Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis.

BACKGROUND: We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS: We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS: We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research.

The evidence for cognitive behavioural therapy in any condition, population or context: a meta-review of systematic reviews and panoramic meta-analysis.

The majority of psychological treatment research is dedicated to investigating the effectiveness of cognitive behavioural therapy (CBT) across different conditions, population and contexts. We aimed to summarise the current systematic review evidence and evaluate the consistency of CBT's effect across different conditions. We included reviews of CBT randomised controlled trials in any: population, condition, format, context, with any type of comparator and published in English. We searched DARE, Cochrane, MEDLINE, EMBASE, PsycINFO, CINAHL, CDAS, and OpenGrey between 1992 and January 2019. Reviews were quality assessed, their data extracted and summarised. The effects upon health-related quality of life (HRQoL) were pooled, within-condition groups. If the across-condition heterogeneity was I2 < 75%, we pooled effects using a random-effect panoramic meta-analysis. We summarised 494 reviews (221 128 participants), representing 14/20 physical and 13/20 mental conditions (World Health Organisation's International Classification of Diseases). Most reviews were lower-quality (351/494), investigated face-to-face CBT (397/494), and in adults (378/494). Few reviews included trials conducted in Asia, South America or Africa (45/494). CBT produced a modest benefit across-conditions on HRQoL (standardised mean difference 0.23; 95% confidence intervals 0.14-0.33, I2 = 32%). The effect's associated prediction interval -0.05 to 0.50 suggested CBT will remain effective in conditions for which we do not currently have available evidence. While there remain some gaps in the completeness of the evidence base, we need to recognise the consistent evidence for the general benefit which CBT offers.

Multifactorial interventions for preventing falls in older people living in the community: a systematic review and meta-analysis of 41 trials and almost 20 000 participants.

OBJECTIVE: To assess the longer term effects of multifactorial interventions for preventing falls in older people living in the community, and to explore whether prespecific trial-level characteristics are associated with greater fall prevention effects. DESIGN: Systematic review with meta-analysis and meta-regression. DATA SOURCES: MEDLINE, EMBASE, CINHAL, CENTRAL and trial registries were searched up to 25 July 2018. STUDY SELECTION: We included randomised controlled trials (≥12 months' follow-up) evaluating the effects of multifactorial interventions on falls in older people aged 65 years and over, living in the community, compared with either usual care or usual care plus advice. REVIEW METHODS: Two authors independently verified studies for inclusion, assessed risk of bias and extracted data. Rate ratios (RaR) with 95% CIs were calculated for rate of falls, risk ratios (RR) for dichotomous outcomes and standardised mean difference for continuous outcomes. Data were pooled using a random effects model. The Grading of Recommendations, Assessment, Development and Evaluation was used to assess the quality of the evidence. RESULTS: We included 41 trials totalling 19 369 participants; mean age 72-85 years. Exercise was the most common prespecified component of the multifactorial interventions (85%; n=35/41). Most trials were judged at unclear or high risk of bias in ≥1 domain. Twenty trials provided data on rate of falls and showed multifactorial interventions may reduce the rate at which people fall compared with the comparator (RaR 0.79, 95% CI 0.70 to 0.88; 20 trials; 10 116 participants; I2=90%; low-quality evidence). Multifactorial interventions may also slightly lower the risk of people sustaining one or more falls (RR 0.95, 95% CI 0.90 to 1.00; 30 trials; 13 817 participants; I2=56%; moderate-quality evidence) and recurrent falls (RR 0.88, 95% CI 0.78 to 1.00; 15 trials; 7277 participants; I2=46%; moderate-quality evidence). However, there may be little or no difference in other fall-related outcomes, such as fall-related fractures, falls requiring hospital admission or medical attention and health-related quality of life. Very few trials (n=3) reported on adverse events related to the intervention. Prespecified subgroup analyses showed that the effect on rate of falls may be smaller when compared with usual care plus advice as opposed to usual care only. Overall, heterogeneity remained high and was not explained by the prespecified characteristics included in the meta-regression. CONCLUSION: Multifactorial interventions (most of which include exercise prescription) may reduce the rate of falls and slightly reduce risk of older people sustaining one or more falls and recurrent falls (defined as two or more falls within a specified time period). TRIAL REGISTRATION NUMBER: CRD42018102549.

Multifactorial and multiple component interventions for preventing falls in older people living in the community.

BACKGROUND: Falls and fall-related injuries are common, particularly in those aged over 65, with around one-third of older people living in the community falling at least once a year. Falls prevention interventions may comprise single component interventions (e.g. exercise), or involve combinations of two or more different types of intervention (e.g. exercise and medication review). Their delivery can broadly be divided into two main groups: 1) multifactorial interventions where component interventions differ based on individual assessment of risk; or 2) multiple component interventions where the same component interventions are provided to all people. OBJECTIVES: To assess the effects (benefits and harms) of multifactorial interventions and multiple component interventions for preventing falls in older people living in the community. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, trial registers and reference lists. Date of search: 12 June 2017. SELECTION CRITERIA: Randomised controlled trials, individual or cluster, that evaluated the effects of multifactorial and multiple component interventions on falls in older people living in the community, compared with control (i.e. usual care (no change in usual activities) or attention control (social visits)) or exercise as a single intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias and extracted data. We calculated the rate ratio (RaR) with 95% confidence intervals (CIs) for rate of falls. For dichotomous outcomes we used risk ratios (RRs) and 95% CIs. For continuous outcomes, we used the standardised mean difference (SMD) with 95% CIs. We pooled data using the random-effects model. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: We included 62 trials involving 19,935 older people living in the community. The median trial size was 248 participants. Most trials included more women than men. The mean ages in trials ranged from 62 to 85 years (median 77 years). Most trials (43 trials) reported follow-up of 12 months or over. We assessed most trials at unclear or high risk of bias in one or more domains.Forty-four trials assessed multifactorial interventions and 18 assessed multiple component interventions. (I2 not reported if = 0%).Multifactorial interventions versus usual care or attention controlThis comparison was made in 43 trials. Commonly-applied or recommended interventions after assessment of each participant's risk profile were exercise, environment or assistive technologies, medication review and psychological interventions. Multifactorial interventions may reduce the rate of falls compared with control: rate ratio (RaR) 0.77, 95% CI 0.67 to 0.87; 19 trials; 5853 participants; I2 = 88%; low-quality evidence. Thus if 1000 people were followed over one year, the number of falls may be 1784 (95% CI 1553 to 2016) after multifactorial intervention versus 2317 after usual care or attention control. There was low-quality evidence of little or no difference in the risks of: falling (i.e. people sustaining one or more fall) (RR 0.96, 95% CI 0.90 to 1.03; 29 trials; 9637 participants; I2 = 60%); recurrent falls (RR 0.87, 95% CI 0.74 to 1.03; 12 trials; 3368 participants; I2 = 53%); fall-related hospital admission (RR 1.00, 95% CI 0.92 to 1.07; 15 trials; 5227 participants); requiring medical attention (RR 0.91, 95% CI 0.75 to 1.10; 8 trials; 3078 participants). There is low-quality evidence that multifactorial interventions may reduce the risk of fall-related fractures (RR 0.73, 95% CI 0.53 to 1.01; 9 trials; 2850 participants) and may slightly improve health-related quality of life but not noticeably (SMD 0.19, 95% CI 0.03 to 0.35; 9 trials; 2373 participants; I2 = 70%). Of three trials reporting on adverse events, one found none, and two reported 12 participants with self-limiting musculoskeletal symptoms in total.Multifactorial interventions versus exerciseVery low-quality evidence from one small trial of 51 recently-discharged orthopaedic patients means that we are uncertain of the effects on rate of falls or risk of falling of multifactorial interventions versus exercise alone. Other fall-related outcomes were not assessed.Multiple component interventions versus usual care or attention controlThe 17 trials that make this comparison usually included exercise and another component, commonly education or home-hazard assessment. There is moderate-quality evidence that multiple interventions probably reduce the rate of falls (RaR 0.74, 95% CI 0.60 to 0.91; 6 trials; 1085 participants; I2 = 45%) and risk of falls (RR 0.82, 95% CI 0.74 to 0.90; 11 trials; 1980 participants). There is low-quality evidence that multiple interventions may reduce the risk of recurrent falls, although a small increase cannot be ruled out (RR 0.81, 95% CI 0.63 to 1.05; 4 trials; 662 participants). Very low-quality evidence means that we are uncertain of the effects of multiple component interventions on the risk of fall-related fractures (2 trials) or fall-related hospital admission (1 trial). There is low-quality evidence that multiple interventions may have little or no effect on the risk of requiring medical attention (RR 0.95, 95% CI 0.67 to 1.35; 1 trial; 291 participants); conversely they may slightly improve health-related quality of life (SMD 0.77, 95% CI 0.16 to 1.39; 4 trials; 391 participants; I2 = 88%). Of seven trials reporting on adverse events, five found none, and six minor adverse events were reported in two.Multiple component interventions versus exerciseThis comparison was tested in five trials. There is low-quality evidence of little or no difference between the two interventions in rate of falls (1 trial) and risk of falling (RR 0.93, 95% CI 0.78 to 1.10; 3 trials; 863 participants) and very low-quality evidence, meaning we are uncertain of the effects on hospital admission (1 trial). One trial reported two cases of minor joint pain. Other falls outcomes were not reported. AUTHORS' CONCLUSIONS: Multifactorial interventions may reduce the rate of falls compared with usual care or attention control. However, there may be little or no effect on other fall-related outcomes. Multiple component interventions, usually including exercise, may reduce the rate of falls and risk of falling compared with usual care or attention control.

A systematic review and meta-analysis of online versus alternative methods for training licensed health care professionals to deliver clinical interventions.

BACKGROUND: Online training is growing in popularity and yet its effectiveness for training licensed health professionals (HCPs) in clinical interventions is not clear. We aimed to systematically review the literature on the effectiveness of online versus alternative training methods in clinical interventions for licensed Health Care Professionals (HCPs) on outcomes of knowledge acquisition, practical skills, clinical behaviour, self-efficacy and satisfaction. METHODS: Seven databases were searched for randomised controlled trials (RCTs) from January 2000 to June 2015. Two independent reviewers rated trial quality and extracted trial data. Comparative effects were summarised as standardised mean differences (SMD) and 95% confidence intervals. Pooled effect sizes were calculated using a random-effects model for three contrasts of online versus (i) interactive workshops (ii) taught lectures and (iii) written/electronic manuals. RESULTS: We included 14 studies with a total of 1089 participants. Most trials studied medical professionals, used a workshop or lecture comparison, were of high risk of bias and had small sample sizes (range 21-183). Using the GRADE approach, we found low quality evidence that there was no difference between online training and an interactive workshop for clinical behaviour SMD 0.12 (95% CI -0.13 to 0.37). We found very low quality evidence of no difference between online methods and both a workshop and lecture for knowledge (workshop: SMD 0.04 (95% CI -0.28 to 0.36); lecture: SMD 0.22 (95% CI: -0.08, 0.51)). Lastly, compared to a manual (n = 3/14), we found very low quality evidence that online methods were superior for knowledge SMD 0.99 (95% CI 0.02 to 1.96). There were too few studies to draw any conclusions on the effects of online training for practical skills, self-efficacy, and satisfaction across all contrasts. CONCLUSIONS: It is likely that online methods may be as effective as alternative methods for training HCPs in clinical interventions for the outcomes of knowledge and clinical behaviour. However, the low quality of the evidence precludes drawing firm conclusions on the relative effectiveness of these training methods. Moreover, the confidence intervals around our effect sizes were large and could encompass important differences in effectiveness. More robust, adequately powered RCTs are needed.

Overprescribing of potentially harmful medication: an observational study in England's general practice.

BACKGROUND: Overprescribing of potentially harmful medication in UK general practice has a complex association with socioeconomic deprivation. AIM: To assess trends in general practice prescribing of five high-risk medications and their relationship with deprivation. DESIGN & SETTING: An observational study was conducted using general practice data from three English regions with varied sociodemographic factors: West Yorkshire and Harrogate (WY), Black Country and West Birmingham (BC), and Surrey and East Sussex (SE). METHOD: Practice-level prescribing data were obtained from 2016-2021 for five drug classes: opioids, hypnotics, gabapentinoids, non-steroidal anti-inflammatory drugs (NSAIDs), and antibacterials. Prescribing trends were demonstrated using a linear model. RESULTS: Reduction in NSAID, opioid, hypnotic and antibacterial prescriptions, and the increase in gabapentinoid prescriptions, were significant at each financial year time period. Index of Multiple Deprivation (IMD) was positively associated with all drug classes except antibacterials, which showed a positive association when incorporating the interaction term between IMD and age.When adjusting for IMD and population, region was independently associated with prescribing rate. Compared with WY, IMD had a smaller association with prescribing in BC for NSAIDs (coefficient = -0.01578, P = 0.004) and antibacterials (coefficient = -0.02769, P = 0.007), whereas IMD had a greater association with prescribing in SE for NSAIDs (coefficient = 0.02443, P<0.001), opioids (coefficient = 0.08919, P<0.001), hypnotics (coefficient = 0.09038, P<0.001), gabapentinoids (coefficient = 0.1095, P<0.001), and antibacterials (coefficient = 0.01601, P = 0.19). CONCLUSION: The association of socioeconomic deprivation with overprescribing of high-risk medication in general practice varies by region and drug type. Geographical location is associated with overprescribing, independent of socioeconomic status.

Effectiveness and cost-effectiveness of a sustainable obesity prevention programme for preschool children delivered at scale 'HENRY' (Health, Exercise, Nutrition for the Really Young): protocol for the HENRY III cluster randomised controlled trial.

INTRODUCTION: One-fifth of children start school already overweight or living with obesity, with rates disproportionately impacting those living in the most deprived areas. Social, environmental and biological factors contribute to excess weight gain and programmes delivered in early years settings aim to support families to navigate these in order to prevent obesity. One of these programmes (Health, Exercise and Nutrition for the Really Young, HENRY) has been delivered in UK community venues (hereon named 'centres') in high deprivation areas since 2008 and aims to help families to provide a healthy start for their preschool children. We aim to establish the effectiveness and cost-effectiveness of HENRY, including its potential role from a wider systems perspective. METHODS AND ANALYSIS: This is a multicentre, open-labelled, two-group, prospective, cluster randomised controlled trial, with cost-effectiveness analysis, systems-based process evaluation and internal pilot. Primary analysis will compare body mass index (BMI) z-score at 12 months in children (n=984) whose parents have attended HENRY to those who have not attended. Secondary outcomes include parent and staff BMI and waist circumference, parenting efficacy, feeding, eating habits, quality of life, resource use and medium term (3 years) BMI z-scores (child and siblings). 82 centres in ~14 local authority areas will be randomised (1:1) to receive HENRY or continue with standard practice. Intention-to-treat analysis will compare outcomes using mixed effects linear regression. Economic evaluation will estimate a within-trial calculation of cost-per unit change in BMI z-score and longer-term trajectories to determine lifelong cost savings (long-term outcomes). A systems process evaluation will explore whether (and how) implementation of HENRY impacts (and is impacted by) the early years obesity system. An established parent advisory group will support delivery and dissemination. ETHICS AND DISSEMINATION: Ethical approval has been granted by the University of York, Health Sciences' Research Governance Committee (HSRGC/2022/537/E). Dissemination includes policy reports, community resources, social media and academic outputs. TRIAL REGISTRATION NUMBER: ISRCTN16529380.

Using healthcare systems data for outcomes in clinical trials: issues to consider at the design stage.

BACKGROUND: Healthcare system data (HSD) are increasingly used in clinical trials, augmenting or replacing traditional methods of collecting outcome data. This study, PRIMORANT, set out to identify, in the UK context, issues to be considered before the decision to use HSD for outcome data in a clinical trial is finalised, a methodological question prioritised by the clinical trials community. METHODS: The PRIMORANT study had three phases. First, an initial workshop was held to scope the issues faced by trialists when considering whether to use HSDs for trial outcomes. Second, a consultation exercise was undertaken with clinical trials unit (CTU) staff, trialists, methodologists, clinicians, funding panels and data providers. Third, a final discussion workshop was held, at which the results of the consultation were fed back, case studies presented, and issues considered in small breakout groups. RESULTS: Key topics included in the consultation process were the validity of outcome data, timeliness of data capture, internal pilots, data-sharing, practical issues, and decision-making. A majority of consultation respondents (n = 78, 95%) considered the development of guidance for trialists to be feasible. Guidance was developed following the discussion workshop, for the five broad areas of terminology, feasibility, internal pilots, onward data sharing, and data archiving. CONCLUSIONS: We provide guidance to inform decisions about whether or not to use HSDs for outcomes, and if so, to assist trialists in working with registries and other HSD providers to improve the design and delivery of trials.

Digital endpoints in clinical trials: emerging themes from a multi-stakeholder Knowledge Exchange event.

BACKGROUND: Digital technologies, such as wearable devices and smartphone applications (apps), can enable the decentralisation of clinical trials by measuring endpoints in people's chosen locations rather than in traditional clinical settings. Digital endpoints can allow high-frequency and sensitive measurements of health outcomes compared to visit-based endpoints which provide an episodic snapshot of a person's health. However, there are underexplored challenges in this emerging space that require interdisciplinary and cross-sector collaboration. A multi-stakeholder Knowledge Exchange event was organised to facilitate conversations across silos within this research ecosystem. METHODS: A survey was sent to an initial list of stakeholders to identify potential discussion topics. Additional stakeholders were identified through iterative discussions on perspectives that needed representation. Co-design meetings with attendees were held to discuss the scope, format and ethos of the event. The event itself featured a cross-disciplinary selection of talks, a panel discussion, small-group discussions facilitated via a rolling seating plan and audience participation via Slido. A transcript was generated from the day, which, together with the output from Slido, provided a record of the day's discussions. Finally, meetings were held following the event to identify the key challenges for digital endpoints which emerged and reflections and recommendations for dissemination. RESULTS: Several challenges for digital endpoints were identified in the following areas: patient adherence and acceptability; algorithms and software for devices; design, analysis and conduct of clinical trials with digital endpoints; the environmental impact of digital endpoints; and the need for ongoing ethical support. Learnings taken for next generation events include the need to include additional stakeholder perspectives, such as those of funders and regulators, and the need for additional resources and facilitation to allow patient and public contributors to engage meaningfully during the event. CONCLUSIONS: The event emphasised the importance of consortium building and highlighted the critical role that collaborative, multi-disciplinary, and cross-sector efforts play in driving innovation in research design and strategic partnership building moving forward. This necessitates enhanced recognition by funders to support multi-stakeholder projects with patient involvement, standardised terminology, and the utilisation of open-source software.

RECREATE: a study protocol for a multicentre pilot cluster randomised controlled trial (cRCT) in UK stroke services evaluating an intervention to reduce sedentary behaviour in stroke survivors (Get Set Go) with embedded process and economic evaluations.

INTRODUCTION: Sedentary behaviour (sitting or lying during waking hours without being otherwise active) is strongly associated with adverse health outcomes, including all-cause, cancer and cardiovascular mortality in adults. Stroke survivors are consistently reported as being more sedentary than healthy age-matched controls, spending more hours sedentary daily and sustaining longer unbroken bouts of sedentary time. An evidence-based and clinically feasible intervention ('Get Set Go') was developed. A pragmatic definitive trial to evaluate Get Set Go was planned; however, due to the unprecedented effects of the COVID-19 pandemic on National Health Service (NHS) services this study was reduced in size and scope to become an external pilot trial. We report the protocol for this external pilot trial, which aims to undertake a preliminary exploration of whether Get Set Go is likely to improve ability to complete extended activities of daily living in the first year post-stroke and inform future trial designs in stroke rehabilitation. METHODS AND ANALYSIS: This study is a pragmatic, multicentre, two-arm, external pilot cluster randomised controlled trial with embedded process and economic evaluations. UK-based stroke services will be randomised 1:1 to the intervention (usual care plus Get Set Go) or control (usual care) arm. Fifteen stroke services will recruit 300-400 stroke inpatient and carer participants, with follow-up at 6, 12 and 24 months. The proposed primary endpoint is stroke survivor self-reported Nottingham Extended Activities of Daily Living scale at 12 months. Endpoint analyses will be exploratory and provide preliminary estimates of intervention effect. The process evaluation will provide valuable information on intervention fidelity, acceptability and how it can be optimised. ETHICS AND DISSEMINATION: The study has been approved by Yorkshire and The Humber - Bradford-Leeds Research Ethics Committee (Ref: 19/YH/0403). Results will be disseminated through journal publications and conference presentations. TRIAL REGISTRATION NUMBER: This trial was registered prospectively on 01 April 2020 (ISRCTN ref: ISRCTN82280581).

A cluster randomised controlled trial, process and economic evaluation of quality improvement collaboratives aligned to a national audit to improve the care for people with diabetes (EQUIPD): study protocol.

BACKGROUND: People with type 1 diabetes and raised glucose levels are at greater risk of retinopathy, nephropathy, neuropathy, cardiovascular disease, sexual health problems and foot disease. The UK National Institute for Health and Care Excellence (NICE) recommends continuous subcutaneous 'insulin pump' therapy for people with type 1 diabetes whose HbA1c is above 69 mmol/mol. Insulin pump use can improve quality of life, cut cardiovascular risk and increase treatment satisfaction. About 90,000 people in England and Wales meet NICE criteria for insulin pumps but do not use one. Insulin pump use also varies markedly by deprivation, ethnicity, sex and location. Increasing insulin pump use is a key improvement priority. Audit and feedback is a common but variably effective intervention. Limited capabilities of healthcare providers to mount effective responses to feedback from national audits, such as the National Diabetes Audit (NDA), undermines efforts to improve care. We have co-developed a theoretically and empirically informed quality improvement collaborative (QIC) to strengthen local responses to feedback with patients and carers, national audits and healthcare providers. We will evaluate whether the QIC improves the uptake of insulin pumps following NDA feedback. METHODS: We will undertake an efficient cluster randomised trial using routine data. The QIC will be delivered alongside the NDA to specialist diabetes teams in England and Wales. Our primary outcome will be the proportion of people with type 1 diabetes and an HbA1c above 69 mmol/mol who start and continue insulin pump use during the 18-month intervention period. Secondary outcomes will assess change in glucose control and duration of pump use. Subgroup analyses will explore impacts upon inequalities by ethnicity, sex, age and deprivation. A theory-informed process evaluation will explore diabetes specialist teams' engagement, implementation, fidelity and tailoring through observations, interviews, surveys and documentary analysis. An economic evaluation will micro-cost the QIC, estimate cost-effectiveness of NDA feedback with QIC and estimate the budget impact of NHS-wide QIC roll out. DISCUSSION: Our study responds to a need for more head-to-head trials of different ways of reinforcing feedback delivery. Our findings will have implications for other large-scale audit and feedback programmes. TRIAL REGISTRATION: ISRCTN82176651 Registered 18 October 2022.

A longitudinal assessment of trial protocols approved by research ethics committees: The Adherance to SPIrit REcommendations in the UK (ASPIRE-UK) study.

BACKGROUND: To assess the quality of reporting of RCT protocols approved by UK research ethics committees before and after the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline. METHODS: We had access to RCT study protocols that received ethical approval in the UK in 2012 (n=103) and 2016 (n=108). From those, we assessed the adherence to the 33 SPIRIT items (i.e. a total of 64 components of the 33 SPIRIT items). We descriptively analysed the adherence to SPIRIT guidelines as proportion of adequately reported items (median and interquartile range [IQR]) and stratified the results by year of approval and sponsor. RESULTS: The proportion of reported SPIRIT items increased from a median of 64.9% (IQR, 57.6-69.2%) in 2012 to a median of 72.5% (IQR, 65.3-78.3%) in 2016. Industry-sponsored RCTs reported more SPIRIT items in 2012 (median 67.4%; IQR, 64.1-69.4%) compared to non-industry-sponsored trials (median 59.8%; IQR, 46.5-67.7%). This gap between industry- and non-industry-sponsored trials increased in 2016 (industry-sponsored: median 75.6%; IQR, 71.2-79.0% vs non-industry-sponsored: median 65.3%; IQR, 51.6-76.3%). CONCLUSIONS: The adherence to SPIRIT guidelines has improved in the UK from 2012 to 2016 but remains on a modest level, especially for non-industry-sponsored RCTs.

Cancer patients' needs assessment in primary care: study protocol for a cluster randomised controlled trial (cRCT), economic evaluation and normalisation process theory evaluation of the needs assessment tool cancer (CANAssess).

INTRODUCTION: Unmet needs in patients with cancer and their carers are common but poorly identified and addressed. The Needs Assessment Tool-Cancer (NAT-C) is a structured consultation guide to identify and triage patient and carer unmet needs. The NAT-C is validated, but its effectiveness in reducing unmet patient and carer needs in primary care is unknown. METHODS AND ANALYSIS: Cluster randomised controlled trial with internal pilot and embedded process evaluation to test the clinical and cost effectiveness of the NAT-C in primary care for people with active cancer in reducing unmet patient and carer need, compared with usual care. We will recruit 1080 patients with active cancer (and carers if relevant) from 54 general practices in England.Participating practices will be randomised 1:1 to either deliver an NAT-guided clinical consultation plus usual care or to usual care alone. Consenting participants with active cancer and their carers (if nominated) will be asked to complete study questionnaires at baseline, 1 and 3 months for all, 6 months except for those recruited outside of the last 3 months of recruitment, and attend an NAT-C appointment if allocated to an intervention practice. An internal pilot will assess: site and participant recruitment, intervention uptake and follow-up rates. The primary outcome, the proportion of patients with an unmet need on the Supportive Care Needs Survey Short Form 34 at 3 months postregistration, will be analysed using a multilevel logistic regression. Mixed-methods process evaluation informed by Normalisation Process Theory will use quantitative survey and interview data from clinicians and key stakeholders in cancer care to develop an implementation strategy for nationwide rollout of the NAT-C if the intervention is cost-effective. ETHICS AND DISSEMINATION: Ethical approval from London-Surrey REC (20/LO/0312). Results will be peer-reviewed, published and made available to research participants. TRIAL REGISTRATION NUMBER: ISRCTN15497400.

A review found inadequate reporting of case-control studies of risk factors for pancreatic cancer.

OBJECTIVES: Case-control studies are often used to identify the risk factors for pancreatic cancer. The objective of this study was to evaluate the reporting of case-control studies of the risk factors for pancreatic cancer using the Strengthening The Reporting of OBservational Studies in Epidemiology (STROBE) for case-control studies checklist. STUDY DESIGN AND SETTING: We conducted a comprehensive literature search of the MEDLINE and EMBASE databases to identify reports of case-control studies published between 2016 and 2018. We scored article reporting using a reporting adherence form developed from the STROBE checklist for case-control studies, consisting of 14 STROBE items related to the title, abstract, methods, and results sections. RESULTS: We included reports of 47 case-control studies investigating a variety of risk factors, such as medical conditions and lifestyle factors. Reporting was inconsistent and inadequate. Efforts to address bias and how the study size was arrived at were particularly poorly described. Study cases were described in more detail than study controls. CONCLUSION: Reporting of case-control studies remains inadequate more than 10 years after the STROBE reporting guideline was published. Our findings suggest that authors do not understand the extent to which study methods and findings should be reported to enable studies to be fully understood, and their methods reproduced.

Cluster randomised controlled feasibility study of HENRY: a community-based intervention aimed at reducing obesity rates in preschool children.

BACKGROUND: Community-based obesity prevention interventions are often commissioned despite the limited evidence base. HENRY (Health, Exercise, Nutrition for the Really Young) is a programme delivered to parents of preschool children across the UK. Early evidence suggests that it may be effective, but a robust evaluation has not been conducted. We initiated a systematic evaluation of HENRY by studying the feasibility of conducting a multi-centre definitive trial to evaluate its effectiveness and cost-effectiveness to prevent obesity. Objectives were to assess the feasibility of recruiting local authorities, centres and parents; test processes and time required to train and certify intervention staff; explore HENRY commissioning processes; identify potential sources (and associated impact) of contamination; and consider the feasibility of trial procedures. METHODS: We conducted a multi-centre, open labelled, two group, prospective, cluster randomised, controlled, feasibility study, with embedded process evaluation and pre-defined criteria for progression to definitive trial. We sought to recruit 120 parents from 12 children's centres, across two UK local authority (government) areas. Within each local authority, we planned to randomise three centres to HENRY and three to 'standard care' control. Our plan was to collect data in family homes at baseline and 12 months, including parent and child height and weight, and parent-reported questionnaires on self-efficacy, feeding, eating habits, quality of life and resource use. Contamination, implementation and study acceptability were explored using parent interviews. RESULTS: We recruited two local authorities and 12 children's centres within eight months. One hundred and seventeen parents were recruited (average 3.9 parents per programme) and follow-up data were collected from 85% of participants. Process data from 20 parents and 24 members of staff indicate that both would benefit from more detail about their involvement as participants, but that methods were acceptable. Contamination was likely, though the impact of this on behaviour was unclear. CONCLUSION: Our findings indicate that a cluster RCT of HENRY to assess its effect on childhood obesity prevention is feasible. This study has allowed us to design a pragmatic definitive trial with minimal bias, taking account of lessons learnt from conducting evaluation research in public health settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03333733 registered 6th November 2017.

A cluster RCT and process evaluation of an implementation optimisation intervention to promote parental engagement enrolment and attendance in a childhood obesity prevention programme: results of the Optimising Family Engagement in HENRY (OFTEN) trial.

BACKGROUND: Poor and variable implementation of childhood obesity prevention programmes reduces their population impact and sustainability. We drew upon ethnographic work to develop a multi-level, theory-based implementation optimisation intervention. This intervention aimed to promote parental enrolment and attendance at HENRY (Health Exercise Nutrition for the Really Young), a UK community obesity prevention programme, by changing behaviours of children's centre and local authority stakeholders. METHODS: We evaluated the effectiveness of the implementation optimisation intervention on HENRY programme enrolment and attendance over a 12-month implementation period in a cluster randomised controlled trial. We randomised 20 local government authorities (with 126 children's centres) to HENRY plus the implementation optimisation intervention or to HENRY alone. Primary outcomes were (1) the proportion of centres enrolling at least eight parents per programme and (2) the proportion of centres with a minimum of 75% of parents attending at least five of eight sessions per programme. Trial analyses adjusted for stratification factors (pre-randomisation implementation of HENRY, local authority size, deprivation) and allowed for cluster design. A parallel mixed-methods process evaluation used qualitative interviews and routine monitoring to explain trial results. RESULTS: Neither primary outcome differed significantly between groups; 17.8% of intervention centres and 18.0% of control centres achieved the parent enrolment target (adjusted difference - 1.2%; 95% CI - 19.5%, 17.1%); 17.1% of intervention centres and 13.9% of control centres achieved the attendance target (adjusted difference 1.2%; 95% CI - 15.7%, 18.1%). Unexpectedly, the trial coincided with substantial national service restructuring, including centre closures and reduced funds. Some commissioning and management teams stopped or reduced delivery of both HENRY and the implementation optimisation intervention due to competing demands. Thus, at follow-up, HENRY programmes were delivered to approximately half the number of parents compared to baseline (n = 433 vs. 881). CONCLUSIONS: During a period in which services were reduced by external policies, this first definitive trial found no evidence of effectiveness for an implementation optimisation intervention promoting parent enrolment to and attendance at an obesity prevention programme. TRIAL REGISTRATION: ClinicalTrials.gov NCT02675699 . Registered on 4 February 2016.

Cognitive-behavioural therapy for a variety of conditions: an overview of systematic reviews and panoramic meta-analysis.

BACKGROUND: Cognitive-behavioural therapy aims to increase quality of life by changing cognitive and behavioural factors that maintain problematic symptoms. A previous overview of cognitive-behavioural therapy systematic reviews suggested that cognitive-behavioural therapy was effective for many conditions. However, few of the included reviews synthesised randomised controlled trials. OBJECTIVES: This project was undertaken to map the quality and gaps in the cognitive-behavioural therapy systematic review of randomised controlled trial evidence base. Panoramic meta-analyses were also conducted to identify any across-condition general effects of cognitive-behavioural therapy. DATA SOURCES: The overview was designed with cognitive-behavioural therapy patients, clinicians and researchers. The Cochrane Library, MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Child Development & Adolescent Studies, Database of Abstracts of Reviews of Effects and OpenGrey databases were searched from 1992 to January 2019. REVIEW METHODS: Study inclusion criteria were as follows: (1) fulfil the Centre for Reviews and Dissemination criteria; (2) intervention reported as cognitive-behavioural therapy or including one cognitive and one behavioural element; (3) include a synthesis of cognitive-behavioural therapy trials; (4) include either health-related quality of life, depression, anxiety or pain outcome; and (5) available in English. Review quality was assessed with A MeaSurement Tool to Assess systematic Reviews (AMSTAR)-2. Reviews were quality assessed and data were extracted in duplicate by two independent researchers, and then mapped according to condition, population, context and quality. The effects from high-quality reviews were pooled within condition groups, using a random-effect panoramic meta-analysis. If the across-condition heterogeneity was I2 < 75%, we pooled across conditions. Subgroup analyses were conducted for age, delivery format, comparator type and length of follow-up, and a sensitivity analysis was performed for quality. RESULTS: A total of 494 reviews were mapped, representing 68% (27/40) of the categories of the International Classification of Diseases, Eleventh Revision, Mortality and Morbidity Statistics. Most reviews (71%, 351/494) were of lower quality. Research on older adults, using cognitive-behavioural therapy preventatively, ethnic minorities and people living outside Europe, North America or Australasia was limited. Out of 494 reviews, 71 were included in the primary panoramic meta-analyses. A modest effect was found in favour of cognitive-behavioural therapy for health-related quality of life (standardised mean difference 0.23, 95% confidence interval 0.05 to 0.41, prediction interval -0.05 to 0.50, I2 = 32%), anxiety (standardised mean difference 0.30, 95% confidence interval 0.18 to 0.43, prediction interval -0.28 to 0.88, I2 = 62%) and pain (standardised mean difference 0.23, 95% confidence interval 0.05 to 0.41, prediction interval -0.28 to 0.74, I2 = 64%) outcomes. All condition, subgroup and sensitivity effect estimates remained consistent with the general effect. A statistically significant interaction effect was evident between the active and non-active comparator groups for the health-related quality-of-life outcome. A general effect for depression outcomes was not produced as a result of considerable heterogeneity across reviews and conditions. LIMITATIONS: Data extraction and analysis were conducted at the review level, rather than returning to the individual trial data. This meant that the risk of bias of the individual trials could not be accounted for, but only the quality of the systematic reviews that synthesised them. CONCLUSION: Owing to the consistency and homogeneity of the highest-quality evidence, it is proposed that cognitive-behavioural therapy can produce a modest general, across-condition benefit in health-related quality-of-life, anxiety and pain outcomes. FUTURE WORK: Future research should focus on how the modest effect sizes seen with cognitive-behavioural therapy can be increased, for example identifying alternative delivery formats to increase adherence and reduce dropout, and pursuing novel methods to assess intervention fidelity and quality. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017078690. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 9. See the NIHR Journals Library website for further project information.

This report is a summary of research examining if a psychological therapy called cognitive­behavioural therapy can improve the quality of life of people living with physical and/or mental conditions. Cognitive­behavioural therapy uses a set of techniques that help individuals to identify and change problematic thoughts or behaviour patterns that might contribute to and maintain their physical or mental symptoms. It can be delivered face to face or through mediums such as the internet. We aimed to understand if cognitive­behavioural therapy helps patients with specific conditions only, or if it can help patients with any condition. We searched relevant databases to find articles that combine the results from multiple trials testing cognitive­behavioural therapy. These are known as systematic reviews. We graded these reviews as providing good- or poor-quality evidence. We identified the conditions for which we had good-quality evidence on whether or not cognitive­behavioural therapy was helpful. From each review, we took numerical data that told us if cognitive­behavioural therapy improved quality of life for that specific condition. Next, we combined all the numerical data together, across all the conditions, to see if there was a consistent benefit of cognitive­behavioural therapy. The statistical analyses found that cognitive­behavioural therapy consistently improved quality of life across all the conditions where it has been tested. We have evidence that it can help children, adolescents and adults, of either sex, who are living in Europe, North America and Australasia. We are unsure if it will help older adults or people living in Africa, Asia or South America, nor do we know if cognitive­behavioural therapy is equally effective across different ethnic groups. It is recommended that future research should prioritise understanding how cognitive­behavioural therapy works, why some people do not want to use cognitive­behavioural therapy and why some patients do not benefit from it.

Family physician referral rates for lumbar spine computed tomography in Newfoundland and Labrador: a cross-sectional analysis using routinely collected data.

BACKGROUND: Reducing computed tomography (CT) examinations of the lumbar spine is one of Choosing Wisely Canada's initial top 10 recommendations. This study's objective was to report the age- and-sex standardized rates of lumbar spine CT ordered by family physicians in 1 health region in Newfoundland and Labrador. METHODS: We conducted a retrospective study using local health data from Meditech, an electronic health record system, from 2013 to 2016 for the Eastern Health Region of Newfoundland and Labrador, the largest health region in the province. Records were included if the referral was for an adult aged 20 years or more, and CT was ordered by a family physician. Lumbar spine CT rates were contextualized with age- and sex-stratified estimates. Population estimates were provided by the Newfoundland and Labrador Centre for Health Information to calculate age- and sex-standardized rates per 100 000 people. We calculated rate ratios to test for statistical significance in differences in rates between years. RESULTS: A total of 14 370 records were examined. The age- and sex-standardized rates of lumbar spine CT per 100 000 were 1225 in 2013, 1393 in 2014, 1556 in 2015 and 1395 in 2016. The rate ratio was 1.137 (95% confidence interval [CI] 1.084-1.194) for the comparison between 2014 and 2013, 1.117 (95% CI 1.067-1.169) between 2015 and 2014, and 0.896 (95% CI 0.857-0.938) between 2016 and 2015. INTERPRETATION: The age- and sex-standardized rates suggest that there was a steady rate of lumbar spine CT examinations being ordered by family physicians in Newfoundland and Labrador in 2013-2016. Although all rate ratios were statistically significant, the magnitude of the difference between years is likely not clinically relevant. These rates are important because they serve as a benchmark for future initiatives to reduce unnecessary referrals for lumbar spine CT.

Evaluation of the implementation of the Back Skills Training (BeST) programme using online training: a cohort implementation study.

OBJECTIVES: 1) Evaluate implementation of the Back Skills Training (BeST) programme, a group cognitive behavioural approach for patients with low back pain (LBP) developed for a clinical trial, into the National Health Service (NHS) in the United Kingdom; 2) Compare patient outcomes with the BeST Trial results. DESIGN: Two stage observational cohort implementation study. PARTICIPANTS: Stage 1: NHS Clinicians enrolled in BeST online training. Stage 2: Patients with LBP attending NHS physiotherapy departments and enrolled in the BeST programme. INTERVENTION: An online training and implementation programme. OUTCOMES: Stage 1: LBP attitudes and beliefs, self-rated competence, intention and actual implementation were collected before, immediately, 4- and 12-months post-training. Stage 2: Patients rated pain, function, recovery and satisfaction before and up to one year after attending the BeST programme. RESULTS: Stage 1: 1324 clinicians (157 NHS Trusts) enrolled in the training; 586 (44%) clinicians (101 NHS Trusts) completed training; 443/586 (76%) clinicians provided post-training data; 253/443 (57%) clinicians intended to implement the programme; 148/381 (39%) clinicians (54 NHS Trusts) provided follow-up data; 49/148 (33.1%) clinicians (27 NHS Trusts) implemented the programme. Attitudes and beliefs shifted towards a biopsychosocial model post-training. Stage 2: 923 patients were enrolled. Patients reported improvements in function (mean change: 1.55; 95%CI: 1.25, 1.86) and pain (-0.84; -1.1, -0.58) at follow-up. The majority rated themselves improved and satisfied with the programme. CONCLUSION: Online training had good reach into NHS Trusts although, not everyone went onto implement the programme. Improvements in function that were consistent with the original trial were demonstrated.