceptions of their roles. In their opinion, PIs are not adequately prepared to incorporate patients’ perspectives, or those of their representatives, into the design and delivery of clinical trials. According to the PO representatives interviewed, researchers are convinced that scientific expertise is the sole legitimate measure for decision-making, especially in the earliest phases of study development. This determines that engagement "depends very much on the sensitivity of the individual physician. If you find a physician who believes in it, then something can be done [...] otherwise, patient involvement does not happen.” (PO11). Some POs also report feeling diffidence coming from researchers, as if their presence could harm researchers’ authority; to this matter, POs note how they want to be involved not to compete with physicians, whose scientific expertise they recognise as fundamental, but to act as complementors who know patients more closely, and who can help integrate their perspectives to, eventually, better address their needs and concerns. One PO representative clearly states: “We do not want to replace doctors. [...] The scientific competence of clinicians is unquestionable, [...] what patient organisations bring is the direct experience of the disease.” (PO3). According to POs, patients experience similar difficulties. The distance and diffidence in researchers' attitude can make patients reluctant to share their views, propose ideas, or openly discuss their experiences and emotions. In some cases, patients appear hesitant to speak freely because they fear that “ saying the wrong thing could somehow affect the relationship with their doctor ” (PO5), with potential consequences for their care journey. While PIs do not report perceiving patients as hesitant in their relationships, some reflect on the tension in the ecosystem through a different lens: researchers mainly identify themselves as guarantors of methodological rigour, suggesting that other forms of engagement could create confusion around responsibilities and roles. In a few cases, concern is expressed about the possibility of POs making requests that are incompatible with scientific procedures or requirements or trying to influence decisions too much. Engagement is not excluded a priori ; however, PIs generally express a willingness to involve patients and patient representatives, on the condition that roles are well defined before collaboration occurs, and sometimes express a desire to limit non-scientific contributions to communication and support. Resistance is mainly linked to uncertainty about boundaries rather than to PPI itself. Fragmentation and representativeness of patient organisations Within the already culturally tense context, POs report that they typically operate in a fragmented landscape: numerous organisations exist, each having “ its own history, its own structure, and its own way of working. Sometimes it is not clear who represents whom” (PO2). According to some representatives, greater coordination among POs would clarify roles and allow more structured collaboration, enabling PIs to identify the right partner more easily. PIs did not provide substantially different contributions; instead, they aligned with the perception of a highly heterogeneous organisational landscape in which POs operate, identifying fragmentation as a primary driver of uncertainty concerning partner identification and legitimacy. Fragmentation of priorities in the research ecosystem The interviews show that POs and PIs identify different needs and preferences, highlighting a fragmentation of priorities embedded in the research ecosystem itself. POs report that trial design is predominantly driven by clinical endpoints and methodological constraints, leaving patient-relevant dimensions, such as treatment burden, daily functioning, and QoL, only partially translated into concrete study outcomes. One PO representative observes: “Quality of life is often mentioned but not translated into concrete outcomes. […] What is scientifically measured in trials does not always reflect what really matters to patients” (PO8); the remark illustrates how POs perceive their role as marginal in shaping core design choices and confirms the existence of a persistent gap between scientifically defined endpoints and what patients experience as meaningful. From the perspective of PIs, this gap is not primarily the result of indifference to patient input, but of structural limitations linked to the need for scientific validity, standardisation, and comparability across studies. Several patient priorities are described as difficult to operationalise within existing regulatory and methodological frameworks, as clinical research relies on endpoints that are “clearly defined and measurable” (PI5), making it harder to incorporate some patient-relevant aspects into trial design. PPI as a marginal activity under operational overload and limited organisational integration Both POs and PIs expand on the concept of operational overload due to additional activities required by PPI. POs' representatives note that PIs already operate in intense conditions and under tight schedules due to clinical practices, administrative and bureaucratic procedures, or regulations. According to POs, such a demanding context results in engagement activities being pursued only when time and resources allow, leaving them outside standard practice and priorities and making them fragmented and less effective. POs often report perceiving PPI as an activity competing with the main priorities of clinical research, rather than as a complementary aspect that can contribute to care improvement; in their opinion, physicians tend to avoid collaboration, making PPI occur in the latest phases of research; however, “ at that point, the margins for intervention are minimal [...] the most important choices have already been made.” (PO6). Early engagement, by contrast, was viewed as essential for shaping research questions and assessing the feasibility of study procedures in the eyes of patients, who are the final users of such studies. PIs confirm the same interpretation when discussing their own working conditions: heavy workload and increasingly complex regulatory procedures seem incompatible with the additional effort required, and the lack of dedicated funding and support emphasises the limit. Even though many PIs seem aware of the benefits PPI can bring, they appear to see it as an extra to the essential tasks of clinical research, mentioning that “the priority is to conduct the study correctly and within the expected timelines. [...] many activities are considered essential, and patient involvement is not always among them.” (PI18). In fact, PIs acknowledge that engagement occurs later. However, they do not consider this a significant issue: in their view, while it might benefit some factors, early engagement risks complicating or delaying trial development. One respondent clearly mentions: “If you involve external actors too early, there is the risk of slowing down the whole development of the trial. At a certain point, you have to move forward. You cannot keep the protocol open for discussion indefinitely.” (PI16). Asymmetries in language and expertise limiting informed and active participation POs identify communication as a key barrier to genuine engagement. Specifically, they report that trials led primarily by researchers are often framed in scientific and technical language, meaning patients “do not always fully understand what they are being asked to participate in” (PO8). In such conditions, the lack of comprehension undermines patients’ ability to participate actively and confines their involvement to marginal activities, thereby weakening the substantive value of engagement. POs representatives read this phenomenon as a direct implication of the already-discussed research culture, which prioritises technical details and precision over patient accessibility and, at times, results in intentional exclusion. Within this context, some respondents from the selected pool of POs argue that they can play a crucial role in mediating language: “patients need someone who helps them understand what is written. Our task is to explain things in a way that patients can follow.” (PO1). POs suggest they can help turn complex information into understandable elements for patients and assist them throughout the research process. Conversely, PIs highlight the many complexities of conducting oncology clinical trials, which pose the challenge of balancing clinical accuracy and accessibility, noting that “some aspects of clinical research are inherently complex; it is not always possible to simplify without losing important information. [...] We have to be careful not to oversimplify scientific content.” (PI18). At the same time, some PIs recognise the challenge and the importance of communicating with non-experts, admitting that training could help solve the problem: patients need to learn some technical terms. In contrast, physicians need guidance on how to communicate appropriately with patients. Limited continuity and feedback in a fragile engagement ecosystem From the POs' perspective, engagement appears sporadic and discontinuous. Engagement initiatives are often linked to specific projects rather than part of regular practice and are also tied to researchers’ personal commitment. Engagement practice then needs to start over every time a new collaboration begins, which carries the burden of assessing the activities PIs and POs can collaborate on, as well as of getting to know each other's competencies before understanding how to behave with one another. Within this context, POs report a systematic lack of feedback. As previously noted, POs are frequently excluded from collaborative processes; however, a more critical issue is that they are often not informed about whether studies proceed or the reasons for their non-involvement. A specular pattern is observed in patients, though with a distinct nuance. POs report that, even when collaboration does occur and patients are actively involved in the research process, researchers often fail to communicate study results. A key concern raised by POs is that research engagement requires patients to make some effort. When patients are not informed about how their contributions have influenced a study's conduct and outcomes, their willingness to participate in future research diminishes. At the same time, feelings of mistrust towards researchers are likely to increase. PIs confirm that the engagement ecosystem is fragile, identifying the lack of shared standards and guidelines as a primary cause. They mention: “Patient involvement today is not structured, [...] there are no clear indications on when and how to involve patients. [...] In the end, the risk is that patient engagement remains something occasional.” (PI16). PIs mainly suggest that, for engagement to be meaningful, it must first be embedded in clinical practice, with structured guidance on how stakeholders should interact and how certain patient-engagement activities should be carried out. Discussion The findings highlight that, although PIs and POs are increasingly aware of the value of PE and PPI, their integration into clinical trial practice remains fragile. Figure 1 provides a synthetic interpretation of the Results section by showing how the barriers identified through the interviews cluster across four interacting dimensions and how their interplay contributes to a fragile engagement ecosystem. In this context, both PIs and POs identify largely overlapping barriers to PPI; however, they interpret and prioritise them differently depending on their respective backgrounds, experiences, and competencies ( 42 ). As a result, the misalignment appears as a systemic tension between different logics of value, particularly evident in the asymmetry of objectives that characterises interactions between researchers and patient organisations ( 15 , 35 , 51 , 52 ). PIs may recognise the relevance of patient-centred concerns, yet perceive them as secondary when confronted with competing priorities such as scientific validity, regulatory compliance, and time constraints ( 53 ). Conversely, consistent with existing literature ( 28 , 36 , 42 , 54 ), interviews confirm that POs tend to interpret this hierarchy of priorities as a signal that experiential knowledge, although formally acknowledged, is not fully incorporated into decision-making processes. This does not necessarily reflect explicit disagreement, but rather a somewhat parallel awareness, accompanied by different urgency thresholds. Alongside these structural tensions, some barriers are perceived as relatively straightforward and widely acknowledged by both parties. Communication issues, particularly those related to technical language and overly complex materials, are often described as obvious obstacles that could be mitigated through simplification and targeted training, in line with previous studies ( 51 , 52 , 55 ). From this perspective, improving shared understanding is not seen as conceptually problematic but as a practical challenge requiring dedicated resources, educational efforts, and time investment. Another relevant issue to address is the need for training ( 56 ) for the two groups ( 16 , 57 ). Interview data confirm international evidence, affirming that patients and POs should acquire technical knowledge about scientific terminology and trial processes ( 5 , 53 , 58 ), while researchers could improve their engagement and communication strategies ( 52 , 59 , 60 ). Beyond individual interactions, respondents emphasised the importance of building relationships between POs and PIs before the formal start of a collaboration. Early and informal connections facilitate mutual understanding and trust, reducing the time typically devoted to role clarification and reciprocal legitimisation ( 61 ). When such relationships are already in place, collaboration during clinical trials becomes smoother, as the preliminary effort required to establish credibility and shared expectations is significantly reduced. However, the feasibility of early relationship-building is constrained by the fragmentation of the engagement ecosystem ( 7 , 33 ). Both PIs and POs highlighted the absence of structured mechanisms to facilitate matchmaking, making it difficult for researchers to identify appropriate organisations and for POs to be considered as potential partners. This lack of coordination reinforces ad hoc engagement practices and limits the scalability of successful collaborations. In some cases, barriers are not merely structural but cultural. The interviews again confirm findings from previous studies ( 51 , 53 , 59 ): a limited willingness to engage persists among certain actors, often rooted in scepticism towards the added value of patient involvement or concerns about the loss of scientific authority. In this context, a potential improvement could be obtained by showcasing international best practices to the parties involved, using them as proof that better results can be achieved when barriers are overcome. Practical, real-world examples could serve to go beyond theoretical notions, legitimising engagement and eventually reducing resistance. Importantly, POs consistently stressed that their goal is not to replace clinicians or compete with their expertise, but to work alongside them as complementary actors. Supporting researchers throughout the collaboration process, rather than positioning engagement as an external imposition, is thus a key strategy to implement to foster openness and avoid potential conflicts. Finally, respondents in some cases mentioned that willingness to engage is present, although opposed to a lack of practical knowledge. The literature confirms that uncertainty regarding roles ( 36 , 62 , 63 ), responsibilities ( 60 ), and appropriate modes of interaction ( 59 ) constitute barriers to PPI, even when the parties involved are willing to implement them. This gap underscores the need for clear, shared guidelines outlining how engagement should be conducted in practice ( 17 , 37 – 41 ). Such guidance should address not only researchers’ behaviours, but also include training for patients and patient organisations, clarifying expectations and supporting all actors in navigating collaboration effectively. At the same time, PPI should become standard practice in clinical research, which can only be feasible if stakeholders formally recognise each other as legitimate partners in research and explicitly set roles and responsibilities for each prior to collaboration. Conclusions This study highlights how PPI in oncology trials is shaped by different interpretations of roles, priorities, and responsibilities within the research ecosystem. While principal investigators and patient organisations recognise similar obstacles, they frame them through distinct lenses, which contributes to engagement being positioned at the margins of trial practice rather than embedded within it. The analysis also shows that POs can contribute a complementary perspective, particularly in early trial phases, by surfacing feasibility, communication, and relevance issues that may otherwise remain unaddressed. Advancing engagement, therefore, depends less on individual willingness and more on clearer operational guidance, dedicated resources, shared training, and stable mechanisms for collaboration. Although based in Italy, the patterns observed reflect conditions widely discussed in international literature. The findings are therefore applicable beyond this context and offer considerations for integrating PPI more effectively into clinical trial methodologies across different settings. Limitations While diversity in size, experience, and focus of the selected interviewees was maximised, the pool is limited and may not represent the entire Italian context. The study is situated within the Italian research context, and regulatory or organisational differences may influence transferability. In addition, perspectives from direct patient participants and the pharmaceutical industries were not included and should be explored in future research. Declarations Acknowledgement We thank all principal investigators and patient organisation representatives who generously shared their time, experiences, and reflections. Their openness in discussing both challenges and opportunities made this research possible. We are grateful to the FAVO for facilitating contact with patient organisations and supporting the recruitment process. We also thank [hidden] for their support in coordinating and conducting interviews with principal investigators and for their contribution to organising materials for the qualitative analysis. This work was carried out within the framework of the [hidden]. Authors’ contributions [hidden] conducted interviews, supervised data collection and analysis, prepared the figure, contributed to the development of the theoretical framework and methodology, and revised and edited the manuscript. [hidden] carried out data collection and analysis, prepared the tables, and drafted the manuscript. [hidden] provided senior supervision, contributed to the overall study design and framing of the manuscript, and secured project funding. Funding This work was supported by the [hidden] project, funded by [hidden]. Ethics approval and consent to participate Ethical approval for this study was obtained from the Ethics Committee of [hidden]. All participants received detailed information about the study and provided informed consent prior to participation. Interviews were conducted in accordance with applicable ethical standards and privacy regulations. Consent for publication Participants provided written consent for the use of anonymised interview excerpts for research and publication purposes. Availability of data and materials The datasets generated and analysed during the current study are not publicly available due to confidentiality and privacy restrictions. Anonymised data may be shared by the corresponding author upon reasonable request and subject to approval by the Ethics Committee of [hidden]. Competing interests The authors declare that they have no competing interests. References Farah E, Kenney M, Kica A, Haddad P, Stewart DJ, Bradford JP. 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Stein S, Bogard E, Boice N, Fernandez V, Field T, Gilstrap A, et al. Principles for interactions with biopharmaceutical companies: the development of guidelines for patient advocacy organizations in the field of rare diseases. Orphanet J Rare Dis. 2018;13:18. 10.1186/s13023-018-0761-2 . PubMed PMID: 29357903; PubMed Central PMCID: PMC5778794. Weiler-Wichtl LJ, Leiss U, Gojo J, Kienesberger A, Hansl R, Hopfgartner M, et al. Good to know – This is PPIE! Development of a training tool for public and patient involvement and engagement in pediatric oncological research. Cancer Rep. 2023;6(6):e1835. 10.1002/cnr2.1835 . Kim JY, Acelas MPB, Granville CA, Getz K. Benchmarking Patient Engagement Capabilities and Preparedness of Drug Development Sponsors. Ther Innov Regul Sci. 2023;57(5):1040–9. 10.1007/s43441-023-00545-x . Nohová I, Andrews J, Votan B, Miller A, Sehouli J, Berger R. Patient involvement in research within the Gynecological Cancer InterGroup: A call to action for a systematic approach: Results from a survey. Health Sci Rep. 2023;6(12):e1735. 10.1002/hsr2 . 1735 PubMed PMID: 38045625; PubMed Central PMCID: PMC10691166. Antes AL, Kuykendall A, DuBois JM. The lab management practices of ‘Research Exemplars’ that foster research rigor and regulatory compliance: A qualitative study of successful principal investigators. PLoS ONE. 2019;14(4):e0214595. 10.1371/journal.pone.0214595 . PubMed PMID: 31017929; PubMed Central PMCID: PMC6481787. D’Antona R, Deandrea S, Sestini E, Pau L, Ferrè F, Angiolini C, et al. Presence and Role of Associations of Cancer Patients and Volunteers in Specialist Breast Centres: An Italian National Survey of Breast Centres Associated with Senonetwork. Curr Oncol. 2023;30(9):8186–95. 10.3390/curroncol30090594 . Ganz-Blaettler U, Liptrott SJ, Tolotti A, Cefalì M, Aeschlimann C, Vilei SB, et al. The active involvement of patients in oncology research. Cancer Treat Rev. 2024;130:102822. 10.1016/j.ctrv.2024.102822 . Adeoye-Olatunde OA, Olenik NL. Research and scholarly methods: Semi-structured interviews. JACCP J Am Coll Clin Pharm. 2021;4(10):1358–67. 10.1002/jac5.1441 . Home - FAVO. - Federazione delle Associazioni di Volontariato in Oncologia [Internet]. [cited 2026 Jan 27]. Available from: https://www.favo.it/ Multi-Act. Manual | Multiact Toolbox [Internet]. [cited 2026 Jan 30]. Available from: https://toolbox.multiact.eu/multi-act-manual#_Toc70265340 Castonguay G, Bédard S, Dubois A, Lessard É, Rivard L, Rouly G, et al. Overcoming barriers to implementation of patient engagement in clinical trials: feasibility testing of an embedded study. Res Involv Engagem. 2025;11:15. 10.1186/s40900-025-00689-0 . PubMed PMID: 40012063; PubMed Central PMCID: PMC11866851. Mosconi P, Colombo C, Paletta P, Gangeri L, Pellegrini C, Garralda E, et al. Public and patient involvement: a survey on knowledge, experience and opinions among researchers within a precision oncology European project. BMC Cancer. 2023;23:814. 10.1186/s12885-023-11262-x . PubMed PMID: 37648965; PubMed Central PMCID: PMC10470190. Böbel S, Gerhardus A, Herbon C, Jilani H, Rathjen KI, Schmiemann G, et al. Engaging nursing home residents in clinical research: insights from a patient advisory board, a patient advocate, and a study team. Res Involv Engagem. 2024;10:111. 10.1186/s40900-024-00648-1 . PubMed PMID: 39468574; PubMed Central PMCID: PMC11514759. Charlesworth G. Public and patient involvement in dementia research: Time to reflect? Dementia. 2018;17(8):1064–7. 10.1177/2397172x18802501 . Thaysen HV, Lomborg K, Seibaek L. Patient involvement in comprehensive, complex cancer surgery: Perspectives of patients, relatives and health professionals. Eur J Cancer Care (Engl). 2019;28(4):e13071. 10.1111/ecc.13071 . Aas SN, Distefano MB, Pettersen I, Gravrok B, Nordvoll LY, Bjaastad JF, et al. Patient and public involvement in health research in Norway: a survey among researchers and patient organisations. Res Involv Engagem. 2023;9:48. 10.1186/s40900-023-00458-x . PubMed PMID: 37422661; PubMed Central PMCID: PMC10329785. Kohn J, Unger Z, Dolatshahi J, Simons H, Rein A. Attitudes toward comparative effectiveness research and patient engagement among reproductive health clinicians. J Comp Eff Res. 2017;6(4):337–45. 10.2217/cer-2016-0068 . De Wit MPT, Koenders MI, Neijland Y, Van Den Hoogen FHJ, Van Der Kraan PM, Van De Loo FAJ, et al. Patient involvement in basic rheumatology research at Nijmegen: a three year’s responsive evaluation of added value, pitfalls and conditions for success. BMC Rheumatol. 2022;6(1). 10.1186/s41927-022-00296-6 . Costa Alencar AB, Selig WKD, Geissler J, Bereczky T, Ubide A, Haerry D, et al. Adopting recommendations for implementing patient involvement in cancer research: a funder’s approach. Res Involv Engagem. 2023;9:6. 10.1186/s40900-023-00410-z . PubMed PMID: 36859346; PubMed Central PMCID: PMC9979457. Vervoort JPM, Konijn WS, Jansen DEMC, Boersma C, de Zeeuw J, Ho-dac –, Pannekeet MM et al. Patient engagement as a collaborative process in a large Dutch COVID-19 vaccination study (RECOVAC) – insight into the contribution of patient engagement and learnings for the future. Res Involv Engagem. 2024;10:96. 10.1186/s40900-024-00622-x PubMed PMID: 39272117; PubMed Central PMCID: PMC11395945. Bloom D, Beetsch J, Harker M, Hesterlee S, Moreira P, Patrick-Lake B, et al. The Rules of Engagement. Ther Innov Regul Sci. 2018;52(2):206–13. doi:10.1177/2168479017720247 PubMed PMID: 29714514; PubMed Central PMCID: PMC5846850. Babatunde S, Ahmed S, Santana MJ, Nielssen I, Zelinsky S, Ambasta A. Working together in health research: a mixed-methods patient engagement evaluation. Res Involv Engagem. 2023;9:62. 10.1186/s40900-023-00475- . w PubMed PMID: 37528438; PubMed Central PMCID: PMC10394768. Puts MTE, Sattar S, Ghodraty-Jabloo V, Hsu T, Fitch M, Szumacher E, et al. Patient engagement in research with older adults with cancer. J Geriatr Oncol. 2017;8(6):391–6. 10.1016/j.jgo.2017.05.002 . Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8741101","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":607544622,"identity":"e67cd0fa-a042-4a5f-ae04-69609be33aab","order_by":0,"name":"Federico De Luca","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYBAC9gYGAwYQYmBIYDwAJOUYGJgbDgBFeHBp4TmA0MIA0mLMwMAI0YJLD0QLA0JLYgNQC0QKlxb25o2PKwrs5BjYkw8c5qmxS9/O3th46EYBg4w9Li08x4oNzxgkGzPwPEs4zHMsOXdnz8GGwzl4HGYvkWMm2WBwILFBIsfgMG8Dc+6GG4n4tfDIvzH/CdGS/wGopT7dgKAWCR4zRqgtDEAthxMIa+FJKwY6LNmYjeeZwcE5x44bQv0iwQMMTBwhdnjjx4Y/dnL87MkPH7ypqZY3Z28+/Dnnj409MJbxAzYYAxpNEgTUIwMDwkpGwSgYBaNghAEAv3FYa7go4AYAAAAASUVORK5CYII=","orcid":"","institution":"Politecnico di Milano","correspondingAuthor":true,"prefix":"","firstName":"Federico","middleName":"","lastName":"De Luca","suffix":""},{"id":607544623,"identity":"2d42b243-1782-4feb-8774-d67678b4ed6b","order_by":1,"name":"Andrea Pozzoni","email":"","orcid":"","institution":"Politecnico di Milano","correspondingAuthor":false,"prefix":"","firstName":"Andrea","middleName":"","lastName":"Pozzoni","suffix":""},{"id":607544624,"identity":"59a47f06-f36e-4163-87b5-d23fb90620dc","order_by":2,"name":"Nicolò Signorelli","email":"","orcid":"","institution":"Politecnico di Milano","correspondingAuthor":false,"prefix":"","firstName":"Nicolò","middleName":"","lastName":"Signorelli","suffix":""},{"id":607544626,"identity":"da411a46-d124-4168-afa2-6d2b6ef5d3d8","order_by":3,"name":"Cristina Masella","email":"","orcid":"","institution":"Politecnico di Milano","correspondingAuthor":false,"prefix":"","firstName":"Cristina","middleName":"","lastName":"Masella","suffix":""}],"badges":[],"createdAt":"2026-01-30 12:39:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8741101/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8741101/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104996175,"identity":"e275fd50-4a0a-48ad-9edd-ad1c75edc923","added_by":"auto","created_at":"2026-03-19 16:11:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":346671,"visible":true,"origin":"","legend":"\u003cp\u003eHow different readings of the same system produce fragile patient public involvement\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8741101/v1/611439fcd52f8713d54c8bcb.png"},{"id":104996205,"identity":"576c14f2-45bc-42d7-8dae-dded9154bf20","added_by":"auto","created_at":"2026-03-19 16:11:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1133858,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8741101/v1/db60a471-7f11-4464-8efe-4cdcb1ec8287.pdf"},{"id":104996086,"identity":"7ec69957-809a-4a81-b2b1-63d0e739ccdd","added_by":"auto","created_at":"2026-03-19 16:11:25","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":18458,"visible":true,"origin":"","legend":"","description":"","filename":"GrippLongForm.docx","url":"https://assets-eu.researchsquare.com/files/rs-8741101/v1/6169ce551429815065ea4468.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Why engagement remains fragile: A qualitative comparison of principal investigators’ and patient organisations’ perspectives in Italy","fulltext":[{"header":"Plain English Summary","content":"\u003cp\u003ePatients and patient organisations are increasingly encouraged to contribute to clinical research so that studies better reflect real-life needs and are easier, fairer, and more relevant for those taking part. This is especially important in cancer research, where treatments and clinical trials can be long, complex, and disruptive to everyday life. However, in Italy, patient involvement is still not routine in research and often depends on individual researchers\u0026apos; willingness.\u003c/p\u003e\n\u003cp\u003eIn this study, we explored why this happens by interviewing two groups: principal investigators, who design and lead clinical studies, and representatives of patient organisations, who support patients and often interact with research teams. We asked about their experiences and about the main difficulties that make patient involvement hard to achieve in practice.\u003c/p\u003e\n\u003cp\u003eBoth groups recognised many of the same problems, but often understood them differently. Some barriers are linked to culture and professional roles, including uncertainty about who should influence research decisions and how much value should be given to patients\u0026rsquo; lived experience. Others are organisational and practical, such as fragmented collaboration, lack of time, heavy workloads, and limited resources. Communication is another challenge, especially when research is presented in highly technical language that non-specialists find difficult to understand. There are also broader system-level problems, including a lack of continuity, limited feedback to patients and organisations, and no clear shared guidance on how involvement should happen.\u003c/p\u003e\n\u003cp\u003eOverall, patient involvement remains fragile because these barriers interact with one another. Clearer guidance, dedicated support, and shared training could help make involvement earlier, more consistent, and more meaningful.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eOver the past decade, the involvement of patients and patients' organisations has become increasingly prominent in clinical research (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Patient Engagement (PE) and Patient and Public Involvement (PPI) are related but distinct: PE refers to individuals\u0026rsquo; participation in their own care (e.g., self-management, shared decision-making), whereas PPI concerns the involvement of patients, caregivers, and the public in shaping health research (e.g., design, conduct, governance, and dissemination) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Accordingly, PE operates mainly at the micro level of care delivery, while PPI functions at meso- and macro-levels by influencing research processes and, indirectly, health system governance (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). A growing body of literature shows the benefits of both PE (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) and PPI (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), including greater recognition and inclusion for patients and the introduction of perspectives that can challenge established assumptions and enrich researchers\u0026rsquo; decision-making (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). In this sense, PE is increasingly framed not only as an ethical commitment but also as a pragmatic strategy to improve research effectiveness (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe relevance of PE is particularly evident in oncology, where clinical trials are often long and complex, involve multiple treatment phases, and entail substantial side effects with profound implications for patients\u0026rsquo; Quality of Life (QoL) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Moreover, oncology is characterised by a high volume of clinical trials aimed at evaluating innovative therapies, making it crucial that patients\u0026rsquo; perspectives are adequately considered when defining research questions, endpoints, and acceptable trade-offs between treatment efficacy and QoL (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Compared with other therapeutic areas, oncology has also developed a relatively strong tradition of collaboration between researchers and patient organisations, making it a particularly informative setting for exploring both the potential and the limitations of PE. Despite its growing endorsement, PPI remains difficult to implement in practice. While numerous frameworks, recommendations, and policy initiatives promote greater patient involvement, operational guidance is often limited, and engagement activities risk becoming tokenistic or poorly embedded within research processes (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR37 CR38 CR39 CR40 CR41\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). Moreover, many existing approaches insufficiently account for the complexity of PPI, which can take different forms across research phases and typically involves a broader constellation of actors beyond clinicians and patients alone (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). This gap between normative aspirations and everyday practice raises pressing questions about what constrains effective PE, its implications for PPI, and under what conditions it can be realised in a meaningful, non-tokenistic way.\u003c/p\u003e \u003cp\u003eThis paper focuses on Italy, where PE and PPI are increasingly visible in policy agendas and scholarly debate. Within this context, the study investigates barriers to engagement and involvement in clinical research that impede the attainment of its anticipated benefits. To develop a more comprehensive account, we draw on two complementary qualitative analyses of stakeholder groups central to oncology clinical trials: principal investigators (PIs), who design and conduct studies, and patient organisations (POs), which represent patients\u0026rsquo; interests and often mediate between patients and the research community.\u003c/p\u003e \u003cp\u003ePIs and POs occupy distinct yet interdependent positions in the research ecosystem. PIs typically prioritise methodological rigour and clinical effectiveness, with a strong emphasis on scientific and regulatory requirements (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). POs, by contrast, are closely attuned to patients\u0026rsquo; lived experience and may provide psychological, logistical, or financial support, while also advocating for patients\u0026rsquo; needs within institutional arenas (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e). Considering these perspectives together is essential to understanding how engagement can be both evidence-informed and experience-grounded, feasible within operational constraints, and sustainable through clearer roles and capabilities across actors. Accordingly, we compare and integrate PIs\u0026rsquo; and POs\u0026rsquo; views to identify convergent and divergent understandings of engagement barriers and to surface organisational, cultural, relational, and systemic challenges. In doing so, the study contributes to ongoing debates on how PPI can move beyond rhetorical commitment toward more structured, durable, and consequential practices in clinical research.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study adopts a qualitative research design, drawing on 34 semi-structured interviews (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e) to investigate barriers to PPI in oncology clinical research from the perspectives of two key stakeholder groups: POs (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;13) and PIs (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;21) (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient organisations interviewees\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGeographical area\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTarget pathology\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSouthern Italy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCancer (generic)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eItaly and Europe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProstate cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCancer associated with genetic mutations\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSouthern Italy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCancer (generic)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNorthern Italy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBreast cancer, Onco-haematology\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNorthern Italy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBladder cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLaryngeal cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNothern Italy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGynaecological cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSouthern Italy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGynaecological cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNorthern Italy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEnd-stage cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCancer (generic)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBreast cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNorthern Italy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLong-term patients and cancer survivors\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrincipal investigators interviewees\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGeographical area\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTarget pathology\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMilan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReggio Emilia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePsyco-oncology\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSarcoma and rare cancers\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSolid cancers\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVerona\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLung and urological cancers\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVerona\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBreast and gynaecological cancers\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMilan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMelanoma and solid cancers\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eForl\u0026igrave;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUrogenital cancers\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eParkinson and neurodegenerative diseases\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNeurology\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBreast cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eForl\u0026igrave;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHematology and biostatistics\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eForl\u0026igrave;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHepatobiliary and pancreatic cancers\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eForl\u0026igrave;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eData scientist\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMilan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eExperimental immunology\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVerona\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRadiotherapy oncology\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReggio Emilia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePalliative care\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMilan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGenomics of cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNeurology\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eForl\u0026igrave;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinical nursing\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMilan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBreast cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePIs were recruited from Italian research institutes active in oncology and related clinical fields. POs were identified with the support of the Italian association of patient organisations in support of cancer patients and their families (Federazione delle Associazioni di Volontariato in Oncologia, FAVO), which facilitated access to organisations involved in patient advocacy and research-related activities thanks to its role as an interlocutor with political, cultural and labour institutions (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e). Patient organisation representatives participated in this study as interviewees providing their perspectives on engagement practices in oncology research. They were not involved in the design, analysis, or interpretation of the study and therefore were not included as co-authors. This reflects the study design, which aimed to analyse patient and public involvement as an object of inquiry rather than to conduct the research through a co-production approach.\u003c/p\u003e \u003cp\u003e All interviews were conducted remotely, audio-recorded with participants\u0026rsquo; informed consent, and transcribed verbatim. The interview guide explored participants\u0026rsquo; prior experiences with patient involvement, perceived barriers and facilitators, organisational and procedural conditions, and suggestions for improving engagement practices across different stages of the clinical research process.\u003c/p\u003e \u003cp\u003eData analysis followed a two-stage qualitative approach that combined inductive and deductive logics. In the first stage, participants\u0026rsquo; experiences of patient organisations' involvement were analysed using an existing framework derived from the literature (\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e) that conceptualises engagement across the phases of clinical research and distinguishes levels of engagement intensity and effectiveness. This initial stage was primarily aimed at systematically describing how PPI had been implemented in practice, based on the interviewees' experience, and at gathering information about the actual context in Italy, regardless of theoretical notions. In the second stage, interview transcripts were analysed to identify barriers to PPI directly from participants\u0026rsquo; accounts. Instead of applying a predefined framework, the analysis followed the structure of the interviews and proceeded through iterative coding and comparison. Reported difficulties, tensions, and critical situations were progressively grouped into recurring thematic clusters across interviews, leading to the identification of the main categories of barriers presented in the Results section.\u003c/p\u003e \u003cp\u003eThis inductive process resulted in six clusters of barriers. In a subsequent interpretative step, these were organised into four cross-cutting dimensions, cultural, organisational, operational, and institutional, which provided a coherent lens for structuring and presenting the findings. While additional aspects emerged during the analysis, this article focuses specifically on the barriers, as other elements primarily served to deepen the understanding of the Italian context beyond the scope of the present paper.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthical approval\u003c/strong\u003e \u003cp\u003ewas obtained from the ethics committee of [hidden]. All participants provided informed consent before participation, and all data were anonymised to ensure confidentiality and compliance with applicable privacy regulations.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eThis research was supported by the [hidden], a national programme funded by [hidden]. The programme aims to develop an integrated, federated platform for the collection, sharing, and analysis of scientific and clinical data across 51 Scientific Institute for Research, Hospitalisation and Healthcare (Istituti di Ricovero e Cura a Carattere Scientifico, IRCCS). These institutions combine clinical care with biomedical and health services research, making them key partners in advancing patient engagement and involvement in oncology research and care (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThis section presents the main barriers to PPI identified through the interviews with PIs and PO representatives. While both groups recognised these barriers, they were often interpreted differently, reflecting their distinct roles and perspectives within the research ecosystem. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e summarises how the identified barriers are organised across four analytical dimensions that guide the presentation of the results.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClassification of patient involvement barriers across cultural, organisational, operational, and institutional dimensions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResults subsection\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCultural\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOrganisational\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOperational\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInstitutional\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCultural resistance and professional identity in negotiating expertise and authority in study design\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFragmentation and representativeness of patient organisations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFragmentation of priorities in the research ecosystem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePPI as a marginal activity under operational overload and limited organisational integration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsymmetries in language and expertise limiting informed and active participation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLimited continuity and feedback in a fragile engagement ecosystem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eCultural resistance and professional identity in negotiating expertise and authority in study design\u003c/h3\u003e\n\u003cp\u003ePOs identify a deep cultural tension stemming from researchers\u0026rsquo; perceptions of their roles. In their opinion, PIs are not adequately prepared to incorporate patients\u0026rsquo; perspectives, or those of their representatives, into the design and delivery of clinical trials. According to the PO representatives interviewed, researchers are convinced that scientific expertise is the sole legitimate measure for decision-making, especially in the earliest phases of study development. This determines that engagement \u003cem\u003e\"depends very much on the sensitivity of the individual physician. If you find a physician who believes in it, then something can be done [...] otherwise, patient involvement does not happen.\u0026rdquo;\u003c/em\u003e (PO11).\u003c/p\u003e \u003cp\u003eSome POs also report feeling diffidence coming from researchers, as if their presence could harm researchers\u0026rsquo; authority; to this matter, POs note how they want to be involved not to compete with physicians, whose scientific expertise they recognise as fundamental, but to act as complementors who know patients more closely, and who can help integrate their perspectives to, eventually, better address their needs and concerns. One PO representative clearly states: \u003cem\u003e\u0026ldquo;We do not want to replace doctors. [...] The scientific competence of clinicians is unquestionable, [...] what patient organisations bring is the direct experience of the disease.\u0026rdquo;\u003c/em\u003e (PO3).\u003c/p\u003e \u003cp\u003eAccording to POs, patients experience similar difficulties. The distance and diffidence in researchers' attitude can make patients reluctant to share their views, propose ideas, or openly discuss their experiences and emotions. In some cases, patients appear hesitant to speak freely because they fear that \u0026ldquo;\u003cem\u003esaying the wrong thing could somehow affect the relationship with their doctor\u003c/em\u003e\u0026rdquo; (PO5), with potential consequences for their care journey.\u003c/p\u003e \u003cp\u003eWhile PIs do not report perceiving patients as hesitant in their relationships, some reflect on the tension in the ecosystem through a different lens: researchers mainly identify themselves as guarantors of methodological rigour, suggesting that other forms of engagement could create confusion around responsibilities and roles. In a few cases, concern is expressed about the possibility of POs making requests that are incompatible with scientific procedures or requirements or trying to influence decisions too much. Engagement is not excluded \u003cem\u003ea priori\u003c/em\u003e; however, PIs generally express a willingness to involve patients and patient representatives, on the condition that roles are well defined before collaboration occurs, and sometimes express a desire to limit non-scientific contributions to communication and support. Resistance is mainly linked to uncertainty about boundaries rather than to PPI itself.\u003c/p\u003e\n\u003ch3\u003eFragmentation and representativeness of patient organisations\u003c/h3\u003e\n\u003cp\u003eWithin the already culturally tense context, POs report that they typically operate in a fragmented landscape: numerous organisations exist, each having \u0026ldquo;\u003cem\u003eits own history, its own structure, and its own way of working. Sometimes it is not clear who represents whom\u0026rdquo;\u003c/em\u003e (PO2). According to some representatives, greater coordination among POs would clarify roles and allow more structured collaboration, enabling PIs to identify the right partner more easily.\u003c/p\u003e \u003cp\u003ePIs did not provide substantially different contributions; instead, they aligned with the perception of a highly heterogeneous organisational landscape in which POs operate, identifying fragmentation as a primary driver of uncertainty concerning partner identification and legitimacy.\u003c/p\u003e\n\u003ch3\u003eFragmentation of priorities in the research ecosystem\u003c/h3\u003e\n\u003cp\u003eThe interviews show that POs and PIs identify different needs and preferences, highlighting a fragmentation of priorities embedded in the research ecosystem itself.\u003c/p\u003e \u003cp\u003ePOs report that trial design is predominantly driven by clinical endpoints and methodological constraints, leaving patient-relevant dimensions, such as treatment burden, daily functioning, and QoL, only partially translated into concrete study outcomes. One PO representative observes: \u003cem\u003e\u0026ldquo;Quality of life is often mentioned but not translated into concrete outcomes. [\u0026hellip;] What is scientifically measured in trials does not always reflect what really matters to patients\u0026rdquo;\u003c/em\u003e (PO8); the remark illustrates how POs perceive their role as marginal in shaping core design choices and confirms the existence of a persistent gap between scientifically defined endpoints and what patients experience as meaningful.\u003c/p\u003e \u003cp\u003eFrom the perspective of PIs, this gap is not primarily the result of indifference to patient input, but of structural limitations linked to the need for scientific validity, standardisation, and comparability across studies. Several patient priorities are described as difficult to operationalise within existing regulatory and methodological frameworks, as clinical research relies on endpoints that are \u003cem\u003e\u0026ldquo;clearly defined and measurable\u0026rdquo;\u003c/em\u003e (PI5), making it harder to incorporate some patient-relevant aspects into trial design.\u003c/p\u003e\n\u003ch3\u003ePPI as a marginal activity under operational overload and limited organisational integration\u003c/h3\u003e\n\u003cp\u003eBoth POs and PIs expand on the concept of operational overload due to additional activities required by PPI.\u003c/p\u003e \u003cp\u003ePOs' representatives note that PIs already operate in intense conditions and under tight schedules due to clinical practices, administrative and bureaucratic procedures, or regulations. According to POs, such a demanding context results in engagement activities being pursued only when time and resources allow, leaving them outside standard practice and priorities and making them fragmented and less effective. POs often report perceiving PPI as an activity competing with the main priorities of clinical research, rather than as a complementary aspect that can contribute to care improvement; in their opinion, physicians tend to avoid collaboration, making PPI occur in the latest phases of research; however, \u0026ldquo;\u003cem\u003eat that point, the margins for intervention are minimal [...] the most important choices have already been made.\u0026rdquo;\u003c/em\u003e (PO6). Early engagement, by contrast, was viewed as essential for shaping research questions and assessing the feasibility of study procedures in the eyes of patients, who are the final users of such studies.\u003c/p\u003e \u003cp\u003ePIs confirm the same interpretation when discussing their own working conditions: heavy workload and increasingly complex regulatory procedures seem incompatible with the additional effort required, and the lack of dedicated funding and support emphasises the limit. Even though many PIs seem aware of the benefits PPI can bring, they appear to see it as an extra to the essential tasks of clinical research, mentioning that \u003cem\u003e\u0026ldquo;the priority is to conduct the study correctly and within the expected timelines. [...] many activities are considered essential, and patient involvement is not always among them.\u0026rdquo;\u003c/em\u003e (PI18). In fact, PIs acknowledge that engagement occurs later. However, they do not consider this a significant issue: in their view, while it might benefit some factors, early engagement risks complicating or delaying trial development. One respondent clearly mentions: \u003cem\u003e\u0026ldquo;If you involve external actors too early, there is the risk of slowing down the whole development of the trial. At a certain point, you have to move forward. You cannot keep the protocol open for discussion indefinitely.\u0026rdquo;\u003c/em\u003e (PI16).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eAsymmetries in language and expertise limiting informed and active participation\u003c/h2\u003e \u003cp\u003ePOs identify communication as a key barrier to genuine engagement. Specifically, they report that trials led primarily by researchers are often framed in scientific and technical language, meaning patients \u003cem\u003e\u0026ldquo;do not always fully understand what they are being asked to participate in\u0026rdquo;\u003c/em\u003e (PO8). In such conditions, the lack of comprehension undermines patients\u0026rsquo; ability to participate actively and confines their involvement to marginal activities, thereby weakening the substantive value of engagement.\u003c/p\u003e \u003cp\u003ePOs representatives read this phenomenon as a direct implication of the already-discussed research culture, which prioritises technical details and precision over patient accessibility and, at times, results in intentional exclusion. Within this context, some respondents from the selected pool of POs argue that they can play a crucial role in mediating language: \u003cem\u003e\u0026ldquo;patients need someone who helps them understand what is written. Our task is to explain things in a way that patients can follow.\u0026rdquo;\u003c/em\u003e (PO1). POs suggest they can help turn complex information into understandable elements for patients and assist them throughout the research process.\u003c/p\u003e \u003cp\u003eConversely, PIs highlight the many complexities of conducting oncology clinical trials, which pose the challenge of balancing clinical accuracy and accessibility, noting that \u003cem\u003e\u0026ldquo;some aspects of clinical research are inherently complex; it is not always possible to simplify without losing important information. [...] We have to be careful not to oversimplify scientific content.\u0026rdquo;\u003c/em\u003e (PI18).\u003c/p\u003e \u003cp\u003eAt the same time, some PIs recognise the challenge and the importance of communicating with non-experts, admitting that training could help solve the problem: patients need to learn some technical terms. In contrast, physicians need guidance on how to communicate appropriately with patients.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eLimited continuity and feedback in a fragile engagement ecosystem\u003c/h3\u003e\n\u003cp\u003eFrom the POs' perspective, engagement appears sporadic and discontinuous. Engagement initiatives are often linked to specific projects rather than part of regular practice and are also tied to researchers\u0026rsquo; personal commitment. Engagement practice then needs to start over every time a new collaboration begins, which carries the burden of assessing the activities PIs and POs can collaborate on, as well as of getting to know each other's competencies before understanding how to behave with one another.\u003c/p\u003e \u003cp\u003eWithin this context, POs report a systematic lack of feedback. As previously noted, POs are frequently excluded from collaborative processes; however, a more critical issue is that they are often not informed about whether studies proceed or the reasons for their non-involvement. A specular pattern is observed in patients, though with a distinct nuance. POs report that, even when collaboration does occur and patients are actively involved in the research process, researchers often fail to communicate study results. A key concern raised by POs is that research engagement requires patients to make some effort. When patients are not informed about how their contributions have influenced a study's conduct and outcomes, their willingness to participate in future research diminishes. At the same time, feelings of mistrust towards researchers are likely to increase.\u003c/p\u003e \u003cp\u003e PIs confirm that the engagement ecosystem is fragile, identifying the lack of shared standards and guidelines as a primary cause. They mention: \u003cem\u003e\u0026ldquo;Patient involvement today is not structured, [...] there are no clear indications on when and how to involve patients. [...] In the end, the risk is that patient engagement remains something occasional.\u0026rdquo;\u003c/em\u003e (PI16). PIs mainly suggest that, for engagement to be meaningful, it must first be embedded in clinical practice, with structured guidance on how stakeholders should interact and how certain patient-engagement activities should be carried out.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe findings highlight that, although PIs and POs are increasingly aware of the value of PE and PPI, their integration into clinical trial practice remains fragile. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e provides a synthetic interpretation of the Results section by showing how the barriers identified through the interviews cluster across four interacting dimensions and how their interplay contributes to a fragile engagement ecosystem.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn this context, both PIs and POs identify largely overlapping barriers to PPI; however, they interpret and prioritise them differently depending on their respective backgrounds, experiences, and competencies (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). As a result, the misalignment appears as a systemic tension between different logics of value, particularly evident in the asymmetry of objectives that characterises interactions between researchers and patient organisations (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e). PIs may recognise the relevance of patient-centred concerns, yet perceive them as secondary when confronted with competing priorities such as scientific validity, regulatory compliance, and time constraints (\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eConversely, consistent with existing literature (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e), interviews confirm that POs tend to interpret this hierarchy of priorities as a signal that experiential knowledge, although formally acknowledged, is not fully incorporated into decision-making processes. This does not necessarily reflect explicit disagreement, but rather a somewhat parallel awareness, accompanied by different urgency thresholds.\u003c/p\u003e \u003cp\u003eAlongside these structural tensions, some barriers are perceived as relatively straightforward and widely acknowledged by both parties. Communication issues, particularly those related to technical language and overly complex materials, are often described as obvious obstacles that could be mitigated through simplification and targeted training, in line with previous studies (\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e). From this perspective, improving shared understanding is not seen as conceptually problematic but as a practical challenge requiring dedicated resources, educational efforts, and time investment. Another relevant issue to address is the need for training (\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e) for the two groups (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e). Interview data confirm international evidence, affirming that patients and POs should acquire technical knowledge about scientific terminology and trial processes (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e), while researchers could improve their engagement and communication strategies (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBeyond individual interactions, respondents emphasised the importance of building relationships between POs and PIs before the formal start of a collaboration. Early and informal connections facilitate mutual understanding and trust, reducing the time typically devoted to role clarification and reciprocal legitimisation (\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e). When such relationships are already in place, collaboration during clinical trials becomes smoother, as the preliminary effort required to establish credibility and shared expectations is significantly reduced.\u003c/p\u003e \u003cp\u003eHowever, the feasibility of early relationship-building is constrained by the fragmentation of the engagement ecosystem (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Both PIs and POs highlighted the absence of structured mechanisms to facilitate matchmaking, making it difficult for researchers to identify appropriate organisations and for POs to be considered as potential partners. This lack of coordination reinforces \u003cem\u003ead hoc\u003c/em\u003e engagement practices and limits the scalability of successful collaborations.\u003c/p\u003e \u003cp\u003eIn some cases, barriers are not merely structural but cultural. The interviews again confirm findings from previous studies (\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e): a limited willingness to engage persists among certain actors, often rooted in scepticism towards the added value of patient involvement or concerns about the loss of scientific authority. In this context, a potential improvement could be obtained by showcasing international best practices to the parties involved, using them as proof that better results can be achieved when barriers are overcome. Practical, real-world examples could serve to go beyond theoretical notions, legitimising engagement and eventually reducing resistance.\u003c/p\u003e \u003cp\u003eImportantly, POs consistently stressed that their goal is not to replace clinicians or compete with their expertise, but to work alongside them as complementary actors. Supporting researchers throughout the collaboration process, rather than positioning engagement as an external imposition, is thus a key strategy to implement to foster openness and avoid potential conflicts.\u003c/p\u003e \u003cp\u003eFinally, respondents in some cases mentioned that willingness to engage is present, although opposed to a lack of practical knowledge. The literature confirms that uncertainty regarding roles (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e, \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e), responsibilities (\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e), and appropriate modes of interaction (\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e) constitute barriers to PPI, even when the parties involved are willing to implement them. This gap underscores the need for clear, shared guidelines outlining how engagement should be conducted in practice (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR38 CR39 CR40\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). Such guidance should address not only researchers\u0026rsquo; behaviours, but also include training for patients and patient organisations, clarifying expectations and supporting all actors in navigating collaboration effectively. At the same time, PPI should become standard practice in clinical research, which can only be feasible if stakeholders formally recognise each other as legitimate partners in research and explicitly set roles and responsibilities for each prior to collaboration.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study highlights how PPI in oncology trials is shaped by different interpretations of roles, priorities, and responsibilities within the research ecosystem. While principal investigators and patient organisations recognise similar obstacles, they frame them through distinct lenses, which contributes to engagement being positioned at the margins of trial practice rather than embedded within it.\u003c/p\u003e \u003cp\u003eThe analysis also shows that POs can contribute a complementary perspective, particularly in early trial phases, by surfacing feasibility, communication, and relevance issues that may otherwise remain unaddressed. Advancing engagement, therefore, depends less on individual willingness and more on clearer operational guidance, dedicated resources, shared training, and stable mechanisms for collaboration.\u003c/p\u003e \u003cp\u003eAlthough based in Italy, the patterns observed reflect conditions widely discussed in international literature. The findings are therefore applicable beyond this context and offer considerations for integrating PPI more effectively into clinical trial methodologies across different settings.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eWhile diversity in size, experience, and focus of the selected interviewees was maximised, the pool is limited and may not represent the entire Italian context. The study is situated within the Italian research context, and regulatory or organisational differences may influence transferability. In addition, perspectives from direct patient participants and the pharmaceutical industries were not included and should be explored in future research.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eWe thank all principal investigators and patient organisation representatives who generously shared their time, experiences, and reflections. Their openness in discussing both challenges and opportunities made this research possible.\u003c/p\u003e\n\u003cp\u003eWe are grateful to the FAVO for facilitating contact with patient organisations and supporting the recruitment process. We also thank [hidden] for their support in coordinating and conducting interviews with principal investigators and for their contribution to organising materials for the qualitative analysis. This work was carried out within the framework of the [hidden].\u003c/p\u003e\n\u003ch2\u003eAuthors\u0026rsquo; contributions\u003c/h2\u003e\n\u003cp\u003e[hidden] conducted interviews, supervised data collection and analysis, prepared the figure, contributed to the development of the theoretical framework and methodology, and revised and edited the manuscript. [hidden] carried out data collection and analysis, prepared the tables, and drafted the manuscript. [hidden] provided senior supervision, contributed to the overall study design and framing of the manuscript, and secured project funding.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis work was supported by the [hidden] project, funded by [hidden].\u003c/p\u003e\n\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eEthical approval for this study was obtained from the Ethics Committee of [hidden]. All participants received detailed information about the study and provided informed consent prior to participation. Interviews were conducted in accordance with applicable ethical standards and privacy regulations.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eParticipants provided written consent for the use of anonymised interview excerpts for research and publication purposes.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eThe datasets generated and analysed during the current study are not publicly available due to confidentiality and privacy restrictions. Anonymised data may be shared by the corresponding author upon reasonable request and subject to approval by the Ethics Committee of [hidden].\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFarah E, Kenney M, Kica A, Haddad P, Stewart DJ, Bradford JP. Beyond Participation: Evaluating the Role of Patients in Designing Oncology Clinical Trials. Curr Oncol. 2023;30(9):8310\u0026ndash;27. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/curroncol30090603\u003c/span\u003e\u003cspan address=\"10.3390/curroncol30090603\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHickmann E, Richter P, Schlieter H. 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J Geriatr Oncol. 2017;8(6):391\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jgo.2017.05.002\u003c/span\u003e\u003cspan address=\"10.1016/j.jgo.2017.05.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"research-involvement-and-engagement","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"riae","sideBox":"Learn more about [Research Involvement and Engagement](http://researchinvolvement.biomedcentral.com/)","snPcode":"40900","submissionUrl":"https://submission.nature.com/new-submission/40900/3","title":"Research Involvement and Engagement","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"patient organisations, patient and public involvement, patient engagement, principal investigators, clinical trials, research involvement, oncology","lastPublishedDoi":"10.21203/rs.3.rs-8741101/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8741101/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Patient engagement and Patient Public Involvement are increasingly promoted to enhance the relevance, feasibility, and ethical grounding of clinical research, particularly in oncology, where trials can be demanding, and quality-of-life trade-offs are substantial. Despite this, engagement often remains fragile and inconsistently embedded in routine trial practices, especially where shared operational standards are limited. This study examines why engagement remains difficult to institutionalise in Italy by comparing perspectives from principal investigators and patient organisation representatives.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We conducted semi-structured remote interviews with principal investigators involved in oncological clinical research and representatives of patient organisations engaged in advocacy and research-related activities. Interviews were audio-recorded with consent, transcribed verbatim, and analysed using an iterative qualitative process focused on barriers to meaningful engagement. Coding and thematic clustering were performed to identify recurring patterns and areas of convergence and divergence across the two stakeholder groups. In a subsequent interpretive step, the resulting barrier themes were organised into four cross-cutting dimensions—cultural, organisational, operational, and institutional—to support comparison and reporting.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Participants in both groups described a shared set of interrelated barriers but interpreted and prioritised them differently. Cultural barriers centred on tensions around expertise, authority, and the perceived legitimacy of experiential knowledge in trial design. Organisational barriers included fragmentation within the patient organisation landscape and misalignment of priorities between scientific endpoints and patient-relevant concerns. Operational barriers reflected workload pressure, limited integration of engagement into trial workflows, and asymmetries in language and expertise that constrained informed participation. Institutional barriers included discontinuity, limited feedback to patients and organisations, and the absence of clear guidance on when and how to engage patients consistently. Together, these factors contributed to engagement being late, episodic, and dependent on individual initiative rather than routine practice.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e PE and PPI in Italian oncology research remain fragile because multiple barriers intersect across culture, organisation, operations, and institutions, while stakeholders often hold different assumptions about roles and value. Strengthening engagement requires more explicit operational guidance, dedicated resources, and shared capacity-building to support earlier, more consistent, and more sustainable collaboration.\u003c/p\u003e","manuscriptTitle":"Why engagement remains fragile: A qualitative comparison of principal investigators’ and patient organisations’ perspectives in Italy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-19 16:10:45","doi":"10.21203/rs.3.rs-8741101/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-16T12:37:40+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-16T12:25:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-07T08:58:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-01T12:40:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"174861753687990616737331911416614234004","date":"2026-04-01T10:25:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"105975297445718261504424758934885445152","date":"2026-03-29T09:50:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"143073105176153664979882495273571932823","date":"2026-03-27T14:34:44+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-16T16:54:17+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-16T16:47:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Research Involvement and Engagement","date":"2026-03-14T18:55:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"research-involvement-and-engagement","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"riae","sideBox":"Learn more about [Research Involvement and Engagement](http://researchinvolvement.biomedcentral.com/)","snPcode":"40900","submissionUrl":"https://submission.nature.com/new-submission/40900/3","title":"Research Involvement and Engagement","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e3b37110-9903-4b7b-b261-7b007f9fc64a","owner":[],"postedDate":"March 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-16T12:53:17+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-19 16:10:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8741101","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8741101","identity":"rs-8741101","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}