Can we achieve better trial recruitment by presenting patient information through multimedia? Meta-analysis of 'studies within a trial' (SWATs).

BACKGROUND: People need high-quality information to make decisions about research participation. Providing information in written format alone is conventional but may not be the most effective and acceptable approach. We developed a structure for the presentation of information using multimedia which included generic and trial-specific content. Our aim was to embed 'Studies Within A Trial' (SWATs) across multiple ongoing trials to test whether multimedia presentation of patient information led to better rates of recruitment. METHODS: Five trials included a SWAT and randomised their participants to receive a multimedia presentation alongside standard information, or standard written information alone. We collected data on trial recruitment, acceptance and retention and analysed the pooled results using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised following an invitation to take part. RESULTS: Five SWATs provided data on the primary outcome of proportion of participants randomised. Multimedia alongside written information results in little or no difference in recruitment rates (pooled odds ratio = 0.96, 95% CI: 0.79 to 1.17, p-value = 0.671, I2 = 0%). There was no effect on any other outcomes. CONCLUSIONS: Multimedia alongside written information did not improve trial recruitment rates. TRIAL REGISTRATION: ISRCTN71952900, ISRCTN 06710391, ISRCTN 17160087, ISRCTN05926847, ISRCTN62869767.

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: A randomized controlled trial.

AIM: The aim was to determine whether specialist-led habit training using Habit Training with Biofeedback (HTBF) is more effective than specialist-led habit training alone (HT) for chronic constipation and whether outcomes of interventions are improved by stratification to HTBF or HT based on diagnosis (functional defaecation disorder vs. no functional defaecation disorder) by radio-physiological investigations (INVEST). METHOD: This was a parallel three-arm randomized single-blinded controlled trial, permitting two randomized comparisons: HTBF versus HT alone; INVEST- versus no-INVEST-guided intervention. The inclusion criteria were age 18-70 years; attending specialist hospitals in England; self-reported constipation for >6 months; refractory to basic treatment. The main exclusions were secondary constipation and previous experience of the trial interventions. The primary outcome was the mean change in Patient Assessment of Constipation Quality of Life score at 6 months on intention to treat. The secondary outcomes were validated disease-specific and psychological questionnaires and cost-effectiveness (based on EQ-5D-5L). RESULTS: In all, 182 patients were randomized 3:3:2 (target 384): HT n = 68; HTBF n = 68; INVEST-guided treatment n = 46. All interventions had similar reductions (improvement) in the primary outcome at 6 months (approximately -0.8 points of a 4-point scale) with no statistically significant difference between HT and HTBF (-0.03 points; 95% CI -0.33 to 0.27; P = 0.85) or INVEST versus no-INVEST (0.22; -0.11 to 0.55; P = 0.19). Secondary outcomes showed a benefit for all interventions with no evidence of greater cost-effectiveness of HTBF or INVEST compared with HT. CONCLUSION: The results of the study at 6 months were inconclusive. However, with the caveat of under-recruitment and further attrition at 6 months, a simple, cheaper approach to intervention may be as clinically effective and more cost-effective than more complex and invasive approaches.

Investigating the impact of London's ultra low emission zone on children's health: children's health in London and Luton (CHILL) protocol for a prospective parallel cohort study.

BACKGROUND: Air pollution harms health across the life course. Children are at particular risk of adverse effects during development, which may impact on health in later life. Interventions that improve air quality are urgently needed both to improve public health now, and prevent longer-term increased vulnerability to chronic disease. Low Emission Zones are a public health policy intervention aimed at reducing traffic-derived contributions to urban air pollution, but evidence that they deliver health benefits is lacking. We describe a natural experiment study (CHILL: Children's Health in London and Luton) to evaluate the impacts of the introduction of London's Ultra Low Emission Zone (ULEZ) on children's health. METHODS: CHILL is a prospective two-arm parallel longitudinal cohort study recruiting children at age 6-9 years from primary schools in Central London (the focus of the first phase of the ULEZ) and Luton (a comparator site), with the primary outcome being the impact of changes in annual air pollutant exposures (nitrogen oxides [NOx], nitrogen dioxide [NO2], particulate matter with a diameter of less than 2.5micrograms [PM2.5], and less than 10 micrograms [PM10]) across the two sites on lung function growth, measured as post-bronchodilator forced expiratory volume in one second (FEV1) over five years. Secondary outcomes include physical activity, cognitive development, mental health, quality of life, health inequalities, and a range of respiratory and health economic data. DISCUSSION: CHILL's prospective parallel cohort design will enable robust conclusions to be drawn on the effectiveness of the ULEZ at improving air quality and delivering improvements in children's respiratory health. With increasing proportions of the world's population now living in large urban areas exceeding World Health Organisation air pollution limit guidelines, our study findings will have important implications for the design and implementation of Low Emission and Clean Air Zones in the UK, and worldwide. CLINICALTRIALS: GOV: NCT04695093 (05/01/2021).

Heterogeneity in pragmatic randomised trials: sources and management.

BACKGROUND: Pragmatic trials aim to generate evidence to directly inform patient, caregiver and health-system manager policies and decisions. Heterogeneity in patient characteristics contributes to heterogeneity in their response to the intervention. However, there are many other sources of heterogeneity in outcomes. Based on the expertise and judgements of the authors, we identify different sources of clinical and methodological heterogeneity, which translate into heterogeneity in patient responses-some we consider as desirable and some as undesirable. For each of them, we discuss and, using real-world trial examples, illustrate how heterogeneity should be managed over the whole course of the trial. MAIN TEXT: Heterogeneity in centres and patients should be welcomed rather than limited. Interventions can be flexible or tailored and control interventions are expected to reflect usual care, avoiding use of a placebo. Co-interventions should be allowed; adherence should not be enforced. All these elements introduce heterogeneity in interventions (experimental or control), which has to be welcomed because it mimics reality. Outcomes should be objective and possibly routinely collected; standardised assessment, blinding and adjudication should be avoided as much as possible because this is not how assessment would be done outside a trial setting. The statistical analysis strategy must be guided by the objective to inform decision-making, thus favouring the intention-to-treat principle. Pragmatic trials should consider including process analyses to inform an understanding of the trial results. Needed data to conduct these analyses should be collected unobtrusively. Finally, ethical principles must be respected, even though this may seem to conflict with goals of pragmatism; consent procedures could be incorporated in the flow of care.

STOP- a training intervention to optimise treatment for smoking cessation in community pharmacies: cluster randomised controlled trial.

BACKGROUND: Community pharmacies serve people with high levels of tobacco-related illness, but throughput in NHS Stop Smoking Services in pharmacies remains relatively low. We investigated the effectiveness of a complex intervention to increase service uptake and retention. METHODS: We randomised 60 pharmacies in England and Wales to the STOP intervention or usual practice in a pragmatic, parallel-group, controlled trial over 11 months. Smokers were blind to the allocation. The intervention was theory-based consultation skills training for pharmacy staff with environmental prompts (badges, calendars and behavioural cues). The primary outcome was the number of smokers attending an initial consultation and setting a quit date. RESULTS: The intervention made no significant difference in setting a quit date, retention or quit rate. A total of 631 adult smokers (service users) enrolled and set a quit date in intervention pharmacies compared to 641 in usual practice pharmacies, a rate ratio of 0.75 (95% CI 0.46 to 1.23) adjusted for site and number of prescriptions. A total of 432 (68%) service users were retained at 4 weeks in intervention and 500 (78%) in usual practice pharmacies (odds ratio 0.80, 0.41 to 1.55). A total of 265 (42%) service users quit smoking at 4 weeks in intervention and 276 (43%) in usual practice pharmacies (0.96, 0.65 to 1.43). The pharmacy staff were positive about the intervention with 90% (56/62) stating that it had improved their skills. Sixty-eight per cent would strongly recommend the training to others although there was no difference in self-efficacy for service delivery between arms. Seventy of 131 (53%) service users did not complete the 6-month follow-up assessment. However, 55/61 (90%) service users who completed follow-up were satisfied or very satisfied with the service. All usual practice arm service users (n = 33) and all but one in the intervention arm (n = 27) would recommend the service to smokers. CONCLUSIONS: We found high levels of retention and acceptable quit rates in the NHS pharmacy stop smoking service. Despite pharmacy staff providing positive feedback on the STOP intervention, it made no difference to service throughput. Thus, other factors may currently limit service capacity to help smokers to quit. TRIAL REGISTRATION: ISRCTN, ISRCTN16351033 . Retrospectively registered.

Current recommendations/practices for anonymising data from clinical trials in order to make it available for sharing: A scoping review.

BACKGROUND/AIMS: There are increasing pressures for anonymised datasets from clinical trials to be shared across the scientific community, and differing recommendations exist on how to perform anonymisation prior to sharing. We aimed to systematically identify, describe and synthesise existing recommendations for anonymising clinical trial datasets to prepare for data sharing. METHODS: We systematically searched MEDLINE®, EMBASE and Web of Science from inception to 8 February 2021. We also searched other resources to ensure the comprehensiveness of our search. Any publication reporting recommendations on anonymisation to enable data sharing from clinical trials was included. Two reviewers independently screened titles, abstracts and full text for eligibility. One reviewer extracted data from included papers using thematic synthesis, which then was sense-checked by a second reviewer. Results were summarised by narrative analysis. RESULTS: Fifty-nine articles (from 43 studies) were eligible for inclusion. Three distinct themes are emerging: anonymisation, de-identification and pseudonymisation. The most commonly used anonymisation techniques are: removal of direct patient identifiers; and careful evaluation and modification of indirect identifiers to minimise the risk of identification. Anonymised datasets joined with controlled access was the preferred method for data sharing. CONCLUSIONS: There is no single standardised set of recommendations on how to anonymise clinical trial datasets for sharing. However, this systematic review shows a developing consensus on techniques used to achieve anonymisation. Researchers in clinical trials still consider that anonymisation techniques by themselves are insufficient to protect patient privacy, and they need to be paired with controlled access.

Can we achieve better recruitment by providing better information? Meta-analysis of 'studies within a trial' (SWATs) of optimised participant information sheets.

BACKGROUND: The information given to people considering taking part in a trial needs to be easy to understand if those people are to become, and then remain, trial participants. However, there is a tension between providing comprehensive information and providing information that is comprehensible. User-testing is one method of developing better participant information, and there is evidence that user-tested information is better at informing participants about key issues relating to trials. However, it is not clear if user-testing also leads to changes in the rates of recruitment in trials, compared to standard trial information. As part of a programme of research, we embedded 'studies within a trial' (SWATs) across multiple ongoing trials to see if user-tested materials led to better rates of recruitment. METHODS: Seven 'host' trials included a SWAT evaluation and randomised their participants to receive routine information sheets generated by the research teams, or information sheets optimised through user-testing. We collected data on trial recruitment and analysed the results across these trials using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised in a host trial following an invitation to take part. RESULTS: Six SWATs (n=27,805) provided data on recruitment. Optimised participant information sheets likely result in little or no difference in recruitment rates (7.2% versus 6.8%, pooled odds ratio = 1.03, 95% CI 0.90 to 1.19, p-value = 0.63, I2 = 0%). CONCLUSIONS: Participant information sheets developed through user testing did not improve recruitment rates. The programme of work showed that co-ordinated testing of recruitment strategies using SWATs is feasible and can provide both definitive and timely evidence on the effectiveness of recruitment strategies. TRIAL REGISTRATION: Healthlines Depression (ISRCTN14172341) Healthlines CVD (ISRCTN27508731) CASPER (ISRCTN02202951) ISDR (ISRCTN87561257) ECLS (NCT01925625) REFORM (ISRCTN68240461) HeLP Diabetes (ISRCTN02123133).

Independence estimators for re-randomisation trials in multi-episode settings: a simulation study.

BACKGROUND: Re-randomisation trials involve re-enrolling and re-randomising patients for each new treatment episode they experience. They are often used when interest lies in the average effect of an intervention across all the episodes for which it would be used in practice. Re-randomisation trials are often analysed using independence estimators, where a working independence correlation structure is used. However, research into independence estimators in the context of re-randomisation has been limited. METHODS: We performed a simulation study to evaluate the use of independence estimators in re-randomisation trials. We focussed on a continuous outcome, and the setting where treatment allocation does not affect occurrence of subsequent episodes. We evaluated different treatment effect mechanisms (e.g. by allowing the treatment effect to vary across episodes, or to become less effective on re-use, etc), and different non-enrolment mechanisms (e.g. where patients who experience a poor outcome are less likely to re-enrol for their second episode). We evaluated four different independence estimators, each corresponding to a different estimand (per-episode and per-patient approaches, and added-benefit and policy-benefit approaches). RESULTS: We found that independence estimators were unbiased for the per-episode added-benefit estimand in all scenarios we considered. We found independence estimators targeting other estimands (per-patient or policy-benefit) were unbiased, except when there was differential non-enrolment between treatment groups (i.e. when different types of patients from each treatment group decide to re-enrol for subsequent episodes). We found the use of robust standard errors provided close to nominal coverage in all settings where the estimator was unbiased. CONCLUSIONS: Careful choice of estimand can ensure re-randomisation trials are addressing clinically relevant questions. Independence estimators are a useful approach, and should be considered as the default estimator until the statistical properties of alternative estimators are thoroughly evaluated.

Improving the healthcare response to domestic violence and abuse in UK primary care: interrupted time series evaluation of a system-level training and support programme.

BACKGROUND: It is unknown whether interventions known to improve the healthcare response to domestic violence and abuse (DVA)-a global health concern-are effective outside of a trial. METHODS: An observational interrupted time series study in general practice. All registered women aged 16 and above were eligible for inclusion. In four implementation boroughs' general practices, there was face-to-face, practice-based, clinically relevant DVA training, a prompt in the electronic medical record, reminding clinicians to consider DVA, a simple referral pathway to a named advocate, ensuring direct access for women to specialist services, overseen by a national, health-focused DVA organisation, fostering best practice. The fifth comparator borough had only a session delivered by a local DVA specialist agency at community venues conveying information to clinicians. The primary outcome was the daily number of referrals received by DVA workers per 1000 women registered in a general practice, from 205 general practices, in all five northeast London boroughs. The secondary outcome was recorded new DVA cases in the electronic medical record in two boroughs. Data was analysed using an interrupted time series with a mixed effects Poisson regression model. RESULTS: In the 144 general practices in the four implementation boroughs, there was a significant increase in referrals received by DVA workers-global incidence rate ratio of 30.24 (95% CI 20.55 to 44.77, p < 0.001). There was no increase in the 61 general practices in the other comparator borough (incidence rate ratio of 0.95, 95% CI 0.13 to 6.84, p = 0.959). New DVA cases recorded significantly increased with an incident rate ratio of 1.27 (95% CI 1.09 to 1.48, p < 0.002) in the implementation borough but not in the comparator borough (incidence rate ratio of 1.05, 95% CI 0.82 to 1.34, p = 0.699). CONCLUSIONS: Implementing integrated referral routes, training and system-level support, guided by a national health-focused DVA organisation, outside of a trial setting, was effective and sustainable at scale, over four years (2012 to 2017) increasing referrals to DVA workers and new DVA cases recorded in electronic medical records.

Predictors of moving on from mental health supported accommodation in England: national cohort study.

BACKGROUND: Around 60 000 people in England live in mental health supported accommodation. There are three main types: residential care, supported housing and floating outreach. Supported housing and floating outreach aim to support service users in moving on to more independent accommodation within 2 years, but there has been little research investigating their effectiveness. AIMS: A 30-month prospective cohort study investigating outcomes for users of mental health supported accommodation. METHOD: We used random sampling, accounting for relevant geographical variation factors, to recruit 87 services (22 residential care, 35 supported housing and 30 floating outreach) and 619 service users (residential care 159, supported housing 251, floating outreach 209) across England. We contacted services every 3 months to investigate the proportion of service users who successfully moved on to more independent accommodation. Multilevel modelling was used to estimate how much of the outcome and cost variations were due to service type and quality, after accounting for service-user characteristics. RESULTS: Overall 243/586 participants successfully moved on (residential care 15/146, supported housing 96/244, floating outreach 132/196). This was most likely for floating outreach service users (versus residential care: odds ratio 7.96, 95% CI 2.92-21.69, P < 0.001; versus supported housing: odds ratio 2.74, 95% CI 1.01-7.41, P < 0.001) and was associated with reduced costs of care and two aspects of service quality: promotion of human rights and recovery-based practice. CONCLUSIONS: Most people do not move on from supported accommodation within the expected time frame. Greater focus on human rights and recovery-based practice may increase service effectiveness.

Cluster over individual randomization: are study design choices appropriately justified? Review of a random sample of trials.

BACKGROUND: Novel rationales for randomizing clusters rather than individuals appear to be emerging from the push for more pragmatic trials, for example, to facilitate trial recruitment, reduce the costs of research, and improve external validity. Such rationales may be driven by a mistaken perception that choosing cluster randomization lessens the need for informed consent. We reviewed a random sample of published cluster randomized trials involving only individual-level health care interventions to determine (a) the prevalence of reporting a rationale for the choice of cluster randomization; (b) the types of explicit, or if absent, apparent rationales for the use of cluster randomization; (c) the prevalence of reporting patient informed consent for study interventions; and (d) the types of justifications provided for waivers of consent. We considered cluster randomized trials for evaluating exclusively the individual-level health care interventions to focus on clinical trials where individual randomization is only theoretically possible and where there is a general expectation of informed consent. METHODS: A random sample of 40 cluster randomized trials were identified by implementing a validated electronic search filter in two electronic databases (Ovid MEDLINE and Embase), with two reviewers independently extracting information from each trial. Inclusion criteria were the following: primary report of a cluster randomized trial, evaluating exclusively an individual-level health care intervention, published between 2007 and 2016, and conducted in Canada, the United States, European Union, Australia, or low- and middle-income country settings. RESULTS: Twenty-five trials (62.5%, 95% confidence interval = 47.5%-77.5%) reported an explicit rationale for the use of cluster randomization. The most commonly reported rationales were those with logistical or administrative convenience (15 trials, 60%) and those that need to avoid contamination (13 trials, 52%); five trials (20%) were cited rationales related to the push for more pragmatic trials. Twenty-one trials (52.5%, 95% confidence interval = 37%-68%) reported written informed consent for the intervention, two (5%) reported verbal consent, and eight (20%) reported waivers of consent, while in nine trials (22.5%) consent was unclear or not mentioned. Reported justifications for waivers of consent included that study interventions were already used in clinical practice, patients were not randomized individually, and the need to facilitate the pragmatic nature of the trial. Only one trial reported an explicit and appropriate justification for waiver of consent based on minimum criteria in international research ethics guidelines, namely, infeasibility and minimal risk. CONCLUSION: Rationales for adopting cluster over individual randomization and for adopting consent waivers are emerging, related to the need to facilitate pragmatic trials. Greater attention to clear reporting of study design rationales, informed consent procedures, as well as justification for waivers is needed to ensure that such trials meet appropriate ethical standards.

Disruption of a primary health care domestic violence and abuse service in two London boroughs: interrupted time series evaluation.

BACKGROUND: Domestic violence and abuse (DVA) is experienced by about 1/3 of women globally and remains a major health concern worldwide. IRIS (Identification and Referral to Improve Safety of women affected by DVA) is a complex, system-level, training and support programme, designed to improve the primary healthcare response to DVA. Following a successful trial in England, since 2011 IRIS has been implemented in eleven London boroughs. In two boroughs the service was disrupted temporarily. This study evaluates the impact of that service disruption. METHODS: We used anonymised data on daily referrals received by DVA service providers from general practices in two IRIS implementation boroughs that had service disruption for a period of time (six and three months). In line with previous work we refer to these as boroughs B and C. The primary outcome was the number of daily referrals received by the DVA service provider across each borough over 48 months (March 2013-April 2017) in borough B and 42 months (October 2013-April 2017) in borough C. The data were analysed using interrupted-time series, non-linear regression with sensitivity analyses exploring different regression models. Incidence Rate Ratio (IRR), 95% confidence intervals and p-values associated with the disruption were reported for each borough. RESULTS: A mixed-effects negative binomial regression was the best fit model to the data. In borough B, the disruption, lasted for about six months, reducing the referral rate significantly (p = 0.006) by about 70% (95%CI = (23,87%)). In borough C, the three-month service disruption, also significantly (p = 0.005), reduced the referral rate by about 49% (95% CI = (18,68%)). CONCLUSIONS: Disrupting the IRIS service substantially reduced the rate of referrals to DVA service providers. Our findings are evidence in favour of continuous funding and staffing of IRIS as a system level programme.

Group antenatal care (Pregnancy Circles) for diverse and disadvantaged women: study protocol for a randomised controlled trial with integral process and economic evaluations.

BACKGROUND: Group antenatal care has been successfully implemented around the world with suggestions of improved outcomes, including for disadvantaged groups, but it has not been formally tested in the UK in the context of the NHS. To address this the REACH Pregnancy Circles intervention was developed and a randomised controlled trial (RCT), based on a pilot study, is in progress. METHODS: The RCT is a pragmatic, two-arm, individually randomised, parallel group RCT designed to test clinical and cost-effectiveness of REACH Pregnancy Circles compared with standard care. Recruitment will be through NHS services. The sample size is 1732 (866 randomised to the intervention and 866 to standard care). The primary outcome measure is a 'healthy baby' composite measured at 1 month postnatal using routine maternity data. Secondary outcome measures will be assessed using participant questionnaires completed at recruitment (baseline), 35 weeks gestation (follow-up 1) and 3 months postnatal (follow-up 2). An integrated process evaluation, to include exploration of fidelity, will be conducted using mixed methods. Analyses will be on an intention to treat as allocated basis. The primary analysis will compare the number of babies born "healthy" in the control and intervention arms and provide an odds ratio. A cost-effectiveness analysis will compare the incremental cost per Quality Adjusted Life Years and per additional 'healthy and positive birth' of the intervention with standard care. Qualitative data will be analysed thematically. DISCUSSION: This multi-site randomised trial in England is planned to be the largest trial of group antenatal care in the world to date; as well as the first rigorous test within the NHS of this maternity service change. It has a recruitment focus on ethnically, culturally and linguistically diverse and disadvantaged participants, including non-English speakers. TRIAL REGISTRATION: Trial registration; ISRCTN, ISRCTN91977441 . Registered 11 February 2019 - retrospectively registered. The current protocol is Version 4; 28/01/2020.

The current use of feasibility studies in the assessment of feasibility for stepped-wedge cluster randomised trials: a systematic review.

BACKGROUND: Stepped-wedge cluster randomised trials (SW-CRTs) are a pragmatic trial design, providing an unprecedented opportunity to increase the robustness of evidence underpinning implementation and quality improvement interventions. Given the complexity of the SW-CRT, the likelihood of trials not delivering on their objectives will be mitigated if a feasibility study precedes the definitive trial. It is not currently known if feasibility studies are being conducted for SW-CRTs nor what the objectives of these studies are. METHODS: Searches were conducted of several databases to identify published feasibility studies which were designed to inform a future SW-CRT. For each eligible study, data were extracted on the characteristics of and rationale for the feasibility study; the process for determining progression to the main trial; how the feasibility study informed the main trial; and whether the main trial went ahead. A narrative synthesis and descriptive analysis are presented. RESULTS: Eleven feasibility studies were identified, which included eight completed study reports and three protocols. Three studies used a stepped-wedge design and these were the only studies to be randomised. Studies were predominantly of a mixed-methods design. Only one study assessed specific features related to the feasibility of using a SW-CRT and one investigated the time taken to complete the study procedures. The other studies were mostly assessing the feasibility and acceptability of the intervention. CONCLUSION: Published feasibility studies for SW-CRTs are scarce and those that are being reported do not investigate issues specific to the complexities of the trial design. When conducting feasibility studies in advance of a definitive SW-CRT, researchers should consider assessing the feasibility of study procedures, particularly those specific to the SW-CRT design, and ensure that the findings are published for the benefit of other researchers.

Randomised controlled trial and economic evaluation of a task-based weight management group programme.

BACKGROUND: Obesity is a rising global threat to health and a major contributor to health inequalities. Weight management programmes that are effective, economical and reach underprivileged groups are needed. We examined whether a multi-modal group intervention structured to cater for clients from disadvantaged communities (Weight Action Programme; WAP) has better one-year outcomes than a primary care standard weight management intervention delivered by practice nurses (PNI). METHODS: In this randomised controlled trial, 330 obese adults were recruited from general practices in London and allocated (2:1) to WAP (N = 221) delivered over eight weekly group sessions or PNI (N = 109) who received four sessions over eight weeks. Both interventions covered diet, physical activity and self-monitoring. The primary outcome was the change in weight from baseline at 12 months. To indicate value to the NHS, a cost effectiveness analysis estimated group differences in cost and Quality-Adjusted Life-Years (QALYs) related to WAP. RESULTS: Participants were recruited from September 2012 to January 2014 with follow-up completed in February 2015. Most participants were not in paid employment and 60% were from ethnic minorities. 88% of participants in each study arm provided at least one recorded outcome and were included in the primary analysis. Compared with the PNI, WAP was associated with greater weight loss overall (- 4·2 kg vs. - 2·3 kg; difference = - 1·9 kg, 95% CI: -3·7 to - 0·1; P = 0·04) and was more likely to generate a weight loss of at least 5% at 12 months (41% vs. 27%, OR = 14·61 95% CI: 2·32 to 91·96, P = 0·004). With an incremental cost-effectiveness ratio (ICER) of £7742/QALY, WAP would be considered highly cost effective compared to PNI. CONCLUSIONS: The task-based programme evaluated in this study can provide a template for an effective and economical approach to weight management that can reach clients from disadvantaged communities. TRIAL REGISTRATION: ISRCTN ISRCTN45820471 . Registered 12/10/2012 (retrospectively registered).

An Olympic Legacy? Did the Urban Regeneration Associated With the London 2012 Olympic Games Influence Adolescent Mental Health?

Public expenditure on large events such as the London 2012 Olympic Games is often justified by the potential legacy of urban regeneration and its associated health and well-being benefits for local communities. In the Olympic Regeneration in East London Study, we examined whether there was an association between urban regeneration related to the 2012 Games and improved mental health in young people. Adolescents aged 11-12 years attending schools in the Olympic host borough of Newham in London or in 3 adjacent comparison London boroughs completed a survey before the 2012 Games and 6 and 18 months after the Games (in 2013 and 2014, respectively). Changes in depressive symptoms and well-being between baseline and each follow-up were examined. A total of 2,254 adolescents from 25 randomly selected schools participated. Adolescents from Newham were more likely to have remained depressed between baseline and the 6- and 18-month follow-up surveys (for 6-month follow-up, relative risk = 1.78, 95% confidence interval: 1.12, 2.83; for 18-month follow-up, relative risk = 1.93, 95% confidence interval: 1.01, 3.70) than adolescents from the comparison boroughs. No differences in well-being were observed. There was little evidence that urban regeneration had any positive influence on adolescent mental health and some suggestion that regeneration may have been associated with maintenance of depressive symptoms. Such programs may have limited short-term impact on the mental health of adolescents.

Improving the healthcare response to domestic violence and abuse in primary care: protocol for a mixed method evaluation of the implementation of a complex intervention.

BACKGROUND: Domestic violence and abuse remains a major health concern. It is unknown whether the improved healthcare response to domestic violence and abuse demonstrated in a cluster randomised controlled trial of IRIS (Identification and Referral to Improve Safety), a complex intervention, including general practice based training, support and referral programme, can be achieved outside a trial setting. AIM: To evaluate the impact over four years of a system wide implementation of IRIS, sequentially into multiple areas, outside the setting of a trial. METHODS: An interrupted time series analysis of referrals received by domestic violence and abuse workers from 201 general practices, in five northeast London boroughs; alongside a mixed methods process evaluation and qualitative analysis. Segmented regression interrupted time series analysis to estimate impact of the IRIS intervention over a 53-month period. A secondary analysis compares the segmented regression analysis in each of the four implementation boroughs, with a fifth comparator borough. DISCUSSION: This is the first interrupted time series analysis of an intervention to improve the health care response to domestic violence. The findings will characterise the impact of IRIS implementation outside a trial setting and its suitability for national implementation in the United Kingdom.

Inclusion and exclusion criteria used in non-specific low back pain trials: a review of randomised controlled trials published between 2006 and 2012.

BACKGROUND: Low back pain is a common health complaint resulting in substantial economic burden. Each year, upwards of 20 randomised controlled trials (RCTs) evaluating interventions for non-specific low back pain are published. Use of the term non-specific low back pain has been criticised on the grounds of encouraging heterogeneity and hampering interpretation of findings due to possible heterogeneous causes, challenging meta-analyses. We explored selection criteria used in trials of treatments for nsLBP. METHODS: A systematic review of English-language reports of RCTs in nsLBP population samples, published between 2006 and 2012, identified from MEDLINE, EMBASE, and the Cochrane Library databases, using a mixed-methods approach to analysis. Study inclusion and exclusion criteria were extracted, thematically categorised, and then descriptive statistics were used to summarise the prevalence by emerging category. RESULTS: We included 168 studies. Two inclusion themes (anatomical area, and symptoms and signs) were identified. Anatomical area was most reported as between costal margins and gluteal folds (n = 8, 5%), while low back pain (n = 150, 89%) with or without referred leg pain (n = 27, 16%) was the most reported symptom. Exclusion criteria comprised 21 themes. Previous or scheduled surgery (n = 84, 50%), pregnancy (n = 81, 48%), malignancy (n = 78, 46%), trauma (n = 63, 37%) and psychological conditions (n = 58, 34%) were the most common. Sub-themes of exclusion criteria mostly related to neurological signs and symptoms: nerve root compromise (n = 44, 26%), neurological signs (n = 34, 20%) or disc herniation (n = 30, 18%). Specific conditions that were most often exclusion criteria were spondylolisthesis (n = 35, 21%), spinal stenosis (n = 31, 18%) or osteoporosis (n = 27, 16%). CONCLUSION: RCTs of interventions for non-specific low back pain have incorporated diverse inclusion and exclusion criteria. Guidance on standardisation of inclusion and exclusion criteria for nsLBP trials will increase clinical homogeneity, facilitating greater interpretation of between-trial comparisons and meta-analyses. We propose a template for reporting inclusion and exclusion criteria.

Novel Three-Day, Community-Based, Nonpharmacological Group Intervention for Chronic Musculoskeletal Pain (COPERS): A Randomised Clinical Trial.

BACKGROUND: Chronic musculoskeletal pain is the leading cause of disability worldwide. The effectiveness of pharmacological treatments for chronic pain is often limited, and there is growing concern about the adverse effects of these treatments, including opioid dependence. Nonpharmacological approaches to chronic pain may be an attractive alternative or adjunctive treatment. We describe the effectiveness of a novel, theoretically based group pain management support intervention for chronic musculoskeletal pain. METHODS AND FINDINGS: We conducted a multi-centre, pragmatic, randomised, controlled effectiveness and cost-effectiveness (cost-utility) trial across 27 general practices and community musculoskeletal services in the UK. We recruited 703 adults with musculoskeletal pain of at least 3 mo duration between August 1, 2011, and July 31, 2012, and randomised participants 1.33:1 to intervention (403) or control (300). Intervention participants were offered a participative group intervention (COPERS) delivered over three alternate days with a follow-up session at 2 wk. The intervention introduced cognitive behavioural approaches and was designed to promote self-efficacy to manage chronic pain. Controls received usual care and a relaxation CD. The primary outcome was pain-related disability at 12 mo (Chronic Pain Grade [CPG] disability subscale); secondary outcomes included the CPG disability subscale at 6 mo and the following measured at 6 and 12 mo: anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), pain acceptance (Chronic Pain Acceptance Questionnaire), social integration (Health Education Impact Questionnaire social integration and support subscale), pain-related self-efficacy (Pain Self-Efficacy Questionnaire), pain intensity (CPG pain intensity subscale), the census global health question (2011 census for England and Wales), health utility (EQ-5D-3L), and health care resource use. Analyses followed the intention-to-treat principle, accounted for clustering by course in the intervention arm, and used multiple imputation for missing or incomplete primary outcome data. The mean age of participants was 59.9 y, with 81% white, 67% female, 23% employed, 85% with pain for at least 3 y, and 23% on strong opioids. Symptoms of depression and anxiety were common (baseline mean HADS scores 7.4 [standard deviation 4.1] and 9.2 [4.6], respectively). Overall, 282 (70%) intervention participants met the predefined intervention adherence criterion. Primary outcome data were obtained from 88% of participants. There was no significant difference between groups in pain-related disability at 6 or 12 mo (12 mo: difference -1.0, intervention versus control, 95% CI -4.9 to 3.0), pain intensity, or the census global health question. Anxiety, depression, pain-related self-efficacy, pain acceptance, and social integration were better in the intervention group at 6 mo; at 12 mo, these differences remained statistically significant only for depression (-0.7, 95% CI -1.2 to -0.2) and social integration (0.8, 95% CI 0.4 to 1.2). Intervention participants received more analgesics than the controls across the 12 mo. The total cost of the course per person was £145 (US$214). The cost-utility analysis showed there to be a small benefit in terms of quality-adjusted life years (QALYs) (0.0325, 95% CI -0.0074 to 0.0724), and on the cost side the intervention was a little more expensive than usual care (i.e., £188 [US$277], 95% CI -£125 [-US$184] to £501 [US$738]), resulting in an incremental cost-effectiveness ratio of £5,786 (US$8,521) per QALY. Limitations include the fact that the intervention was relatively brief and did not include any physical activity components. CONCLUSIONS: While the COPERS intervention was brief, safe, and inexpensive, with a low attrition rate, it was not effective for reducing pain-related disability over 12 mo (primary outcome). For secondary outcomes, we found sustained benefits on depression and social integration at 6 and 12 mo, but there was no effect on anxiety, pain-related self-efficacy, pain acceptance, pain intensity, or the census global health question at 12 mo. There was some evidence that the intervention may be cost-effective based on a modest difference in QALYs between groups. TRIAL REGISTRATION: ISRCTN Registry 24426731.

Percutaneous tibial nerve stimulation versus sham electrical stimulation for the treatment of faecal incontinence in adults (CONFIDeNT): a double-blind, multicentre, pragmatic, parallel-group, randomised controlled trial.

BACKGROUND: Percutaneous tibial nerve stimulation (PTNS) is a new ambulatory therapy for faecal incontinence. Data from case series suggest it has beneficial outcomes in 50-80% patients; however its effectiveness against sham electrical stimulation has not been investigated. We therefore aimed to assess the short-term efficacy of PTNS against sham electrical stimulation in adults with faecal incontinence. METHODS: We did a double-blind, multicentre, pragmatic, parallel-group, randomised controlled trial (CONtrol of Faecal Incontinence using Distal NeuromodulaTion [CONFIDeNT]) in 17 specialist hospital units in the UK that had the skills to manage patients with faecal incontinence. Eligible participants aged 18 years or older with substantial faecal incontinence for whom conservative treatments (such as dietary changes and pelvic floor exercises) had not worked, were randomly assigned (1:1) to receive either PTNS (via the Urgent PC neuromodulation system) or sham stimulation (via a transcutaneous electrical nerve stimulation machine to the lateral forefoot) once per week for 12 weeks. Randomisation was done with permuted block sizes of two, four, and six, and was stratified by sex and then by centre for women. Patients and outcome assessors were both masked to treatment allocation for the 14-week duration of the trial (but investigators giving the treatment were not masked). The primary outcome was a clinical response to treatment, which we defined as a 50% or greater reduction in episodes of faecal incontinence per week. We assessed this outcome after 12 treatment sessions, using data from patients' bowel diaries. Analysis was by intention to treat, and missing data were multiply imputed. This trial is registered with the ISRCTN registry, number 88559475, and is closed to new participants. FINDINGS: Between Jan 23, 2012, and Oct 31, 2013, we randomly assigned 227 eligible patients (of 373 screened) to receive either PTNS (n=115) or sham stimulation (n=112). 12 patients withdrew from the trial: seven from the PTNS group and five from the sham group (mainly because they could not commit to receiving treatment every week). Two patients (one in each group) withdrew because of an adverse event that was unrelated to treatment (exacerbation of fibromyalgia and rectal bleeding). 39 (38%) of 103 patients with full data from bowel diaries in the PTNS group had a 50% or greater reduction in the number of episodes of faecal incontinence per week compared with 32 (31%) of 102 patients in the sham group (adjusted odds ratio 1·28, 95% CI 0·72-2·28; p=0·396). No serious adverse events related to treatment were reported in the trial. Seven mild, related adverse events were reported in each treatment group, mainly pain at the needle site (four in PTNS, three in sham). INTERPRETATION: PTNS given for 12 weeks did not confer significant clinical benefit over sham electrical stimulation in the treatment of adults with faecal incontinence. Further studies are warranted to determine its efficacy in the long term, and in patient subgroups (ie, those with urgency). FUNDING: National Institute for Health Research.