Background:In the last decade many clinical research centers in Italy have increasingly implemented and improved their quality standards and effectiveness of processes through the adoption of a quality management system also according to the certification ISO 9001:2015.Objective:The aim of this project is to evaluate expected benefits and barriers of ISO 9001 certification for a Clinical Trial Center.Material and methods:On April 2021, the Italian Group of Data Manager and Clinical Research Coordinator spread an anonymous online survey to healthcare professionals operating in clinical research and quality management systems at research sites.Results:Reported benefits of ISO oriented Quality Management System adoption include continual improvement and better-quality processes (73.3%), assuring corrective actions (63.6%), planning internal audits (60.2%) and risk management approach (60.7%). The most important barriers to QMS implementation are increased logistical and/or organizational activities (40.9%) and insufficient training on quality programs (29.5%).Conclusions:Implementing a quality management system represents a challenge for the Clinical Trial Center and helps to improve quality standards and risk management approach. The use of electronic tools is poor and could be increased in the future. Lastly, improvement of continuous QMS trainings should be necessary for updating professionals and optimizing activities within the Clinical Trial Center.

The need to identify appropriate formulae to decentralize the clinical trials (DCTs) and enabling their implementation outside hospitals became a dramatic priority during COVID-19 pandemic. However, many obscure points remain concerning DCTs, starting from the regulatory definition. In June 22, Life Science Innovation shared an anonymous online survey with the Italian Group of Data Manager to investigate how DCTs' elements were widespread in Italian clinical research centers. The final survey was structured with 14 questions and remained open for 15 days. The survey was completed by 35 study coordinators, mostly (54.3%, n=19) from public hospitals, with a median work experience of 8 years. Just over half (48.6%, n=17) declared they could count on Electronic Medical Records, while Electronic Case Report Forms were widely (74.2%, n=26) used. Only in 2 cases (5.7%) these tools are integrated. Over 60% of respondents (n=22) declared no experience in conducting DCTs but the vast majority (72.7%, n=16) expressed interest for the future. The lack of interest is mainly (50%) due to the need of specific skills. Analyzing the answers on the specific digital solutions (n=24, multiple answers option), the most used ones, regardless of the pandemic emergency, are devices (eg sensors) for remote parameter collection (60%), tools for collecting patients' data like apps for monitoring the therapeutic adherence (60%) and for delivering Electronic Patient Reported Outcomes (60%). More than half of the respondents (60%) declare a future interest in the remote informed consent process. On a 1-10 scale (strongly disagree - strongly agree), DCTs are considered not fully useful to increase patient adherence (mean score 6.6) or to reduce research time (5.8) and costs (5.9). Even lower (5.5) the suggestion that DCTs could increase patient involvement. There is a convergent thinking that DCTs can increase the amount of Real-world data collected (7.5) and that they require very specific skills (8) as well as address key data privacy and security (8) issues. Despite the pandemic experience, the interest in a greater diffusion of studies with a partial or total digital component remains limited and crucial aspects should be addressed regarding Italy's ability to implement DCTs in short run.

Many benefits have been recognized concerning the use of social media in the medical field, especially in oncology and clinical research and can be an opportunity for a better relationship between patients and healthcare professionals.The scope of this project is to investigate the use of social networks for professional purposes among professionals working in clinical research in Italy.A specific anonymous survey was created by the Italian Group of Study Coordinators to explore the use of social media among clinical research professionals.The survey was composed of 13 questions grouped into different investigational sections and the attitudes and perceptions of professionals were assessed using ten-point Likert scales, continuous percentage scale or different answer options.According to respondents the most used social network for business purposes is Facebook (74.7%), followed by LinkedIn (69.0%), with Research Gate particularly appreciated in the 30-49 years range.The evaluation of the respondents with respect to the real usefulness of social networks for work is average (median score 5.93 on a 1-10 scale), without major differences between different age groups (5.90 in 18-29 years' group; 5.93 in 30-49; 5.66 in 50-55).The evaluation of the usefulness by cancer patients is also average (median score: 6.00), with a pessimism that characterizes above all the group of 50-65 years' respondents (5.18 vs. 5.86 in 18-29 years' and 6 in 30-49 years' group).Social media can help break down traditional barriers that prevent interaction among healthcare professionals as well as between providers, scientists, patients, and caregivers.Given the popularity and almost universal appeal of social media, we encourage physicians and institutions to learn and engage more in this ongoing evolution. Impact statement:The use of social media by Italian clinical research professionals is quite widespread but characterized by a profound heterogeneity among professional figures and in the different hospitals.

The “Researchers’ Pyramid” has represented the first main effort to formally recognize in Italy a specific category of professionals that, despite working in the healthcare field, has never been able to benefit from the stabilization options granted to the rest of the medical and healthcare staff. Stabilization of researchers by the Pyramid should in fact represent a chance to hire a large number of professionals that have been working in local pub1 Biostatistics and Clinical Trials Unit,IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy 2 Department of Public Health and Paediatrics, University of Turin, Turin, Italy 3 Paediatric Haematology-Oncology Department, Regina Margherita Children’s Hospital, A.O.U. Città della Salute di Torino, Turin, Italy 4 Terapie Cellulari e Medicina Trasfusionale, AOU Careggi, Florence, Italy 5 Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy 6 Clinica di Ematologia, AOU Ospedali Riuniti Umberto I, G.M. Lancisi, G. Salesi, Ancona, Italy 7 Oncologia Medica 1, Molinette Hospital, A.O.U. Citta della Salute di Torino, Turin, Italy 8 Oncologia, AUSL Modena Area Sud Ospedale di Sassuolo, Sassuolo, Modena, Italy 9 Oncology Clinical Trial Office, SC Oncologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy CORRESPONDING AUTHOR:

The paper provides an overview of the actions taken to preserve clinical research during the pandemic, some of which it would be important to maintain in the future.

Social Network have become immensely popular in recent years and provides new opportunities for health care personnel and institutions to interact with patients and other professionals, transforming communication, training and healthcare assistance. In particular, doctors and health professionals increasingly use social networks to update and train themselves. The Italian Group of Data Managers (GIDMcrc) explore the use of Social Network among professionals involved in clinical research in Italy with an online anonymous survey of 13 questions, available from mid-February to mid-April. At 15 April 2020, 100 research professionals completed the survey: 52 clinical research coordinators, 23 physicians, 20 nurses and 5 others, mainly aged between 30 and 49 (n=79). The majority of respondents reported using Social Network rarely/sometimes, mainly to receive information (n=30, 54%), to find and share information in equal measure (n=13, 24%) or to share information only (n=10, 18,5%). 33% said to use them often. Among frequent users: 73% (n=24) log into Social Networks mostly to find and share information in equal measure (n=23, 70%). Only 13% do not use it. The most used Social Networks are Facebook (65%) and LinkedIn (61%). Almost half of the respondents (n=43) have been contacted by patients through social networks, mainly via Facebook (60%), e-mail (42%), WhatsApp (37%). 48% of respondents uses e-mails or other messaging systems to communicate with the patient or manage appointments, but only 15% have been trained on the use of Social Network. This survey provides insight into the use of Social Network among research professionals, highlightings that the majority use them to search for information. Half of the professionals were contacted by patients looking for information or for managing their appointments. However, all this is done without specific training. If patients, healthcare professionals and researchers were informed and instructed about the correct use of Social Network, there could be benefits for research, like: faster recruitment in clinical trials, involvement of patients in the study design, sharing of trial results. In the near future, we would like to extend the survey to European colleagues, to see if there are any differences compared to Italy.

During Coronavirus pandemic, public opinion has returned to a great deal of interest in clinical research and the key role of researchers. Particularly in Italy, deeply affected by the emergency, people have returned to believe in the work of health professionals and have loudly asked for a profound research effort, a field hitherto suspiciously looked at. Yet, until then, few had worried about nation's big contradictions as the total nonexistence of the profession of the researcher in the National Health System. The only effort in the recent years has been a ministerial reform "Researchers' pyramid", a 10 year working path characterized by a 5 year contract, renewable once and with annual reconfirmation exams, with the final hope of recognition within the national health system. An initiative that has been the subject of strong contradictions. In September 2019, the Italian Group of Clinical Research Coordinators shared an online survey, meant for the Italian biomedical research personnel, to investigate opinions about the reform. The questionnaire was completed by 147 respondents, the majority (53.1%) employed at public research institute or public Hospitals/University/Local Health Company (34.0%).Respondent's job for the greater part corresponded to a profession included in the "Clinical Research Assistant" (55.1%) and "Clinical Researcher" categories (25.9%). Over half declared to be optimistic regarding the actual benefit of the reform for employment stability. Between "not optimistic respondents", 50% considers Pyramid a false stabilization path. Concerns were also expressed in relation to the evaluation criteria, considered too exclusive and often not suitable by a third of the interviewed. Many individuals (41.5%) report the poor valorization of personnel and much apprehension was recorded relating to the possibility of extending the reform to other institutes. The reform overall seems an important opportunity for entry level personnel, a watered-down compromise for expert professionals. The fear conveyed from the great majority of the interviewed is that the pyramid is only a trick. When the emergency is over, will institutions finally begin to understand the importance of research? A job, not just a passion.

Background: During the COVID-19 Coronavirus pandemic, public opinion has returned to a great deal of interest in clinical research and the key role of researchers in periods of health emergency If on the one hand the emergency has reawakened confidence in the work of researchers in the population, on the other it has revealed leaks in the system that insiders have known for a long time Italian research has always been characterized by great contradictions While Italy boasts the most prestigious researchers worldwide, it is highly penalized by low investments and the inability to provide a stable career path to researchers and support staff A first important step to at least partially solve the problem was the ministerial reform known as ' Researchers' pyramid', an initiative that has been the subject of strong contradictions Methods: In September 2019, the Italian Group of Data Manager shared an online survey, meant for the italian biomedical research personnel, to investigate opinions about the reform Results: The questionnaire was completed by 147 respondents, the majority being employed at public IRCCS/IZP (n=78, 53 1%) or public Hospitals/University/Local Health Company (n=50, 34 0%) The respondent's profession was not included in those listed in the Pyramid in the minority of cases (n=28, 19%), while for the greater part it corresponded to a profession included in the 'Clinical Research Assistant' (n=21, 55 1%) and 'Clinical Researcher' categories (n=38, 25 9%) Over half of respondents declared to be optimistic regarding the actual benefit of the reform for employment stability Over half (63 4%) of the 'not optimistic respondents' considers the Pyramid a false path towards stabilization Concerns were also expressed in relation to the evaluation criteria during the ten-year period, considered by a third of the interviewed to be too exclusive and often not very suitable Many individuals (41 5%) report the poor valorization of personnel and much apprehension was recorded relating to the possibility of extending the reform to other institutes Conclusions: The reform overall seems like an important opportunity for entry level or inexperienced personnel, a watered-down compromise for expert professionals But above all: only IRCCS are worthy of doing research The fear conveyed from the great majority of the interviewed is that the pyramid is only a trick When the emergency is over, will institutions finally begin to consider research a real job

COVID-19 pandemic has impacted all health care areas, including clinical research, especially in the countries most affected by the emergency, such as Italy. This forced a profound reorganization of experimental sites and Clinical Trials Units (CTU), in accordance with the specific guidelines gradually drawn up by the regulatory agencies. In April 2020 the Italian Group of Clinical Research Coordinators spread an anonymous web survey consisted of 21 questions about the reorganization of CTUs and the managements of trials since the start of pandemic. 142 representatives of Italian CTUs completed the survey; women was 86% and the age group 26-35 years was the mainly represented (50.7%). A total of 15 on 21 Italian regions were represented with a good national coverage. The majority of respondents (85.2%) said that, due to the emergency, the CTU activity has been reorganized, mainly through the alternation of smart working and shifts on site (64.5%) or the activation of a totally smart working method (27.3%). Within the cohort that had the opportunity to work, partially or totally, from home (81.7%), most respondents (69.8%) stated they benefited from a high level of accessibility to hospital records, in many cases (50.6%) both patient records and shared document areas. In very few cases, the employer has provided additional tools for staff, such as PCs (15.5%) or phones (0.9%) company, while many respondents (49.1%) said they had not even received assistance from their IT service. With regard to the opinion on the effectiveness of the smart working activity,the average score was 6.3 on a scale of about 1–10. Most of the Clinical Trials Units have been reorganized so that deferred activities can be carried out away from the hospital, guaranteeing, on average, wide remote access to the necessary documentation. Certainly, it would be necessary to improve the IT and electronic equipment that employees benefit from so as to optimize all activities and ensure rapid and high-quality performances, even in non-emergency situations.

The increasing complexity that characterizes the world of clinical trials, both in terms of procedures and bureaucracy, has made it necessary to create dedicated infrastructures composed of experienced and qualified personnel, who constantly work to ensure high ethical and qualitative standards. A key role in these infrastructures is played by the clinical research coordinator, a key figure able to manage the workflow required, placing himself as a reference for the coordination of the various activities and professional figures involved. The literature has widely demonstrated how the presence of this professional figure is a valid contribution both from a documentary and administrative point of view as well as a crucial resource for what concerns the indicators of ethics and quality of research. Despite that, there is no yet an institutional recognition of the professional figure, neither a specific economical agreement within the National Health System. The lack of institutional recognition is causing a worrying phenomenon of migration of qualified personnel towards contract research organizations and pharmaceutical companies. That could be detrimental to the competitiveness of Italian clinical research and hinder the possibility of offering innovative experiments therapies to patients, with serious ethical consequences.

Background: Conducting clinical trials in oncology is becoming more complicated and many studies are struggling with patient recruitment. One reason for this is the difficulty in involving patients in trials. Today patient's awareness of and active involvement in clinical research (CR) is frequently discussed, but an estimate of the patient's understanding is still not known. Several studies have evaluated the patients understanding of procedures, but few of them have analyzed their understanding about research. The aim of this study was to evaluate the level of understanding of CR in cancer patients. Patients and methods: This was a cross-sectional, observational survey study. Patients with a diagnosis of any kind of tumor (oncologic or hematologic) attending a visit in the Oncohematology department of IRST IRCCS or Oncohematology Unit in AVR of Rimini, Ravenna, Lugo and Faenza Hospital and able to complete the questionnaire were included in the survey. Patients accessing for the first time were excluded. A questionnaire, based on a previous one used by AIFA in 2010, including 10 statements about CR, some questions about previous participation and the willingness to participate in a clinical study, one question about the interest to learn more about CR as well as some demographic questions, was developed. The anonymous questionnaire was administrated to patients from December 2015 to March 2016. Patients responding correctly to at least 80% of the ten questions on CR, were considered to have a good understanding of CR. Results: The questionnaire was given to 967 patients and completed by 769 (79.5%). The mean age was 63 ± 13 years, 60% were females and 44% had a high school diploma or a higher degree. 22% of patients showed to have a good understanding of CR. 13% had participated in a clinical trial and 53% would be willing to participate in a trial studying a new drug. The main reason for accepting participation was the patient's trust in their physician (53%). The main reason for refusing participation was that not all risks are known (61%). 75% of the patients would be interested in taking part in meetings regarding CR. Conclusions: The patients' understanding of CR is poor, as it has been shown in other international studies. The survey revealed to be a useful tool to assess the understanding of CR in patients accessing our centers thus helping us to prepare and provide them with adequate informative material to improve understanding and consciousness about CR.

Background: Collaboration between team members is essential in order to improve clinical effectiveness and care quality in cancer clinical trials, as they have become increasingly complex and require a fully integrated multidisciplinary team. There is no sufficient knowledge of neither the interactions and communication strategies between nurses and CRCs in cancer centers nor the communication strategy enhancement to achieve optimal conduction of clinical trials in the healthcare setting. Nurses and CRCs of IRST scheduled a series of meetings to improve care quality for patients involved in CTs and promote the integration between professionals. Methods: Based on a previous survey that had highlighted this lack, a series of meetings was scheduled to improve the exchange of knowledge and skills, define operative procedures to ensure a correct and complete data collection, identify paths and tools to facilitate the conduct of clinical trials. During the meetings participants also provided an update of ongoing studies, discussed any relevant issue, proposed actions for improvement, presented the results of the studies already completed and published. Results: From March 2010 to March 2015, 11 meetings were held and attended by an average of 15 nurses (of the ward and day hospital) and 8 CRCs of the Biostatistics and Clinical Trials Unit. A meeting report was compiled and participants' attendance was recorded in each meeting. All items showed a trend of improvement, with significant reduction in the number of missing data and protocol violations reported to the Ethics Committee and the Principal Investigator. New procedures have been produced for the collection and management of hematologic samples for centralized laboratories, the recording of vital signs, the devices utilization and the sharing of trial documents in e-medical records, such as protocol, informed consent and information for patients and GPs. The presence of a nurse at the Selection Visit (SV) and at the Initiation Study Visit (SIV) was introduced. Conclusions: Optimal integration between different professionals requires personal motivation, organization, sharing of common goals. Multidisciplinary meetings to discuss, plan together and share knowledge improve collaboration among professionals and help to increase the quality of clinical research and to ensure the patients receive the best care.

Background: Cancer clinical trials (CT) have become more complex and require dedicated personnel (Clinical Research Coordinators [CRC]) involved in activities including regulatory and administrative aspects and protocol- and patient-related procedures.Few experiences on how to measure the workload (WL) of a CT have been published.We measured the specific WL of CRCs using a simple, objective tool developed at our institute. Methods: The WL measurement tool considers 3 aspects of trial complexity: protocol management-related WL and patient (pt) management-related WL, subdivided into pt treatment management-related WL and pt follow-up management-related WL. A partial score is calculated for each section based on the specific score for: a) study promoter (profit, no profit); b) frequency of monitoring site visits; c) disease setting (advanced, adjuvant, neoadjuvant); d) number of centralized procedures; e) frequency of hospital visits to receive treatment; f) type of follow-up.The WL score pertaining to the study protocol (a-b) is trial-specific and not related to pt numbers. Scores for the treatment and follow-up sections are multiplied by the number of pts still undergoing treatment (c-d-e) and the number undergoing follow-up (f). The total WL for each trial is the sum of protocol-related partial scores and pt-related partial scores. IRST WLs were measured each month by 19 full-time CRCs in 7 sites of the Romagna Oncology Network to evaluate the reproducibility (when the study was active in two or more network sites) and accuracy of the measurement tool. Results: From 1.04.15 to 31.03.15, 215 CRC WLs were calculated. Each CRC was involved in a median of 22 trials (range 5-52). More than 50% of studies were active in two or more Network sites and score reproducibility was very high (> 90%), with little difference in the number of centralized procedures and frequency of site monitoring visits.Variations in total WL scores among CRCs (from 270 to 950) and differences over time (up to 15% from month to month) were observed, reflecting the subjective perceived workload, regardless of the involved number of ongoing trials and recruited pts. A monthly score of between 450 and 600 was hypothesized as an appropriate WL value for a full-time CRC. Conclusions: The IRST WL measurement tool could be a valuable aid to evaluating clinical trial complexity, estimating appropriate workloads for full-time CRCs, and planning personnel resource requirements.

Introduction Familial mesial temporal lobe epilepsy (FMTLE) is characterized by prominent psychic and autonomic seizures, often without hippocampal sclerosis (HS) or a previous history of febrile seizures (FS), and good prognosis. The genetics of this condition is largely unknown.We present the electroclinical and genetic findings of 15 MTLE Italian families. Patients and methods FMTLE was defined when two or more first-degree relatives had epilepsy suggesting a mesial temporal lobe origin. The occurrence of seizures with auditory auras was considered an exclusion criterion. Patients underwent video-EEG recordings, 1.5-Tesla MRI particularly focused on hippocampal analysis, and neuropsychological evaluation. Genetic study included genotyping and linkage analysis of candidate loci at 4q, 18q, 1q, and 12q as well as screening for LGI1/Epitempin mutations. Results Most of the families showed an autosomal dominant inheritance pattern with incomplete penetrance. Fifty-four (32 F) affected individuals were investigated. Twenty-one (38.8 %) individuals experienced early FS. Forty-eight individuals fulfilled the criteria for MTLE. Epigastric/visceral sensation (72.9 %) was the most common type of aura, followed by psychic symptoms (35.4 %), and déjà vu (31.2 %). HS occurred in 13.8% of individuals, three of whom belonged to the same family. Prognosis of epilepsy was generally good. Genetic study failed to show LGI1/Epitempin mutations or significative linkage to the investigated loci. Discussion FMTLE may be a more common than expected condition, clinically and genetically heterogeneous. Some of the reported families, grouped on the basis of a specific aura, may represent an interesting subgroup on whom to focus future linkage studies.

Autosomal dominant lateral temporal epilepsy (ADTLE) is a syndrome characterized by ictal auditory phenomena suggesting a lateral temporal lobe seizure onset and is associated with mutations in the leucine-rich, glioma inactivated 1 (LGI1) gene.1,2 The structure of the LGI1 protein includes, in the N-terminal portion, three leucine-rich repeats (LRR). The function of LGI1 and the mechanisms underlying epilepsy in patients with LGI1 mutations are not established. However, LGI1 is involved in the control of survival of neuroblastoma cell lines.3 This feature and the structural homology between LGI1 and other LRR proteins essential for the development of the CNS3 make it conceivable that LGI1 mutations could imply some structural abnormalities of the lateral temporal lobe as the substratum underlying partial epilepsy in ADTLE. Neuropathologic data are lacking and conventional MRI studies failed to show consistent findings in ADTLE.1,2 Voxel-based analyses enable detection of subtle regional differences in MR images.4,5 ### Methods. We performed voxel-based analyses of T1-weighted, diffusion-tensor, and magnetization transfer (MT) images of the brain in 8 patients (3 women and 5 men, mean age 49 ± 13 years) with ADTLE and LGI1 mutations and 24 healthy control subjects (14 women and 10 men, mean …

Telephone-induced seizures have recently been described as a distinct form of idiopathic reflex epilepsy in which seizures are repeatedly and exclusively triggered by answering the telephone.1 Typical auras consist of auditory or vertiginous symptoms and the inability to speak or understand spoken voices. These features, along with specific EEG ictal findings in one patient, suggest that this condition involves the lateral temporal area.1 Autosomal dominant partial epilepsy with auditory features (ADPEAF; OMIM 600512), or autosomal dominant lateral temporal epilepsy (ADLTE), is a rare familial partial epilepsy syndrome with onset in childhood/adolescence and benign evolution.2,3 The hallmark of the syndrome consists of the presence of typical auditory auras or ictal aphasia in most affected family members, sometimes triggered by environmental sounds and noises. ADPEAF is associated in about half of the families with mutations of the leucine-rich, glioma-inactivated 1 ( LGI1)/Epitempin gene,3,4 the function of which is still unclear. Earlier we described a series of sporadic patients with idiopathic partial epilepsy with auditory features (IPEAF) who were clinically indistinguishable from ADPEAF cases5 …