Catherine Arundel

Screening in the community to reduce fractures in older women (SCOOP): a randomised controlled trial

BACKGROUND Despite effective assessment methods and medications targeting osteoporosis and related fractures, screening for fracture risk is not currently advocated in the UK. We tested whether a community-based screening intervention could reduce fractures in older women. METHODS We did a two-arm randomised controlled trial in women aged 70-85 years to compare a screening programme using the Fracture Risk Assessment Tool (FRAX) with usual management. Women were recruited from 100 general practitioner (GP) practices in seven regions of the UK: Birmingham, Bristol, Manchester, Norwich, Sheffield, Southampton, and York. We excluded women who were currently on prescription anti-osteoporotic drugs and any individuals deemed to be unsuitable to enter a research study (eg, known dementia, terminally ill, or recently bereaved). The primary outcome was the proportion of individuals who had one or more osteoporosis-related fractures over a 5-year period. In the screening group, treatment was recommended in women identified to be at high risk of hip fracture, according to the FRAX 10-year hip fracture probability. Prespecified secondary outcomes were the proportions of participants who had at least one hip fracture, any clinical fracture, or mortality; and the effect of screening on anxiety and health-related quality of life. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN 55814835. FINDINGS 12 483 eligible women were identified and participated in the trial, and 6233 women randomly assigned to the screening group between April 15, 2008, and July 2, 2009. Treatment was recommended in 898 (14%) of 6233 women. Use of osteoporosis medication was higher at the end of year 1 in the screening group compared with controls (15% vs 4%), with uptake particularly high (78% at 6 months) in the screening high-risk subgroup. Screening did not reduce the primary outcome of incidence of all osteoporosis-related fractures (hazard ratio [HR] 0·94, 95% CI 0·85-1·03, p=0·178), nor the overall incidence of all clinical fractures (0·94, 0·86-1·03, p=0·183), but screening reduced the incidence of hip fractures (0·72, 0·59-0·89, p=0·002). There was no evidence of differences in mortality, anxiety levels, or quality of life. INTERPRETATION Systematic, community-based screening programme of fracture risk in older women in the UK is feasible, and could be effective in reducing hip fractures. FUNDING Arthritis Research UK and Medical Research Council.

Systematic review: height-adjustable workstations to reduce sedentary behaviour in office-based workers

BACKGROUND Time spent sitting in the workplace is an important contributor to overall sedentary risk. Installation of height-adjustable workstations has been proposed as a feasible approach for reducing occupational sitting time in office workers. AIMS To provide an accurate overview of the controlled trials that have evaluated the effects of height-adjustable workstation interventions on workplace sitting time in office-based workers. METHODS A comprehensive search was conducted up until March 2014 in the following databases: Medline, PsychINFO, CENTRAL, EMBASE and PEDro. To identify unpublished studies and grey literature, the reference lists of relevant official or scientific web pages were also checked. Studies assessing the effectiveness of height-adjustable workstations using a randomized or non-randomized controlled design were included. RESULTS The initial search yielded a total of 8497 citations. After a thorough selection process, five studies were included with 172 participants. A formal quality assessment indicated that risk of bias was high in all studies and heterogeneity in interventions and outcomes prevented meta-analysis. Nevertheless, all studies reported that height-adjustable workstation interventions reduced occupational sitting time in office workers. There was insufficient evidence to determine effects on other relevant health outcomes (e.g. body composition, musculoskeletal symptoms, mental health). CONCLUSIONS There is insufficient evidence to make firm conclusions regarding the effects of installing height-adjustable workstations on sedentary behaviour and associated health outcomes in office workers. Larger and longer term controlled studies are needed, which include more representative populations.

Obsessive Compulsive Treatment Efficacy Trial (OCTET) comparing the clinical and cost effectiveness of self-managed therapies: study protocol for a randomised controlled trial.

BackgroundUK National Institute of Health and Clinical Excellence guidelines for obsessive compulsive disorder (OCD) specify recommendations for the treatment and management of OCD using a stepped care approach. Steps three to six of this model recommend treatment options for people with OCD that range from low-intensity guided self-help (GSH) to more intensive psychological and pharmacological interventions. Cognitive behavioural therapy (CBT), including exposure and response prevention, is the recommended psychological treatment. However, whilst there is some preliminary evidence that self-managed therapy packages for OCD can be effective, a more robust evidence base of their clinical and cost effectiveness and acceptability is required.Methods/DesignOur proposed study will test two different self-help treatments for OCD: 1) computerised CBT (cCBT) using OCFighter, an internet-delivered OCD treatment package; and 2) GSH using a book. Both treatments will be accompanied by email or telephone support from a mental health professional. We will evaluate the effectiveness, cost and patient and health professional acceptability of the treatments.DiscussionThis study will provide more robust evidence of efficacy, cost effectiveness and acceptability of self-help treatments for OCD. If cCBT and/or GSH prove effective, it will provide additional, more accessible treatment options for people with OCD.Trial registrationCurrent Controlled Trials: ISRCTN73535163. Date of registration: 5 April 2011

Clinical effectiveness, cost-effectiveness and acceptability of low-intensity interventions in the management of obsessive-compulsive disorder: the Obsessive-Compulsive Treatment Efficacy randomised controlled Trial (OCTET).

BACKGROUND The Obsessive-Compulsive Treatment Efficacy randomised controlled Trial emerged from a research recommendation in National Institute for Health and Care Excellence obsessive-compulsive disorder (OCD) guidelines, which specified the need to evaluate cognitive-behavioural therapy (CBT) treatment intensity formats. OBJECTIVES To determine the clinical effectiveness and cost-effectiveness of two low-intensity CBT interventions [supported computerised cognitive-behavioural therapy (cCBT) and guided self-help]: (1) compared with waiting list for high-intensity CBT in adults with OCD at 3 months; and (2) plus high-intensity CBT compared with waiting list plus high-intensity CBT in adults with OCD at 12 months. To determine patient and professional acceptability of low-intensity CBT interventions. DESIGN A three-arm, multicentre, randomised controlled trial. SETTING Improving Access to Psychological Therapies services and primary/secondary care mental health services in 15 NHS trusts. PARTICIPANTS Patients aged ≥ 18 years meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for OCD, on a waiting list for high-intensity CBT and scoring ≥ 16 on the Yale-Brown Obsessive Compulsive Scale (indicative of at least moderate severity OCD) and able to read English. INTERVENTIONS Participants were randomised to (1) supported cCBT, (2) guided self-help or (3) a waiting list for high-intensity CBT. MAIN OUTCOME MEASURES The primary outcome was OCD symptoms using the Yale-Brown Obsessive Compulsive Scale - Observer Rated. RESULTS Patients were recruited from 14 NHS trusts between February 2011 and May 2014. Follow-up data collection was complete by May 2015. There were 475 patients randomised: supported cCBT (n = 158); guided self-help (n = 158) and waiting list for high-intensity CBT (n = 159). Two patients were excluded post randomisation (one supported cCBT and one waiting list for high-intensity CBT); therefore, data were analysed for 473 patients. In the short term, prior to accessing high-intensity CBT, guided self-help demonstrated statistically significant benefits over waiting list, but these benefits did not meet the prespecified criterion for clinical significance [adjusted mean difference -1.91, 95% confidence interval (CI) -3.27 to -0.55; p = 0.006]. Supported cCBT did not demonstrate any significant benefit (adjusted mean difference -0.71, 95% CI -2.12 to 0.70). In the longer term, access to guided self-help and supported cCBT, prior to high-intensity CBT, did not lead to differences in outcomes compared with access to high-intensity CBT alone. Access to guided self-help and supported cCBT led to significant reductions in the uptake of high-intensity CBT; this did not seem to compromise patient outcomes at 12 months. Taking a decision-making approach, which focuses on which decision has a higher probability of being cost-effective, rather than the statistical significance of the results, there was little evidence that supported cCBT and guided self-help are cost-effective at the 3-month follow-up compared with a waiting list. However, by the 12-month follow-up, data suggested a greater probability of guided self-help being cost-effective than a waiting list from the health- and social-care perspective (60%) and the societal perspective (80%), and of supported cCBT being cost-effective compared with a waiting list from both perspectives (70%). Qualitative interviews found that guided self-help was more acceptable to patients than supported cCBT. Professionals acknowledged the advantages of low intensity interventions at a population level. No adverse events occurred during the trial that were deemed to be suspected or unexpected serious events. LIMITATIONS A significant issue in the interpretation of the results concerns the high level of access to high-intensity CBT during the waiting list period. CONCLUSIONS Although low-intensity interventions are not associated with clinically significant improvements in OCD symptoms, economic analysis over 12 months suggests that low-intensity interventions are cost-effective and may have an important role in OCD care pathways. Further research to enhance the clinical effectiveness of these interventions may be warranted, alongside research on how best to incorporate them into care pathways. TRIAL REGISTRATION Current Controlled Trials ISRCTN73535163. 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. 21, No. 37. See the NIHR Journals Library website for further project information.

Low-intensity cognitive-behaviour therapy interventions for obsessive-compulsive disorder compared to waiting list for therapist-led cognitive-behaviour therapy: 3-arm randomised controlled trial of clinical effectiveness

Background Obsessive-compulsive disorder (OCD) is prevalent and without adequate treatment usually follows a chronic course. “High-intensity” cognitive-behaviour therapy (CBT) from a specialist therapist is current “best practice.” However, access is difficult because of limited numbers of therapists and because of the disabling effects of OCD symptoms. There is a potential role for “low-intensity” interventions as part of a stepped care model. Low-intensity interventions (written or web-based materials with limited therapist support) can be provided remotely, which has the potential to increase access. However, current evidence concerning low-intensity interventions is insufficient. We aimed to determine the clinical effectiveness of 2 forms of low-intensity CBT prior to high-intensity CBT, in adults meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for OCD. Methods and findings This study was approved by the National Research Ethics Service Committee North West–Lancaster (reference number 11/NW/0276). All participants provided informed consent to take part in the trial. We conducted a 3-arm, multicentre randomised controlled trial in primary- and secondary-care United Kingdom mental health services. All patients were on a waiting list for therapist-led CBT (treatment as usual). Four hundred and seventy-three eligible patients were recruited and randomised. Patients had a median age of 33 years, and 60% were female. The majority were experiencing severe OCD. Patients received 1 of 2 low-intensity interventions: computerised CBT (cCBT; web-based CBT materials and limited telephone support) through “OCFighter” or guided self-help (written CBT materials with limited telephone or face-to-face support). Primary comparisons concerned OCD symptoms, measured using the Yale-Brown Obsessive Compulsive Scale–Observer-Rated (Y-BOCS-OR) at 3, 6, and 12 months. Secondary outcomes included health-related quality of life, depression, anxiety, and functioning. At 3 months, guided self-help demonstrated modest benefits over the waiting list in reducing OCD symptoms (adjusted mean difference = −1.91, 95% CI −3.27 to −0.55). These effects did not reach a prespecified level of “clinically significant benefit.” cCBT did not demonstrate significant benefit (adjusted mean difference = −0.71, 95% CI −2.12 to 0.70). At 12 months, neither guided self-help nor cCBT led to differences in OCD symptoms. Early access to low-intensity interventions led to significant reductions in uptake of high-intensity CBT over 12 months; 86% of the patients allocated to the waiting list for high-intensity CBT started treatment by the end of the trial, compared to 62% in supported cCBT and 57% in guided self-help. These reductions did not compromise longer-term patient outcomes. Data suggested small differences in satisfaction at 3 months, with patients more satisfied with guided self-help than supported cCBT. A significant issue in the interpretation of the results concerns the level of access to high-intensity CBT before the primary outcome assessment. Conclusions We have demonstrated that providing low-intensity interventions does not lead to clinically significant benefits but may reduce uptake of therapist-led CBT. Trial registration International Standard Randomized Controlled Trial Number (ISRCTN) Registry ISRCTN73535163.

Successful recruitment to trials: findings from the SCIMITAR+ Trial

BackgroundRandomised controlled trials (RCT) can struggle to recruit to target on time. This is especially the case with hard to reach populations such as those with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking cessation intervention for people with severe mental ill health achieved their recruitment ahead of time and target. This article reports strategies that helped us to achieve this with the aim of aiding others recruiting from similar populations.MethodsSCIMITAR+ is a multi-centre pragmatic two-arm parallel-group RCT, which aimed to recruit 400 participants with severe mental ill health who smoke and would like to cut down or quit. The study recruited primarily in secondary care through community mental health teams and psychiatrists with a smaller number of participants recruited through primary care. Recruitment opened in October 2015 and closed in December 2016, by which point 526 participants had been recruited. We gathered information from recruiting sites on strategies which led to the successful recruitment in SCIMITAR+ and in this article present our approach to trial management along with the strategies employed by the recruiting sites.ResultsAlongside having a dedicated trial manager and trial management team, we identified three main themes that led to successful recruitment. These were: clinicians with a positive attitude to research; researchers and clinicians working together; and the use of NHS targets. The overriding theme was the importance of relationships between both the researchers and the recruiting clinicians and the recruiting clinicians and the participants.ConclusionsThis study makes a significant contribution to the limited evidence base of real-world cases of successful recruitment to RCTs and offers practical guidance to those planning and conducting trials. Building positive relationships between clinicians, researchers and participants is crucial to successful recruitment.

Learning from OCTET – exploring the acceptability of clinical trials management methods

BackgroundConducting research can be time consuming, difficult and challenging. Guidance and pragmatic advice focussing on randomised controlled trial conduct are available but do not necessarily constitute comprehensive guidance. A successful trial is one that recruits to time and target and collects high-quality data within the originally agreed budget. Standardised trial management tools have outlined key project management elements for a successful trial as a method of ensuring good practice in research trials: initiation, planning, execution, monitoring and closure. Lessons are also frequently learnt during the development and conduct of trials but rarely shared for the benefit of others.For the wider research team, the key focus will always be on the execution and delivery of a study. The aim of this study was to evaluate the acceptability of clinical trials management methods, focussing on study execution and monitoring, as implemented in the National Institute for Health Research Health Technology Assessment Programme-funded Obsessive Compulsive Treatment Efficacy Trial (OCTET).MethodsWorkshops, questionnaires and semi-structured interviews were used to explore acceptability of trial management methods with members of the OCTET Trial research team. Nine members participated in the focus group, 10 completed a questionnaire and 20 were interviewed as part of qualitative work for the main OCTET study. Data was collected and analysed using thematic analysis.ResultsSix key themes were identified: support; communication; processes; resources; training and ethos. Clear and open communication, enthusiasm and accessibility of the trial managers and chief investigator were consistently noted as an important facet of the successful running of the trial. Clear resources and training materials were also found to be crucial in helping staff to work within the trial setting. Constructive suggestions were also made for improvement of these resources; for example, including both checklists and flowcharts within trial processes.ConclusionOrganisation, openness and positivity are crucial for executing a trial successfully, whilst clear and focussed processes and resources are essential in monitoring and controlling the trial progress. Although derived from a single study, these findings are likely to be applicable to the successful conduct of all trials. Trial managers should consider developing these elements when setting up a study.Trial registrationClinical Trial Registry, ID: ISRCTN73535163. Registered prospectively on 5 April 2011.

Pilot feasibility randomized clinical trial of negative-pressure wound therapy versus usual care in patients with surgical wounds healing by secondary intention: Feasibility study of negative-pressure wound therapy

Surgical wounds healing by secondary intention (SWHSI) are increasingly being treated with negative‐pressure wound therapy (NPWT) despite a lack of high‐quality research evidence regarding its clinical and cost‐effectiveness. This pilot feasibility RCT aimed to assess the methods for and feasibility of conducting a future definitive RCT of NPWT for the treatment of SWHSI.

A randomized, embedded trial of pre-notification of trial participation did not increase recruitment rates to a falls prevention trial

OBJECTIVES To design and evaluate the effectiveness of a pre-notification leaflet about research to increase recruitment to a randomized controlled trial (RCT). METHODS A methodological, two-arm, RCT was conducted, embedded within an existing cohort RCT (REFORM). Participants were randomized for the embedded trial, using a 1:2 ratio (intervention : control) before being randomized for REFORM. Controls received a trial recruitment pack. The intervention group received an additional pre-notification leaflet 2-3 weeks before the recruitment pack. Primary and secondary analyses were conducted using relative risk, the Cox proportional hazards model and incremental cost-effectiveness ratios. RESULTS Of the 1436 intervention group participants, 73 (5.1%) were randomized into the REFORM trial compared with 126 (4.4%) of the 2878 control group participants. The associated relative risk (1.16) was not statistically significant [95% confidence interval (CI) 0.88-1.56]. Return rate was not significantly increased (relative risk 1.10, 95% CI 0.92-1.28) nor time to return decreased (hazard ratio: 1.11, 95% CI 0.93-1.33). Incremental cost-effectiveness ratios indicated the intervention may be cost-effective if the true estimate of effect was close to the upper bound of the associated 95% CI. CONCLUSION Pre-notification for potential trial participants demonstrated a small difference to randomization (0.7% difference) and return rates (1.1% difference) in favour of the intervention. Results should however be interpreted with caution as CIs for these estimates cross the point of no effect. Nevertheless, this research enhances existing evidence for pre-notification to increase recruitment rates, with further development and assessment of this potentially cost-effective intervention being recommended.

A nested randomised controlled trial of a leaflet, containing information on research, to increase the recruitment rate of reform (reducing falls with orthoses and a multifaceted podiatry) trial participants

Background Poor recruitment is a major problem in randomised trials. Although pre-notification has been demonstrated to be an effective strategy for increasing response rates to postal questionnaires (Edwards et al, 2010), the usefulness of this approach to aid trial recruitment has never been evaluated. This study, nested within the NIHR funded REFORM Trial, aimed to identify whether increasing understanding of research in potential trial participants, prior to being approached for consent, can increase trial recruitment.