Using Pens as an Incentive for Trial Recruitment of Older Adults : An Embedded Randomised Controlled Trial

Background: Meeting recruitment targets for randomised controlled trials is challenging. This trial evaluated the effectiveness of including a pen within the trial invitation pack on the recruitment of older adults into a randomised controlled trial. Methods: This trial was embedded within the Occupational Therapist Intervention Study, a falls-prevention randomised controlled trial. Potential participants (n = 1862), who were posted an invitation pack from two General Practitioner practices, were randomised to either not receive a pen (n = 1295) or receive a pen (n = 648) with their invitation pack, using a 2:1 ratio. The primary outcome was the likelihood of being randomised, and therefore fully recruited, to the host trial. To be randomised to the host trial, participants had to: return a consent form and screening form; be eligible on their screening form; and return a baseline questionnaire and a monthly falls calendar. Secondary outcomes were: the likelihood of returning (and time to return) a screening form; being eligible for the host trial; and remaining in the trial for at least 3 months. Results: The likelihood of being randomised to the host trial did not differ between the pen group (4.5%) and no pen group (4.3%; odds ratio 1.04; 95% confidence interval: 0.65 to 1.67; p = 0.86). There were marginal differences in secondary outcomes in favour of the pen group, particularly in screening form return rates, though these differences were not statistically significant. Conclusion: Pens may not be an effective incentive for the recruitment of older adults into randomised controlled trials, though future trials are required. Registration: ISRCTN22202133; SWAT 37

Biomarker Driven Antifungal Stewardship (BioDriveAFS) in acute leukaemia—a multi-centre randomised controlled trial to assess clinical and cost effectiveness: a study protocol for a randomised controlled trial

BACKGROUND: Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and β-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing). METHODS: BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed. DISCUSSION: The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship. TRIAL REGISTRATION: ISRCTN11633399. Registered 24/06/2022

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