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.

Predictors of meningococcal vaccine uptake in university and college students: a systematic review and meta-analysis.

Objective: To identify predictors of meningococcal vaccine uptake among university and college students, the most common carriers of meningococcal disease. Participants: University or college students aged 18 to 25 years. Methods: Multiple databases, citations, and gray literature were systematically searched in April 2017 and January 2019, for articles reporting rates and predictors of vaccine uptake. Included studies underwent quality appraisal, and, where suitable, meta-analyses were performed. Results: Twenty-one articles, covering 18 studies from six countries, were included. They were mostly cross-sectional surveys of routine vaccination. Meta-analyses were conducted on six predictors. Higher vaccination uptake was associated with being a first year student, an undergraduate student, not being an international student, perceiving meningococcal disease as a risk, and being female. Conclusion: Identified key predictors correspond with previous studies and other vaccines. The findings should inform the delivery and communication of meningococcal vaccination to university and college students.

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.

A multicentre, randomized, parallel group, superiority study to compare the clinical effectiveness and cost-effectiveness of external frame versus internal locking plate for complete articular pilon fracture fixation in adults.

AIMS: A pilon fracture is a severe ankle joint injury caused by high-energy trauma, typically affecting men of working age. Although relatively uncommon (5% to 7% of all tibial fractures), this injury causes among the worst functional and health outcomes of any skeletal injury, with a high risk of serious complications and long-term disability, and with devastating consequences on patients' quality of life and financial prospects. Robust evidence to guide treatment is currently lacking. This study aims to evaluate the clinical and cost-effectiveness of two surgical interventions that are most commonly used to treat pilon fractures. METHODS: A randomized controlled trial (RCT) of 334 adult patients diagnosed with a closed type C pilon fracture will be conducted. Internal locking plate fixation will be compared with external frame fixation. The primary outcome and endpoint will be the Disability Rating Index (a patient self-reported assessment of physical disability) at 12 months. This will also be measured at baseline, three, six, and 24 months after randomization. Secondary outcomes include the Olerud and Molander Ankle Score (OMAS), the five-level EuroQol five-dimenison score (EQ-5D-5L), complications (including bone healing), resource use, work impact, and patient treatment preference. The acceptability of the treatments and study design to patients and health care professionals will be explored through qualitative methods. DISCUSSION: The two treatments being compared are the most commonly used for this injury, however there is uncertainty over which is most clinically and cost-effective. The Articular Pilon Fracture (ACTIVE) Trial is a sufficiently powered and rigorously designed study to inform clinical decisions for the treatment of adults with this injury. Cite this article: Bone Jt Open 2021;2(3):150-163.

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.