Do recruitment SWAT interventions have an impact on participant retention in randomised controlled trials? A systematic review.

BACKGROUND: Evidence-based methods for randomised controlled trial recruitment and retention are extremely valuable. Despite increased testing of these through studies within a trial, there remains limited high-certainty evidence for effective strategies. In addition, there has been little consideration as to whether recruitment interventions also have an impact on participant retention. METHODS: A systematic review was conducted. Studies were eligible if they were randomised controlled trials using a recruitment intervention and which also assessed the impact of this on retention at any time point. Searches were conducted through MEDLINE, EMBASE, Cochrane Library, and the Northern Ireland Hub for Trials Methodology Research SWAT Repository. Two independent reviewers screened the search results and extracted data for eligible studies using a piloted extraction form. RESULTS: A total of 7815 records were identified, resulting in 10 studies being included in the review. Most studies (n = 6, 60%) focussed on the information given to participants (n = 6, 60%), with two (20%) focussing on incentives, and two focussing on trial design and recruiter interventions. Due to intervention heterogeneity, none of the interventions could be meta-analysed. Only one study found any statistically significant effect of letters including a photograph (odds ratio: 5.40, 95% CI 1.12-26.15, p = 0.04). CONCLUSION: Assessment of the impacts of recruitment strategies, evaluated in a SWAT, on retention of participants in the host trial remains limited. Assessment of the impact of recruitment interventions on retention is recommended to minimise future research costs and waste.

Out of pocket expenses in obsessive compulsive disorder.

BACKGROUND: Despite anecdotal evidence that the out of pocket costs of OCD can be substantial in some cases, there is no evidence on how many people they affect, or the magnitude of these costs. AIMS: This paper explores the type and quantity of out of pocket expenses reported by a large sample of adults with OCD. METHODS: Data on out of pocket expenses were collected from participants taking part in the OCTET multi-centre randomised controlled trial. Participants were aged 18+, meeting DSM-IV criteria for OCD, and scoring 16+ on the Yale Brown Obsessive Compulsive Scale. Individual-level resource use data including a description and estimated cost of out of pocket expenses were measured using an adapted version of the Adult Service Use Schedule (AD-SUS): a questionnaire used to collect data on resource use. RESULTS: Forty-five percent (208/465) reported out of pocket expenses due to their OCD. The mean cost of out of pocket expenses was £19.19 per week (SD £27.56 SD), range £0.06-£224.00. CONCLUSIONS: Future economic evaluations involving participants with OCD should include out of pocket expenses, but careful consideration of alternative approaches to the collection and costing of this data is needed.

Smoking cessation in severe mental illness: combined long-term quit rates from the UK SCIMITAR trials programme.

Smoking contributes to health inequalities for people with severe mental illness (SMI). Although smoking cessation interventions are effective in the short term, there are few long-term trial-based estimates of abstinence. The SCIMITAR trials programme includes the largest trial to date of a smoking cessation intervention for people with SMI, but this was underpowered to detect anticipated long-term quit rates. By pooling pilot and full-trial data we found that quit rates were maintained at 12 months (OR = 1.67, 95% CI 1.02-2.73, P = 0.04). Policymakers can now be confident that bespoke smoking cessation interventions produce successful short- and long-term quitting.

Exploring feedback from research nurses in relation to the design and conduct of a randomised controlled trial of wound care treatments: A sequential, dependent, mixed-methods study.

BACKGROUND: Research nurse involvement in trials is crucial to successful conduct, however their feedback on trial design and conduct is not necessarily always collected and shared. This study was designed to explore research nurse feedback in relation to study and protocol design and implementation in the National Institute for Health Research Programme Grants for Applied Research funded Surgical Wounds Healing by Secondary Intention pilot and feasibility trial (SWHSI). The primary aim of this study was to inform the design and conduct of a proposed future, larger study in this area. Given the evidence gap, it was deemed prudent to share these findings for the benefit of others. METHODS: A sequential, dependent mixed methods study, comprising a Likert scale questionnaire and semi-structured interviews, explored the experiences, in relation to study design and conduct, of research nurses involved in the trial. Of the 10 research nurses involved in the trial, eight nurses completed a questionnaire and were interviewed. Questionnaire data was analysed using descriptive statistics and interview data using thematic analysis. RESULTS: A range of questionnaire responses were provided, however at least 50% (n = 4) of respondents indicated that they were happy with both the study design and conduct. Interview data identified key themes to consider when involving research nurses in the design, delivery and conduct of RCTs; removing barriers to recruitment, time management, engagement strategies and resource provision. CONCLUSION: Engagement of research nurses is important to enable effective trial conduct. Research teams should therefore consider how best to obtain and include input from all members of the research team from the outset. Furthermore, the sharing of feedback on research design and conduct, from the perspective of research nurses delivering trial recruitment and retention, remains crucial to effective and efficient trial conduct. TRIAL REGISTRATION: Clinical Trial Registry: ISRCTN12761776. Date of registration: 10th December 2015.

Hydroxychloroquine Effectiveness in Reducing Symptoms of Hand Osteoarthritis: A Randomized Trial.

Background: Synovitis is believed to play a role in producing symptoms in persons with hand osteoarthritis, but data on slow-acting anti-inflammatory treatments are sparse. Objective: To determine the effectiveness of hydroxychloroquine versus placebo as an analgesic treatment of hand osteoarthritis. Design: Randomized, double-blind, placebo-controlled clinical trial with 12-month follow-up. (ISRCTN registry number: ISRCTN91859104). Setting: 13 primary and secondary care centers in England. Participants: Of 316 patients screened, 248 participants (82% women; mean age, 62.7 years) with symptomatic (pain ≥4 on a 0- to 10-point visual analogue scale) and radiographic hand osteoarthritis were randomly assigned and 210 (84.7%) completed the 6-month primary end point. Intervention: Hydroxychloroquine (200 to 400 mg) or placebo (1:1) for 12 months with ongoing usual care. Measurements: The primary end point was average hand pain during the previous 2 weeks (on a 0- to 10-point numerical rating scale [NRS]) at 6 months. Secondary end points included self-reported pain and function, grip strength, quality of life, radiographic structural change, and adverse events. Baseline ultrasonography was done. Results: At 6 months, mean hand pain was 5.49 points in the placebo group and 5.66 points in the hydroxychloroquine group, with a treatment difference of -0.16 point (95% CI, -0.73 to 0.40 point) (P = 0.57). Results were robust to adjustments for adherence, missing data, and use of rescue medication. No significant treatment differences existed at 3, 6, or 12 months for any secondary outcomes. The percentage of participants with at least 1 joint with synovitis was 94% (134 of 143) on grayscale ultrasonography and 59% on power Doppler. Baseline structural damage or synovitis did not affect treatment response. Fifteen serious adverse events were reported (7 in the hydroxychloroquine group [3 defined as possibly related] and 8 in the placebo group). Limitation: Hydroxychloroquine dosage restrictions may have reduced efficacy. Conclusion: Hydroxychloroquine was no more effective than placebo for pain relief in patients with moderate to severe hand pain and radiographic osteoarthritis. Primary Funding Source: Arthritis Research UK.

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.

Undertaking Studies Within A Trial to evaluate recruitment and retention strategies for randomised controlled trials: lessons learnt from the PROMETHEUS research programme.

Background: Randomised controlled trials ('trials') are susceptible to poor participant recruitment and retention. Studies Within A Trial are the strongest methods for testing the effectiveness of strategies to improve recruitment and retention. However, relatively few of these have been conducted. Objectives: PROMoting THE Use of Studies Within A Trial aimed to facilitate at least 25 Studies Within A Trial evaluating recruitment or retention strategies. We share our experience of delivering the PROMoting THE Use of Studies Within A Trial programme, and the lessons learnt for undertaking randomised Studies Within A Trial. Design: A network of 10 Clinical Trials Units and 1 primary care research centre committed to conducting randomised controlled Studies Within A Trial of recruitment and/or retention strategies was established. Promising recruitment and retention strategies were identified from various sources including Cochrane systematic reviews, the Study Within A Trial Repository, and existing prioritisation exercises, which were reviewed by patient and public members to create an initial priority list of seven recruitment and eight retention interventions. Host trial teams could apply for funding and receive support from the PROMoting THE Use of Studies Within A Trial team to undertake Studies Within A Trial. We also tested the feasibility of undertaking co-ordinated Studies Within A Trial, across multiple host trials simultaneously. Setting: Clinical trials unit-based trials recruiting or following up participants in any setting in the United Kingdom were eligible. Participants: Clinical trials unit-based teams undertaking trials in any clinical context in the United Kingdom. Interventions: Funding of up to £5000 and support from the PROMoting THE Use of Studies Within A Trial team to design, implement and report Studies Within A Trial. Main outcome measures: Number of host trials funded. Results: Forty-two Studies Within A Trial were funded (31 host trials), across 12 Clinical Trials Units. The mean cost of a Study Within A Trial was £3535. Twelve Studies Within A Trial tested the same strategy across multiple host trials using a co-ordinated Study Within A Trial design, and four used a factorial design. Two recruitment and five retention strategies were evaluated in more than one host trial. PROMoting THE Use of Studies Within A Trial will add 18% more Studies Within A Trial to the Cochrane systematic review of recruitment strategies, and 79% more Studies Within A Trial to the Cochrane review of retention strategies. For retention, we found that pre-notifying participants by card, letter or e-mail before sending questionnaires was effective, as was the use of pens, and sending personalised text messages to improve questionnaire response. We highlight key lessons learnt to guide others planning Studies Within A Trial, including involving patient and public involvement partners; prioritising and selecting strategies to evaluate and elements to consider when designing a Study Within A Trial; obtaining governance approvals; implementing Studies Within A Trial, including individual and co-ordinated Studies Within A Trials; and reporting Study Within A Trials. Limitations: The COVID-19 pandemic negatively impacted five Studies Within A Trial, being either delayed (n = 2) or prematurely terminated (n = 3). Conclusions: PROMoting THE Use of Studies Within A Trial significantly increased the evidence base for recruitment and retention strategies. When provided with both funding and practical support, host trial teams successfully implemented Studies Within A Trial. Future work: Future research should identify and target gaps in the evidence base, including widening Study Within A Trial uptake, undertaking more complex Studies Within A Trial and translating Study Within A Trial evidence into practice. Study registration: All Studies Within A Trial in the PROMoting THE Use of Studies Within A Trial programme had to be registered with the Northern Ireland Network for Trials Methodology Research Study Within A Trial Repository. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/55/80) and is published in full in Health Technology Assessment; Vol. 28, No. 2. See the NIHR Funding and Awards website for further award information.

A Study Within A Trial is a research study nested inside a larger 'host trial', promoting the use of Studies Within A Trial aimed to do Study Within A Trial routine practice in clinical trial units by funding and supporting at least 25 Studies Within A Trial. The best way to test health and social care treatments is to do a randomised controlled trial ('trial'), where some patients get the treatment being tested and some do not. The results of different groups are compared to see if the treatment improves care. Recruiting patients and keeping them involved in trials is often very difficult. Research teams often do not know how best to recruit and keep patients engaged as the methods have not been tested to see if they work. The best way to test these methods is by doing a Study Within A Trial. We test a programme of Studies Within A Trial for recruiting and keeping patients engaged in trials. Trial teams were able to apply for funding of up to £5000 and receive support from Promoting the use of Study Within A Trial team to do Studies Within A Trial. We used our experience of doing Studies Within A Trial to outline lessons learnt for doing Studies Within A Trial. We funded 42 Studies Within A Trial and gave teams necessary advice to do them. We significantly increased the knowledge for both recruitment and retention strategies, and found 'pre-notifying' before sending questionnaires, sending pens and personalised text messages were all effective for increasing responses by participants. We tested Studies Within A Trial across several different trials at the same time to find out more quickly whether their methods worked. We highlight key lessons learnt to guide others doing Studies Within A Trial, including involving patient partners; picking the right strategy to test; getting ethical approvals; how to do and report Studies Within A Trial. Promoting the use of studies within a trial was successful and supported more Studies Within A Trial than planned. We hope our experience will support those doing Studies Within A Trial in the future.

Recruitment and retention interventions in surgical and wound care trials: A systematic review.

BACKGROUND: Recruitment and retention to surgical trials has previously been reported to be problematic, resulting in research waste. Surgery often results in wounds, meaning these trials are likely to have similar populations. There is currently no systematic assessment of effective strategies for these populations and hence, systematic assessment of these was deemed to be of importance. METHODS: A systematic review was conducted. Studies were eligible if they were randomised controlled trials undertaken to test an intervention to improve recruitment or retention within a surgical or wound based host randomised controlled trial. MEDLINE, EMBASE, Cochrane Library, ORRCA Database and the Northern Ireland Hub for Trials Methodology Research SWAT Repository Store were searched. Two independent reviewers screened the search results and extracted data for eligible studies using a piloted extraction form. A narrative synthesis was used due to a lack of heterogeneity between strategies which prevented meta-analysis. RESULTS: A total of 2133 records were identified which resulted in 13 ultimately being included in the review; seven on recruitment and six on retention. All included studies were based within surgical host trials. Four of the seven recruitment studies focussed on the provision of consent information to participants, one focussed on study set up and one on staff training, with only one relating to consent information finding any significant effect. A range of retention strategies were assessed by the included studies, however only two found (pen vs no pen, mailing strategies) found any significant effect. CONCLUSION: The included studies within a trial were all conducted within surgical trials. There was significant variation in strategies used, and limited replications and therefore further assessment may be warranted. Given the lack of studies embedded within wound care trials, further studies in this area are recommended. TRIAL REGISTRATION: PROSPERO (CRD42020205475).

Compression therapies for the treatment of venous leg ulcers: study protocol for a process evaluation in a randomised controlled trial, VenUS 6.

BACKGROUND: The VenUS 6 parallel-group randomised controlled trial (RCT) will compare the clinical and cost-effectiveness of compression wraps, two-layer compression bandage and evidence-based compression therapy, comprising of two-layers of hosiery or four-layer bandages, for healing time of venous leg ulcers. We will conduct an embedded process evaluation to evaluate the implementation of the trial and the various compression therapies and to gain a more in-depth understanding of trial participant and nursing staff views and experiences of these therapies. METHODS: This process evaluation will be a mixed-method study, embedded into a wider RCT. Qualitative data will be collected through semi-structured individual in-depth interviews with trial participants and staff members. Quantitative data will be collected using patient questionnaires and case report forms that are part of the main trial data collection process. Interview transcripts will be analysed using the Framework Analysis and interview data will be integrated with quantitative RCT data using the RE-AIM framework and the Pillar Integration Process. DISCUSSION: We describe the protocol for a process evaluation, designed to assess the implementation of the various venous leg ulcer compression therapies as evaluated in VenUS6, and the experiences of trial participants and nursing staff using these. This protocol provides one example of how an embedded mixed-method process evaluation can be conducted. TRIAL REGISTRATION: ISRCTN 67321719 ( https://doi.org/10.1186/ISRCTN67321719 ). Prospectively registered on 14 September 2020. Recruitment Infographic SWAT-MRC Hub for Trials Methodology Research SWAT repository #116. Registered on 13 April 2020. Retention Thank You Card SWAT-MRC Hub for Trials Methodology Research SWAT repository #119. Registered on 13 April 2020. Retention Newsletter SWAT-MRC Hub for Trials Methodology Research SWAT repository #28. Registered on 01 July 2007. Retention Pen SWAT-MRC Hub for Trials Methodology Research SWAT repository #92. Registered on 01 April 2019. PROTOCOL VERSION: V1.5, 26 May 2022.

Can learnings from the COVID-19 pandemic improve trial conduct post-pandemic? A case study of strategies used by the DISC trial.

Background: RCTs often face issues such as slow recruitment, poor intervention adherence and high attrition, however the 2020/2021 COVID-19 pandemic intensified these challenges. Strategies employed by the DISC trial to overcome pandemic-related barriers to recruitment, treatment delivery and retention may be useful to help overcome routine problems. Methods: A structured survey and teleconference with sites was undertaken. Key performance indicators in relation to recruitment, treatment delivery and retention were compared descriptively before and after the pandemic started. This was situated also in relation to qualitative opinions of research staff. Results: Prior to the pandemic, retention was 93.6%. Increased support from the central trial management team and remote data collection methods kept retention rates high at 81.2% in the first 6 months of the pandemic, rising to 89.8% in the subsequent 6 months. Advertising the study to patients resulted in 12.8 patients/month enquiring about participation, however only six were referred to recruiting sites. Sites reported increased support from junior doctors resolved research nurse capacity issues. One site avoided long delays by using theatre space in a private hospital. Conclusions: Recruitment post-pandemic could be improved by identification of barriers, increased support from junior doctors through the NIHR associate PI scheme and advertising. Remote back-up options for data collection can keep retention high while reducing patient and site burden. To future proof studies against similar disruptions and provide more flexibility for participants, we recommend that RCTs have a back-up option of remote recruitment, a back-up location for surgeries and flexible approaches to collecting data.

Reverse shoulder arthroplasty versus hemiarthroplasty versus non-surgical treatment for older adults with acute 3- or 4-part fractures of the proximal humerus: study protocol for a randomised controlled trial (PROFHER-2: PROximal Fracture of Humerus Evaluation by Randomisation - Trial Number 2).

BACKGROUND: Proximal humerus fractures (PHF) are common and painful injuries, with the majority resulting from falls from a standing height. As with other fragility fractures, its age-specific incidence is increasing. Surgical treatment with hemiarthroplasty (HA) and reverse shoulder arthroplasty (RSA) have been increasingly used for displaced 3- and 4-part fractures despite a lack of good quality evidence as to whether one type of arthroplasty is superior to the other, and whether surgery is better than non-surgical management. The PROFHER-2 trial has been designed as a pragmatic, multicentre randomised trial to compare the clinical and cost-effectiveness of RSA vs HA vs Non-Surgical (NS) treatment in patients with 3- and 4-part PHF. METHODS: Adults over 65 years of age presenting with acute radiographically confirmed 3- or 4-part fractures, with or without associated glenohumeral joint dislocation, who consent for trial participation will be recruited from around 40 National Health Service (NHS) Hospitals in the UK. Patients with polytrauma, open fractures, presence of axillary nerve palsy, pathological (other than osteoporotic) fractures, and those who are unable to adhere to trial procedures will be excluded. We will aim to recruit 380 participants (152 RSA, 152 HA, 76 NS) using 2:2:1 (HA:RSA:NS) randomisation for 3- or 4-part fractures without joint dislocation, and 1:1 (HA:RSA) randomisation for 3- or 4-part fracture dislocations. The primary outcome is the Oxford Shoulder Score at 24 months. Secondary outcomes include quality of life (EQ-5D-5L), pain, range of shoulder motion, fracture healing and implant position on X-rays, further procedures, and complications. Independent Trial Steering Committee and Data Monitoring Committee will oversee the trial conduct, including the reporting of adverse events and harms. DISCUSSION: The PROFHER-2 trial is designed to provide a robust answer to guide the treatment of patients aged 65 years or over who sustain 3- and 4-part proximal humeral fractures. The pragmatic design and recruitment from around 40 UK NHS hospitals will ensure immediate applicability and generalisability of the trial findings. The full trial results will be made available in a relevant open-access peer-reviewed journal. TRIAL REGISTRATION: ISRCTN76296703. Prospectively registered on 5th April 2018.

Bah humbug! Association between sending Christmas cards to trial participants and trial retention: randomised study within a trial conducted simultaneously across eight host trials.

OBJECTIVES: To determine the effectiveness of sending Christmas cards to participants in randomised controlled trials to increase retention rate at follow-ups, and to explore the feasibility of doing a study within a trial (SWAT) across multiple host trials simultaneously. DESIGN: Randomised SWAT conducted simultaneously across eight host trials. SETTING: Eight randomised controlled trials researching various areas including surgery and smoking cessation. PARTICIPANTS: 3223 trial participants who were still due at least one follow-up from their host randomised controlled trial. INTERVENTION: Participants were randomised (1:1, separately by each host trial) to either received a Christmas card in mid-December 2019 or to not receive a card. MAIN OUTCOME MEASURE: Proportion of participants completing their next follow-up (retention rate) within their host randomised controlled trial. RESULTS: 1469 participants (age 16-94 years; 70% (n=1033) female; 96% (813/847) white ethnicity) across the eight host randomised controlled trials were involved in the analysis (cut short owing to covid-19). No evidence was found of a difference in retention rate between the two arms for any of the host trials when analysed separately or when the results were combined (85.3% (639/749) for cards versus 85.4% (615/720) for no card; odds ratio 0.96, 95% confidence interval 0.71 to 1.29; P=0.77). No difference was observed when comparing just participants who were due a follow-up in the 30 days after receiving the card (odds ratio 0.96, 0.42 to 2.21). No evidence of a difference in time to complete the questionnaire was found (hazard ratio 1.01, 95% confidence interval 0.91 to 1.13; P=0.80). These results were robust to post hoc sensitivity analyses. The cost of this intervention was £0.76 (€0.91; $1.02) per participant, and it will have a carbon footprint of approximately 140 g CO2 equivalent per card. One benefit of this approach was the need to only submit one ethics application. CONCLUSIONS: Sending Christmas cards to participants in randomised controlled trials does not increase retention. Undertaking a SWAT within multiple randomised controlled trials at the same time is, however, possible. This approach should be used more often to build an evidence base to support selection of recruitment and retention strategies. Although no evidence of a boost to retention was found, embedding a SWAT in multiple host trials simultaneously has been shown to be possible. STUDY REGISTRATION: SWAT repository https://www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/FileStore/Filetoupload,846275,en.pdf#search=SWAT%2082.

Cost-effectiveness of hydroxychloroquine versus placebo for hand osteoarthritis: economic evaluation of the HERO trial.

Background: An economic evaluation alongside the Hydroxychloroquine Effectiveness in Reducing symptoms of hand Osteoarthritis (HERO) trial was undertaken to assess the cost-effectiveness of hydroxychloroquine compared with placebo for symptomatic treatment of hand osteoarthritis for patients with at least moderate hand pain and inadequate response to current therapies. Methods: A trial-based cost-utility analysis was undertaken from the perspective of the UK National Health Service and Personal Social Services over a 12-month time horizon, using evidence from 248 participants included in the HERO trial, conducted in England. Patient-level data were collected prospectively over a 12-month period, using participant-completed questionnaires and investigator forms, to collect healthcare utilisation, costs and quality-adjusted life years (QALYs) using the EQ-5D-5L. The base-case analysis was conducted on an intention-to-treat basis and used multiple imputation methods to deal with missing data. Results were presented in terms of incremental cost-effectiveness ratios (incremental cost per QALY) and net health benefit, with uncertainty surrounding the findings explored using cost-effectiveness acceptability curves. Results: The base-case analysis estimated slightly lower costs on average (-£11.80; 95% confidence interval (CI) -£15.60 to -£8.00) and marginally fewer QALYs (-0.0052; 95% CI -0.0057 to -0.0047) for participants in the hydroxychloroquine group versus placebo group at 12 months. The resulting incremental cost-effectiveness ratio of £2,267 per QALY lost indicated that although costs were saved, health-related quality of life was lost. Even assuming symmetrical preferences regarding losses and gains for health benefits, the findings do not fall within the cost-effective region. Similar findings arose for analyses conducted from the societal perspective and using complete cases only. Conclusions: This economic evaluation indicates that hydroxychloroquine is unlikely to provide a cost-effective pain relief option for improving health-related quality of life in adult patients with moderate-to-severe hand osteoarthritis.

Negative pressure wound therapy versus usual care for surgical wounds healing by secondary intention (SWHSI-2 trial): study protocol for a pragmatic, multicentre, cross surgical specialty, randomised controlled trial.

BACKGROUND: The majority of surgical wounds are closed (for example with sutures or staples) and so heal by primary intention. Where closure is not possible, or the wound subsequently breaks down, wounds may be left to heal from the bottom up (healing by secondary intention). Surgical wound healing by secondary intention (SWHSI) frequently presents a significant management challenge. Additional treatments are often required during the course of healing, and thus a significant financial burden is associated with treating these wounds. Increasingly, negative pressure wound therapy (NPWT) is used in the management of SWHSI. This wound dressing system provides a negative pressure (vacuum) to the wound, removing fluid into a canister, which is believed to be conducive to wound healing. Despite the increasing use of NPWT, there is limited robust evidence for the effectiveness of this device. A well-designed and conducted randomised controlled trial is now required to ascertain if NPWT is a clinically and cost-effective treatment for SWHSI. METHODS: SWHSI-2 is a pragmatic, multi-centre, cross surgical specialty, two arm, parallel group, randomised controlled superiority trial. Adult patients with a SWHSI will be randomised to receive either NPWT or usual care (no NPWT) and will be followed up for 12 months. The primary outcome will be time to healing (defined as full epithelial cover in absence of a scab) in number of days since randomisation. Secondary outcomes will include key clinical events (hospital admission or discharge, treatment status, reoperation, amputation, antibiotic use and death), wound infection, wound pain, health-related quality of life, health utility and resource use. DISCUSSION: Given the increasing use of NPWT, despite limited high-quality supporting evidence, the SWHSI-2 Trial will provide robust evidence on the clinical and cost-effectiveness of NPWT in the management of SWHSI. The SWHSI-2 Trial opened to recruitment in May 2019 and is currently recruiting across 20 participating centres. TRIAL REGISTRATION: ISRCTN 26277546 . Prospectively registered on 25 March 2019.

Dupuytren's interventions surgery versus collagenase (DISC) trial: study protocol for a pragmatic, two-arm parallel-group, non-inferiority randomised controlled trial.

BACKGROUND: Dupuytren's contracture is a fibro-proliferative disease of the hands affecting over 2 million UK adults, particularly the white, male population. Surgery is the traditional treatment; however, recent studies have indicated that an alternative to surgery-collagenase clostridium histolyticum (collagenase)-is better than a placebo in the treatment of Dupuytren's contracture. There is however no robust randomised controlled trial that provides a definitive answer on the clinical effectiveness of collagenase compared with limited fasciectomy surgery. Dupuytren's intervention surgery vs collagenase trial (DISC) trial was therefore designed to fill this evidence gap. METHODS/DESIGN: The DISC trial is a multi-centre pragmatic two-arm parallel-group, randomised controlled trial. Participants will be assigned 1:1 to receive either collagenase injection or surgery (limited fasciectomy). We aim to recruit 710 adult participants with Dupuytren's contracture. Potential participants will be identified in primary and secondary care, screened by a delegated clinician and if eligible and consenting, baseline data will be collected and randomisation completed. The primary outcome will be the self-reported patient evaluation measure assessed 1 year after treatment. Secondary outcome measures include the Unité Rhumatologique des Affections de la Main Scale, the Michigan Hand Questionnaire, EQ-5D-5L, resource use, further procedures, complications, recurrence, total active movement and extension deficit, and time to return to function. Given the limited evidence comparing recurrence rates following collagenase injection and limited fasciectomy, and the importance of a return to function as soon as possible for patients, the associated measures for each will be prioritised to allow treatment effectiveness in the context of these key elements to be assessed. An economic evaluation will assess the cost-effectiveness of treatments, and a qualitative sub-study will assess participants' experiences and preferences of the treatments. DISCUSSION: The DISC trial is the first randomised controlled trial, to our knowledge, to investigate the clinical and cost-effectiveness of collagenase compared to limited fasciectomy surgery for patients with Dupuytren's contracture. TRIAL REGISTRATION: Clinical.Trials.gov ISRCTN18254597 . Registered on April 11, 2017.

Challenges and solutions to nicotine replacement therapy access: observations from SCIMITAR.

BACKGROUND: Given that smoking results in poor physical and mental health, reducing tobacco harm is of high importance. Recommendations published by the National Institute for Health and Care Excellence to reduce smoking harms included provision of support, use of nicotine containing products and commissioning of smoking cessation services. AIMS: This report explores the difficulties in obtaining such support, as observed in a recently conducted randomised controlled trial in patients with severe mental ill health, and outlines suggestions to improve facilitation of provision. METHOD: Data collected during the Smoking Cessation Intervention for Severe Mental Ill Health Trial (SCIMITAR+) (trial Registration ISRCTN72955454), was reviewed to identify the difficulties experienced, across the trial, with regards to access and provision of nicotine replacements therapy (NRT). Actions taken to facilitate access and provision of NRT were collated to outline how provision could be better facilitated. RESULTS: Access to NRT varied across study settings and in some instances proved impossible for patients to access. Difficulty in access was irrespective of a diagnosis of severe mental ill health. Where NRT was provided, this was not always provided in accordance with NICE guidelines. CONCLUSIONS: Availability of smoking cessation support, and NRT provision would benefit from being made clearer, simpler and more easily accessible so as to enhance smoking cessation rates.

E-cigarette use and associated factors among smokers with severe mental illness.

INTRODUCTION: Smoking is more prevalent among people with severe mental illness (SMI) than the general population. E-cigarettes could provide an effective means of helping people to quit smoking. The aim of this paper is to explore the use of e-cigarettes and factors related to their use in people smokers with SMI. METHODS: This is a cross sectional study including adult smokers with a documented diagnosis of SMI (ICD-10) recruited to the SCIMITAR + trial (2015-2016) from primary and secondary care. At baseline, participants were asked for demographic information and about their use of e-cigarettes. Data was were analysed to explore factors associated with e-cigarette use. After testing bivariate associations, logistic regressions were conducted. RESULTS: Among 526 participants, 58.7% were male, mean age 46 years (SD 12.1), the majority (70.3%) had tried an e-cigarette. Among those who had ever tried an e-cigarette, over half (54.6%) reported the reason was to quit smoking, while 13.9% reported that the reason was to reduce smoking. Having an educational qualification of GCSE or higher (odds ratio 2.17, 95% CI 1.22 to 3.86, p = 0.008) and having made a quit attempt in the past six months (OR 1.66, 95% CI 1.04 to 2.63, p = 0.032) was associated with ever having tried an e-cigarette. CONCLUSIONS: Ever use of an e-cigarette was associated with education levels and recent quit attempts. Future trials could explore the effectiveness of e-cigarettes as a cessation aid in this participant group.

Cost-effectiveness of a specialist smoking cessation package compared with standard smoking cessation services for people with severe mental illness in England: a trial-based economic evaluation from the SCIMITAR+ study.

AIMS: To evaluate the cost-effectiveness of a specialist smoking cessation package for people with severe mental illness DESIGN: Incremental cost-effectiveness analysis was undertaken from the UK National Health Service and Personal Social Services perspective over a 12-month time horizon. Total costs, including smoking cessation, health-care and social services costs and quality-adjusted life years (QALYs), derived from the five-level EuroQol 5-dimension (EQ-5D-5 L), collected from a randomized controlled trial, were used as outcome measures. The bootstrap technique was employed to assess the uncertainty. SETTING: Sixteen primary care and 21 secondary care mental health sites in England. PARTICIPANTS: Adult smokers with bipolar affective disorder, schizoaffective disorder or schizophrenia and related illnesses (n = 526). INTERVENTION AND COMPARATOR: A bespoke smoking cessation (BSC) package for people with severe mental illness offered up to 12 individual sessions with a mental health smoking cessation practitioner versus usual care (UC). Of the participants who were randomized, 261 were in UC group and 265 were in BSC group. MEASUREMENTS: BSC intervention cost was estimated from the treatment log. Costs of UC, health-care and social services and EQ-5D-5 L were collected at baseline, 6- and 12-month follow-ups. Incremental costs and incremental QLAYs were estimated using regression adjusting for respective baseline values and other baseline covariates. FINDINGS: The mean total cost in the BSC group was £270 [95% confidence interval (CI) = -£1690 to £1424] lower than in the UC group, while the mean QALYs were 0.013 (95% CI = -0.008 to 0.045) higher, leading to BSC dominating UC (76% probability of cost-effective at £20 000/QALY). CONCLUSIONS: A bespoke smoking cessation package for people with severe mental illness is likely to be cost-effective over 12 months compared with usual care provided by the UK's National Health Service and personal social services.

Study within a trial (SWAT) protocol. Investigating the effect of personalised versus non-personalised study invitations on recruitment: An embedded randomised controlled recruitment trial.

INTRODUCTION: Recruitment into clinical trials is a common challenge experienced by healthcare researchers. Currently, there is little evidence regarding strategies to improve recruitment into clinical trials. However, preliminary research suggests the personalisation of study invitation letters may increase recruitment rates. As such, there is a need to investigate the effectiveness of personalisation strategies on trial recruitment rates. This study within a trial (SWAT) will investigate the effect of personalised versus non-personalised study invitation letters on recruitment rates into the host trial ENGAGE, a feasibility study of an internet-administered, guided, Cognitive-Behavioural Therapy (CBT) based self-help intervention for parents of children previously treated for cancer. METHODS: An embedded randomised controlled trial (RCT) will investigate the effectiveness of a personalised study invitation letter including the potential participant's name and address compared with a standard, non-personalised letter without name or address, on participant recruitment rates into the ENGAGE study. The primary outcome is differences in the proportion of participants recruited, examined using logistic regression. Results will be reported as adjusted odds ratios with 95% confidence intervals. DISCUSSION: Even moderate effects of the personalisation of study invitation letters on recruitment rates could be of significant value by shortening study length, saving resources, and providing a faster answer to the clinical question posed by the study. This protocol can be used as a template for other researchers who wish to contribute to the evidence base for trial decision-making, by embedding a similar SWAT into their trial. TRIAL REGISTRATION: ISRCTN 57233429; ISRCTN 18404129; SWAT 112, Northern Ireland Hub for Trials Methodology Research SWAT repository (2018 OCT 1 1231).

Study reporting guidelines: How valid are they?

Reporting guidelines help improve the reporting of specific study designs, and clear guidance on the best approaches for developing guidelines is available. The methodological strength, or validation of guidelines is however unclear. This article explores what validation of reporting guidelines might involve, and whether this has been conducted for key reporting guidelines.