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Background: The UK Clinical Research Collaboration (UKCRC) registered Clinical Trials Units (CTUs) Network aims to support high-quality, efficient and sustainable clinical trials research in the UK. To better understand the challenges in efficient trial conduct, and to help prioritise tackling these challenges, we surveyed CTU staff. The aim was to identify important inefficiencies during two key stages of the trial conduct life cycle: (i) from grant award to first participant, (ii) from first participant to reporting of final results., Methods: Respondents were asked to list their top three inefficiencies from grant award to recruitment of the first participant, and from recruitment of the first participant to publication of results. Free text space allowed respondents to explain why they thought these were important. The survey was constructed using SurveyMonkey and circulated to the 45 registered CTUs in May 2013. Respondents were asked to name their unit and job title, but were otherwise anonymous. Free-text responses were coded into broad categories., Results: There were 43 respondents from 25 CTUs. The top inefficiency between grant award and recruitment of first participant was reported as obtaining research and development (R&D) approvals by 23 respondents (53%), contracts by 22 (51%), and other approvals by 13 (30%). The top inefficiency from recruitment of first participant to publication of results was failure to meet recruitment targets, reported by 19 (44%) respondents. A common comment was that this reflected overoptimistic or inaccurate estimates of recruitment at site. Data management, including case report form design and delays in resolving data queries with sites, was reported as an important inefficiency by 11 (26%) respondents, and preparation and submission for publication by 9 (21%)., Conclusions: Recommendations for improving the efficiency of trial conduct within the CTUs network include: further reducing unnecessary bureaucracy in approvals and contracting; improving training for site staff; realistic recruitment targets and appropriate feasibility; developing training across the network; improving the working relationships between chief investigators and units; encouraging funders to release sufficient funding to allow prompt recruitment of trial staff; and encouraging more research into how to improve the efficiency and quality of trial conduct.

Background: The United Arab Emirates (UAE) is faced with a rapidly increasing burden of non-communicable diseases including obesity, diabetes, and cardiovascular disease. The UAE Healthy Future study is a prospective cohort designed to identify associations between risk factors and these diseases amongst Emiratis. The study will enroll 20,000 UAE nationals aged ≥18 years. Environmental and genetic risk factors will be characterized and participants will be followed for future disease events. As this was the first time a prospective cohort study was being planned in the UAE, a pilot study was conducted in 2015 with the primary aim of establishing the feasibility of conducting the study. Other objectives were to evaluate the implementation of the main study protocols, and to build adequate capacity to conduct advanced clinical laboratory analyses., Methods: Seven hundred sixty nine UAE nationals aged ≥18 years were invited to participate voluntarily in the pilot study. Participants signed an informed consent, completed a detailed questionnaire, provided random blood, urine, and mouthwash samples and were assessed for a series of clinical measures. All specimens were transported to the New York University Abu Dhabi laboratories where samples were processed and analyzed for routine chemistry and hematology. Plasma, serum, and a small whole blood sample for DNA extraction were aliquoted and stored at -80 °C for future analyses., Results: Overall, 517 Emirati men and women agreed to participate (68% response rate). Of the total participants, 495 (95.0%), 430 (82.2%), and 492 (94.4%), completed the questionnaire, physical measurements, and provided biological samples, respectively., Conclusions: The pilot study demonstrated the feasibility of recruitment and completion of the study protocols for the first large-scale cohort study designed to identify emerging risk factors for the major non-communicable diseases in the region.

The UK Biobank cohort is a population-based cohort of 500,000 participants recruited in the United Kingdom (UK) between 2006 and 2010. Approximately 9.2 million individuals aged 40-69 years who lived within 25 miles (40 km) of one of 22 assessment centers in England, Wales, and Scotland were invited to enter the cohort, and 5.5% participated in the baseline assessment. The representativeness of the UK Biobank cohort was investigated by comparing demographic characteristics between nonresponders and responders. Sociodemographic, physical, lifestyle, and health-related characteristics of the cohort were compared with nationally representative data sources. UK Biobank participants were more likely to be older, to be female, and to live in less socioeconomically deprived areas than nonparticipants. Compared with the general population, participants were less likely to be obese, to smoke, and to drink alcohol on a daily basis and had fewer self-reported health conditions. At age 70-74 years, rates of all-cause mortality and total cancer incidence were 46.2% and 11.8% lower, respectively, in men and 55.5% and 18.1% lower, respectively, in women than in the general population of the same age. UK Biobank is not representative of the sampling population; there is evidence of a "healthy volunteer" selection bias. Nonetheless, valid assessment of exposure-disease relationships may be widely generalizable and does not require participants to be representative of the population at large., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.

Large prospective cohort studies are critical for identifying etiologic factors for disease, but they require substantial long-term research investment. Such studies can be conducted as multisite consortia of academic medical centers, combinations of smaller ongoing studies, or a single large site such as a dominant regional health-care provider. Still another strategy relies upon centralized conduct of most or all aspects, recruiting through multiple temporary assessment centers. This is the approach used by a large-scale national resource in the United Kingdom known as the "UK Biobank," which completed recruitment/examination of 503,000 participants between 2007 and 2010 within budget and ahead of schedule. A key lesson from UK Biobank and similar studies is that large studies are not simply small studies made large but, rather, require fundamentally different approaches in which "process" expertise is as important as scientific rigor. Embedding recruitment in a structure that facilitates outcome determination, utilizing comprehensive and flexible information technology, automating biospecimen processing, ensuring broad consent, and establishing essentially autonomous leadership with appropriate oversight are all critical to success. Whether and how these approaches may be transportable to the United States remain to be explored, but their success in studies such as UK Biobank makes a compelling case for such explorations to begin.

The UK Biobank is a major UK collaborative research project to recruit and follow longitudinally the health of 500,000 volunteers aged between 40-69 years. It will provide important biological samples and environmental exposure data. As such, it will constitute a resource for many future investigations of the separate and combined effects of genetic, environmental and lifestyle factors on human morbidity, mortality and health.

A randomized, double-blind, cross-over study was undertaken to determine the effects of novel bicarbonate (38 mM) and bicarbonate (25 mM)/lactate (15 mM) containing peritoneal dialysis (PD) solutions on infusion pain in patients who experienced inflow pain with conventional lactate (40 mM) solution. Pain was assessed using a verbal rating scale and the validated McGill Pain Questionnaire (MPQ). Eighteen patients were recruited to the study. Both novel solutions resulted in highly statistically significant reductions in inflow pain compared to the control lactate solution, as assessed with both the verbal rating scale and the MPQ. For all pain variables assessed, the bicarbonate/lactate solution was more effective than the bicarbonate solution in alleviating pain. In conclusion, both solutions reduced the infusion pain experienced with control solution, but the bicarbonate/lactate solution appears to be the most effective. In contrast to the most widespread current treatment, which is the manual injection of sodium bicarbonate, the bicarbonate/lactate solution does not have the associated increased risk of peritonitis.

The action of a novel 5-HT3 receptor antagonist, AS-5370, has been studied on two electrophysiological models for 5-HT3 receptors: whole-cell patch-clamp recordings from mouse neuroblastoma-rat glioma (NG108-15) cells and grease-gap recordings from rat isolated vagus nerve. The 5-hydroxytryptamine (5-HT)-induced fast inward current of voltage-clamped NG108-15 cells was antagonized by 1 nM AS-5370 in an insurmountable manner. On the rat vagus, AS-5370 reduced the maximum depolarizing response to 5-HT in a concentration-dependent manner. The IC50 for AS-5370 on the rat vagus was 0.3-1.0 nM. The EC50 for 5-HT on the rat vagus was not appreciably affected by AS-5370. On the rat vagus, the (R) enantiomer of AS-5370 was about 30 times more potent than the (S) enantiomer. The antagonist action of AS-5370 on these two cell types was compared with that of (+)-tubocurarine. Unlike tubocurarine, the effect of AS-5370 on NG108-15 cells was not readily reversed during wash. On the rat vagus, tubocurarine antagonized in a competitive manner with an IC50 of 0.3-1.0 microM (pKb = 7.2). It is concluded that AS-5370 is a potent 5-HT3 receptor antagonist on both NG108-15 cells and the rat vagus, but it does not act in a competitive manner.