Use of routinely collected data in a UK cohort of publicly funded randomised clinical trials.
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ABSTRACT:
SUBMITTER: McKay AJ
PROVIDER: S-EPMC7607478 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Clinical trials generally each collect their own data despite routinely collected health data (RCHD) increasing in quality and breadth. Our aim is to quantify UK-based randomised controlled trials (RCTs) accessing RCHD for participant data, characterise how these data are used and thereby recommend how more trials could use RCHD. METHODS:We conducted a systematic review of RCTs accessing RCHD from at least one registry in the UK between 2013 and 2018 for the purposes of informing or supplementing participant data. A list of all registries holding RCHD in the UK was compiled. In cases where registries published release registers, these were searched for RCTs accessing RCHD. Where no release register was available, registries were contacted to request a list of RCTs. For each identified RCT, information was collected from all publicly available sources (release registers, websites, protocol etc.). The search and data extraction were undertaken between January and May 2019. RESULTS:We identified 160 RCTs accessing RCHD between 2013 and 2018 from a total of 22 registries; this corresponds to only a very small proportion of all UK RCTs (about 3%). RCTs accessing RCHD were generally large (median sample size 1590), commonly evaluating treatments for cancer or cardiovascular disease. Most of the included RCTs accessed RCHD from NHS Digital (68%), and the most frequently accessed datasets were mortality (76%) and hospital visits (55%). RCHD was used to inform the primary trial (82%) and long-term follow-up (57%). There was substantial variation in how RCTs used RCHD to inform participant outcome measures. A limitation was the lack of information and transparency from registries and RCTs with respect to which datasets have been accessed and for what purposes. CONCLUSIONS:In the last five years, only a small minority of UK-based RCTs have accessed RCHD to inform participant data. We ask for improved accessibility, confirmed data quality and joined-up thinking between the registries and the regulatory authorities. TRIAL REGISTRATION:PROSPERO CRD42019123088.
| S-EPMC7218527 | biostudies-literature
Project description:BackgroundA promising approach to reduce the increasing costs of clinical trials is the use of routinely collected health data as participant data. However, the quality of this data could limit its usability as trial participant data.MethodsThe BOSS trial is a randomised controlled trial comparing regular endoscopies versus endoscopies at need in patients with Barrett's oesophagus with primary endpoint death. Data on death and cancer collected every 2 years after randomisation (trial-specific data) were compared to data received annually (all patients on one date) from the routinely collected health data source National Health Service (NHS) Digital. We investigated completeness, agreement and timeliness and looked at the implications for the primary trial outcome. Completeness and agreement were assessed by evaluating the number of reported and missing cases and any disparities between reported dates. Timeliness was considered by graphing the year a death was first reported in the trial-specific data against that for NHS Digital data. Implications on the primary trial outcome, overall survival, of using one of the data sources alone were investigated using Kaplan-Meier graphs. To assess the utility of cause of death and cancer diagnoses, oesophageal cancer cases were compared.ResultsNHS Digital datasets included more deaths and often reported them sooner than the trial-specific data. The number reported as being from oesophageal cancer was similar in both datasets. Due to time lag in reporting and missing cases, the event rate appeared higher using the NHS Digital data.ConclusionNHS Digital death data is useful for calculating overall survival where trial-specific follow-up is only every 2 years from randomisation and the follow-up requires patient response. The cancer data was not a large enough sample to assess usability. We suggest that this assessment of registry data is done for more phase III RCTs and for more registry data to get a more complete picture of when RCHD would be useful in phase III RCT.Trial registrationISRCTN54190466 (BOSS) 1 Oct 2009.
| S-EPMC8474902 | biostudies-literature
Project description:ObjectivesEvaluate current data sharing activities of UK publicly funded Clinical Trial Units (CTUs) and identify good practices and barriers.Study design and settingWeb-based survey of Directors of 45 UK Clinical Research Collaboration (UKCRC)-registered CTUs.ResultsTwenty-three (51%) CTUs responded: Five (22%) of these had an established data sharing policy and eight (35%) specifically requested consent to use patient data beyond the scope of the original trial. Fifteen (65%) CTUs had received requests for data, and seven (30%) had made external requests for data in the previous 12 months. CTUs supported the need for increased data sharing activities although concerns were raised about patient identification, misuse of data, and financial burden. Custodianship of clinical trial data and requirements for a CTU to align its policy to their parent institutes were also raised. No CTUs supported the use of an open access model for data sharing.ConclusionThere is support within the publicly funded UKCRC-registered CTUs for data sharing, but many perceived barriers remain. CTUs are currently using a variety of approaches and procedures for sharing data. This survey has informed further work, including development of guidance for publicly funded CTUs, to promote good practice and facilitate data sharing.
| S-EPMC4742521 | biostudies-literature
Project description:BackgroundStudies that use routinely collected health data (RCD studies) are advocated to complement evidence from randomized controlled trials (RCTs) for comparative effectiveness research and to inform health care decisions when RCTs would be unfeasible. We aimed to evaluate the current use of routinely collected health data to complement RCT evidence.MethodsWe searched PubMed for RCD studies published to 2010 that evaluated the comparative effectiveness of medical treatments on mortality using propensity scores. We identified RCTs of the same treatment comparisons and evaluated how frequently the RCD studies analyzed treatments that had not been compared previously in randomized trials. When RCTs did exist, we noted the claimed motivations for each RCD study. We also analyzed the citation impact of the RCD studies.ResultsOf 337 eligible RCD studies identified, 231 (68.5%) analyzed treatments that had already been compared in RCTs. The study investigators rarely claimed that it would be unethical (6/337) or difficult (18/337) to perform RCTs on the same question. Evidence from RCTs was mentioned or cited by authors of 213 RCD studies. The most common motivations for conducting the RCD studies were alleged limited generalizability of trial results to the "real world" (37.6%), evaluation of specific outcomes (31.9%) or specific populations (23.5%), and inconclusive or inconsistent evidence from randomized trials (25.8%). Studies evaluating "real world" effects had the lowest citation impact.InterpretationMost of the RCD studies we identified explored comparative treatment effects that had already been investigated in RCTs. The objective of such studies needs to shift more toward answering pivotal questions that are not supported by trial evidence or for which RCTs would be unfeasible.
| S-EPMC4933635 | biostudies-literature
Project description:ObjectivesTo determine how quickly randomised controlled trials funded by the Health Research Council of New Zealand (HRC) were registered and published, and whether time to publication differed by trial result.DesignWe created a retrospective cohort of trials offered funding from 1999 to 2017 by seeking lists of candidate studies using the Official Information Act 1982. These lists were supplemented by searching the HRC's online research repository and an open-access database on Figshare. One investigator searched for trial registrations and for dissemination using electronic databases, university websites and ResearchGate. One investigator extracted data from the obtained studies and a second investigator independently corroborated the data entry from a 10% random sample.ResultsWe identified 258 trials that were offered funding, 252 trials were conducted and 229 (90.9%) were registered, 179 prospectively by the date of the final search (24 March 2022). Overall, 236 trials were completed by the date of the last search and in 209 (88.6%) trials the results had been disseminated, 200 (84.7%) of which were by journal publication. We obtained the results for 214 trials, 91 (42.5%) of which were positive, 120 (56.1%) of which were null and 3 (1.4%) of which were negative. Median time to publication was 22.7 months for positive trials and 21.5 months for combined null or negative trials (log rank test p=0.83). Median time since trial completion in the trials that had not been published was 43.6 months (IQR 17.1-108.2 months).ConclusionsBetween 1999 and 2017, almost 9 out of every 10 HRC-funded trials had been registered and a similar proportion of completed trials had been published with no difference in time to publication based on type of result. However, only a slim majority of trials had published within the 2-year time frame set by the WHO.
| S-EPMC9540847 | biostudies-literature
Project description:ObjectivesTo evaluate the characteristics of individuals recorded as having a dementia diagnosis in different routinely collected records and to examine the extent of overlap of dementia coding across data sources. Also, to present comparisons of secondary and primary care records providing value for researchers using routinely collected records for dementia outcome capture.Study designA prospective cohort study.Setting and participantsA cohort of 25 639 men and women in Norfolk, aged 40-79 years at recruitment (1993-1997) followed until 2018 linked to routinely collected to identify dementia cases. Data sources include mortality from death certification and National Health Service (NHS) hospital or secondary care records. Primary care records for a subset of the cohort were also reviewed.Primary outcome measureDiagnosis of dementia (any-cause).ResultsOver 2000 participants (n=2635 individuals) were found to have a dementia diagnosis recorded in one or more of the data sources examined. Limited concordance was observed across the secondary care data sources. We also observed discrepancies with primary care records for the subset and report on potential linkage-related selection bias.ConclusionsUse of different types of record linkage from varying parts of the UK's health system reveals differences in recorded dementia diagnosis, indicating that dementia can be identified to varying extents in different parts of the NHS system. However, there is considerable variation, and limited overlap in those identified. We present potential selection biases that might occur depending on whether cause of death, or primary and secondary care data sources are used. With the expansion of using routinely collected health data, researchers must be aware of these potential biases and inaccuracies, reporting carefully on the likely extent of limitations and challenges of the data sources they use.
| S-EPMC9204445 | biostudies-literature
Project description:BACKGROUND:In the UK, routinely recorded data may benefit prospective studies including randomised controlled trials (RCTs). In an on-going study, we aim to assess the feasibility of access and agreement of routinely recorded clinical and non-clinical data compared to data collected during a RCT using standard prospective methods. This paper will summarise available UK routinely recorded data sources and discuss our experience with the feasibility of accessing routinely recorded data for participants of a RCT before finally proposing recommendations for improving the access and implementation of routinely recorded data in RCTs. METHODS:Setting: the case study RCT is the Standard and New Antiepileptic Drugs II (SANAD II) trial, a pragmatic, UK, multicentre, phase IV RCT assessing the clinical and cost-effectiveness of antiepileptic drug treatments for newly diagnosed epilepsy. PARTICIPANTS:98 participants have provided written consent to permit the request of routinely recorded data. Study procedures: routinely recorded clinical and non-clinical data were identified and data requested through formal applications from available data holders for the duration that participants have been recruited into SANAD II. The feasibility of accessing routinely recorded data during a RCT is assessed and recommendations for improving access proposed. RESULTS:Secondary-care clinical and socioeconomic data is recorded on a national basis and can be accessed, although there are limitations in the application process. Primary-care data are recorded by a number of organisations on a de-identified basis but access for specific individuals has not been feasible. Access to data recorded by non-clinical sources, including The Department for Work and Pensions and The Driving and Vehicle Licensing Agency, was not successful. CONCLUSIONS:Recommendations discussed include further research to assess the attributes of routinely recorded data, an assessment of public perceptions and the development of strategies to collaboratively improve access to routinely recorded data for research. TRIAL REGISTRATION:International Standard Randomised Controlled Trials, ISRCTN30294119 . Registered on 3 July 2012. EudraCT No: 2012-001884-64. Registered on 9 May 2012.
| S-EPMC5569524 | biostudies-literature
Project description:BackgroundOpinions and practices vary around the issue of performing multiple statistical tests in randomised controlled trials (RCTs). We carried out a study to collate information about opinions and practices using a methodological rapid review and a survey, specifically of publicly funded pragmatic RCTs that are not seeking marketing authorisation. The aim was to identify the circumstances under which researchers would make a statistical adjustment for multiplicity.MethodsA review was performed extracting information from articles reporting primary analyses of pragmatic RCTs in one of seven high quality medical journals, in January to June (inclusive) 2018. A survey (Survey Monkey) eliciting opinions and practices around multiplicity was distributed to the 47 registered clinical trials units (CTUs) in the UK.ResultsOne hundred and thirty-eight RCTs were included in the review, and survey responses were received from 27/47 (57%) CTUs. Both the review and survey indicated that adjusting for multiplicity was considered most important for multiple treatment comparisons; adjustment was performed for 11/23 (48%) published trials, and 24/27 (89%) CTU statisticians reported they would consider adjustment. Opinions and practices varied around adjustment for multiplicity arising from multiple primary outcomes and interim analyses. Adjustment was considered less important for multiplicity due to multiple secondary outcomes (adjustment performed for 17/136 [13%] published trials and 3/27 [11%] CTU statisticians would consider adjustment) and subgroup analyses (8/85 [9%] published trials adjusted and 6/27 CTU [22%] statisticians would consider adjustment).ConclusionsThere is variation in opinions about adjustment for multiplicity among both statisticians reporting RCTs and applied statisticians working in CTUs. Further guidance is needed on the circumstances in which adjustment should be considered in relation to primary trial hypotheses, and if there are any situations in which adjustment would be recommended in the context of secondary analyses.
| S-EPMC8818238 | biostudies-literature
Project description:OBJECTIVES:Proton pump inhibitors (PPIs) are commonly prescribed for prevention and treatment of gastrointestinal conditions or for gastroprotection from other drugs. Research suggests they are linked to increased dementia risk. We use linked national health data to examine the association between PPI use and the development of incident dementia. METHODS AND FINDINGS:A population-based study using electronic health-data from the Secure Anonymised Information Linkage (SAIL) Databank, Wales (UK) from 1999 to 2015. Of data available on 3,765,744 individuals, a cohort who had ever been prescribed a PPI was developed (n = 183,968) for people aged 55 years and over and compared to non-PPI exposed individuals (131,110). Those with prior dementia, mild-cognitive-impairment or delirium codes were excluded. Confounding factors included comorbidities and/or drugs associated with them. Comorbidities might include head injury and some examples of medications include antidepressants, antiplatelets and anticoagulants. These commonly prescribed drugs were investigated as it was not feasible to explore all drugs in this study. The main outcome was a diagnosis of incident dementia. Cox proportional hazard regression modelling was used to calculate the Hazard ratio (HR) of developing dementia in PPI-exposed compared to unexposed individuals while controlling for potential confounders. The mean age of the PPI exposed individuals was 69.9 years and 39.8% male while the mean age of the unexposed individuals was 72.1 years and 41.1% male. The rate of PPI usage was 58.4% (183,968) and incident dementia rate was 11.8% (37,148/315,078). PPI use was associated with decreased dementia risk (HR: 0.67, 95% CI: 0.65 to 0.67, p<0.01). CONCLUSIONS:This study, using large-scale, multi-centre health-data was unable to confirm an association between PPI use and increased dementia risk. Previously reported links may be associated with confounders of people using PPI's, such as increased risk of cardiovascular disease and/or depression and their associated medications which may be responsible for any increased risk of developing dementia.
| S-EPMC7500586 | biostudies-literature
Project description:BackgroundTherapeutic hypothermia is standard of care in high-income countries for babies born with signs of hypoxic ischaemic encephalopathy, but optimal feeding during treatment is uncertain and practice is variable. This study aimed to assess the association between feeding during therapeutic hypothermia and clinically important outcomes.MethodsWe did a population-level retrospective cohort study using the UK National Neonatal Research Database. We included all babies admitted to National Health Service neonatal units in England, Scotland, and Wales between Jan 1, 2010, and Dec 31, 2017, who received therapeutic hypothermia for 72 h or died during this period. For analysis, we created matched groups using propensity scores and compared outcomes in babies who were fed versus unfed enterally during therapeutic hypothermia. The primary outcome was severe necrotising enterocolitis, either confirmed at surgery or causing death. Secondary outcomes include pragmatically defined necrotising enterocolitis (a recorded diagnosis of necrotising enterocolitis in babies who received at least 5 consecutive days of antibiotics while also nil by mouth during their neonatal unit stay), late-onset infection (pragmatically defined as 5 consecutive days of antibiotic treatment commencing after day 3), survival to discharge, measures of breastmilk feeding, and length of stay in neonatal unit.Findings6030 babies received therapeutic hypothermia, of whom 1873 (31·1%) were fed during treatment. Seven (0·1%) babies were diagnosed with severe necrotising enterocolitis and the number was too small for further analyses. We selected 3236 (53·7%) babies for the matched feeding analysis (1618 pairs), achieving a good balance for all recorded background variables. Pragmatically defined necrotising enterocolitis was rare in both groups (incidence 0·5%, 95% CI 0·2-0·9] in the fed group vs 1·1% [0·7-1·4] in the unfed group). The enterally fed group had fewer pragmatically defined late-onset infections (difference -11·6% [95% CI -14·0 to -9·3]; p<0·0001), higher survival to discharge (5·2% [3·9-6·6]; p<0·0001), higher proportion of breastfeeding at discharge (8·0% [5·1-10·8]; p<0·0001), and shorter neonatal unit stays (-2·2 [-3·0 to -1·2] days; p<0·0001) compared with the unfed group.InterpretationNecrotising enterocolitis is rare in babies receiving therapeutic hypothermia. Enteral feeding during hypothermia is safe and associated with beneficial outcomes compared with not feeding, although residual confounding could not be completely ruled out. Our findings support starting milk feeds during therapeutic hypothermia.FundingUK National Institute for Health Research Health Technology Assessment programme 16/79/13.
| S-EPMC8131202 | biostudies-literature