Clinical Trials Unit Research Articles

Editorial introductions.

Editorial introductions.

Costs and staffing resource requirements for adaptive clinical trials: quantitative and qualitative results from the Costing Adaptive Trials project

BackgroundAdaptive designs offer great promise in improving the efficiency and patient-benefit of clinical trials. An important barrier to further increased use is a lack of understanding about which additional resources are required to conduct a high-quality adaptive clinical trial, compared to a traditional fixed design.The Costing Adaptive Trials (CAT) project investigated which additional resources may be required to support adaptive trials.MethodsWe conducted a mock costing exercise amongst seven Clinical Trials Units (CTUs) in the UK. Five scenarios were developed, derived from funded clinical trials, where a non-adaptive version and an adaptive version were described. Each scenario represented a different type of adaptive design.CTU staff were asked to provide the costs and staff time they estimated would be needed to support the trial, categorised into specified areas (e.g. statistics, data management, trial management). This was calculated separately for the non-adaptive and adaptive version of the trial, allowing paired comparisons.Interviews with 10 CTU staff who had completed the costing exercise were conducted by qualitative researchers to explore reasons for similarities and differences.ResultsEstimated resources associated with conducting an adaptive trial were always (moderately) higher than for the non-adaptive equivalent. The median increase was between 2 and 4% for all scenarios, except for sample size re-estimation which was 26.5% (as the adaptive design could lead to a lengthened study period). The highest increase was for statistical staff, with lower increases for data management and trial management staff.The percentage increase in resources varied across different CTUs. The interviews identified possible explanations for differences, including (1) experience in adaptive trials, (2) the complexity of the non-adaptive and adaptive design, and (3) the extent of non-trial specific core infrastructure funding the CTU had.ConclusionsThis work sheds light on additional resources required to adequately support a high-quality adaptive trial. The percentage increase in costs for supporting an adaptive trial was generally modest and should not be a barrier to adaptive designs being cost-effective to use in practice.Informed by the results of this research, guidance for investigators and funders will be developed on appropriately resourcing adaptive trials.

Patient and public involvement in randomised clinical trials: a mixed-methods study of a clinical trials unit to identify good practice, barriers and facilitators

BackgroundWhile patient and public involvement (PPI) in clinical trials is beneficial and mandated by some funders, formal guidance on how to implement PPI is limited and challenges have been reported. We aimed to investigate how PPI is approached within a UK Clinical Trials Unit (CTU)’s portfolio of randomised controlled trials, perceived barriers to/facilitators of its successful implementation, and perspectives on the CTU’s role in PPI.MethodsA mixed-methods study design, involving (1) an online survey of 26 trial managers (TMs) and (2) Interviews with Trial Management Group members and public contributors from 8 case-study trials. Quantitative survey data were summarised using descriptive statistics and interview transcripts analysed thematically. Two public contributors advised throughout and are co-authors.Results(1) 21 TMs completed the survey; (2) 19 in-depth interviews were conducted with public contributors (n=8), TMs (n=5), chief investigators (n=3), PPI coordinators (n=2) and a researcher. 15/21 TMs surveyed reported that a public contributor was on the trial team, and 5 used another PPI method. 12/21 TMs reported that public contributors were paid (range £10–50/h). 5 TMs reported that training was provided for public contributors and few staff members had received any formal PPI training. The most commonly reported tasks undertaken by public contributors were the review of participant-facing materials/study documents and advising on recruitment/retention strategies. Public contributors wanted and valued feedback on changes made due to their input, but it was not always provided. Barriers to successful PPI included recruitment challenges, group dynamics, maintaining professional boundaries, negative attitudes to PPI amongst some researchers, a lack of continuity of trial staff, and the academic environment. Successful PPI required early and explicit planning, sharing of power and ownership of the trial with public contributors, building and maintaining relationships, and joint understanding and clarity about expectations/roles. CTUs have an important role to play in supporting recruitment, signposting and coordinating PPI.ConclusionsWhile highly valuable, PPI in trials is currently variable. PPI representatives are recruited informally, may not be provided with any training and are paid inconsistently across trials. Study findings can help optimise PPI in trials and ensure researchers and public contributors are adequately supported.

Dairy intake and risk of major cardiovascular events: a prospective cohort study of 0.5 million Chinese adults

Abstract Background Evidence on the association between dairy consumption and risk of cardiovascular disease has been highly inconsistent, with findings suggesting either harmful, neutral or beneficial effects. In addition, a very large majority of the previous studies on this topic were conducted among populations in Europe and North America who usually consume a higher amount of dairy products and very few data, particularly prospective data, come from China where the dairy consumption level is low. Purpose We therefore investigated the associations between intake of dairy products and incidence of several major types of cardiovascular diseases in Chinese adults. Methods During 2004–2008, the prospective China Kadoorie Biobank Study recruited slightly over 0.5 million adults from ten diverse regions (five urban and five rural) across China. Information on the consumption frequency of dairy products was collected at baseline and periodic resurveys, using a validated interviewer-administered laptop-based questionnaire. Over a mean follow-up of 10.9 years, there were 47,128 incident ischaemic heart disease events, 43,481 ischaemic strokes and 9749 intracerebral haemorrhages among 489,595 study participants, who did not report a prior history of cardiovascular disease at baseline. Cox regression analyses were performed to estimate multivariable-adjusted hazard ratios (HRs) for incident events associated with dairy intake. Results Overall, 69.3% of participants reported never or rare consumption (i.e. non-consumers) and 11.3% of them reported regular consumption (i.e. ≥4 days/week) of dairy products, with milk accounting for the largest proportion of total dairy intake (∼77%). Male and female regular dairy consumers had 2.1/1.5 and 1.7/1.1 mmHg lower systolic/diastolic blood pressure, respectively compared to non-consumers. In a subset (∼18,000) of participants with blood lipid levels measured, regular dairy consumers had ∼0.1 mmol/L higher LDL levels than non-consumers. After adjusting for a range of potential confounders, including sociodemographic and lifestyle factors, BMI and other dietary factors, dairy consumption was positively and significantly associated with risk of ischaemic heart disease, with the adjusted HR per 50 g/day increase in usual dairy consumption being 1.11 (95% confidence interval [CI] 1.09–1.14). Dairy consumption was not significantly associated with risk of ischemic stroke but was inversely associated with risk of intracerebral haemorrhage, with each 50 g/day increase in usual dairy consumption being associated with 17% lower risk (HR 0.83, 0.78–0.88). These associations remained significant after additional adjustment for systolic blood pressure. Conclusion In this large study of Chinese adults, higher intake of dairy products was associated with a higher risk of ischaemic heart disease but a lower risk of intracerebral haemorrhage. The exact mechanisms underlying such associations require further investigation. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The CKB baseline survey and the first re-survey were supported by the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up has been supported by Wellcome grants to Oxford University (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z) and grants from the National Key Research and Development Program of China (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) and from the National Natural Science Foundation of China (91843302). The UK Medical Research Council (MC_UU_00017/1,MC_UU_12026/2 MC_U137686851), Cancer Research UK (C16077/A29186; C500/A16896) and the British Heart Foundation (CH/1996001/9454), provide core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit at Oxford University for the project.

Associations of red meat, poultry, fish and egg intake with risk of cardiovascular disease: an 11-year prospective study of the China Kadoorie Biobank

Abstract Background Higher red meat intake and lower fish intake have been associated with increased risk of cardiovascular disease (CVD), while the relevance of poultry and egg intake for CVD incidence remains inconclusive. Furthermore, most of the prospective evidence comes from studies in the Western populations, with limited data from China where the CVD patterns are largely different. Purpose We therefore investigated the associations of red meat, poultry, fish and egg intake with risks of several major types of CVD in Chinese adults. Methods The China Kadoorie Biobank is a prospective study which recruited ∼512,000 adult participants from ten diverse localities during 2004–08. At baseline and periodic resurveys, information on the consumption frequency of major food groups was collected using a validated interviewer-administered laptop-based questionnaire, together with medical history, socio-demographic and other lifestyle factors. During an average follow-up of 10.9 years, 47,128 incident ischaemic heart disease events, 43,481 ischaemic strokes and 9749 intracerebral haemorrhages were recorded among 489,595 participants, who did not have a prior history of CVD at baseline. Cox regression was used to calculate adjusted hazard ratios (HRs) relating dietary exposures to CVD risk. Results There were 47.2%, 1.4%, 9.0% and 24.1% of participants at baseline who regularly consumed (i.e. ≥4 days/week) red meat, poultry, fish and eggs, respectively. After adjusting for potential confounders, including body mass index and other dietary factors under study, egg consumption was significantly associated with lower risks of ischaemic heart disease and ischaemic stroke, with each 50 g/day increase in estimated habitual egg consumption being associated with 18% (HR 0.82, 95% confidence interval [CI] 0.75–0.90) and 24% lower risks (HR 0.76, 95% CI 0.69–0.84), respectively. Inverse associations were also observed between intakes of red meat, fish and eggs and risk of intracerebral haemorrhage, with adjusted HRs for 50 g/day higher intake being 0.84 (95% CI 0.74–0.97), 0.86 (95% CI 0.74–0.99) and 0.42 (95% CI 0.34–0.51), respectively. Conclusion This large prospective study of Chinese adults showed that higher intake of eggs was associated with lower risks of ischaemic heart disease and ischaemic stroke. Moreover, higher intakes of red meat, fish and eggs were each associated with a lower risk of intracerebral haemorrhage. Further investigation of the potential mechanisms that underlie the observed associations is required. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): The CKB baseline survey and the first re-survey were supported by the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up has been supported by Wellcome grants to Oxford University (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z) and grants from the National Key Research and Development Program of China (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) and from the National Natural Science Foundation of China (91843302). The UK Medical Research Council (MC_UU_00017/1,MC_UU_12026/2 MC_U137686851), Cancer Research UK (C16077/A29186; C500/A16896) and the British Heart Foundation (CH/1996001/9454), provide core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit at Oxford University for the project. MG. Kakkoura is supported by the Wellcome Trust, Our Planet Our Health (Livestock, Environment and People - LEAP) (205212/Z/16/Z).

Thoracoscopic surgical ablation versus catheter ablation as first-line treatment for long-standing persistent atrial fibrillation: the CASA-AF RCT

Background Standalone thoracoscopic surgical ablation may be more effective than catheter ablation in patients with long-standing persistent atrial fibrillation. Objectives To determine whether or not surgical ablation is clinically superior to catheter ablation as the first-line treatment strategy in long-standing persistent atrial fibrillation. Design This was a prospective, multicentre, randomised control trial. Setting Four NHS tertiary centres in England. Participants Adults with long-standing persistent atrial fibrillation, who had European Heart Rhythm Association symptom scores > 2 and who were naive to previous catheter ablation or thoracic/cardiac surgery. Interventions Minimally invasive thoracoscopic surgical ablation and conventional catheter ablation (control intervention). Main outcome measures The primary outcome was freedom from atrial fibrillation/tachycardia ≥ 30 seconds after a single procedure without antiarrhythmic drugs (class 1C/3) at 1 year, excluding a 3-month blanking period. The secondary outcomes include the intervention-related major complication rate; clinical success (≥ 75% reduction in arrhythmia burden); and changes in symptoms, quality of life and cost-effectiveness. Methods Patients (n = 120) were randomised to surgical ablation (n = 60) or catheter ablation (n = 60). An implanted loop recorder provided continuous cardiac monitoring following ablation. Follow-up visits were at 3, 6, 9 and 12 months. Loop recorder data were reviewed monthly by a physiologist who was blinded to the randomisation outcome. Results The study treatment was received by 55 patients in the surgical ablation arm and 60 patients in the catheter ablation arm; five patients withdrew from surgical ablation before treatment. Data from randomised and treated patients were analysed as per intention to treat. Patients had a mean age of 62.3 (standard deviation 9.6) years, were predominantly male (74%), had a mean left atrial diameter of 44.6 mm (standard deviation 6 mm) and were in continuous atrial fibrillation for 22 months (range 16–31 months). At 12 months, 26% of patients in the surgical ablation arm (14/54) and 28% of patients in the catheter ablation arm (17/60) were free from atrial arrhythmias after a single procedure without antiarrhythmic drugs (odds ratio 1.13, 95% confidence interval 0.46 to 2.83; p = 0.84). An arrhythmia burden reduction of ≥ 75% was seen in 36 out of 54 (67%) patients in the surgical ablation arm, compared with 46 out of 60 (77%) patients in the catheter ablation arm (odds ratio 1.64, 95% confidence interval 0.67 to 4.08; p = 0.3). Procedure-related serious complications within 30 days of the intervention occurred in 15% (8/55) of patients in the surgical ablation arm (including one death) compared with 10% (6/60) of patients in the catheter ablation arm (p = 0.46). Surgical ablation was associated with significantly higher costs (£23,221 vs. £18,186; p = 0.02) and fewer quality-adjusted life-years than catheter ablation (0.76 vs. 0.83; p = 0.02). Limitations This study was conducted in four highly specialised cardiology centres that have substantial experience in both treatment modalities; therefore, the results may not be widely generalisable. The study was not powered to detect small differences in efficacy. Conclusions We found no evidence to suggest that standalone thoracoscopic surgical ablation outcomes were superior to catheter ablation outcomes in achieving freedom from atrial arrhythmia after a single procedure without antiarrhythmic drugs. Moreover, surgical ablation is associated with a longer hospital stay, smaller improvements in quality of life and higher health-care costs than catheter ablation (standard care therapy). Future work Evaluation of the impact of ablation treatments on sinus rhythm maintenance and quality of life with extended follow-up to 3 years. Model-based economic analysis to estimate long-term benefits, harms and costs of surgical and catheter ablation compared with antiarrhythmic drug therapy in long-standing persistent atrial fibrillation patients. Trial registration Current Controlled Trials ISRCTN18250790 and ClinicalTrials.gov NCT02755688. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This study was supported by the UK Clinical Research Collaboration-registered King’s Clinical Trials Unit at King’s Health Partners, which is part funded by the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Evaluation, Trials and Studies Coordinating Centre. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 18. See the NIHR Journals Library website for further project information.

Involving patients in academic clinical research: It’s time to walk the talk

Involving patients in academic clinical research ensures that research questions and clinical research outcomes are addressed and implemented in a manner relevant to patients. As one of our key strategic goals in the new 2021–2024 performance period, the Swiss Clinical Trial Organisation (SCTO) and its Clinical Trial Unit (CTU) Network are placing greater emphasis on the implementation of patient and public involvement (PPI) in academic clinical research. In pursuit of this strategic goal, the SCTO sent out a survey to relevant stakeholders in order to identify and characterise all PPI initiatives and projects in Switzerland and thereby establish the status quo. As a next step, the SCTO envisions establishing a central coordination and contact point that is pathology-independent and spans organisations. We aim for a sustainable, inclusive PPI approach in academic clinical research that is established in close collaboration with our partners and stakeholders.

Regulatory aspects of patient and public involvement in academic clinical research in Switzerland

Patient and public involvement (PPI) describes the active engagement of patients and the public in different aspects of clinical research. This Deep Dive article covers the current situation of PPI in academic clinical research in Switzerland, giving examples of local support and initiatives that are currently offered by university hospital clinical trial units (CTUs) and also addressing the lack of legislation related to PPI. In addition, it provides an overview of data protection regulations to be considered when working with data generated during PPI and ends with a discussion of the key issues related to PPI in Switzerland.

1835P Clinical outcome and prognostic factors for Asian patients in phase I clinical trials

Overall survival (OS) of phase 1 (P1) cancer patients (pts) is difficult to predict. The Royal Marsden Hospital (RMH) prognostic score (which incorporates serum albumin, LDH, and no. of metastatic sites) and neutrophil-lymphocyte ratio (NLR) have been validated to predict OS in P1 trial pts in the Western population but not Asian pts. It is also important to validate the RMH score and NLR for newer phase I studies, including immunotherapy and vaccine studies. This study aims to validate the RMH score and NLR in a P1 clinical trials unit in Singapore and is the largest Asian study to date which includes novel P1 therapies.

MP67-14 SCIENTIFIC AUTHORSHIP OF COCHRANE SYSTEMATIC REVIEWS IN UROLOGY: A 2020 ANALYSIS

You have accessJournal of UrologyGlobal Health/Humanitarian (MP67)1 Sep 2021MP67-14 SCIENTIFIC AUTHORSHIP OF COCHRANE SYSTEMATIC REVIEWS IN UROLOGY: A 2020 ANALYSIS Ahmad Ozair, Nishanth Subash, and Abhinav Sonkar Ahmad OzairAhmad Ozair More articles by this author , Nishanth SubashNishanth Subash More articles by this author , and Abhinav SonkarAbhinav Sonkar More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002028.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cochrane systematic reviews are widely considered to be amongst the highest level of evidence available with their conclusions often impacting policy and practice. Some countries and/or regions are reported to have a disproportionately higher representation in their authorship. However, it is unclear as to which countries have contributed the highest to Cochrane reviews in urology and what is the current state of collaboration existing between their authors. This study sought to determine authorship patterns and collaborative networks of Cochrane reviews in urology. METHODS: We searched and extracted data from the Cochrane Database for systematic reviews published under the Cochrane Urology Group by 20 June, 2020. We included both active reviews and those withdrawn for updation. For graphical representation, we used the Social Network Visualizer (https://socnetv.org/) and treated a collaborative author group belonging to a single country, e.g., MRC Clinical Trials Unit (UK), as a single author. RESULTS: A total of 80 eligible reviews were found, authored by a total of 430 authors. Co-authors disproportionately belonged to the US (30.5%) and UK (22.3%), followed by Germany (13.5%), South Korea (7.2%), China (4.9%), Australia (4.7%), Brazil (4.4%), Netherlands (3.5%), Canada (1.9%), Argentina and India (1.6% each), Italy (1.6%) and the rest (Fig. 1). A network analysis of collaborations between authors of different countries was generated (Fig. 2). Lead authors belonged maximally to US and UK (23.8% each), followed by South Korea (11.3%) and Germany (10%). Countries/regions, which otherwise contribute actively to urology literature, that had little/no representation included majority of Latin American and African countries, France, Spain and Japan. CONCLUSIONS: The US and the UK are found to be the biggest contributors to the highest-quality evidence in urology, consistent with citation analysis of urology literature. Capacity-building efforts are needed in several countries for getting academic urologists involved with Cochrane. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e514-e515 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ahmad Ozair More articles by this author Nishanth Subash More articles by this author Abhinav Sonkar More articles by this author Expand All Advertisement Loading ...

PriME-PGx: La Princesa University Hospital Multidisciplinary Initiative for the Implementation of Pharmacogenetics

The implementation of clinical pharmacogenetics in daily practice is limited for various reasons. Today, however, it is a discipline in full expansion. Accordingly, in the recent times, several initiatives promoted its implementation, mainly in the United States but also in Europe. In this document, the genotyping results since the establishment of our Pharmacogenetics Unit in 2006 are described, as well as the historical implementation process that was carried out since then. Finally, this progress justified the constitution of La Princesa University Hospital Multidisciplinary Initiative for the Implementation of Pharmacogenetics (PriME-PGx), promoted by the Clinical Pharmacology Department of Hospital Universitario de La Princesa (Madrid, Spain). Here, we present the initiative along with the two first ongoing projects: the PROFILE project, which promotes modernization of pharmacogenetic reporting (i.e., from classic gene-drug pair reporting to complete pharmacogenetic reporting or the creation of pharmacogenetic profiles specific to the Hospital’s departments) and the GENOTRIAL project, which promotes the communication of relevant pharmacogenetic findings to any healthy volunteer participating in any bioequivalence clinical trial at the Clinical Trials Unit of Hospital Universitario de La Princesa (UECHUP).

Predicting the Risk of Stroke and Delirium During Cardiac Surgery Using a Novel EEG Based Index of Interhemispheric Synchronization

Introduction: Neurological complications after surgery (e.g. stroke, delirium and cognitive dysfunction) remain a major concern despite advancements in surgical and anaesthetic techniques and technology. The aim of this study was to evaluate whether a novel electroencephalogram (EEG)-based index of interhemispheric synchronization, between two prefrontal EEG channels, could predict stroke or delirium following cardiac surgery. Methods: Two-channel EEG was analyzed in 803 patients undergoing cardiac surgery, without prior documentation of stroke. 31 patients suffered from stroke upon waking up from surgery (stroke group), for another 48 patients post-operative delirium was documented (delirium group) and the rest (724 patients) did not suffer from a documented neurological complication (no dysfunction group). A novel EEG-based index, the Lateral Interconnection Ratio (LIR) index, of frontal interhemispheric synchronization was calculated every 10 seconds and compared among the three patient groups over five key periods during surgery: start, pre-bypass, on-bypass, post-bypass, and end of surgery. The LIR index was analyzed in a blinded manner, without knowledge of patient group affiliation, and only compared among groups at the final analysis step. Results: The LIR index of patients with stroke decreased by 0.17±0.11 (mean±95% CI) from the start of surgery period to the immediate post bypass period in comparison to its relative stability of -0.03±0.02 in the no dysfunction group (p<0.0001). The LIR index of patients with delirium decreased from the start of surgery period to the end of surgery period by 0.20±0.13 in comparison to its relative stability of 0.02±0.02 in the no dysfunction group (p≈0.001). Summary: LIR index drops may provide an intraoperative alert to the occurrence of brain injury. The timing of LIR drops (post-bypass or end of surgery) may provide hints regarding the pathophysiology of the injury. For even better results it might be advisable to continue the monitoring during the post-operative period, especially while the patient is still anesthetized in the ICU, as there is continued risk for stroke and delirium also after surgery ends. Funding: The original study (Clinicaltrials.gov identifier: NCT02976584) was supported by the Bangerter-Rhyner Foundation and the Clinical Trials Unit of the University Hospital of Bern, University of Bern, Switzerland. Drs Hight & Kaiser were supported by the Department of Anaesthesiology and Pain Medicine, Bern University Hospital, University of Bern, Bern, Switzerland. Declaration of Interest: GS and DBS are spouses. GS founded several companies in the field of EEG analysis and DBS consulted one of these companies up to ~1 year ago. However, the present study is not related to these companies and their technology. It is based on developments in GS academic laboratory at Rambam Health Care Campus. The other authors have no conflict of interest to declare. Ethical Approval: The ethics committee of the canton of Bern, Switzerland, approved the prospective observational study (KEK#210/15). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for observational studies was used to guide the methods of the study and to structure the manuscript

Hospitalizations in solid tumor phase I clinical trial patients: Incidence, pattern and clinical outcomes at an Australian phase I clinical trial unit.

Participation in early-phase clinical trials has become a prominent part of medical oncology patient management. We examined the incidence and pattern of hospitalizations in early-phase clinical trial patients and the associated clinical outcomes. We conducted a retrospective review of 194 patients with solid tumors treated on phase I clinical trials between July 2014 and October 2018 at a phase I trial unit. Unplanned hospitalizations occurring during the study period were characterized and correlated with treatment response and duration of trial participation. Among 194 patients, 104 hospitalizations were recorded involving 62 patients (31%). Nineteen percent of patients were hospitalized for cancer-related complications and 8% for treatment toxicity. No significant correlation was seen between the hospitalization and age, sex, tumor type, or trial drug. Best response to trial therapy was complete response, partial response, stable disease, and progressive disease in 5%, 11%, 37%, and 47% of patients, respectively. Median duration on trial was 86days (range 0-1,412). Twenty-two patients (11%) remained on trial for more than 12 months. Overall, hospitalization did not impact treatment response or trial duration. However, cancer-related hospitalization was associated with significantly lower response (p<0.001) and early patient attrition (p<0.001). Resolution of the hospitalization event was associated with improved response (p=0.002) and longer duration on trial (p<0.001). The treatment related mortality was 0.5% (n=1). Approximately one third of patients required hospitalization, most commonly for cancer-related complications which correlated with poorer clinical outcomes. Hospitalizations related to treatment toxicity were infrequent. A significant proportion of patients derived significant therapeutic benefit. Phase I clinical trials provide a valuable treatment option for patients with cancer.

Formalising the induction of patient and public involvement contributors on trial oversight committees

BackgroundClinical Trials Units are encouraged to integrate Patient and Public Involvement (PPI) into all aspects of trial design, running and oversight. This research explored the induction and training of PPI Contributors joining trial oversight committees and was used to update the Medical Research Council Clinical Trials Unit at University College London’s (MRC CTU at UCL) induction pack for new PPI Contributors.MethodsPublished and unpublished materials provided by other CTUs and research organisations on training for PPI Contributors on oversight committees were reviewed, with themes then triangulated to identify the most common topics covered in induction training. A face-to-face workshop with PPI Contributors from the MRC CTU at UCL reviewed a draft updated Induction Pack. Findings from these discussions were incorporated into a revised induction pack which was then re-reviewed by the workshop attendees.ResultsNo published literature on this subject was found. However, several common themes were identified from unpublished materials. Workshop attendees agreed with most of the themes suggested in the initial draft pack based on the literature search and also provided a number of additional topics for discussion.ConclusionsThere is very little consistency in the induction of PPI Contributors on oversight committees. Whilst most local guidance explains the general role of a PPI Contributor, more context and background of the particular trial needs to be provided to allow for adequate induction of new committee members. The Induction Pack created provides a framework upon which trial managers can build a full picture of their study.

Brief early adolescent multi-family therapy (BEAM) trial for anorexia nervosa: a feasibility randomized controlled trial protocol

IntroductionMulti-family therapy (MFT) is a recommended treatment for adolescent anorexia nervosa internationally. Despite recent significant advances in single-family therapy, the evidence base for MFT remains relatively small. Several individual and family factors have been associated with poorer outcomes in single-family therapy, many of which may be addressed or ameliorated by MFT if delivered early in treatment. This trial aims to determine the feasibility and acceptability of adding a five-day multi-family therapy group to the early stages of family therapy for anorexia nervosa. Secondary objectives are to explore effect size changes in key individual and family factors across treatment.MethodsThis feasibility trial will use a randomised controlled design. Sixty adolescents (age 10–17 inclusive) with anorexia nervosa or atypical anorexia nervosa and their parents will be recruited from a community-based specialist eating disorder service in London, UK. Participants will be randomly allocated to receive six months of eating disorder focussed family therapy with a five-day MFT group (experimental group) or without (control group). Block randomisation will be conducted by the King’s Clinical Trials Unit and researchers will be blind to participants’ intervention allocation. Feasibility, acceptability and secondary outcomes measures will be collected at baseline, post-MFT, end of treatment, six-month and 12-month follow-up. Feasibility and acceptability will be assessed according to trial sign-up rates, retention, measure completion rates and satisfaction. Secondary outcomes include physical health improvements, changes in psychiatric symptoms, emotion regulation and reflective function capacity, expressed emotion, parental difficulties and therapeutic alliance. Descriptive data and exploration analysis of trends and effect sizes will be reported upon at trial completion.DiscussionThe five-day MFT program developed for this study is novel, brief and more accessible than previous MFT models. The inclusion of a data collection point during treatment and follow-up will allow for an investigation of trends during and after treatment. This will allow exploration and comparison of future potential mediators and moderators of MFT and FT-AN outcomes and how these may differ between treatments.Trial registrationISRCTN registry; ISRCTN93437752, on 27 January 2021.

The Care of Children With Cancer During the COVID-19 Pandemic.

The COVID-19 pandemic has considerably changed health services for children with cancer worldwide by creating barriers throughout the care continuum. Reports available at this time suggest that asymptomatic and mild upper and lower respiratory tract syndromes are the most common presentation of COVID-19 in children with cancer. Nonetheless, severe cases of COVID-19 and deaths secondary to the infection have been reported. In addition to the direct effects of the severe acute respiratory syndrome coronavirus 2, children with cancer have suffered from the collateral consequences of the pandemic, including decreased access to diagnosis and cancer-directed therapy. The COVID-19 pandemic has presented unprecedented challenges to safe and effective care of children with cancer, including their enrollment in therapeutic clinical trials. Data from the Children's Oncology Group and Cancer Research U.K. Clinical Trials Unit show variability in the enrollment of children with cancer in clinical trials during the COVID-19 pandemic. However, the overall effects on outcomes for children with cancer undergoing care during the pandemic remain largely unknown. In this article, we review the current knowledge about the direct and collateral effects of the COVID-19 pandemic, including on clinical trial enrollment and operations.

Genetic profiling across multiple cancer types using molecular prescreening comprehensive gene panels offered by clinical trials (CT).

3060 Background: Genetic profiling (GP) is essential not only for understanding tumor biology but also helps to identify potential genes for targeted therapies. At the same time, selected CT provide an individual genomic profile panel during the pre-screening phase. Here, we demonstrate our experience using these panels. Methods: We selected 14 CT from our Early Drug Development Clinical Trial Unit at Hospital Clinic of Barcelona that included analysis of gene panels in tumor (Foundation One, ArcherDX, Therascreen and Sophia Genetics) or plasma (Resolution Bioscience ctDx). These panels analyzed mutations, fusions, amplifications, microsatellite instability (MSI) and tumor mutational burden (TMB), among others. We collected information about types of cancers, molecular alterations and therapies chosen according to the results of GP. The platform OncoKB (Chakravarty JCO PO, 2017) was used to define genes with potential target therapies and levels of evidence (LE) for those targets (from LE 1 –FDA-recognized biomarker predictive of response to an FDA-approved drug- to LE 4 –Compelling biological evidence supports the biomarker as being predictive of response to a drug). Descriptive statistics were used. Results: From March 2017 to January 2021 we analyzed samples from 410 patients (pts) with CNS (19.3%), urothelial (18.3%), prostate (17.6%), breast (15.4%), ovarian (9.3%), esophageal and gastric (5.4%), colorectal (4.4%), pancreas (2.7%), endometrial (2.4%), cholangiocarcinoma (1.2%), cervix (1%), HNSCC (1%), renal (1%), lung (0.5%), liver (0.2%) fallopian tube (0.2%) and paraganglioma (0.2%). 352 pts (85.8%) had at least 1 genetic alteration. The most frequently altered genes were TP53 (153 pts, 46.2%), INSR (19 pts, 22.8%), TERT (76 pts, 22%), CDKN2A (65 pts, 19.9%), FAM175A (11 pts, 19.3%), CDKN2B (54 pts, 18.1%), MLL2 (53 pts, 17.7%), PTEN (52 pts, 16%), MTAP (45 pts, 15.7%), PIK3CA (52 pts, 15%) and ATM (55 pts, 14.4%). TMB ranged from 0 to 76.9 mut/Mb (median 2.5 mut/Mb). MSI was found in 3 pts (1.5%). 196 pts (47.1%) had an OncoKB LE 1 alteration, 105 pts (25.6%) if we restrict the options to their specific cancer type. 16 pts (3.9%) received a matched therapy: 6 pts received an off-label drug, 6 pts were included in the same CT for which the pre-screening was performed and 4 pts were included in a different CT. Additionally, 13 pts (3.2%) received a matched therapy either with OncoKB LE 4 (5 pts received an off-label drug and 3 were included in a different CT) or not included in OncoKB (8 pts included in the same CT of the pre-screening). As a whole, 29 pts (7.1%) received a matched drug according to their genomic results. Conclusions: Comprehensive gene panel testing offered through CT allows the identification of targets to enroll pts, although the recruitment was 1.5%. However, 7.1% of the pts received a matched therapy due to the molecular information of these gene panels.

The impact of the COVID-19 pandemic on oncology clinical trial recruitment in an Irish cancer center.

e18756 Background: The COVID-19 pandemic has created unprecedented disruptions to cancer clinical trial research across the world due to a temporary global suspension of patients’ recruitment to cancer clinical trials. Access to clinical trials permits better treatment options and best clinical practice standards for patients with cancer. We present the impact of the COVID-19 pandemic on cancer clinical trial activity at the Cancer Clinical Trials Unit (CCTU) at the Mid-Western Cancer Centre, University Hospital Limerick (UHL). Over the last 4 years 28 clinical trials, both interventional and translational, have opened here, across a variety of primary disease sites, with 5 trials opened in 2017, 11 in 2018, 7 in 2019 but only 2 in the first 10 months of 2020 until 3 further trials were opened in December. Methods: CCTU records were reviewed to identify the number of patients screened and consented to participate in cancer clinical trials at UHL in 2020, which were compared directly with corresponding numbers for 2019. Results: In 2019, 17 clinical trials were open and recruiting at the CCTU, UHL. During 2020, 19 trials were recruiting although during the 1st surge of the COVID-19 pandemic recruitment was essentially suspended and CCTU staff were redeployed throughout the hospital. 1st Six months 2020 vs 2019 In the six months from January 2020 until the end of June 2020, 99 patients were screened and only 15 (15.2%) signed informed consent to participate in a cancer clinical trial. When these figures are directly compared with the first six months of 2019, there is a 33% reduction in patients screened for participation (147 vs 99) and a 60% reduction in patients consented (37 vs 15) to clinical trials. 12 Months 2020 vs 2019 In total during 2019, 376 patients were screened for inclusion to participate and 49 (13%) patients signed informed consent to participate in a clinical trial within CCTU at UHL. In 2020, 914 patients were screened for participation with 51 patients consented to participate (5.6%). The majority (45/51 (88%)) of patients consented to cancer clinical trials in 2020 at the CCTU, UHL were recruited to translational based studies and only 6 (12%) consented to interventional studies compared with 2019 when 30/49 (61%) consented to translational and 30/49 (39%) to interventional studies. Conclusions: During the COVID-19 pandemic, the percentage of patients consented to participation in a clinical trial reduced significantly, as compared to the previous year (5.6% vs 13%). Fewer interventional studies have recruited patients during 2020. As we enter the third surge of COVID-19 infections in Ireland, we must continue to monitor and identify effective strategies to navigate the ever-changing situation for cancer clinical trials, in an attempt to maintain access to high quality cancer clinical trial opportunities for our patients.

Patient Experiences of Postinfectious Olfactory Dysfunction

Introduction: To highlight the importance of the need for new treatment modalities, this study aimed to characterise the experience of patients with postinfectious olfactory dysfunction (PIOD) in terms of the treatment they received. Methods: An online survey was hosted by the Norwich Clinical Trials Unit on the secure REDCap server. Members of the charity Fifth Sense (the UK charity that represents and supports people affected by smell and taste disorders) were invited to participate. Results: There were 149 respondents, of whom 127 had identified themselves as having (or had) PIOD. The age range of respondents to the survey was 28–85 years, with a mean of 58 ± 12 years, with the duration of their disorder <5 years in 63% of cases. Respondents reported experiencing variable treatment with oral and/or intranasal steroids given typically (28%), often with no benefit, but with 50% receiving no treatment whatsoever; only 3% reported undertaking olfactory training. Over two-thirds of patients experience parosmia and, up to 5 years from the onset of the problem, were still actively seeking a solution. Conclusion: There appears to be a need to encourage greater use of guidelines for olfactory disorders amongst medical practitioners and also to develop more effective treatments for patients with PIOD, where there is clearly an unmet need.

Accessing routinely collected health data to improve clinical trials: recent experience of access

BackgroundRoutinely collected electronic health records (EHRs) have the potential to enhance randomised controlled trials (RCTs) by facilitating recruitment and follow-up. Despite this, current EHR use is minimal in UK RCTs, in part due to ongoing concerns about the utility (reliability, completeness, accuracy) and accessibility of the data. The aim of this manuscript is to document the process, timelines and challenges of the application process to help improve the service both for the applicants and data holders.MethodsThis is a qualitative paper providing a descriptive narrative from one UK clinical trials unit (MRC CTU at UCL) on the experience of two trial teams’ application process to access data from three large English national datasets: National Cancer Registration and Analysis Service (NCRAS), National Institute for Cardiovascular Outcomes Research (NICOR) and NHS Digital to establish themes for discussion. The underpinning reason for applying for the data was to compare EHRs with data collected through case report forms in two RCTs, Add-Aspirin (ISRCTN 74358648) and PATCH (ISRCTN 70406718).ResultsThe Add-Aspirin trial, which had a pre-planned embedded sub-study to assess EHR, received data from NCRAS 13 months after the first application. In the PATCH trial, the decision to request data was made whilst the trial was recruiting. The study received data after 8 months from NICOR and 15 months for NHS Digital following final application submission. This concluded in May 2020. Prior to application submission, significant time and effort was needed particularly in relation to the PATCH trial where negotiations over consent and data linkage took many years.ConclusionsOur experience demonstrates that data access can be a prolonged and complex process. This is compounded if multiple data sources are required for the same project. This needs to be factored in when planning to use EHR within RCTs and is best considered prior to conception of the trial. Data holders and researchers are endeavouring to simplify and streamline the application process so that the potential of EHR can be realised for clinical trials.