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)

Study within a trial 119 : The effectiveness of a thank you card to improve trial follow up; a randomised study within a trial

Background With attrition common in randomised trials, strategies are needed to minimise this. Many retention strategies include ‘thanks’ elements however there is currently no evidence of the effectiveness of a ‘thank you’ intervention separate to other trial activity or information. This Study Within A Trial (SWAT) sought to assess if a thank you card increases completion of the host trial primary outcome. Methods A two arm SWAT, using a 1:1 (intervention:control) allocation ratio, embedded within the DISC trial. The primary outcome was the difference in retention rate at 1 year post-treatment. Secondary outcomes were outcome data completeness, cost, and retention at 2 years post-treatment. Analyses were conducted using logistic regression adjusting for SWAT and host trial allocation. Results A total of 358 participants were randomised and included in the SWAT analyses. Completion of the 1-year outcome visit was 89.7% (n = 157) in the intervention group and 90.2% (165) in the control group (adjusted odds ratio (OR) 0.95, 95% CI 0.48 to 1.90, p = .89). There was no evidence of a difference in completeness of key outcome data (adjusted OR 1.84, 95% CI 0.71 to 4.73, p = .20) or retention at 2 years post treatment (adjusted OR 1.13, 95% CI 0.59 to 2.17, p = .72). Conclusion It remains unclear if thank you cards increased the rate of primary outcome follow-up completion within the DISC trial. However, as the first evaluation of a distinct ‘thank you’ intervention for improving retention rates, further replications are required to determine effectiveness, ideally in populations other than older, male, Caucasians

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

Background Given, smoking results in poor physical and mental health, reducing tobacco harm is of high importance. Recommendations published by 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. Methods Data collected during the Smoking Cessation Intervention for severe Mental Ill Health Trial (SCIMITAR+) trial, was reviewed to identify the difficulties experienced, across the trial, with regards to access and provision of NRT. Actions taken to facilitate access and provision of NRT were collated to outline how provision could be better facilitated. Results Access to nicotine replacements therapy (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

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

Simon Gilbody, Emily Peckham, Della Bailey, Catherine Arundel, Paul Heron, , , , and members of the SCIMITAR+ collaborative

Patient-reported quality of life factors in vascular surgical wounds healing by secondary intention (SWHSI) : a qualitative patient and public involvement (PPI) exploration

Background: Surgical wounds healing by secondary intention (SWHSI) represent a significant burden to patients and services. An understanding of quality of life factors affecting this population is essential to recognise the impact of this wound entity on patients. Understanding of the patient experience is necessary to building effective services and designing high-quality research studies to improve care in this population. Methods: Twelve individuals with lived experience of living with a SWHSI or caring for a person with a SWHSI were recruited to one of two focus groups. Participants were identified from those who had previously been recruited into the NIHR-funded SWHSI-2 trial (NIHR17/42/94; a study assessing healing of surgical wound healing by secondary intention). All participants in this cohort had lower limb SWHSIs and a history of peripheral vascular disease. Sessions followed a general topic guide and were guided by the research team. Sessions were audio-recorded, transcribed and analysed using thematic analysis methods. Results: Four main areas of impact on quality of life were identified: mental health, physical symptoms, lifestyle symptoms and service-based impacts. There was a clear heterogeneity of experience seen within the group, with some reporting a more significant impact than others. This was ascribed to the loss of social and professional functioning, and the subsequent impact on mental health. There was a differential impact of this on younger participants (who tended to be employed and hold caring roles for children or family members) compared to older participants who did not have these social roles to fulfil, and were less affected in these areas. The need for improved preoperative counselling was highlighted, as many participants reported feeling unprepared for the postoperative course. Conclusions: This study considered the experiences of patients with a SWHSI and identified the main areas of impact on quality of life. This work will help to underpin future research into treatments and services for the SWHSI population. It may also form the basis for identifying an appropriate patient-reported outcome measure (PROM) related to quality of life in SWHSI for use in the research setting. Limitations of the study included the number and diversity of participants, and the impact of the SARS-CoV-2 (COVID-19) pandemic on the experiences of participants. Further exploration of the area through formal qualitative study is warranted to understand the breadth, generalisability and possible future applications of the work

SCIMITAR+ Trial: A randomised study within a trial (SWAT) of a contingent financial reward to improve trial follow-up

Objectives To evaluate the effectiveness of a contingent financial incentive (£10 note in addition to a routinely provided £10 voucher) versus no contingent financial incentive, on improving the retention rate in a randomised controlled trial (RCT). Methods A two arm ‘Study within a Trial’ (SWAT) embedded within a host RCT (SCIMITAR+). Participants were randomised to the SWAT using a 2:1 (intervention:control) allocation ratio. The primary outcome measure was the proportion of participants completing a CO breath measurement at the first SCIMITAR+ follow up time point (6 months). Secondary outcomes were withdrawing from follow-up after contact and time from assessment due date to completion. Analyses were conducted using logistic or Cox Proportional Hazards regression as appropriate. Results A total of 434 participants were randomised into this SWAT. Completion of the CO breath measurement at 6 months was 88.5% (n=247) in the intervention arm of the SWAT and 85.4% (n=123) in the control arm. The difference (3.1%) was not statistically significant (p=0.36; OR 1.29, 95% CI 0.71-2.33, p=0.41). There was also no evidence of a difference in the proportion of participants withdrawing from follow-up after contact (intervention n=7 (2.5%), control n=5 (3.5%); OR 0.76, 95% CI 0.23-2.44, p=0.64), nor in terms of proximity of 6-month visit completion to due date (HR 1.07, 95% CI 0.86-1.33, p=0.55). Conclusion Contingent financial incentives did not statistically significantly increase rates of face-to-face follow-up completion within the SCIMITAR+ trial population. However, the sample size of this SWAT was constrained by the size of the host trial and power was limited. This SWAT adds to the body of evidence for initiatives to increase response rates in trials. Key Words SWAT, retention; randomized controlled tria

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

Objective 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 3,223 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 measures Proportion of participants that completed 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. Trial Registration SWAT 82: Sending Christmas cards to trial participants to improve retention (SWAT repository - https://www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/FileStore/Filetoupload,846275,en.pdf#search=SWAT%2082

Standard smoking cessation services in sites participating in the SCIMITAR+ trial for people with severe mental ill health

Aims and method: SCIMITAR+ trial was commissioned to evaluate the effectiveness of a bespoke smoking cessation intervention for people with severe mental ill health compared to usual services. It is difficult to define what constitutes ‘usual care’ in stop smoking services. We aimed to define what this was during the trial. Twenty-two NHS healthcare providers participated in a bespoke survey asking about usual care in their area. Results: All sites offered smoking cessation support, however, service provider and service type varied substantially. In some cases services were not streamlined, meaning that people received smoking cessation counselling from one organisation and smoking cessation medication from another. Clinical implications: To better implement the NICE guideline PH48, clearer referral pathways need to be implemented and communicated to patients, staff and carers. People with SMI need to be able to access services that combine Nicotine Replacement Therapy and behavioural support in a streamlined manner

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 randomised controlled trial (RCT). Methods: A methodological, two arm, randomised controlled trial was conducted, embedded within an existing cohort RCT (REFORM). Participants were randomised for the embedded trial, using a 1:2 (intervention:control) allocation ratio, prior to being randomised for the REFORM RCT. Controls received a trial recruitment pack. The intervention group received an additional pre-notification leaflet 2 to 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 1,436 intervention group participants, 73 (5.1%) were randomised into the REFORM trial compared to 126 (4.4%) of the 2,878 control group participants. The associated relative risk (1.16) was not statistically significant (95% CI 0.88 - 1.56). The leaflet did not significantly increase return rate (RR 1.10, 95% CI 0.92 -1.28) or decrease time to return (Hazard Ratio: 1.11, 95% CI 0.93 -1.33). Incremental Cost Effectiveness Ratios indicated that the intervention may be cost-effective if the true estimate of effect were close to the upper bound of the associated 95% CI. Conclusion: A pre-notification leaflet to potential trial participants demonstrated a small difference in favour of the intervention with regards randomisation (0.7% difference) and return rates (1.1% difference).Results should however be interpreted with caution as confidence intervals 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

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 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. The Dupuytren’s Interventions 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 at 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. ISRCTN registry identifier: ISRCTN18254597. Prospectively registered on 11th April 2017. https://doi.org/10.1186/ISRCTN18254597 Keywords: Dupuytren’s contracture, Collagenase clostridium histolyticum, limited fasciectomy, surgery, correction, randomised controlled tria