The Medical Science Liaison Role in Spain: Opinion of the Commercial Department Personnel.

INTRODUCTION: The Medical Science Liaison (MSL) works in a cross-functional way, especially with the commercial department. The aim of the present study was to evaluate the knowledge of these positions about the MSL role in their companies and describe the grade of internal interaction between them in daily practice. METHODS: An online survey was completed by 151 employees from commercial departments between January and April 2020. It consisted of 29 or 31 items, depending on answers. RESULTS: Of participants, 22.5% and 77.5% occupied management or non-management positions, respectively. Most respondents stated that the MSL role belongs primarily to the medical department (94.6%), considered important that promotional materials are elaborated or supported by the medical department (95.4%), highlighted the importance of sharing their daily activity with MSLs (77.8%) and vice versa (89.3%). The most valuable activity of MSLs was clinical sessions (55.3%), followed by speaker briefings (16.0%), and data discussions (14.7%). Most useful activities of MSLs for participant's day to day were external training (sessions to healthcare providers, HCPs, 34.9%), support of key opinion leaders' (KOLs) unmet needs (22.1%), and feedback from fieldwork aimed at redefining new strategies of the company (15.4%). The mean overall assessment (0-10) of the MSL was 8.1. CONCLUSION: The MSL represents a key role inside pharmaceutical and biotechnological companies, providing scientific value. The members of the commercial departments interact with the MSL on a daily basis and consider that it is a strategic position with a great future that adds value within the company.

The Medical Science Liaison Role in Spain: A Survey Capturing the Opinion of Medical Department Professionals.

BACKGROUND: Literature that addresses the role of Medical Science Liaison (MSL) is currently limited. To the best of our knowledge, this is the first survey in Spain that gathers opinions from professionals whose work is either in or related to the medical departments from pharmaceutical companies. METHODS: A survey delivered by the SurveyMonkey online platform was completed by 101 pharmaceutical industry professionals (medical advisor/manager, 31.7%; medical director, 26.7%; medical information, 12.9%; and MSL manager, 11.9%). RESULTS: The median score for the global impression of the MSL was 8.7. The collaboration goes beyond formation since 85.1% of the respondents believed that MSLs should actively collaborate in both clinical trials and investigator-initiated studies, they should have more involvement with market access (51.5%), and they play an important role in compliance (94.0%). There was a tendency toward granting MSLs more responsibilities in terms of budget (73.3%) and their participation in the elaboration of the Medical Plan (91.1%). This position was considered as a strategic partner both internally and externally (76.2%). CONCLUSION: MSL is a well-known field-based profile with increasing importance and responsibilities. MSLs represent a strategic position as internal collaborators in the company, whose success relies on cross-functional work. The MSL's profile is in constant development, currently facing challenges such as adapting to remote interactions, or providing a clear definition with the best metrics to measure their performance as a non-promotional position.

The medical science liaison role in Spain: A nationwide survey.

CONTEXT AND AIMS: The Medical Science Liaison's (MSL's) value to the company has evolved into a more strategic role with a wide variety of responsibilities. We conducted an online survey of current MSLs nationwide to assess their profile, activity development, performance evaluation, and career development. SUBJECTS AND METHODS: A 37-item survey was hosted on SurveyMonkey© and accessible from December 2018 to February 2019. The survey was open to current MSLs from different pharmaceutical companies in Spain and included questions about the participant profile, activity development, performance evaluation, and career development. STATISTICAL ANALYSIS USED: The results were expressed as valid percentages; to establish relationships between the answers to different questions, exclusion and comparison filters were used on the web platform. RESULTS: A total of 179 MSLs responded to the anonymous survey. Off-label information management (79%), relationships with key opinion leaders (76%), continuous medical training for HCPs (70%), involvement in clinical trials/investigator-initiated trials (68%), and elaboration of the National Strategy (67%) were mentioned as the top new competencies. Fifty-eight percent spend an average of 61%-80% of their time out in the field and 68% use remote interactions. Fifty-six percent did not agree that their current performance metrics are a reflection of their true value. Forty-five percent of the participants disagreed when asked if their activity is easily balanced with their personal lives. CONCLUSIONS: Based on our findings, we believe that there is a need to consider the MSL's strategic priorities, to define metrics that accurately assess MSL performance, and to find ways to fully maximize their limited time.

The Medical Science Liaison Role in Spain: A Survey About the Opinion of HealthCare Professionals.

PURPOSE/AIM: There are limited studies addressing the knowledge of healthcare professionals (HCPs) on the Medical Science Liaison (MSL) role. The objective of this study was to determine the percentage of HCPs that know the role, and to describe their opinion about the utility of the MSL activities on their clinical practice. METHODS: An online survey was completed by 107 HCPs between June 2019 and January 2020 through three Scientific Societies. It consisted of 17 or 25 questions, depending on the answers. RESULTS: Most HCPs (73.8%) knew the MSL role inside the pharmaceutical industry and were able to differentiate the MSL role from others in marketing/sales departments (77.6%). Support for research projects (70.8%) and training courses (68.1%) were the most valuable activities. Participants scored the credibility of data provided by the MSL with a mean of 7.5 (out of 10), and the added value that the MSL provides to their clinical practice with a mean of 6.9. Among HCPs unfamiliar with the role (26.2%), 60% of them are interested in meeting with the local MSL. CONCLUSION: Our study demonstrates that the MSL role is well-known by HCPs, mostly Key Opinion Leaders, and they agree on the importance of working together in scientific projects on, e.g., disease awareness, medical training, or clinical trials. Given the advance of targeted therapies and the move toward personalized medicine, the MSL role will be in more demand and necessary for HCPs in the years to come.

A Novel Circulating MicroRNA for the Detection of Acute Myocarditis.

BACKGROUND: The diagnosis of acute myocarditis typically requires either endomyocardial biopsy (which is invasive) or cardiovascular magnetic resonance imaging (which is not universally available). Additional approaches to diagnosis are desirable. We sought to identify a novel microRNA for the diagnosis of acute myocarditis. METHODS: To identify a microRNA specific for myocarditis, we performed microRNA microarray analyses and quantitative polymerase-chain-reaction (qPCR) assays in sorted CD4+ T cells and type 17 helper T (Th17) cells after inducing experimental autoimmune myocarditis or myocardial infarction in mice. We also performed qPCR in samples from coxsackievirus-induced myocarditis in mice. We then identified the human homologue for this microRNA and compared its expression in plasma obtained from patients with acute myocarditis with the expression in various controls. RESULTS: We confirmed that Th17 cells, which are characterized by the production of interleukin-17, are a characteristic feature of myocardial injury in the acute phase of myocarditis. The microRNA mmu-miR-721 was synthesized by Th17 cells and was present in the plasma of mice with acute autoimmune or viral myocarditis but not in those with acute myocardial infarction. The human homologue, designated hsa-miR-Chr8:96, was identified in four independent cohorts of patients with myocarditis. The area under the receiver-operating-characteristic curve for this novel microRNA for distinguishing patients with acute myocarditis from those with myocardial infarction was 0.927 (95% confidence interval, 0.879 to 0.975). The microRNA retained its diagnostic value in models after adjustment for age, sex, ejection fraction, and serum troponin level. CONCLUSIONS: After identifying a novel microRNA in mice and humans with myocarditis, we found that the human homologue (hsa-miR-Chr8:96) could be used to distinguish patients with myocarditis from those with myocardial infarction. (Funded by the Spanish Ministry of Science and Innovation and others.).

Immune-Regulatory Molecule CD69 Controls Peritoneal Fibrosis.

Patients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated inflammation as a key contributor in peritoneal damage. The leukocyte antigen CD69 modulates the setting and progression of autoimmune and inflammatory diseases by controlling the balance between Th17 and regulatory T cells (Tregs). However, the relevance of CD69 in tissue fibrosis remains largely unknown. Thus, we explored the role of CD69 in fibroproliferative responses using a mouse model of peritoneal fibrosis induced by dialysis fluid exposure under either normal or uremic status. We found that cd69-/- mice compared with wild-type (WT) mice showed enhanced fibrosis, mesothelial to mesenchymal transition, IL-17 production, and Th17 cell infiltration in response to dialysis fluid treatment. Uremia contributed partially to peritoneal inflammatory and fibrotic responses. Additionally, antibody-mediated CD69 blockade in WT mice mimicked the fibrotic response of cd69-/- mice. Finally, IL-17 blockade in cd69-/- mice decreased peritoneal fibrosis to the WT levels, and mixed bone marrow from cd69-/- and Rag2-/-γc-/- mice transplanted into WT mice reproduced the severity of the response to dialysis fluid observed in cd69-/- mice, showing that CD69 exerts its regulatory function within the lymphocyte compartment. Overall, our results indicate that CD69 controls tissue fibrosis by regulating Th17-mediated inflammation.

Immunosuppression-Independent Role of Regulatory T Cells against Hypertension-Driven Renal Dysfunctions.

Hypertension-associated cardiorenal diseases represent one of the heaviest burdens for current health systems. In addition to hemodynamic damage, recent results have revealed that hematopoietic cells contribute to the development of these diseases by generating proinflammatory and profibrotic environments in the heart and kidney. However, the cell subtypes involved remain poorly characterized. Here we report that CD39(+) regulatory T (TREG) cells utilize an immunosuppression-independent mechanism to counteract renal and possibly cardiac damage during angiotensin II (AngII)-dependent hypertension. This mechanism relies on the direct apoptosis of tissue-resident neutrophils by the ecto-ATP diphosphohydrolase activity of CD39. In agreement with this, experimental and genetic alterations in TREG/TH cell ratios have a direct impact on tissue-resident neutrophil numbers, cardiomyocyte hypertrophy, cardiorenal fibrosis, and, to a lesser extent, arterial pressure elevation during AngII-driven hypertension. These results indicate that TREG cells constitute a first protective barrier against hypertension-driven tissue fibrosis and, in addition, suggest new therapeutic avenues to prevent hypertension-linked cardiorenal diseases.

Maintenance of immune tolerance by Foxp3+ regulatory T cells requires CD69 expression.

Although FoxP3(+) regulatory T cells are key players in the maintenance of immune tolerance and autoimmunity, the lack of specific markers constitute an obstacle to their use for immunotherapy protocols. In this study, we have investigated the role of the C-type lectin receptor CD69 in the suppressor function of Tregs and maintenance of immune tolerance towards harmless inhaled antigens. We identified a novel FoxP3(+)CD69(+) Treg subset capable to maintain immune tolerance and protect to developing inflammation. Although CD69(+) and CD69(-)FoxP3(+) Tregs exist in homeostasis, only CD69-expressing Tregs express high levels of CTLA-4, ICOS, CD38 and GITR suppression-associated markers, secrete high amounts of TGFß and have potent suppressor activity. This activity is regulated by STAT5 and ERK signaling pathways and is impaired by antibody-mediated down-regulation of CD69 expression. Moreover, immunotherapy with FoxP3(+)CD69(+) Tregs restores the homeostasis in Cd69(-/-) mice, that fail to induce tolerance, and is also highly proficient in the prevention of inflammation. The identification of the FoxP3(+)CD69(+) Treg subset paves the way toward the development of new therapeutic strategies to control immune homeostasis and autoimmunity.

The leukocyte activation antigen CD69 limits allergic asthma and skin contact hypersensitivity.

BACKGROUND: Allergic diseases have a major health care impact in industrialized countries. The development of these diseases is influenced by exposure to allergen and to immunological and genetic factors. However, the molecular mechanisms underlying the inflammatory response that triggers allergy are not well defined. OBJECTIVE: We have investigated the role of the leukocyte activation antigen CD69 in the regulation of two allergic diseases, asthma and contact dermatitis. METHODS: Analysis of two models of allergic diseases in CD69 knockout and wild-type mice: ovalbumin-induced allergic airway inflammation (BALB/c genetic background) and contact hypersensitivity to oxazolone (C57BL/6J genetic background). RESULTS: CD69 deficiency dramatically enhanced the inflammatory response in the ovalbumin-induced asthma model of antigen-induced airway allergy. CD69 knockout mice showed exacerbated pulmonary eosinophil recruitment, high vascular cell adhesion molecule 1 expression levels in lung vasculature, and enhanced T(H)2 and T(H)17 cytokines in the bronchoalveolar space and lung tissue. In the hapten-induced cutaneous contact hypersensitivity model, both CD69 deficiency and treatment with anti-CD69 mAb increased inflammation. Treatment with contact allergens induced enhanced T(H)1 and T(H)17 responses in CD69 deficient mice, and neutralizing anti-IL-17 antibodies reduced skin inflammation. In both experimental systems, adoptive transfer of lymph node cells from CD69 knockout mice increased the inflammatory response in recipient mice. CONCLUSION: These results demonstrate that the early activation receptor CD69 is an intrinsic modulator of immune allergic processes through the negative regulation of allergen-induced T-cell effector responses.