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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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%).
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.
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.
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.
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.
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
UK Biobank is a very large prospective study which aims to provide a resource for the investigation of the genetic, environmental and lifestyle determinants of a wide range of diseases of middle age ...and later life. Between 2006 and 2010, over 500,000 men and women aged 40 to 69 years were recruited and extensive data on participants' lifestyles, environment, medical history and physical measures, along with biological samples, were collected. The health of the participants is now being followed long-term, principally through linkage to a wide range of health-related records, with validation and characterisation of health-related outcomes. Further enhancements are also underway to improve phenotype characterisation, including internet-based dietary assessment, biomarker measurements on the baseline blood samples and, in sub-samples of the cohort, physical activity monitoring and proposals for extensive brain and body imaging. UK Biobank is now available for use by all researchers, without exclusive or preferential access, for any health-related research that is in the public interest. The open-access nature of the resource will allow researchers from around the world to conduct research that leads to better strategies for the prevention, diagnosis and treatment of a wide range of life-threatening and disabling conditions.
► UK Biobank is a resource for the investigation of the determinants of a wide range of diseases. ► UK Biobank is now open for use by all researchers world-wide. ► Researchers can apply to use the data for any health-related research that is in the public interest. ► Participants' health is being followed long-term, with detailed characterisation of outcomes. ► Further enhancements are also underway to improve phenotype characterisation.
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.
1) To use data-driven method to examine clinical codes (risk factors) of a medical condition in primary care electronic health records (EHRs) that can accurately predict a diagnosis of the condition ...in secondary care EHRs. 2) To develop and validate a disease phenotyping algorithm for rheumatoid arthritis using primary care EHRs.
This study linked routine primary and secondary care EHRs in Wales, UK. A machine learning based scheme was used to identify patients with rheumatoid arthritis from primary care EHRs via the following steps: i) selection of variables by comparing relative frequencies of Read codes in the primary care dataset associated with disease case compared to non-disease control (disease/non-disease based on the secondary care diagnosis); ii) reduction of predictors/associated variables using a Random Forest method, iii) induction of decision rules from decision tree model. The proposed method was then extensively validated on an independent dataset, and compared for performance with two existing deterministic algorithms for RA which had been developed using expert clinical knowledge.
Primary care EHRs were available for 2,238,360 patients over the age of 16 and of these 20,667 were also linked in the secondary care rheumatology clinical system. In the linked dataset, 900 predictors (out of a total of 43,100 variables) in the primary care record were discovered more frequently in those with versus those without RA. These variables were reduced to 37 groups of related clinical codes, which were used to develop a decision tree model. The final algorithm identified 8 predictors related to diagnostic codes for RA, medication codes, such as those for disease modifying anti-rheumatic drugs, and absence of alternative diagnoses such as psoriatic arthritis. The proposed data-driven method performed as well as the expert clinical knowledge based methods.
Data-driven scheme, such as ensemble machine learning methods, has the potential of identifying the most informative predictors in a cost-effective and rapid way to accurately and reliably classify rheumatoid arthritis or other complex medical conditions in primary care EHRs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Despite increasing international interest, there is a lack of evidence about the most efficient, effective and acceptable ways to implement patient and public involvement (PPI) in clinical ...trials.
Objective
To identify the priorities of UK PPI stakeholders for methodological research to help resolve uncertainties about PPI in clinical trials.
Design
A modified Delphi process including a two round online survey and a stakeholder consensus meeting.
Participants
In total, 237 people registered of whom 219 (92%) completed the first round. One hundred and eighty‐seven of 219 (85%) completed the second; 25 stakeholders attended the consensus meeting.
Results
Round 1 of the survey comprised 36 topics; 42 topics were considered in round 2 and at the consensus meeting. Approximately 96% of meeting participants rated the top three topics as equally important. These were as follows: developing strong and productive working relationships between researchers and PPI contributors; exploring PPI practices in selecting trial outcomes of importance to patients; and a systematic review of PPI activity to improve the accessibility and usefulness of trial information (eg participant information sheets) for participants.
Conclusions
The prioritized methodological research topics indicate important areas of uncertainty about PPI in trials. Addressing these uncertainties will be critical to enhancing PPI. Our findings should be used in the planning and funding of PPI in clinical trials to help focus research efforts and minimize waste.
We performed a systematic review of the accuracy of patient self-report of stroke to inform approaches to ascertaining and confirming stroke cases in large prospective studies.
We sought studies ...comparing patient self-report against a reference standard for stroke. We extracted data on survey method(s), response rates, participant characteristics, the reference standard used, and the positive predictive value (PPV) of self-report. Where possible we also calculated sensitivity, specificity, negative predictive value (NPV), and stroke prevalence. Study-level risk of bias was assessed using the Quality Assessment of Diagnostic Studies tool (QUADAS-2).
From >1500 identified articles, we included 17 studies. Most asked patients to report a lifetime history of stroke but a few limited recall time to ≤5 years. Some included questions for transient ischaemic attack (TIA) or stroke synonyms. No study was free of risk of bias in the QUADAS-2 assessment, the most frequent causes of bias being incomplete reference standard data, absence of blinding of adjudicators to self-report status, and participant response rates (<80%). PPV of self-report ranged from 22-87% (17 studies), sensitivity from 36-98% (10 studies), specificity from 96-99.6% (10 studies), and NPV from 88.2-99.9% (10 studies). PPV increased with stroke prevalence as expected. Among six studies with available relevant data, if confirmed TIAs were considered to be true rather than false positive strokes, PPV of self-report was >75% in all but one study. It was not possible to assess the influence of recall time or of the question(s) asked on PPV or sensitivity.
Characteristics of the study population strongly influence self-report accuracy. In population-based studies with low stroke prevalence, a large proportion of self-reported strokes may be false positives. Self-report is therefore unlikely to be helpful for identifying cases without subsequent confirmation, but may be useful for case ascertainment in combination with other data sources.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
JD has received research funding from The Wellcome Trust, British Heart Foundation, UK Medical Research Council, BUPA Foundation, Denka, diaDexus, European Research Council, European Union, Evelyn ...Trust, Fogarty International Centre, GlaxoSmithKline, Merck, National Heart, Lung and Blood Institute, National Health Service Blood and Transplant, National Institute for Health Research, National Institute of Neurological Disorders and Stroke, Novartis, Pfizer, Roche, UK Biobank. Provenance: Not commissioned; externally peer reviewed Summary Points * UK Biobank is a very large and detailed prospective study with over 500,000 participants aged 40-69 years when recruited in 2006-2010. * The study has collected and continues to collect extensive phenotypic and genotypic detail about its participants, including data from questionnaires, physical measures, sample assays, accelerometry, multimodal imaging, genome-wide genotyping and longitudinal follow-up for a wide range of health-related outcomes. * Wide consultation; input from scientific, management, legal, and ethical partners; and industrial-scale, centralised processes have been essential to the development of this resource. * UK Biobank is available for open access, without the need for collaboration, to any bona fide researcher who wishes to use it to conduct health-related research for the benefit of the public.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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