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

No difference found in time to publication by statistical significance of trial results: a methodological review

Objective: Time-lag from study completion to publication is a potential source of publication bias in randomised controlled trials. This study sought to update the evidence base by identifying the effect of the statistical significance of research findings on time to publication of trial results.Design: Literature searches were carried out in four general medical journals from June 2013 to June 2014 inclusive (BMJ, JAMA, the Lancet and the New England Journal of Medicine). Setting: Methodological review of four general medical journals. Participants: Original research articles presenting the primary analyses from phase 2, 3 and 4 parallel-group randomised controlled trials were included. Main outcome measures: Time from trial completion to publication.Results: The median time from trial completion to publication was 431 days (n ¼ 208, interquartile range 278–618). A multivariable adjusted Cox model found no statistically significant difference in time to publication for trials reporting positive or negative results (hazard ratio: 0.86, 95% CI 0.64 to 1.16, p ¼ 0.32). Conclusion: In contrast to previous studies, this review did not demonstrate the presence of time-lag bias in time to publication. This may be a result of these articles being published in four high-impact general medical journals that may be more inclined to publish rapidly, whatever the findings. Further research is needed to explore the presence of time-lag bias in lower quality studies and lower impact journals

Yorkshire Lung Screening Trial (YLST): protocol for a randomised controlled trial to evaluate invitation to community-based low-dose CT screening for lung cancer versus usual care in a targeted population at risk

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ. INTRODUCTION: Lung cancer is the world's leading cause of cancer death. Low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in the US National Lung Screening Trial. Here, we present the Yorkshire Lung Screening Trial (YLST), which will address key questions of relevance for screening implementation. METHODS AND ANALYSIS: Using a single-consent Zelen's design, ever-smokers aged 55-80 years registered with a general practice in Leeds will be randomised (1:1) to invitation to a telephone-based risk-assessment for a Lung Health Check or to usual care. The anticipated number randomised by household is 62 980 individuals. Responders at high risk will be invited for LDCT scanning for lung cancer on a mobile van in the community. There will be two rounds of screening at an interval of 2 years. Primary objectives are (1) measure participation rates, (2) compare the performance of PLCOM2012 (threshold ≥1.51%), Liverpool Lung Project (V.2) (threshold ≥5%) and US Preventive Services Task Force eligibility criteria for screening population selection and (3) assess lung cancer outcomes in the intervention and usual care arms. Secondary evaluations include health economics, quality of life, smoking rates according to intervention arm, screening programme performance with ancillary biomarker and smoking cessation studies. ETHICS AND DISSEMINATION: The study has been approved by the Greater Manchester West research ethics committee (18-NW-0012) and the Health Research Authority following review by the Confidentiality Advisory Group. The results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and on the YLST website. TRIAL REGISTRATION NUMBERS: ISRCTN42704678 and NCT03750110

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

Staff training to improve participant recruitment into surgical randomised controlled trials : a feasibility Study Within A Trial (SWAT) across four host randomised controlled trials simultaneously

Objective To test the feasibility of undertaking a simultaneous Study Within A Trial (SWAT) to train staff who recruit participants into surgical randomised controlled trials (RCTs), by assessing key uncertainties around recruitment, randomisation, intervention delivery and data collection. Study design and setting Twelve surgical RCTs were eligible. Interested sites (clusters) were randomised 1:1, with recruiting staff (surgeons and nurses) offered training or no training. The primary outcome was the feasibility of recruiting sites across multiple surgical trials simultaneously. Secondary outcomes included numbers/types of staff enrolled, attendance at training, training acceptability, confidence in recruiting and participant recruitment rates six months later. Results Four RCTs (33%) comprising 91 sites participated. Of these, 29 sites agreed to participate (32%) and were randomised to intervention (15 sites, 29 staff) or control (14 sites, 29 staff). Research nurses attended and found the training to be acceptable; no surgeons attended. In the intervention group, there was evidence of increased confidence when pre and post training scores were compared (mean difference in change 1.42; 95% CI 0.56, 2.27; p = 0.002) – there was no effect on recruitment rate. Conclusion It was feasible to randomise sites across four surgical RCTs in a simultaneous SWAT design. However, as small numbers of trials and sites participated, and no surgeons attended training, strategies to improve these aspects are needed for future evaluations. Trial registration ISRCTN registry: DISC (ISRCTN18254597), registered on 4th April 2017; PROFHER 2 (ISRCTN76296703), registered on 5th April 2018; IntAct (ISRCTN13334746), registered on 10th April 2017; and START:REACTS (ISRCTN17825590), registered on 5th March 2018. The training SWAT has been submitted to the MRC SWAT repository (SWAT111) Keywords: Randomised controlled trial (RCT), Study Within A Trial (SWAT), recruitment, staff training, professional education, feasibility study, surgical trial

Researchers’ experiences of pharmacy involvement : a UK cross-sectional survey

Objectives We aimed to explore the experiences and opinions of researchers who have involved pharmacy professionals in research studies. Pharmacy teams are valued healthcare professionals, with a wide knowledge base and skill set. They have regular contact with service users who may be interested in research, placing them in a good position for collaboration with researchers. Methods Cross-sectional survey circulated to researchers in the UK; analysed using descriptive, quantitative methods. Key findings A total of 238 responses were received from researchers, mainly within hospitals and universities. Most had more than 10 years of experience (45%) and had worked on 2–10 studies involving pharmacies (54%), frequently requiring hospital services (74%). Two-thirds of researchers had worked on clinical trials of investigational medicinal products. Most researchers worked with pharmacy teams that all had previous research experience (78%) yet did not involve them in participant recruitment (85%). Pharmacy staff frequently managed or dispensed medication (43%), however also engaged with other research-related tasks. Their previous experience and keenness were desirable qualities for researchers. Many respondents had a positive experience of collaboration and acknowledged various advantages (e.g. developing training/knowledge) and disadvantages (e.g. staffing issues). Conclusions Researchers’ positive impression of working with the pharmacy sector bodes well for future collaborations. Many had experience with pharmacy, however, those more unfamiliar should consider the roles staff could perform; and pharmacy teams and professional bodies should advocate their involvement. For collaboration to prosper, we should promote the benefits of research engagement and consider how to overcome known challenges

The current role, and perceived benefits and barriers of secondary care pharmacists facilitating patient participation in Clinical Trials of Investigational Medicinal Products (CTIMPs) conducted within the NHS: A cross-sectional survey.

Rationale, aims and objectives: Secondary care pharmacists are well positioned within the healthcare system to communicate with patients, and provide guidance and advice regarding drug treatments. They are able to broaden the opportunities to raise the profile of CTIMPs, and positively influence research. This research aimed to investigate the perceived benefits and barriers of secondary care pharmacists being involved in Clinical Trials of Investigational Medicinal Products (CTIMPs), their current role, and the perceived benefits and barriers of developing their role in facilitating patient participation for CTIMPs (e.g. by identifying or recruiting potential participants). Methods: A cross-sectional quantitative online survey circulated to pharmacy professionals within the UK. Results: Involvement in CTIMPs and the facilitation of patient participation offered several benefits including improved communication and relationships with other healthcare professionals, developing the profession, developing training and knowledge, and exploring a personal interest. The main barriers to involvement included a lack of opportunities or awareness of opportunities, time, and funding or resources. Those employed at sites with a larger number of CTIMPs agreed more with the disadvantages, however they also showed greater agreeance towards the benefits of pharmacy being involved in facilitating patient participation. Conclusions: Most respondents do not currently have a role in identifying or recruiting potential participants. Despite this, being involved in CTIMPs and the facilitation of patient participation was suggested to offer several benefits. Given many participants agreed there are barriers to their involvement, future research should focus on exploring organisational and individual challenges with the aim of enabling pharmacists to support recruitment activities