Pragmatic Randomized Controlled Trial Research Articles

The role of healthcare professionals’ communication in trial participation decisions: a qualitative investigation of recruitment consultations and patient interviews across three RCTs

BackgroundAlthough the challenges of recruiting to randomised controlled trials (RCTs) are well documented, few studies have focused on the impact that the communication between recruiters and patients has on patients’ participation decisions. Recruiters are thought to influence patient decision-making, but the mechanisms by which this occurs are unclear. The aim of this research was to investigate how patients interpret and use the information conveyed to them by healthcare professionals (HCPs) in trial participation decisions.MethodsThree pragmatic UK-based multicentre RCTs were purposively sampled to provide contrasting clinical specialities. Data collection was integrated into each RCT, including audio-recordings of patient recruitment consultations and interviews with patients. Where possible, consultation audio-recordings were linked to interviews to explore how information communicated by recruiters was interpreted and used by patients during their decision-making. Data were analysed thematically, using the constant comparison approach.ResultsTwenty audio-recorded recruitment consultations were obtained across the 3 RCTs, combined with 42 interviews with patients who had consented to or declined RCT participation. Consultation and interview data were ‘linked’ for 17 individual patients. Throughout the patient’s clinical pathway, HCPs (both those involved in the RCT and not) influenced patients’ perceptions of treatment need and benefit by indicating that they preferred a particular treatment option for the patient as an individual. Whilst patients valued and were influenced by information conveyed by HCPs, they also drew on support from other sources and ultimately framed RCT participation decisions as their own. Patients’ willingness to be randomised hinged on perceptions of whether they stood to benefit from a particular treatment and the availability of those treatments outside of the trial.ConclusionThis study supports the need for training and support for healthcare professionals involved throughout the clinical pathway of patients eligible for RCTs, as all healthcare professionals who interact with patients have the potential to influence their perceptions of treatments being compared in the trial.Trial registrationOPTIMA ISRCTN42400492. Prospectively registered on 26 June 2012.Prepare for Kidney Care ISRCTN17133653. Prospectively registered on 31 May 2017.MARS 2 ISRCTN44351742. Retrospectively registered on 5 September 2018.

Clinical benefits of modifying the evening light environment in an acute psychiatric unit: A single-centre, two-arm, parallel-group, pragmatic effectiveness randomised controlled trial.

The impact of light exposure on mental health is increasingly recognised. Modifying inpatient evening light exposure may be a low-intensity intervention for mental disorders, but few randomised controlled trials (RCTs) exist. We report a large-scale pragmatic effectiveness RCT exploring whether individuals with acute psychiatric illnesses experience additional benefits from admission to an inpatient ward where changes in the evening light exposure are integrated into the therapeutic environment. From 10/25/2018 to 03/29/2019, and 10/01/2019 to 11/15/2019, all adults (≥18 years of age) admitted for acute inpatient psychiatric care in Trondheim, Norway, were randomly allocated to a ward with a blue-depleted evening light environment or a ward with a standard light environment. Baseline and outcome data for individuals who provided deferred informed consent were used. The primary outcome measure was the mean duration of admission in days per individual. Secondary outcomes were estimated mean differences in key clinical outcomes: Improvement during admission (The Clinical Global Impressions Scale-Improvement, CGI-I) and illness severity at discharge (CGI-S), aggressive behaviour during admission (Broset Violence Checklist, BVC), violent incidents (Staff Observation Aggression Scale-Revised, SOAS-R), side effects and patient satisfaction, probabilities of suicidality, need for supervision due to suicidality, and change from involuntary to voluntary admission. The Intent to Treat sample comprised 476 individuals (mean age 37 (standard deviation (SD) 13.3); 193 (41%) were male, 283 (59%) were female). There were no differences in the mean duration of admission (7.1 days for inpatients exposed to the blue-depleted evening light environment versus 6.7 days for patients exposed to the standard evening light environment; estimated mean difference: 0.4 days (95% confidence interval (CI) [-0.9, 1.9]; p = 0.523). Inpatients exposed to the blue-depleted evening light showed higher improvement during admission (CGI-I difference 0.28 (95% CI [0.02, 0.54]; p = 0.035), Number Needed to Treat for clinically meaningful improvement (NNT): 12); lower illness severity at discharge (CGI-S difference -0.18 (95% CI [-0.34, -0.02]; p = 0.029), NNT for mild severity at discharge: 7); and lower levels of aggressive behaviour (difference in BVC predicted serious events per 100 days: -2.98 (95% CI [-4.98, -0.99]; p = 0.003), NNT: 9). There were no differences in other secondary outcomes. The nature of this study meant it was impossible to blind patients or clinical staff to the lighting condition. Modifying the evening light environment in acute psychiatric hospitals according to chronobiological principles does not change duration of admissions but can have clinically significant benefits without increasing side effects, reducing patient satisfaction or requiring additional clinical staff. Clinicaltrials.gov NCT03788993; 2018 (CRISTIN ID 602154).

A review of Neurosurgical RCTs in the Cochrane Database of Systematic Reviews: Key findings and implications for future research

Evidence available to clinicians and patients to inform treatment decisions is ideally produced by randomised controlled trials (RCT). The objective of this study was to assess the extent to which Neurosurgical practice is supported by RCT-level evidence. A search of the Cochrane Library was conducted to find reviews of the effectiveness of Neurosurgical operative interventions. Data were extracted on the intervention, patient population and outcome measures as well as the strength of evidence, as rated by the Cochrane authors. The extracted data were analysed to identify the gaps and areas of (in)consistency across the RCTs included within the Cochrane Reviews. A total of 52 Cochrane reviews met the inclusion criteria, which covered 8 Neurosurgical subspecialties. However, only 28 were published after 2015. There was limited coverage of multiple commonly performed Neurosurgical interventions and 9 reviews found no RCTs related to their selected topic. In 28 reviews, results were synthesized from 5 or fewer trials. Primary outcomes also varied among trials examining similar interventions. The overall quality rating of the evidence for the different subspecialties varied, with the majority of reviews rating the evidence as being from very low to low. The RCT level evidence supporting Neurosurgical practice is varied and the outcomes tested remain predominantly heterogenous. There remain important Neurosurgical conditions where treatment strategies are not underpinned by high quality evidence. Pragmatic RCTs, well-designed observational studies as well as robust audit and registry processes may provide the real-world evidence for treatment decisions in Neurosurgical care.

Study protocol of a randomized control trial on the effectiveness of improvisational music therapy for autistic children

BackgroundMusic therapy is the clinical use of musical interventions to improve mental and physical health across multiple domains, including social communication. Autistic children, who have difficulties in social communication and often increased anxiety, tend to show a strong preference for music, because it can be structured and systematic, and therefore more predictable than social interaction. This makes music therapy a promising medium for therapeutic support and intervention. Previous clinical trials of music therapy compared to traditional therapy for autistic children have shown encouraging but nevertheless mixed results.Key aimsThe primary aim is to conduct a randomised controlled trial (RCT) of improvisational music therapy for autistic children and test its effectiveness in at improving social communication and wellbeing, and to reduce anxiety.Research planThe RCT will be conducted with 200 autistic children in the UK aged 7 to 11 years old. Participants will be randomly assigned to either improvisational music therapy or support as usual. The trial will be an assessor-blind, pragmatic two-arm cluster RCT comparing the impact of 12-weeks of improvisational music therapy in addition to support as usual, vs. support as usual for autistic children.MethodsResearchers who are blind to which arm the children are in will conduct assessments and obtain data via caregiver reports. The primary outcome will be the absolute change in the total score of the Brief Observation of Social Communication Change (BOSCC) assessed at baseline, T1 (13 weeks) and T2 (39 weeks) follow-ups. The BOSCC consists of specific items that were developed to identify changes in social-communication behaviours. Secondary outcome measures include: (1) Parent reported anxiety scale for youth with ASD (Note that we do not use the term ‘ASD’ or Autism Spectrum Disorder, because many autistic people feel it is stigmatising. Instead, we use the term ‘autism’) (PRAS-ASD) (2) Young Child Outcome Rating Scale, for wellbeing (YCORS), (3) Strengths and Difficulties Questionnaire (SDQ); and (4) Vineland Adaptive Behaviour Scale (VABS). (5) The Children’s Communication Checklist-2 (CCC-2) will be completed to evaluate pragmatic speech with fluent speakers only; (6) The Music Engagement Scale (MES); and (7) Assessment of the Quality of Relationship (AQR) will be used to evaluate the child-therapist relationships using video-analysis of music therapy sessions. Additional data will be collected by administering the Wechsler Abbreviated Scale of Intelligence (WASI-II), Music at Home Questionnaire (M@H), and children’s versions of the Empathy Quotient (EQ) and Systemizing Quotient (SQ). Audio and video data from the therapy sessions will be collected and analysed (using both human and computer-based feature-coding, e.g., machine learning and AI-driven methods) to identify how music and non-musical interactions foster change throughout the therapy.DiscussionThis study aims to observe if the interactions, engagement, and therapeutic modalities fostered during music therapy sessions can translate to non-musical contexts and improve autistic children’s social communication skills, identifying possible mediating factors contributing to the effectiveness of music therapy, potentially informing policy making and governance.Trial registrationThis randomised control trial is registered with the NIH U.S. National Library of Medicine: https://clinicaltrials.gov/search?term=NCT06016621, clinicalTrials.gov Identifier: NCT0601662, Registration Date 19th August 2023.

Evaluation of the analytical and clinical performance of a high-sensitivity troponin I point-of-care assay in the Mersey Acute Coronary Syndrome Rule Out Study (MACROS-2).

The objective of this study is to evaluate the analytical and diagnostic performance of a high-sensitivity point-of-care (POC) cardiac troponin I assay, the Quidel TriageTrue™ (QuidelOrtho Inc, San Diego, USA), compared to central laboratory testing (CLT) in accelerated diagnostic protocols (ADP) in real time in a clinical environment. In a nested sub-study of a pragmatic randomised control trial, consecutive patients with suspected acute coronary syndrome (ACS) and chest pain <12 h duration were randomised to the ESC 0/1 and 0/3-h ADP. Subjects underwent sampling for Quidel TriageTrue POC hs-TnI whole blood and plasma, CLT hs-TnT Roche Elecsys and a validated, NICE approved CLT High sensitivity cardiac troponin I (hs-TnI) (Siemens Attellica) at each time point. Assay imprecision was assessed by repeat analysis of whole blood samples at three levels (low, near 10 % CV 5-10 ng/L, medium, approximating 99th percentile 15-25 ng/L and high, 3-5 times the 99th percentile, 60-100 ng/L). Final diagnosis was adjudicated at 6weeks by Roche hs-TnT using the 4th universal definition of myocardial infarction (MI). A total of 1,157 patients consented and had both investigational POC whole blood and plasma and central lab hs-cTn available. The median age was 59, 47.2 % were female and 15 % had suffered a previous MI. Assay imprecision of whole blood POC TriageTrue revealed 10 % CV at 8.6 ng/L (>50 % lower than 99th percentile [20.5 ng/L]) and a 20 % CV at 1.2 ng/L. Receiver operator characteristics (ROC) curves were computed for each assay against adjudicated index type 1 MI to study clinical performance. At all-time points there were excellent performance for whole blood POC TriageTrue: area under the curve (AUC) 0.97 [95 % CI 0.94-098], 0.98 [95 % CI 0.97-1.00] and 0.95 [95 % CI 0.92-0.98] at time 0, 1 and 3 h respectively. There was statistical equivalence for performance of whole blood and plasma POC TriageTrue hs-TnI and laboratory Siemens Atellica hs-TnI. The whole blood POC TriageTrue hs-TnI assay demonstrates imprecision levels consistent with high sensitivity characteristics and has a clinical performance equivalent to an established, validated and NICE approved laboratory Siemens Atellica hs-TnI.

A pilot pragmatic randomized controlled trial of a nicotine metabolite ratio-guided smoking cessation intervention in a lung health and screening program

IntroductionPatients with pulmonary nodules detected through lung cancer screening or as incidental findings are often followed in lung health and screening programs. The use of personalized pharmacotherapy for smoking cessation informed by the nicotine metabolite ratio (NMR), a measure of nicotine metabolism, has not yet been evaluated in this setting. This pilot randomized controlled trial (RCT) evaluated the feasibility of conducting a larger trial. MethodsThrough a pragmatic RCT design, participants were recruited from a Mid-Atlantic lung health and screening program. Eligible participants smoked >5 cigarettes per day and completed a blood draw to determine NMR before being randomized to standard or NMR-guided care treatment arms. Standard care participants were offered nicotine replacement therapy (NRT) or varenicline and a referral to phone-based smoking cessation counseling. NMR-guided participants received standard care except they were provided a personalized medication recommendation based on their NMR. Study outcomes included measures of feasibility, medication uptake, and treatment matching (i.e., uptake of the optimal medication). ResultsMore than 80 % of 205 screened patients were eligible. However, only 37 (22 %) of these patients enrolled in the study, with a mean age of 65 years, 43 % female, and 25 % Black. Nearly all patients who declined cited a disinterest in smoking cessation. Participants in both treatment arms had high rates of medication uptake (68 %), with NMR-guided participants showing a trend towards greater treatment matching (55 % vs. 29 %). ConclusionsThe results of this pilot study provide support for conducting a larger RCT of an NMR-guided smoking cessation intervention in a lung health and screening setting. Consideration should be given to augmenting the intervention to address barriers to study entry.

Beta-blocker initiation under dobutamine infusion in acute advanced heart failure: a target trial emulation with observational data.

In patients with advanced heart failure requiring dobutamine infusion, it is usually recommended to initiate beta-blockers after weaning from dobutamine. However, beta-blockers are sometimes initiated under dobutamine infusion in a real-world scenario. The association between such early beta-blocker initiation with clinical outcomes is unknown. Therefore, this study investigates the association between initiating beta-blockers under dobutamine infusion and survival outcomes. This observational study with a multicentre inpatient-care database emulated a pragmatic randomized controlled trial (RCT) of the beta-blocker initiation strategy. First, 1151 patients on dobutamine and not on beta-blockers on the day of heart failure admission (Day 0) were identified. Among 1095 who met eligibility criteria, patients who were eventually initiated beta-blockers under dobutamine infusion by Day 7 (early initiation strategy) were 1:1 matched to those who were not initiated (conservative strategy). The methods of cloning, censoring, and weighting were applied to emulate the target trial. Patients were followed up for up to 30 days. The primary outcome was all-cause death. Among 780 matched patients (median age, 81 years), the adjusted hazard ratio was 1.11 (95% confidence interval 0.75-1.64, P = 0.59) for the early initiation strategy. The estimated 30-day all-cause mortalities in the early initiation strategy and the conservative strategy were 19.3% (10.6-30.7) and 16.2% (9.2-25.3), respectively. The results were consistent when we used different days to determine strategies (i.e. 5 and 9) instead of 7 days. The present observational study emulating a pragmatic RCT found no positive or negative association between beta-blocker initiation under dobutamine infusion and overall survival.

Medical Assistant Health Coaching for Type 2 Diabetes in Primary Care: Results From a Pragmatic Cluster Randomized Controlled Trial.

This cluster (clinic-level) randomized controlled trial (RCT) compared medical assistant (MA) health coaching (MAC) with usual care (UC) among at-risk adults with type 2 diabetes in two diverse real-world primary care environments: a federally qualified health center (FQHC; Neighborhood Healthcare) and a large nonprofit private insurance-based health system (Scripps Health). A total of 600 adults with type 2 diabetes who met one or more of the following criteria in the last 90 days were enrolled: HbA1c ≥8% and/or LDL cholesterol ≥100 mg/dL and/or systolic blood pressure (SBP) ≥140 mmHg. Participants at MAC clinics received in-person and telephone self-management support from a specially trained MA health coach for 12 months. Electronic medical records were used to examine clinical outcomes in the overall sample. Behavioral and psychosocial outcomes were evaluated in a subsample (n = 300). All clinical outcomes improved significantly over 1 year in the overall sample (P < 0.001). The reduction in HbA1c was significantly greater in the MAC versus UC group (unstandardized Binteraction = -0.06; P = 0.002). A significant time by group by site interaction also showed that MAC resulted in greater improvements in LDL cholesterol than UC at Neighborhood Healthcare relative to Scripps Health (Binteraction = -1.78 vs. 1.49; P < 0.05). No other statistically significant effects were observed. This was the first large-scale pragmatic RCT supporting the real-world effectiveness of MAC for type 2 diabetes in U.S. primary care settings. Findings suggest that this team-based approach may be particularly effective in improving diabetes outcomes in FQHC settings.

Strengths, challenges, and strategies for implementing pragmatic multicenter randomized controlled trials (RCTs): example of the Personalized Citizen Assistance for Social Participation (APIC) trial

BackgroundRandomized controlled trials (RCTs) are rigorous scientific research designs for evaluating intervention effectiveness. However, implementing RCTs in a real-world context is challenging. To develop strategies to improve its application, it is essential to understand the strengths and challenges of this design. This study thus aimed to explore the strengths, challenges, and strategies for improving the implementation of a pragmatic multicenter, prospective, two-arm RCT evaluating the effects of the Personalized Citizen Assistance for Social Participation (Accompagnement-citoyen Personnalisé d’Intégration Communautaire: APIC; weekly 3-h personalized stimulation sessions given by a trained volunteer over a 12-month period) on older adults’ health, social participation, and life satisfaction.MethodsA multiple case study was conducted with 14 participants, comprising one research assistant, seven coordinators, and six managers of six community organizations serving older adults, who implemented the APIC in the context of a RCT. Between 2017 and 2023, qualitative data were extracted from 24 group meetings, seven semi-directed interviews, emails exchanged with the research team, and one follow-up document.ResultsAged between 30 and 60 (median ± SIQR: 44.0 ± 6.3), most participants were women from organizations already offering social participation interventions for older adults and working with the public sector. Reported strengths of this RCT were its relevance in assessing an innovative intervention to support healthy aging, and the sharing of common goals, expertise, and strategies with community organizations. Challenges included difficulties recruiting older adults, resistance to potential control group assignments, design complexity, and efforts to mobilize and engage volunteers. The COVID-19 pandemic lockdown and health measures exacerbated challenges related to recruiting older adults and mobilizing volunteers and complicated delivery of the intervention. The strategies that mostly overcame difficulties in recruiting older adults were reducing sample size, simplifying recruitment procedures, emphasizing the health follow-up, extending partnerships, and recognizing and supporting volunteers better. Because of the lockdown and physical distancing measures, the intervention was also adapted for remote delivery, including via telephone or videoconferencing.ConclusionKnowledge of the strengths and challenges of pragmatic RCTs can contribute to the development of strategies to facilitate implementation studies and better evaluate health and social participation interventions delivered under real-life conditions.Trial registrationNCT03161860; Pre-results. Registered on May 22, 2017.

Implementing geriatric assessment for dose optimization of CDK 4/6 inhibitors in older breast cancer patients (IMPORTANT trial): A pragmatic randomized-controlled trial.

TPS1132 Background: Current evidence from both randomized trials and real-world evidence studies suggests that older patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer derive clinical benefit from the addition of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy. However, a higher risk for adverse events due to CDK4/6 inhibitors among older patients is evident, leading to a trend of initiating CDK4/6 inhibitors at a lower dose in clinical practice, though without evidence. The aim of the present randomized trial is to investigate whether lower initial dose of CDK4/6 inhibitors combined with endocrine therapy is comparable to full dose in older patients with advanced HR+/HER2-breast cancer that are assessed as vulnerable/frail based on comprehensive geriatric assessment (CGA). Methods: We designed a multi-national, open-label, pragmatic randomized controlled trial with non-inferiority approach. Patients ≥70 years old with advanced HR+/HER2- breast cancer with no curative intention, no prior treatment in an advanced setting, and suitable to receive a combination of CDK4/6 inhibitors plus endocrine therapy according to treating physician, are eligible for study inclusion. After informed consent, included patients fill out a self-administered CGA tool and categorized accordingly to fit, vulnerable, or frail, depending on the number of impaired CGA domains. Fit patients receive full dose of CDK4/6 inhibitors and endocrine therapy whereas vulnerable/frail patients are randomized to either -1 level lower CDK4/6 inhibitor dose or full dose and endocrine therapy. The randomization is stratified by type of CDK 4/6 inhibitor, type of endocrine therapy, and level of vulnerability. The treating physician decides on the choice of CDK4/6 inhibitor (abemaciclib, ribociclib, palbociclib) and endocrine therapy (aromatase inhibitors, fulvestrant). The primary endpoint is time to treatment failure whereas secondary endpoints include overall treatment utility, progression-free survival, overall survival, time to chemotherapy initiation, toxicity, quality-of-life, time to quality-of-life deterioration and cost-effectiveness. The evaluation of disease progression, toxicity assessment, and the follow-up strategy resembles clinical practice to enhance the pragmatic design approach of IMPORTANT trial. The trial also enables a hybrid decentralized approach where the initial patient visit is in-person whereas the visits for efficacy and toxicity evaluation can be performed digitally according to local practices. In total, 495 patients are planned to be included to allow 346 vulnerable/frail patients to be randomized. Enrollment: The trial is open for recruitment since February 2024 with a recruitment period of 30 months. Clinical trial information: NCT06044623 .

PERI-operative biologic DMARD management: Stoppage or COntinuation during orthoPaEdic operations (the PERISCOPE trial) – a study protocol for a pragmatic, UK multicentre, superiority randomised controlled trial with an internal pilot, economic evaluation and nested qualitative study

IntroductionBiological disease-modifying antirheumatic drugs (bDMARDs) have revolutionised the treatment of inflammatory arthritis (IA). However, many people with IA still require planned orthopaedic surgery to reduce pain and improve function. Currently,...

An Australian Football Themed Health Behaviour Change Intervention for Men With Cardiovascular Disease is Feasible and Acceptable: Results From a Feasibility Randomised Trial

Physical activity (PA) and weight management are critical for cardiovascular disease (CVD) secondary prevention. However, PA adherence during or after cardiac rehabilitation is low. Here, we assess the feasibility and acceptability of the Australian football-themed Aussie Fans in Training (Aussie-FIT) program and associated trial procedures when adapted for men with CVD. A pragmatic randomised control trial, with waitlist control arm, and follow-up measures at 3 and 6 months. Men with a CVD diagnosis and body mass index ≥25 kg/m2 were recruited from community and clinical settings, and randomised, following baseline measures of health and health behaviours. The intervention arm attended 12 face-to-face football-themed education and PA sessions. Feasibility (recruitment, retention, attendance, and adherence to trial procedures) was assessed via mixed methods. A total of 74% (64/86) of participants expressing interest met the eligibility criteria. Of those, 49 men (mean age=61.4, standard deviation=9.5, mean body mass index=31.3, standard deviation=4.2) were randomised. Program attendance rates (87% attended ≥80% of sessions) and retention (92%) were high. Trial retention at the primary end point (3 months) was high (86%) and at the 6-month follow-ups reduced to 67%. Program and trial procedures were acceptable, except for the request to visit a pathologist for the blood draw. Using a football theme and setting may be a feasible way to engage men with CVD in health behaviour change. Given the existing pilot evidence for men at risk of CVD, and that recruitment rates were under the target, trialling a program for men with or at risk of CVD is recommended.

Alemtuzumab, Cladribine, Fingolimod, Natalizumab, and Rituximab as First-Line Treatments in Adults With Highly Active Relapsing-Remitting Multiple Sclerosis

What Is the Problem? Relapsing-remitting multiple sclerosis (RRMS), the most common disease course of multiple sclerosis (MS), is a chronic immune-mediated disease with clearly defined episodes of new or increasing neurologic symptoms followed by periods of relative stability. In contrast, the highly active, aggressive disease course leads to rapid disability, and these patients face an unmet need. The principal goal of MS treatment is to delay and prevent the accumulation of disability by reducing the frequency of relapses. Currently reimbursed first-line drugs fail to prevent the consequences of irreversible damage to the nervous system. There has been a paradigm shift in clinical practice toward the use of a high-efficacy treatment strategy as early as possible during the inflammatory process to provide optimal clinical benefits in preserving neurologic function in patients with highly active RRMS. What Did We Do? A systematic review of the clinical effectiveness and safety of alemtuzumab, natalizumab, cladribine, fingolimod, and rituximab relative to current first-line drugs in adults with highly active RRMS was conducted; it identified post hoc subgroup analyses from 5 randomized controlled trials (RCTs) and 1 prospective comparative cohort study. What Did We Find? Evidence was uncertain and conclusions were limited by risk of bias and small sample sizes; conclusions for some outcome comparisons were also limited by imprecision and incomplete reporting. Compared to placebo, cladribine and natalizumab may result in a clinically important reduction in relapses, disability, and key MRI lesions. Alemtuzumab may result in a clinically important reduction in relapses compared to interferon, while fingolimod may result in a clinically important reduction in relapses compared to placebo. The clinical evidence was insufficient to determine the effect of fingolimod on relapses when compared with interferon. Harms outcomes, when reported, appeared consistent with the known harms profile of the drugs. Assessment of the effectiveness and safety of rituximab could not be performed due to the lack of evidence. Evidence was also lacking for many important outcomes such as health-related quality of life (HRQoL), instrumental activities of daily living, symptoms, and cognitive outcomes. No evidence could be identified to inform on treatment sequencing. Two pragmatic RCTs (the TREAT-MS and DELIVER-MS trials) are currently ongoing, aiming to compare an early, high-efficacy treatment strategy versus a traditional escalation treatment strategy, which may inform treatment sequencing. Further research is needed to compensate for clinical data gaps to inform an appropriate and relevant economic evaluation. What Does This Mean? Jurisdictions may reconsider the current reimbursement criteria for drugs used in the first-line setting specifically for adults demonstrating highly active RRMS; however, caution should be taken given the gaps and uncertainty in evidence. Upon request from public drug plans, this review may inform a future implementation advice panel or expert committee recommendation.

Behavioral skills training for teaching safety skills to mental health service providers compared to training-as-usual: a pragmatic randomized control trial.

Violence in the healthcare workplace has been a global concern for over two decades, with a high prevalence of violence towards healthcare workers reported. Workplace violence has become a healthcare quality indicator and embedded in quality improvement initiatives of many healthcare organizations. The Centre for Addiction and Mental Health (CAMH), Canada's largest mental health hospital, provides all clinical staff with mandated staff safety training for self-protection and team-control skills. These skills are to be used as a last resort when a patient is at imminent risk of harm to self or others. The purpose of this study is to compare the effectiveness of two training methods of this mandated staff safety training for workplace violence in a large psychiatric hospital setting. Using a pragmatic randomized control trial design, this study compares two approaches to teaching safety skills CAMH's training-as-usual (TAU) using the 3D approach (description, demonstration and doing) and behavioural skills training (BST), from the field of applied behaviour analysis, using instruction, modeling, practice and feedback loop. Staff were assessed on three outcome measures (competency, mastery and confidence), across three time points: before training (baseline), immediately after training (post-training) and one month later (follow-up). This study was registered with the ISRCTN registry on 06/09/2023 (ISRCTN18133140). With a sample size of 99 new staff, results indicate that BST was significantly better than TAU in improving observed performance of self-protection and team-control skills. Both methods were associated with improved skills and confidence. However, there was a decrease in skill performance levels at the one-month follow-up for both methods, with BST remaining higher than TAU scores across all three time points. The impact of training improved staff confidence in both training methods and remained high across all three time points. The study findings suggest that BST is more effective than TAU in improving safety skills among healthcare workers. However, the retention of skills over time remains a concern, and therefore a single training session without on-the-job-feedback or booster sessions based on objective assessments of skill may not be sufficient. Further research is needed to confirm and expand upon these findings in different settings.

VaNoLaH trial: a study protocol—a multinational randomised controlled trial including two identical substudies comparing vaginal versus vNOTES (vaginal natural orifice transluminal surgery) hysterectomy or laparoscopic versus vNOTES hysterectomy

IntroductionHysterectomy is one of the most common surgeries performed in women. Minimally invasive methods are on the rise globally as they have been shown to decrease surgical morbidity compared with...

Abstract 3942: Mailed at-home self-sampling for HPV testing increases screening participation among under-screened patients in a U.S. safety net health system: Results of the PRESTIS trial

Abstract Background: In global settings, self-sampling for human papillomavirus (HPV) testing is associated with a pooled 2-fold increase in cervical cancer screening participation over usual care among underscreened persons. The Prospective Evaluation of Self-Testing to Increase Screening (PRESTIS) Trial is the first pragmatic randomized controlled trial (RCT) in the U.S. to evaluate the effectiveness of mailed at-home self-sampling for HPV testing in a safety net health system setting. Safety net systems provide care to medically underserved individuals at elevated cervical cancer risk. We hypothesized that patients who were mailed a self-sampling kit would have greater screening participation compared with those receiving usual care; and that patient navigation, a patient-centered intervention to address barriers to care, would further increase participation. Methods: PRESTIS is a three-arm pragmatic RCT of n=2,270 patients in a U.S. safety net health system who are under-screened for cervical cancer (i.e., no Pap in 3.5 years or Pap/HPV co-test in 5.5 years). Eligible participants were identified through the electronic health record (EHR) and randomized to arms: 1) telephone recall to provider-performed screening (usual care); 2) telephone recall + mailed self-sampling kit for HPV testing; or 3) telephone recall + mailed self-sampling kit + telephone-based patient navigation. Self-sampled swabs were tested for high-risk (HR)-HPV. HR-HPV+ patients were navigated to clinical follow-up. The primary outcome, incidence of screening participation, was ascertained by EHR review at 6 months post-randomization and defined as return of a completed kit or attendance for provider-performed screening. Results: Participants were enrolled 02/2020-08/2023. Primary outcomes have been ascertained for n=2,115 participants. Participants were predominantly Hispanic/Latina (68.6%); 53.4% indicated Spanish as primary language; and 60.3% were uninsured. Mean age was 47.9 years (SD: 10.4 years); median time since last screening test was 9.5 years (range: 1.6-21.7 years). In intent-to-treat analyses, screening participation was 15.3% (95% CI 13.0% - 17.9%) in Arm 1; 44.0% (40.4% - 47.6%) in Arm 2; and 51.4% (47.7% - 55.0%) in Arm 3. Relative incidence of screening in Arms 2 and 3 versus Arm 1 was 2.90 (2.42 - 3.47) and 3.36 (2.82 - 4.01), respectively. Relative incidence of screening in Arm 3 versus Arm 2 was 1.16 (1.04 - 1.29). Conclusion: Compared with usual care, mailed at-home self-sampling increased screening participation among an under-screened population by almost three-fold when used alone and over 3.3-fold when combined with telephone-based patient navigation. After FDA approval, self-sampling for HR-HPV testing has the potential to dramatically increase participation in cervical cancer screening in underserved populations. Citation Format: Jane R. Montealegre, Elizabeth Y. Chiao, Matthew L. Anderson, Susan G. Hilsenbeck, Shaun Bulsara, Susan L. Parker, Maria Daheri, Trisha L. Amboree, Kathleen M. Schmeler, Maria L. Jibaja-Weiss, Mohammad Zare, Ashish A. Deshmukh, Michael E. Scheurer. Mailed at-home self-sampling for HPV testing increases screening participation among under-screened patients in a U.S. safety net health system: Results of the PRESTIS trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3942.

The Efficacy of Real-time Computer-aided Detection of Colonic Neoplasia in Community Practice: A Pragmatic Randomized Controlled Trial

BackgroundThe use of computer-aided detection (CADe) has increased the adenoma detection rates (ADR) during colorectal cancer (CRC) screening/surveillance in randomized controlled trials (RCT) but has not shown benefit in real-world implementation studies. We performed a single-center pragmatic RCT to evaluate the impact of real-time CADe on ADR in colonoscopy performed by community gastroenterologists. MethodsWe enrolled 1100 patients undergoing colonoscopy for CRC screening, surveillance, positive fecal-immunohistochemical tests, and diagnostic indications at one community-based center from 09/2022 to 03/2023. Patients were randomly assigned (1:1) to traditional-colonoscopy or real-time CADe Blinded pathologists analyzed histopathologic findings. The primary outcome was adenoma detection rate (ADR, the percentage of patients with at least 1 histologically proven adenoma or carcinoma). Secondary outcomes were adenomas detected per colonoscopy (APC), sessile-serrated lesion detection rate (SSLDR), and non-neoplastic resection rate. ResultsThe median age was 55.5 (IQR 50-62), 61% were female, 72.7% were Hispanic ethnicity, and 9.1% had inadequate bowel preparation. The ADR for the CADe group was significantly higher than the traditional-colonoscopy group (42.5% vs. 34.4%, p=0.005). The mean APC was significantly higher in the CADe group compared to the traditional-colonoscopy group (0.89±1.46 vs. 0.60±1.12, p<0.001). The improvement in adenoma detection was driven by increased detection of <5 mm adenomas. CADe had a higher SSLDR than traditional-colonoscopy (4.7% vs. 2.0%, p=0.01) The improvement in ADR with CADe was significantly higher in the first half of the study (47.2% vs. 33.7%, p=0.002) compared to the second half (38.7% vs. 34.9%, p=0.33). ConclusionsIn a single-center pragmatic randomized controlled trial, real-time CADe modestly improved ADR and APC in average-detector community endoscopists. (ClinicalTrials.gov number, NCT05963724).

Adapting, implementing and evaluating a navigation intervention for older people with cancer and their family caregivers in six countries in Europe: the Horizon Europe-funded EU NAVIGATE project.

Navigation interventions could support, educate and empower older people with cancer and/or their family caregivers by addressing barriers and ensuring timely access to needed services and resources throughout the continuum of supportive, palliative and end-of-life care. European Union (EU) NAVIGATE is an interdisciplinary and cross-country Horizon Europe-funded project (2022-2027) aiming to evaluate the effectiveness, cost-effectiveness and implementation of a navigation intervention for older people with cancer and their family caregivers in Europe. EU NAVIGATE aims to advance the evidence on cancer patient navigation in Europe. Adaptation, implementation and evaluation of a navigation intervention with an international pragmatic randomized controlled trial (RCT) and embedded mixed-method process evaluation at its core. A logic model guides dissemination and impact-generating strategies. EU NAVIGATE involves six experienced EU academic partners; one EU national cancer league with their affiliated academic partner; three EU dissemination partners; and a Canadian partner. We adapted the Canadian Navigation: Connecting, Advocating, Resourcing, and Engaging (Nav-CARE©) volunteer programme to healthcare contexts in Belgium, Ireland, Italy, the Netherlands, Poland and Portugal following the new ADAPT guidance. Nav-CARE was developed over the past 15 years and supports people with declining health and their families to improve their quality of life and well-being, foster empowerment and facilitate timely and equitable access to healthcare and social services. In EU NAVIGATE, the navigation intervention is being provided by trained and mentored social workers in Poland and by trained and mentored volunteers in the other five countries. Via a pragmatic RCT with process evaluation, we implement and evaluate the navigation intervention to study its impact on older people with cancer and their family caregivers. We also aim to understand its cost-effectiveness, how to optimally implement it in different countries, and its differential effects in patient subgroups. We will also map existing cancer navigation interventions in Europe, the United States and Canada to position EU NAVIGATE within the field of navigation interventions worldwide. EU NAVIGATE aims to deliver high-quality evidence on a navigation intervention for older people with cancer in Europe and to develop practice and policy recommendations for sustainable implementation of navigation interventions in Europe and beyond.

The HOMESIDE Study-A Research Project to Support People Living With Dementia and Their Family Caregivers: Preliminary Report on Reading Intervention.

The behavioral and psychological symptoms of dementia (BPSD) can be challenging for family caregivers to cope with, leading to distress and fatigue. It is therefore important to offer effective strategies to reduce the impact of BPSD. The HOMESIDE randomized controlled trial (RCT) was testing purposefully developed interventions to improve the quality of life and wellbeing of dyads of people with dementia and family caregivers as a result of reduction of BPSD. HOMESIDE RCT was conducted in Australia, Germany, Norway, Poland and the United Kingdom between 2019 and 2022. The study design was a three-arm parallel-group single-blinded, pragmatic RCT with a sample size of 432 dyads. Dyads were randomly allocated to one of three treatment conditions: Music Intervention plus Standard Care; or Reading Intervention plus Standard Care; or Standard Care only. The Reading Intervention (RI) within the HOMESIDE RCT aimed to evoke shared discussion, reminiscence, meaningful shared experiences and consequently enrich everyday life, interaction and the emotional connection between the caregiver (CG) and carereceiver (CR); as well as to enhance activities of daily living and to promote relaxation or stimulation as appropriate. This paper describes the underlying conceptual framework, the content, and delivery of the Reading Intervention within the HOMESIDE RCT.

Rationale and design of the THIRST Alert feasibility study: a pragmatic, single-centre, parallel-group randomised controlled trial of an interruptive alert for oral fluid restriction in patients treated with intravenous furosemide

IntroductionAcute heart failure (HF) is a major cause of unplanned hospitalisation characterised by excess body water. A restriction in oral fluid intake is commonly imposed on patients as an adjunct...