ISO 9001:2015 standard implementation in clinical trial centers: An exploratory analysis of benefits and barriers in Italy.

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.

Municipal Epidemiological Report (REC): a new fast monitoring tool for exposed population. The experience on Trino municipality, ex nuclear power plant. Mortality 1970-2019.

The law of March 2019 established the municipal epidemiological report to make easier the rapid and lowresource monitoring of the exposed population. Environmental observatory active in Trino since 2014 has equipped this tool and making the first evalution of the risk with census sections from 1970 to 2018. The result highlighted that overall mortality (for total gender) show a decreasing trend while for oncological diseases the results are more difficult to interpret especially in areas close to former industrial sites or contaminated sites. Next step is producing a REC with data for 2019 and divided by gender.

New European Clinical Trial Regulation: perception and expectations in Italy.

BACKGROUND: In July 2012, the European Commission formalized the proposal for a European Clinical Trial Regulation that should replace the European Clinical Trials Directive 2001/20/CE. The new Regulation 536/2014 entered into force in June 2014 and it was expected to be applied not earlier than May 2016. Indeed, at the time, all required central tools are not yet available and new forecasts indicate it will become effective at the end of 2018. The aims of the Regulation are the promotion of higher standards in patient's safety and increasing transparency in Clinical Trials, also by changing the application process. METHODS: An online survey was conducted among the Italian's Clinical Research Coordinators and Clinical Investigators to examine the perception and knowledge about the upcoming changes in Clinical Trials. A total of 190 Clinical Research Coordinators and 80 Clinical Investigators were surveyed. RESULTS: Clinicians are less aware of the content of the Regulation than Clinical Research Coordinators, who demonstrate an extensive expertise on the topic (84.4%), mainly reached through self-training. The majority of the Investigators (74%) believes that their site's facilities and staff already met all the requirements imposed by the Regulation while Clinical Research Coordinators are less optimistic: 65.2% of them believes that the site staff is not yet fully aware of changes associated to its implementation. CONCLUSIONS: The general opinion of the interviewed is that the new Regulation will strongly affect the trial management regardless of their type and phase, and the fulfillment of the imposed requirements represents an opportunity that Italy should not miss to increase its attractiveness to the pharmaceutical market.

A phase I dose escalation trial of tremelimumab (CP-675,206) in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer.

BACKGROUND: Tremelimumab (CP-675,206) is a fully human monoclonal antibody binding to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) on T cells that stimulates the immune system by blocking the CTLA4-negative regulatory signal. Combination with standard chemotherapy may strengthen antitumor therapy. This is a phase Ib, multisite, open-label, nonrandomized dose escalation trial evaluating the safety, tolerability, and maximum tolerated dose (MTD) of tremelimumab combined with gemcitabine in patients with metastatic pancreatic cancer. PATIENTS AND METHODS: Gemcitabine (1000 mg/m(2) on days 1, 8, and 15 of each 28-day cycles) was administrated with escalating doses of i.v. tremelimumab (6, 10, or 15 mg/kg) on day 1 of each 84-day cycle for a maximum of 4 cycles. The first 18 patients had an initial 4-week gemcitabine-only lead-in period. Dose-limiting toxicities (DLTs) related to tremelimumab were evaluated during the first 6 weeks after the first dose of tremelimumab. RESULTS: From June 2008 to August 2011, 34 patients were enrolled and received at least one dose of tremelimumab. No DLTs related to tremelimumab were observed at any dose, even when the maximum dose established for tremelimumab (15 mg/kg) was used. Most frequent grade 3/4 toxicities were asthenia (11.8%) and nausea (8.8%). Only one patient had a serious drug-related event (diarrhea with dehydration). The median overall survival was 7.4 months (95% confidence interval 5.8-9.4 months). At the end of treatment, two patients achieved partial response. Both patients received tremelimumab 15-mg/kg group (n = 2/19, 10.5%). CONCLUSION: Tremelimumab plus gemcitabine demonstrated a safety and tolerability profile, warranting further study in patients with metastatic pancreatic cancer. CLINICALTRIALSGOV ID: NCT00556023.