A novel experience-based internet intervention for smoking cessation : feasibility randomised controlled trial

The iPEx programme presents independent research funded by the UK National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme (RP-PG-0608-10147). The views expressed in this paper are those of the authors, representing iPEx, and not necessarily those of the NHS, the NIHR or the Department of Health.Peer reviewedPublisher PD

The quality of reports of randomised trials in 2000 and 2006: comparative study of articles indexed in PubMed

Objectives To examine the reporting characteristics and methodological details of randomised trials indexed in PubMed in 2000 and 2006 and assess whether the quality of reporting has improved after publication of the Consolidated Standards of Reporting Trials (CONSORT) Statement in 2001

Assessing health research grant applications: A retrospective comparative review of a one-stage versus a two-stage application assessment process

BackgroundResearch funders use a wide variety of application assessment processes yet there is little evidence on their relative advantages and disadvantages. A broad distinction can be made between processes with a single stage assessment of full proposals and those that first invite an outline, with full proposals invited at a second stage only for those which are shortlisted. This paper examines the effects of changing from a one-stage to a two-stage process within the UK's National Institute for Health Research's (NIHR) Research for Patient Benefit (RfPB) Programme which made this change in 2015.MethodsA retrospective comparative design was used to compare eight one-stage funding competitions (912 applications) with eight two-stage funding competitions (1090 applications). Comparisons were made between the number of applications submitted, number of peer and lay reviews required, the duration of the funding round, average external peer review scores, and the total costs involved.ResultsThere was a mean number of 114 applications per funding round for the one-stage process and 136 for the two-stage process. The one-stage process took a mean of 274 days and the two-stage process 348 days to complete, although those who were not funded (i.e. the majority) were informed at a mean of 195 days (mean 79 days earlier) under the two-stage process. The mean peer review score for full applications using the one-stage process was 6.46 and for the two-stage process 6.82 (5.6% difference using a 1-10 scale (with 10 being the highest), but there was no significant difference between the lay reviewer scores. The one-stage process required a mean of 423 peer reviews and 102 lay reviewers and the two-stage process required a mean of 208 peer reviews and 50 lay reviews (mean difference of 215 peer reviews and 52 lay reviews) per funding round. Overall cost per funding round changed from £148,908 for the one-stage process to £105,342 for the two-stage process saving approximately £43,566 per round.ConclusionWe conclude that a two-stage application process increases the number of applications submitted to a funding round, is less burdensome and more efficient for all those involved with the process, is cost effective and has a small increase in peer reviewer scores. For the addition of fewer than 11 weeks to the process substantial efficiencies are gained which benefit funders, applicants and science. Funding agencies should consider adopting a two-stage application assessment process

Mixed effects approach to the analysis of the stepped wedge cluster randomised trial—Investigating the confounding effect of time through simulation

<div><p>Background</p><p>A stepped wedge cluster randomised trial (SWCRT) is a multicentred study which allows an intervention to be rolled out at sites in a random order. Once the intervention is initiated at a site, all participants within that site remain exposed to the intervention for the remainder of the study.</p><p>The time since the start of the study (“calendar time”) may affect outcome measures through underlying time trends or periodicity. The time since the intervention was introduced to a site (“exposure time”) may also affect outcomes cumulatively for successful interventions, possibly in addition to a step change when the intervention began.</p><p>Methods</p><p>Motivated by a SWCRT of self-monitoring for bipolar disorder, we conducted a simulation study to compare model formulations to analyse data from a SWCRT under 36 different scenarios in which time was related to the outcome (improvement in mood score). The aim was to find a model specification that would produce reliable estimates of intervention effects under different scenarios. Nine different formulations of a linear mixed effects model were fitted to these datasets. These models varied in the specification of calendar and exposure times.</p><p>Results</p><p>Modelling the effects of the intervention was best accomplished by including terms for both calendar time and exposure time. Treating time as categorical (a separate parameter for each measurement time-step) achieved the best coverage probabilities and low bias, but at a cost of wider confidence intervals compared to simpler models for those scenarios which were sufficiently modelled by fewer parameters. Treating time as continuous and including a quadratic time term performed similarly well, with slightly larger variations in coverage probability, but narrower confidence intervals and in some cases lower bias. The impact of misspecifying the covariance structure was comparatively small.</p><p>Conclusions</p><p>We recommend that unless there is a priori information to indicate the form of the relationship between time and outcomes, data from SWCRTs should be analysed with a linear mixed effects model that includes separate categorical terms for calendar time and exposure time. Prespecified sensitivity analyses should consider the different formulations of these time effects in the model, to assess their impact on estimates of intervention effects.</p></div

Prescriber commitment posters to increase prudent antibiotic prescribing in English general practice: a cluster randomized controlled trial

Unnecessary antibiotic prescribing contributes to Antimicrobial Resistance posing a major public health risk. Estimates suggest as many as half of antibiotics prescribed for respiratory infections may be unnecessary. We conducted a three-armed unblinded cluster randomized controlled trial (ISRCTN trial registry 83322985). Interventions were a commitment poster (CP) advocating safe antibiotic prescribing or a CP plus an antimicrobial stewardship message (AM) on telephone appointment booking lines, tested against a usual care control group. The primary outcome measure was antibiotic item dispensing rates per 1000 population adjusted for practice demographics. The outcome measures for post-hoc analysis were dispensing rates of antibiotics usually prescribed for upper respiratory tract infections and broad spectrum antibiotics. In total, 196 practice units were randomized to usual care (n = 60), CP (n = 66), and CP&AM (n = 70). There was no effect on the overall dispensing rates for either interventions compared to usual care (CP 5.673, 95%CI −9.768 to 21.113, p = 0.458; CP&AM, −12.575, 95%CI −30.726 to 5.576, p = 0.167). Secondary analysis, which included pooling the data into one model, showed a significant effect of the AM (−18.444, 95%CI −32.596 to −4.292, p = 0.012). Fewer penicillins and macrolides were prescribed in the CP&AM intervention compared to usual care (−12.996, 95% CI −34.585 to −4.913, p = 0.018). Commitment posters did not reduce antibiotic prescribing. An automated patient antimicrobial stewardship message showed effects and requires further testing

Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: the MRC spine stabilisation trial

ObjectivesTo assess the clinical effectiveness of surgical stabilisation (spinal fusion) compared with intensive rehabilitation for patients with chronic low back pain.Design Multicentre randomised controlled trial.Setting15 secondary care orthopaedic and rehabilitation centres across the United Kingdom.Participants 349 participants aged 18-55 with chronic low back pain of at least one year's duration who were considered candidates for spinal fusion.InterventionLumbar spine fusion or an intensive rehabilitation programme based on principles of cognitive behaviour therapy.Main outcome measure The primary outcomes were the Oswestry disability index and the shuttle walking test measured at baseline and two years after randomisation. The SF-36 instrument was used as a secondary outcome measure.Results 176 participants were assigned to surgery and 173 to rehabilitation. 284 (81%) provided follow-up data at 24 months. The mean Oswestry disability index changed favourably from 46.5 (SD 14.6) to 34.0 (SD 21.1) in the surgery group and from 44.8 (SD14.8) to 36.1 (SD 20.6) in the rehabilitation group. The estimated mean difference between the groups was –4.1 (95% confidence interval –8.1 to –0.1, P = 0.045) in favour of surgery. No significant differences between the treatment groups were observed in the shuttle walking test or any of the other outcome measures.Conclusions Both groups reported reductions in disability during two years of follow-up, possibly unrelated to the interventions. The statistical difference between treatment groups in one of the two primary outcome measures was marginal and only just reached the predefined minimal clinical difference, and the potential risk and additional cost of surgery also need to be considered. No clear evidence emerged that primary spinal fusion surgery was any more beneficial than intensive rehabilitation

A targeted psychological treatment for sleep problems in young people at ultra-high risk of psychosis in England (SleepWell): a parallel group, single-blind, randomised controlled feasibility trial

Background Sleep disturbance is common and problematic for young people at ultra-high risk of psychosis. Sleep disruption is a contributory causal factor in the occurrence of mental health problems, including psychotic experiences, anxiety, and depression. The implication is that treating sleep problems might have additional benefits on mental health outcomes in individuals at high risk. The present study had two aims: first, to establish the feasibility and acceptability of a randomised controlled trial to treat sleep problems with the aim of reducing psychotic experiences in young people at ultra-high risk of psychosis; and second, to provide proof of concept of the clinical efficacy of the treatment. Methods We did a parallel group, single-blind, randomised controlled feasibility trial in two National Health Service trusts in England. Eligible participants were aged 14–25 years, a patient of mental health services, assessed as being at ultra-high risk of psychosis on the Comprehensive Assessment of At-Risk Mental States, and having current sleep problems (score of ≥15 on the self-report Insomnia Severity Index [ISI]). Participants were randomly assigned (1:1) to either a targeted psychological therapy for sleep problems (SleepWell) plus usual care or usual care alone via an automated online system, with non-deterministic minimisation that balanced participants for ISI score and referring service. The SleepWell therapy was delivered on an individual basis in approximately eight 1-h sessions over 12 weeks. Assessments were done at 0, 3, and 9 months, with trial assessors masked to treatment allocation. The key feasibility outcomes were the numbers of patients identified, recruited, and retained, treatment uptake, and data completion. Treatment acceptability was measured with the Abbreviated Acceptability Rating Profile (AARP). In preliminary clinical assessments, the primary clinical outcome was insomnia at 3 and 9 months assessed with the ISI, reported by randomised group (intention-to-treat analysis). Safety was assessed in all randomly assigned participants. The trial was prospectively registered on ISRCTN, 85601537, and is completed. Findings From Nov 18, 2020, to Jan 26, 2022, 67 young people were screened, of whom 40 (60%) at ultra-high risk of psychosis were recruited. Mean age was 16·9 years (SD 2·5; range 14–23), and most participants identified as female (n=19 [48%]) or male (n=19 [48%]) and as White (n=32 [80%]). 21 participants were randomly assigned to SleepWell therapy plus usual care and 19 to usual care alone. All participants provided data on at least one follow-up visit. 39 (98%) of 40 participants completed the primary outcome assessment at 3 and 9 months. 20 (95%) of 21 participants assigned to SleepWell therapy received the prespecified minimum treatment dose of at least four sessions. The median treatment acceptability score on the AARP was 48 (IQR 46 to 48; n=17; maximum possible score 48). At the post-intervention follow-up (3 months), compared with the usual care alone group, the SleepWell therapy group had a reduction in insomnia severity (ISI adjusted mean difference –8·12 [95% CI –11·60 to –4·63]; Cohen's d=–2·67 [95% CI –3·81 to –1·52]), which was sustained at 9 months (ISI adjusted mean difference –5·83 [–9·31 to –2·35]; Cohen's d=–1·91 [–3·06 to –0·77]). Among the 40 participants, eight adverse events were reported in six participants (two [11%] participants in the usual care group and four [19%] participants in the SleepWell therapy group). One serious adverse event involving hospital admission for a physical health problem was reported in the SleepWell therapy group, and one patient in the usual care alone group transitioned to psychosis. None of these events were classed as being related to trial treatment or procedures. Interpretation A randomised controlled trial of a targeted psychological sleep therapy for young people at ultra-high risk of psychosis is feasible. Patients can be retained in the trial and assessments done by masked assessors. Uptake of the sleep therapy was high, and we found preliminary evidence of sustained reductions in sleep problems. A definitive multicentre trial is now needed. Funding NIHR Research for Patient Benefit and NIHR Oxford Health Biomedical Research Centre

Primary care treatment of insomnia: study protocol for a pragmatic, multicentre, randomised controlled trial comparing nurse-delivered sleep restriction therapy to sleep hygiene (the HABIT trial).

Introduction Insomnia is a prevalent sleep disorder that negatively affects quality of life. Multicomponent cognitive-behavioural therapy (CBT) is the recommended treatment but access remains limited, particularly in primary care. Sleep restriction therapy (SRT) is one of the principal active components of CBT and could be delivered by generalist staff in primary care. The aim of this randomised controlled trial is to establish whether nurse-delivered SRT for insomnia disorder is clinically and cost-effective compared with sleep hygiene advice. Methods and analysis In the HABIT (Health-professional Administered Brief Insomnia Therapy) trial, 588 participants meeting criteria for insomnia disorder will be recruited from primary care in England and randomised (1:1) to either nurse-delivered SRT (plus sleep hygiene booklet) or sleep hygiene booklet on its own. SRT will be delivered over 4 weekly sessions; total therapy time is approximately 1 hour. Outcomes will be collected at baseline, 3, 6 and 12 months post-randomisation. The primary outcome is self-reported insomnia severity using the Insomnia Severity Index at 6 months. Secondary outcomes include health-related and sleep-related quality of life, depressive symptoms, use of prescribed sleep medication, diary and actigraphy-recorded sleep parameters, and work productivity. Analyses will be intention-to-treat. Moderation and mediation analyses will be conducted and a cost-utility analysis and process evaluation will be performed. Ethics and dissemination Ethical approval was granted by the Yorkshire and the Humber - Bradford Leeds Research Ethics Committee (reference: 18/YH/0153). We will publish our primary findings in high-impact, peer-reviewed journals. There will be further outputs in relation to process evaluation and secondary analyses focussed on moderation and mediation. Trial results could make the case for the introduction of nurse-delivered sleep therapy in primary care, increasing access to evidence-based treatment for people with insomnia disorder

Effectiveness and cost-effectiveness of a fully self-guided internet-based intervention for sub-clinical social anxiety symptoms : protocol for a randomised controlled trial

Design and objective: This paper describes the protocol for a large-scale pragmatic, randomised controlled trial and economic evaluation to investigate the effectiveness and cost-effectiveness of the self-directed E-Couch social anxiety module versus a waiting list control condition, for reducing sub-clinical social anxiety symptoms in the general population. Study population: Community-based adults (aged 18+) with social anxiety symptoms that do not meet the criteria for social anxiety disorder recruited via a direct-to-consumer advertisement on national websites. Intervention and control: Intervention is the self-guided E-Couch social anxiety module. Control group participants are placed on a waiting list to receive the intervention at the end of the trial. Both groups receive email and text message reminders. Outcome measures: The primary outcome will be change in self-reported social anxiety score using the Social Phobia Inventory (SPIN). Secondary outcomes will be the changes in the following self-report measures: Brief Fear of Negative Evaluation scale (BFNE-S); depression (CES-D); mental wellbeing (SWEMWEBS); health status (SF36); use of health services; safety events; and adherence, retention, and attrition rates. All measures will be administered at baseline, 6 weeks, and 3, 6 and 12 months. Analysis: A mixed effects model will be used to analyse the effect of the intervention on the primary and secondary outcomes (intention to treat analysis). Secondary analyses will explore moderators and mediators of effect. A prospective economic evaluation, conducted from a NHS and social care perspective, will provide estimates of cost utility and cost-effectiveness. An interview study will be conducted with 20 participants to explore issues including acceptability, adherence, retention and attrition

Effectiveness and cost-effectiveness of a self-guided internet intervention for social anxiety symptoms in a general population sample : randomized controlled trial

Background: Many people are accessing digital self-help for mental health problems, often with little evidence of effectiveness.Social anxiety is one of the most common sources of mental distress in the population and many people with symptoms do not seek help for what represents a significant public health problem. Objective: Two group randomized controlled trial conducted in England between 11th May 2016 and 27th June 2018. Adults with social anxiety symptoms who were not receiving treatment for social anxiety were recruited using online advertisements. All participants had unrestricted access to usual care and were randomized in a 1:1 ratio to either a web-based unguided self-help intervention based on cognitive-behavioural principles, or to a waiting list control group. All outcomes were collected through self-report online questionnaires. The primary outcome was the change in 17-item self-report Social Phobia Inventory (SPIN-17) score from baseline to 6 weeks using a linear mixed-effect model that used data from all timepoints (6 weeks, 3, 6, 12 months). Methods: Two group randomized controlled trial conducted in England between 11th May 2016 and 27th June 2018. Adults with social anxiety symptoms who were not receiving treatment for social anxiety were recruited using online advertisements. All participants had unrestricted access to usual care and were randomized in a 1:1 ratio to either a web-based unguided self-help intervention based on cognitive-behavioural principles, or to a waiting list control group. All outcomes were collected through self-report online questionnaires. The primary outcome was the change in 17-item self-report Social Phobia Inventory (SPIN-17) score from baseline to 6 weeks using a linear mixed-effect model that used data from all timepoints (6 weeks, 3, 6, 12 months). Results: 2212 participants were randomized. Six were excluded from analyses as ineligible. Of the 2116 eligible randomized participants (mean age 37 years, 80% women), 70.1% (1484/2116) had follow-up data available for analysis, and 56.9% (1205/2116) had data on the primary outcome, although attrition was higher in the intervention arm. At 6 weeks the mean (95% CI, P value) adjusted difference in change in SPIN-17 score in the intervention group compared to control, was -1.94 (-3.13 to -0.75, P=0.0014), a standardised mean difference effect size of 0.2. The improvement was maintained at 12 months. Given the high drop-out, sensitivity analyses explored missing data assumptions and were consistent with the primary analysis finding. The economic evaluation demonstrated cost-effectiveness with a small health status benefit and a reduction in health service utilisation. Conclusions: For people with social anxiety symptoms who are not receiving other forms of help, this study suggests that an online self-help tool based on cognitive behavioural principles can provide a small improvement in social anxiety symptoms compared with no intervention, although drop-out rates were high. Clinical Trial: ClinicalTrials.gov NCT02451878. https://clinicaltrials.gov/ct2/show/NCT0245187