Where do we go from here? - Opportunities and barriers to the career development of trial managers: a survey of UK-based trial management professionals

BackgroundClinical trials commonly have a dedicated trial manager and effective trial management is essential to the successful delivery of high-quality trials. Trial managers have diverse experience and currently there is no standardised structured career pathway. The UK Trial Managers’ Network (UKTMN) surveyed its members to understand what is important to them with respect to career development since this would be important in the development of any initiative intended to develop a skilled workforce.MethodsWe conducted an online survey of UKTMN members, who are trial management professionals, working on academic-led trials in the UK. Members were asked what they perceive as opportunities and barriers to career development. Two reminders were sent to facilitate completion of the survey, and responders were offered the opportunity to enter a prize draw for waived fees at the UKTMN annual meeting. Data were analysed descriptively by using Stata (version 15.1), and free-text responses were reviewed for themes.ResultsThe survey was sent to 819 UKTMN members; 433 responses were received, although 13 were from non-UKTMN members; thus 420 respondents' data were included in analyses. Respondents were representative of UKTMN membership; however, more responses were received by trial managers based in registered clinical trials units (CTUs). The top three opportunities for career development were (i) training, (ii) helping design trials and (iii) undertaking relevant qualifications. The top three barriers were (i) funding, (ii) few opportunities to get involved in development activities aside from managing a trial and (iii) unclear organisational career pathway. Almost all respondents (401/420, 95.4%) considered career development either very or quite important. Although all respondents had a day-to-day role in managing trials, there was huge disparity between job titles.ConclusionCareer development is important to trial managers yet there is a lack of a structured pathway. The enablers and disablers to career development for trial managers should be clearly considered by the clinical trial community and, in particular, employers, sponsors and funders in order to develop a highly skilled workforce of trial managers, who are key to the delivery of trials

It is unprecedented : trial management during the COVID-19 pandemic and beyond

Funding: UKTMN is funded by the Nuffield Department of Population Health (NDPH) at the University of Oxford. Acknowledgments: We thank Graeme MacLennan, Director of the Centre for Health Care Randomised Trials (CHaRT) for the inspiration for this article and UKTMN members for their input into its content. We also thank the huge clinical trial community, both nationally and internationally, for continuing to run clinical trials in these challenging times, and for regulatory agencies to adapting their processes to enable efficiencies.Peer reviewedPublisher PD

RUNX1 is a driver of renal cell carcinoma correlating with clinical outcome

The recurring association of specific genetic lesions with particular types of cancer is a fascinating, and largely unexplained area of cancer biology. This is particularly true of clear cell renal cell carcinoma (ccRCC) where although key mutations such as loss of VHL is an almost ubiquitous finding, there remains a conspicuous lack of targetable genetic drivers. In this study, we have identified a previously unknown pro-tumorigenic role for the RUNX genes in this disease setting. Analysis of patient tumor biopsies together with loss of function studies in preclinical models established the importance of RUNX1 and RUNX2 in ccRCC. Patients with high RUNX1 (and RUNX2) expression exhibited significantly poorer clinical survival compared to patients with low expression. This was functionally relevant as deletion of RUNX1 in ccRCC cell lines reduced tumor cell growth and viability in vitro and in vivo. Transcriptional profiling of RUNX1-CRISPR-deleted cells revealed a gene signature dominated by extracellular matrix remodelling, notably affecting STMN3, SERPINH1, and EPHRIN signaling. Finally, RUNX1 deletion in a genetic mouse model of kidney cancer improved overall survival and reduced tumor cell proliferation. In summary, these data attest to the validity of targeting a RUNX1-transcriptional program in ccRCC. [Abstract copyright: Copyright ©2020, American Association for Cancer Research.

Development of a standardised set of metrics for monitoring site performance in multicentre randomised trials: a Delphi study

BackgroundSite performance is key to the success of large multicentre randomised trials. A standardised set of clear and accessible summaries of site performance could facilitate the timely identification and resolution of potential problems, minimising their impact.The aim of this study was to identify and agree a core set of key performance metrics for managing multicentre randomised trials.MethodsWe used a mixed methods approach to identify potential metrics and to achieve consensus about the final set, adapting methods that are recommended by the COMET Initiative for developing core outcome sets in health care.We used performance metrics identified from our systematic search and focus groups to create an online Delphi survey. We invited respondents to score each metric for inclusion in the final core set, over three survey rounds. Metrics scored as critical by ≥70% and unimportant by 50% of participants voting for inclusion were retained.ResultsRound 1 of the Delphi survey presented 28 performance metrics, and a further six were added in round 2. Of 294 UK-based stakeholders who registered for the Delphi survey, 211 completed all three rounds.At the consensus meeting, 17 metrics were discussed and voted on: 15 metrics were retained following survey round 3, plus two others that were preferred by consensus meeting participants. Consensus was reached on a final core set of eight performance metrics in three domains: (1) recruitment and retention, (2) data quality and (3) protocol compliance. A simple tool for visual reporting of the metrics is available from the Nottingham Clinical Trials Unit website.ConclusionsWe have established a core set of metrics for measuring the performance of sites in multicentre randomised trials. These metrics could improve trial conduct by enabling researchers to identify and address problems before trials are adversely affected. Future work could evaluate the effectiveness of using the metrics and reporting tool