European survey on national harmonization in clinical research.

BACKGROUND: Clinical trials remain key to the development of evidence-based medical practice. However, they are becoming increasingly complex, mainly in a multinational setting. To address these challenges, the European Union (EU) adopted the Clinical Trial Regulation EU No. 536/2014 (CTR). Once in force, the CTR will lead to more consistent rules and simplification of procedures for conducting clinical trials throughout the EU. Existing harmonization initiatives and "research infrastructures" for clinical trials may facilitate this process. This publication offers a snapshot of the current level of harmonization activities in academic clinical research in Europe. METHODS: A survey was performed among the member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardized questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the harmonization of academic clinical research processes at national level, to facilitate the exchange of expertise and experience among countries, and to identify new fields of action. RESULTS: Most scientific partners already have in place various working groups and harmonization activities at national level. Furthermore, they are involved in and open to sharing their know-how and documents. Since harmonization was mainly a bottom-up approach up until now, the extent and topics dealt with are diverse and there is only little cross-networking and cross-country exchange so far. CONCLUSIONS: Currently, the ECRIN member countries offer a very solid base and collaborative spirit for further aligning processes and exchanging best practices for clinical research in Europe. They can support a smooth implementation of the EU CTR and may act as single contact with consolidated expertise in a country.

An investigation into the factors affecting investigator-initiated trial start-up in Ireland.

BACKGROUND: In common with many countries, Ireland has seen an increasing trend in the number of clinical trials conducted over the past few years. Yet, as elsewhere, trialists in Ireland face several problems and barriers in the starting-up of clinical trials. These barriers impede trial activity significantly, with consequent impacts on patient care. It is critical to understand these issues, to develop approaches to facilitate trial start up. This study identifies the challenges in conducting clinical trials in Ireland and specifically the contractual, ethical, logistical, and regulatory barriers that hinder the start-up of investigator-led trials in Ireland. METHODS: Data for this study were collected in two stages. In the first stage, a survey was conducted among trialists in Ireland. A total of 44 trialists responded to the survey, and information was collected about their experience in conducting clinical trials, the scale and nature of their most recently completed trial, and the details of specific barriers they encountered during the starting-up of the trial. In the second stage, nine semi-structured interviews were conducted with the awardees of 2018 Irish Health Research Board's Definitive Intervention Feasibility Award. These interviews facilitated a deeper exploration of issues and problems in conducting clinical trials in Ireland. RESULTS: This study identified several issues and bottlenecks in starting-up clinical trials in Ireland with contracts and ethical approval cited as the major issues. The data shows that site identification and activation was also problematic in some cases. Several respondents reported difficulties in accessing dedicated time for protocol development and believe that support in this area can be greatly beneficial. It was reported that availability of skilled staff members like statisticians and data managers was as an issue, especially for small trials. CONCLUSION: This study found that several factors impact trial initiation and progression in Ireland. Delays associated with obtaining contract and ethics approval are perceived as major barriers. Specialist supports in areas such as ethics and regulatory affairs and availability of specialised staff members in areas such as statistics and data management are key actions to enable enhanced clinical trial activity in Ireland.

A multidisciplinary approach to online support for device research translation: regulatory change and clinical engagement.

OBJECTIVES: To promote medical device EU regulatory understanding in the biomedical research community and encourage greater levels of clinical engagement to further medical device research innovation, translation and effective clinical trials. METHODS: An interdisciplinary, iterative, needs-based design approach was used to develop medical device regulatory training, information and clinical expertise resources. RESULTS: A multimedia based self-paced e-Learning course focusing on the 'Fundamentals of Medical Device Design and Regulation' was produced in tandem with an interactive online web portal: Medtech Translate. CONCLUSIONS: Health research translation relies on both clinical input and regulation to drive progress and to ensure quality and safety standards from concept development to clinical investigation. A lack of regulatory awareness and access to clinical expertise has the potential to significantly impact on health research translation and ambition for market. Our interdisciplinary academic-regulator-clinical-industry led approach meets the need for a coordinated stakeholder response to support innovation and promote growth in the medical technology sector.

Two broad-specificity dipeptide hydrolysing activities from cytoplasm of guinea pig brain, both of which contain prolinase but neither of which contain carnosinase activity.

Two dipeptide hydrolysing activities were purified from cytoplasm of guinea pig brain. Dipeptide hydrolase I has been shown to be a strict dipeptidase requiring a free amino and a free carboxy terminus, while dipeptide hydrolase II displays very low activity against Leu-Leu-Leu. Of the 41 dipeptides presented to both enzymes, 25 were hydrolysed by both enzymes, while six (including carnosine) were hydrolysed by neither. Six were hydrolysed solely by dipeptide hydrolase I and four were hydrolysed solely by Pro-Leu hydrolase II. Kinetic analysis suggested that dipeptides which were hydrolysed with unfavourable kinetics or which were not hydrolysed by one dipeptide hydrolase were generally hydrolysed with more favourable kinetics by the other dipeptide hydrolase. Dipeptide hydrolase I displays optimum activity at pH 9.0, while dipeptide hydrolase II was optimally active at pH 8.0. Both enzymes were inhibited by 1,10-phenanthroline, p-chloromercuribenzoate and bestatin. Dipeptide hydrolase II was more strongly inhibited by arphamenine B than was dipeptide hydrolase I. Dipeptide hydrolase II was also inhibited by N-ethyl maleimide, while dipeptide hydrolase I was inhibited by dithiothreitol. Native M(r) values of 70,000 and 67,000 were computed for dipeptide hydrolase I and dipeptide hydrolase II, respectively. Sodium dodecyl sulphate polyacrylamide gel electrophoresis conducted with each enzyme under denaturing conditions suggested that both enzymes were comprised of a single polypeptide chain.