Multisite Randomized Control Trial Research Articles

Generalizability of Randomized Clinical Trial Outcomes for Diabetes Control Resulting From Bariatric Surgery

Objective: To assess the external validity of randomized controlled trials (RCTs) of bariatric surgical treatment on diabetes control. Background: Multisite RCTs provide the strongest evidence supporting clinical treatments and have the greatest internal validity. However, characteristics of trial participants may not be representative of patients receiving treatment in the real world. There is a need to assess how the results of RCTs generalize to all contemporary patient populations undergoing treatments. Methods: All patients undergoing sleeve gastrectomy at University of California Los Angeles (UCLA) between January 8, 2018 and May 19, 2023 had their baseline characteristics, weight change, and diabetes control compared with those enrolled in the surgical treatment and medications potentially eradicate diabetes efficiently (STAMPEDE) and diabetes surgery study (DSS) RCTs of bariatric surgery’s effect on diabetes control. Weight loss and diabetes control were compared between UCLA patients who did and did not fit the entry criteria for these RCTs. Results: Only 65 (17%) of 387 patients with diabetes fulfilled the eligibility criteria for STAMPEDE, and 29 (7.5%) fulfilled the criteria for DSS due to being older, having higher body mass index, and lower HbA1c. UCLA patients experienced slightly less weight loss than patients in the RCTs but had similar diabetes control. The 313 (81%) patients not eligible for study entry into either RCT had similar long-term diabetes control as those who were eligible for the RCTs. Conclusions: Even though only a very small proportion of patients undergoing bariatric surgery met the eligibility criteria for the 2 major RCTs, most patients in this contemporary cohort had similar outcomes. Diabetes outcomes from STAMPEDE and DSS generalize to most patients undergoing bariatric surgery for diabetes control.

Efficacy of Early Intervention for Infants With Cerebral Palsy in an LMIC: An RCT.

To test efficacy of a parent-delivered multidomain early intervention (Learning through Everyday Activities with Parents [LEAP-CP]) for infants with cerebral palsy (CP) compared with equal-dose of health advice (HA), on (1) infant development; and (2) caregiver mental health. It was hypothesized that infants receiving LEAP-CP would have better motor function, and caregivers better mental health. This was a multisite single-blind randomized control trial of infants aged 12 to 40 weeks corrected age (CA) at risk for CP (General Movements or Hammersmith Infant Neurologic Examination). Both LEAP-CP and HA groups received 15 fortnightly home-visits by a peer trainer. LEAP-CP is a multidomain active goal-directed intervention. HA is based on Key Family Practices, World Health Organization. Primary outcomes: (1) infants at 18 months CA: Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT mobility); and (2) caregiver: Depression Anxiety and Stress Scale. Of eligible infants, 153 of 165 (92.7%) were recruited (86 males, mean age 7.1±2.7 months CA, Gross Motor Function Classification System at 18 m CA: I = 12, II = 25, III = 9, IV = 18, V = 32). Final data were available for 118 (77.1%). Primary (PEDI-CAT mobility mean difference = 0.8 (95% CI -1.9 to 3.6) P = .54) and secondary outcomes were similar between-groups. Modified-Intention-To-Treat analysis on n = 96 infants with confirmed CP showed Gross Motor Function Classification System I and IIs allocated to LEAP-CP had significantly better scores on PEDI-CAT mobility domain (mean difference 4.0 (95% CI = 1.4 to 6.5), P = .003) compared with HA. Although there was no overall effect of LEAP-CP compared with dose-matched HA, LEAP-CP lead to superior improvements in motor skills in ambulant children with CP, consistent with what is known about targeted goal-directed training.

Stop and Think: A Case Study Illustrating the Implementation of Bright IDEAS-YA Being Delivered via Telehealth to a Young Adult Cancer Patient.

Bright IDEAS-Young Adults (Bright IDEAS-YA) is a problem-solving skills training intervention that has been adapted for young adults with cancer. Presently, a multisite randomized control trial is being conducted to determine Bright IDEAS-YA's efficacy in supporting a young adult population. This case study demonstrates the young adult adaptation of Bright IDEAS - Bright IDEAS-YA - being delivered to a young adult cancer patient via telehealth. Telehealth is a novel delivery method for Bright IDEAS and Bright IDEAS-YA that was established due to COVID-19 safety precautions. The patient, who reported challenges in several life domains, was taught how to apply the Bright IDEAS-YA framework over six telehealth sessions. After completing the Bright IDEAS-YA framework, the patient reported increased feelings of confidence in managing new stressors, which was corroborated through outcome measures delivered during and following intervention. This case illustrates how early psychosocial intervention following a cancer diagnosis, delivered via telehealth, can help patients develop and implement personal strategies to reduce stress levels.

Testing the effectiveness of a Fatigue and Activity Management Education for Work (FAME-W) intervention for individuals with inflammatory arthritis: Study protocol for a randomized control trial.

A work-focused fatigue management intervention, Fatigue and Activity Management Education for Work (FAME-W) programme was developed for individuals with inflammatory arthritis (IA) to manage fatigue in order to maintain demands of their work activities and tasks. This paper presents the protocol for a randomized control trial that will test the effectiveness and acceptability of FAME-W in improving work performance. This protocol presents a multisite randomized control trial and mixed methods process evaluation. Eligible participants will be aged 18-65 years with a diagnosis of inflammatory arthritis and will be in paid employment. The primary outcome of the study will be Work Role Functioning (WRF) questionnaire, and the secondary outcomes will be fatigue, mood, health-related quality of life (HRQOL) and pain. Data will be collected immediately pre- and post-intervention and at 3months of follow-up. The process evaluation will consist of focus groups and individual interviews to explore participants' experiences of FAME-W. Occupational therapists delivering the programme will complete a facilitator log to assess the fidelity and quality of intervention implementations. Facilitators will participate in individual interviews to explore intervention delivery and acceptability. Results will be expected to show that FAME-W will improve work performance by helping participants gain self-management strategies around managing fatigue and other symptoms related to fatigue. It is hoped that FAME-W will be an effective and acceptable intervention for individuals with IA in improving work performance by helping them manage their symptoms. ClinicalTrials.gov: NCT05138445, Registered on 30 November 2021.

“It was just right:” Patient experience, acceptability, and perceived utility of a novel financial navigation program in oncology.

279 Background: Cancer-related financial hardship is prevalent and associated with poor health outcomes. CAFÉ is a multi-site randomized control trial (RCT) testing a financial navigation intervention to reduce financial hardship for people newly diagnosed with cancer. Methods: The CAFÉ trial randomized participants (n=371) to usual care or one of two intervention arms. Participants randomized to the intervention arms received either brief (one proactive outreach) or extended (three proactive outreaches) contact from a navigator along with access to navigation services for 6 months. At the final outreach call, we asked participants to answer open-ended questions about the perceived acceptability and helpfulness of the program. Navigators recorded verbatim notes, and a trained qualitative methodologist conducted content analysis. Results: Among 69 participants (35 extended; 34 brief) who completed final outreach calls, to date, 65% were female, average age was 63 years, and 3 were Spanish-language speakers. Cancer diagnoses included: breast (35%), prostate (16%), colorectal (7%), lung (4%), and other (38%). Almost all (99%; 68) expressed high satisfaction with the navigation program. Most (83%; 57) reported easy rapport-building (e.g., sharing needs; feeling listened to). Most (81%; 56) found the frequency of outreach appropriate to their needs and reported navigators were accessible when needed (72%: 50). Most participants (84%; 58) found their experience helpful, including the proactive outreach and advocacy provided by the navigators. Useful program components included answering patients cost-related questions and identifying financial resources (74%; 41); satisfaction about the navigator’s expertise (72%; 50); and ongoing reminders about patient actions (e.g. applying for medical financial assistance) (48%; 33). Areas for improvement included offering more personalized financial resources; more support applying for such resources; extending the service beyond 6 months; and starting outreach closer to cancer diagnosis date. Brief arm participants less often endorsed appropriate frequency (74% vs 86%) and ease of contact (68% vs 77%) than those in the extended arm. Conclusions: Components of the CAFÉ financial navigation program found to be highly acceptable included proactive outreach, ongoing support and navigator knowledge; ease of rapport-building; and accessibility. Future analyses will determine the effectiveness of the CAFÉ program on financial, health and healthcare outcomes. Clinical trial information: NCT05018000 .

The Mindfulness-Based Kindness Curriculum for Preschoolers: An Applied Multi-Site Randomized Control Trial

ObjectivesThis study examined the impact of the Mindfulness-Based Kindness Curriculum (MBKC) on social-emotional, executive function, and academic skills of preschoolers.MethodSixteen preschool and 4K (4-year-old kindergarten) classrooms (245 children, 57.6% ethnically diverse, 69.8% low SES) were randomly assigned to either a curriculum-as-usual (CAU) or MBKC group taught by trained classroom teachers. Measures, as reported by children, teachers, and parents, were collected prior to and after implementation of the MBKC.ResultsTrained classroom teachers effectively implemented the MBKC. Teachers rated MBKC children significantly higher on outcome measures of social-emotional skills (e.g., sharing, prosocial skills, empathy), executive functioning (e.g., planning/organizing, working memory), and academic skills (e.g., physical development, language, math) than CAU children. Parents rated MBKC children as having significantly higher levels of cognitive empathy compared to parents’ ratings of CAU children. MBKC children were significantly more likely to engage in sharing behavior with a sick child, though children’s self-ratings indicated no effect of the MBKC on mindfulness skills or self-efficacy. Unlike previous research, the MBKC did not benefit initially lower functioning children more than initially higher functioning children.ConclusionsConsistent with previous research, children given the MBKC appeared to benefit in terms of higher social-emotional competency, prosocial behavior, and executive functioning. The MBKC proved to be a useful complement to their other social-emotional learning programming. The present study expands the literature on the application of mindfulness with preschool children and highlights important implications of teaching and measuring mindfulness skills in young children, thereby identifying specific issues to address in future studies.PreregistrationThis study was not preregistered.

Pain Informed Movement for people with knee osteoarthritis: Protocol for a pilot randomized controlled trial

ObjectiveConservative pain management strategies for knee osteoarthritis (KOA) have limited effectiveness and do not employ a pain-mechanism informed approach. Pain Informed Movement is a novel intervention combining mind-body techniques with neuromuscular exercise and pain neuroscience education (PNE), aimed at improving endogenous pain modulation. While the feasibility and acceptability of this program has been previously established, it now requires further evaluation in comparison to standard KOA care. DesignThis protocol describes the design of a pilot two-arm randomized controlled trial (RCT) with an embedded qualitative component. The primary outcome is complete follow-up rate. With an allocation ratio of 1:1, 66 participants (33/arm) (age ≥40 years, KOA diagnosis or meeting KOA NICE criteria, and pain intensity ≥3/10), will be randomly allocated to two groups that will both receive 8 weeks of twice weekly in-person exercise sessions. Those randomized to Pain Informed Movement will receive PNE and mind-body technique instruction provided initially as videos and integrated into exercise sessions. The control arm will receive neuromuscular exercise and standard OA education. Assessment will include clinical questionnaires, physical and psychophysical tests, and blood draws at baseline and program completion. Secondary outcomes are program acceptability, burden, rate of recruitment, compliance and adherence, and adverse events. Participants will be invited to an online focus group at program completion. ConclusionThe results of this pilot RCT will serve as the basis for a larger multi-site RCT aimed at determining the program's effectiveness with the primary outcome of assessing the mediating effects of descending modulation on changes in pain.

Study protocol paper for the multi-site feasibility evaluation of mobile and technology-assisted aftercare services for crisis stabilization units

BackgroundLaw enforcement frequently responds to substance abuse and mental health crises. Crisis stabilization units (CSUs) operate as a public-receiving facility to provide short-term stabilization services for individuals experiencing these crises and offer law enforcement an important alternative to arrest. However, there is limited understanding about how and when law enforcement decides to use CSUs. There is also the challenge of retaining individuals in treatment after CSU stabilization to prevent future crises and persistent engagement with police. This study will respond to these gaps by exploring CSU procedures and examining the feasibility and acceptability of a technology-assisted mobile aftercare intervention designed for individuals brought to a CSU by law enforcement.MethodsThis study will consist of three aims. Aim 1 will include qualitative interviews with law enforcement and CSU-affiliated mental health staff (n=80) regarding CSU utilization and collaboration logistics between the groups. Findings from Aim 1 will be synthesized for the development of an implementation guide of our intervention, mobile, and technology-assisted aftercare, designed for individuals brought to a CSU by law enforcement, during Aim 2. During Aim 2, intervention services will be pilot-tested for 6 months through a small sample (n=24), randomized control trial (RCT). Control participants will receive standard services available for individuals discharging from a CSU. Treatment participants will receive the mobile aftercare intervention. Qualitative and quantitative data will be collected at 2 weeks, 3 months, and 6 months post-recruitment for all study participants. Aims 1 and 2 will inform the design of a multi-site RCT to compare CSUs with and without mobile and technology-assisted aftercare (Aim 3).DiscussionThe study will offer decision making and procedural insight into law enforcement use of CSUs as an alternative to jail and provide opportunities to inform that process. This research will provide outcome trends for those who go through standard CSU services compared to those who receive mobile and technology-assisted aftercare services. The current study will inform a larger RCT efficacy study of CSUs with and without technology-assisted aftercare services.Trial registrationThis study was registered on ClinicalTrials.gov (reference #NCT04899934) on May 25, 2021.

Feasibility and acceptability of continuous identity cognitive therapy as a recovery-oriented suicide treatment for Veterans: A study protocol

BackgroundSuicide is a leading cause of death among Veterans, with rates significantly higher than the general population. To address this issue, it is crucial to develop and implement more effective treatments for Veterans with suicidal thoughts and/or behaviors, particularly those in the post-acute suicidal episode (PASE) stage. The present study aims to establish the feasibility and acceptability of a novel, recovery-oriented treatment called Continuous Identity Cognitive Therapy (CI-CT) for PASE Veterans. MethodsThis 3-year open-label pilot study will include three one-arm trials and a pilot randomized controlled trial (RCT). A total of 57 Veterans with a history of an acute suicidal episode within the previous year will be recruited. Primary outcome measures will include changes in personal recovery, suicidal thoughts, and behaviors. Secondary outcomes will include changes in self-identity, life satisfaction, and hopefulness. Feasibility and acceptability will be assessed through attendance and retention rates, drop-out rates, and client satisfaction. ConclusionThis study aims to develop and evaluate the feasibility and acceptability of a novel recovery-oriented intervention for Veterans experiencing PASE. If the intervention is found to be feasible and acceptable, a manualized version will be finalized and a large-scale multi-site RCT will be designed to assess its clinical efficacy on a broader Veteran population. The results of this trial will aid in the development of effective treatment and provide valuable insights into the preliminary feasibility, acceptability, and effectiveness of this approach in reducing suicidal thoughts and behaviors and promoting recovery and rehabilitation in this population.

A multi-site pilot randomized clinical trial of the Treatment and Education Approach for Childhood-onset Lupus (TEACH) program: study design and COVID-19 adaptations

BackgroundChildhood-onset Systemic Lupus Erythematosus (cSLE) is an autoimmune disease associated with fatigue, mood symptoms, and pain. Fortunately, these symptoms are potentially modifiable with psychological intervention such as cognitive-behavioral therapy (CBT). The Treatment and Education Approach for Childhood-onset Lupus (TEACH) program is a CBT intervention developed to target these symptoms for adolescents and young adults with cSLE. This pilot randomized controlled trial (RCT) aims to determine the feasibility and effect of TEACH for youth with cSLE. Adjustments to the study protocol following the COVID-19 pandemic are also described.MethodsThis two-arm multisite RCT will explore the feasibility (primary outcome) and effect (secondary outcome) of a remotely delivered TEACH protocol. Participants will be randomized to a six-week remotely delivered TEACH program plus medical treatment as usual (TAU) or TAU alone. We will include patients ages 12–22 years presenting to rheumatology clinics from six sites. Validated measures of fatigue, depressive symptoms, and pain will be obtained at baseline and approximately eight and 20 weeks later. Protocol adjustments were also made due to the COVID-19 pandemic, in collaboration with the investigative team, which included patients and caregivers.ConclusionsFindings from this multi-site RCT aim to document the feasibility of TEACH and provide an estimate of effect of a remotely delivered TEACH protocol on fatigue, depression, and pain symptoms in youth with cSLE as compared to standard medical treatment alone. This findings may positively impact clinical care for patients with cSLE. Clinical trials.gov registration: NCT04335643.

Using a Multi-Site RCT to Predict Impacts for a Single Site: Do Better Data and Methods Yield More Accurate Predictions?

Multi-site randomized controlled trials (RCTs) provide unbiased estimates of the average impact in the study sample. However, their ability to accurately predict the impact for individual sites outside the study sample, to inform local policy decisions, is largely unknown. To extend prior research on this question, we analyzed six multi-site RCTs and tested modern prediction methods—lasso regression and Bayesian Additive Regression Trees (BART)—using a wide range of moderator variables. The main study findings are that: (1) all of the methods yielded accurate impact predictions when the variation in impacts across sites was close to zero (as expected); (2) none of the methods yielded accurate impact predictions when the variation in impacts across sites was substantial; and (3) BART typically produced “less inaccurate” predictions than lasso regression or than the Sample Average Treatment Effect. These results raise concerns that when the impact of an intervention varies considerably across sites, statistical modeling using the data commonly collected by multi-site RCTs will be insufficient to explain the variation in impacts across sites and accurately predict impacts for individual sites.

Comparing the clinical and cost-effectiveness of remote (telehealth and online) cognitive behavioral therapy-based treatments for high-impact chronic pain relative to usual care: study protocol for the RESOLVE multisite randomized control trial

BackgroundCognitive behavioral therapy for chronic pain (CBT-CP) is an effective but underused treatment for high-impact chronic pain. Increased access to CBT-CP services for pain is of critical public health importance, particularly for rural and medically underserved populations who have limited access due to these services being concentrated in urban and high income areas. Making CBT-CP widely available and more affordable could reduce barriers to CBT-CP use.MethodsAs part of the National Institutes of Health Helping to End Addiction Long-term® (NIH HEAL) initiative, we designed and implemented a comparative effectiveness, 3-arm randomized control trial comparing remotely delivered telephonic/video and online CBT-CP-based services to usual care for patients with high-impact chronic pain. The RESOLVE trial is being conducted in 4 large integrated healthcare systems located in Minnesota, Georgia, Oregon, and Washington state and includes demographically diverse populations residing in urban and rural areas. The trial compares (1) an 8-session, one-on-one, professionally delivered telephonic/video CBT-CP program; and (2) a previously developed and tested 8-session online CBT-CP-based program (painTRAINER) to (3) usual care augmented by a written guide for chronic pain management. Participants are followed for 1 year post-allocation and are assessed at baseline, and 3, 6, and 12 months post-allocation. The primary outcome is minimal clinically important difference (MCID; ≥ 30% reduction) in pain severity (composite of pain intensity and pain-related interference) assessed by a modified 11-item version of the Brief Pain Inventory-Short Form at 3 months. Secondary outcomes include pain severity, pain intensity, and pain-related interference scores, quality of life measures, and patient global impression of change at 3, 6, and 12 months. Cost-effectiveness is assessed by incremental cost per additional patient with MCID in primary outcome and by cost per quality-adjusted life year achieved. Outcome assessment is blinded to group assignment.DiscussionThis large-scale trial provides a unique opportunity to rigorously evaluate and compare the clinical and cost-effectiveness of 2 relatively low-cost and scalable modalities for providing CBT-CP-based treatments to persons with high-impact chronic pain, including those residing in rural and other medically underserved areas with limited access to these services.Trial registrationClinicalTrials.gov NCT04523714. This trial was registered on 24 August 2020.

Developing a Bayesian hierarchical model for a prospective individual patient data meta-analysis with continuous monitoring

BackgroundNumerous clinical trials have been initiated to find effective treatments for COVID-19. These trials have often been initiated in regions where the pandemic has already peaked. Consequently, achieving full enrollment in a single trial might require additional COVID-19 surges in the same location over several years. This has inspired us to pool individual patient data (IPD) from ongoing, paused, prematurely-terminated, or completed randomized controlled trials (RCTs) in real-time, to find an effective treatment as quickly as possible in light of the pandemic crisis. However, pooling across trials introduces enormous uncertainties in study design (e.g., the number of RCTs and sample sizes might be unknown in advance). We sought to develop a versatile treatment efficacy assessment model that accounts for these uncertainties while allowing for continuous monitoring throughout the study using Bayesian monitoring techniques.MethodsWe provide a detailed look at the challenges and solutions for model development, describing the process that used extensive simulations to enable us to finalize the analysis plan. This includes establishing prior distribution assumptions, assessing and improving model convergence under different study composition scenarios, and assessing whether we can extend the model to accommodate multi-site RCTs and evaluate heterogeneous treatment effects. In addition, we recognized that we would need to assess our model for goodness-of-fit, so we explored an approach that used posterior predictive checking. Lastly, given the urgency of the research in the context of evolving pandemic, we were committed to frequent monitoring of the data to assess efficacy, and we set Bayesian monitoring rules calibrated for type 1 error rate and power.ResultsThe primary outcome is an 11-point ordinal scale. We present the operating characteristics of the proposed cumulative proportional odds model for estimating treatment effectiveness. The model can estimate the treatment’s effect under enormous uncertainties in study design. We investigate to what degree the proportional odds assumption has to be violated to render the model inaccurate. We demonstrate the flexibility of a Bayesian monitoring approach by performing frequent interim analyses without increasing the probability of erroneous conclusions.ConclusionThis paper describes a translatable framework using simulation to support the design of prospective IPD meta-analyses.

Abstract A032: Dignity therapy effects by race: Chaplain and nurse implementation in pragmatic, multisite stepped-wedge randomized control trial

Abstract Aim: As a brief psychotherapy for individuals facing mortal threat, Dignity Therapy (DT) effects on spiritual outcomes are unknown, especially as an intervention to support cancer health equity for racial minority patients. Our study aim was to compare usual outpatient palliative care and such care along with nurse-led or chaplain-led DT groups for main effects on dignity impact and the interaction of DT with race. Methods: We conducted the 4-step, stepped-wedge randomized control trial at 4 NCI designated cancer centers and 2 academic cancer centers across the United States. Half of the sites were randomized to chaplain-led DT and half to nurse-led DT. Of the 645 recruited cancer patients (age ≥ 55 years) receiving outpatient palliative care, 579 (59% female, mean age 66.4±7.4 years, 78% White, 77% Christian religion, 62% stage 4 cancer) provided data for intent-to-treat analysis. Over 6 weeks, patients completed pretest/posttest measures including the Dignity Impact Scale (DIS, primary outcome) ranging from low impact of 7 to highest impact of 35. In step 1-3, study procedures were completed in person. In step 4 (during the COVID-19 pandemic), when all sites were providing the intervention, study procedures were completed via Zoom. We used multiple imputation and regression analysis adjusting for pretest DIS, study site, and study step. Results: Of the 579 patients, 317 were in the DT group and 262 in the usual care group. The vast majority of the sample was White (n=448) along with 103 Blacks, 5 Asians, 2 Pacific Islanders, 1 Native American, 13 other races (all minorities were combined as Other Race), and 7 were missing race data. At pretest, the mean DIS score was 24.3±4.3 in the DT group and 25.9±4.3 in the usual care group. Adjusting for pretest DIS scores, study site, and study step, the chaplain-led (β=1.7, p=.02) and nurse-led (β=2.1, p=.005) groups reported significantly higher posttest DIS scores than the usual care groups. Adjusting for age, gender, race, education, and income, the effect on DIS scores remained significant for both DT groups. We then examined the interaction between race and DT with the entire sample and observed that the interaction was not significant (p=.73) and the sizes of DT effects were similar for White (β=1.9, p=.005) and the Other Race (β=1.6, p=.055) patients. Conclusions: Whether led by chaplains or nurses, DT was effective in improving dignity impact for older adult outpatient palliative care patients with cancer. DT, a patient-centered approach, has promise as an intervention to improve health equity in support of dignity for racial minorities. This rigorous trial of DT is a landmark step in gero-oncology palliative care and spiritual health services research focused on cancer health equity. Citation Format: Diana J. Wilkie, George Fitchett, Tasha M. Schoppee, Marvin O. Degado Guay, Joshua Hauser, Sheri M. Kittelson, Sean O-Mahony, Michael W. Rabow, Tammie E. Quest, Sheldon Solomon, Yingwei Yao, George Hadzo, Harvey Max Chochinov, Linda L. Emanuel. Dignity therapy effects by race: Chaplain and nurse implementation in pragmatic, multisite stepped-wedge randomized control trial [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A032.

Stakeholder-driven development and implementation of CRICIT: an app to support high-quality data capture and protocol monitoring for outpatient clinical trials with vulnerable populations.

Choosing an appropriate electronic data capture system (EDC) is a critical decision for all randomized controlled trials (RCT). In this paper, we document our process for developing and implementing an EDC for a multisite RCT evaluating the efficacy and implementation of an enhanced primary care model for individuals with opioid use disorder who are returning to the community from incarceration. Informed by the Knowledge-to-Action conceptual framework and user-centered design principles, we used Claris Filemaker software to design and implement CRICIT, a novel EDC that could meet the varied needs of the many stakeholders involved in our study. CRICIT was deployed in May 2021 and has been continuously iterated and adapted since. CRICIT's features include extensive participant tracking capabilities, site-specific adaptability, integrated randomization protocols, and the ability to generate both site-specific and study-wide summary reports. CRICIT is highly customizable, adaptable, and secure. Its implementation has enhanced the quality of the study's data, increased fidelity to a complicated research protocol, and reduced research staff's administrative burden. CRICIT and similar systems have the potential to streamline research activities and contribute to the efficient collection and utilization of clinical research data.

Crisis-focused Cognitive Behavioural Therapy for psychosis (CBTp) in acute mental health inpatient settings (the CRISIS study): protocol for a pilot randomised controlled trial

BackgroundCognitive Behavioural Therapy for psychosis (CBTp) has an established evidence base and is recommended by clinical guidelines to be offered during the acute phases of psychosis. However, few research studies have examined the efficacy of CBTp interventions specifically adapted for the acute mental health inpatient context with most research trials being conducted with white European community populations.AimsThe aim of this study is to conduct a pilot randomised controlled trial (RCT), which incorporates the examination of feasibility markers, of a crisis-focused CBTp intervention adapted for an ethnically diverse acute mental health inpatient population, in preparation for a large-scale randomised controlled trial. The study will examine the feasibility of undertaking the trial, the acceptability and safety of the intervention and the suitability of chosen outcome measures. This will inform the planning of a future, fully powered RCT.MethodsA single-site, parallel-group, pilot RCT will be conducted examining the intervention. Drawing on principles of coproduction, the intervention has been adapted in partnership with key stakeholders: service users with lived experience of psychosis and of inpatient care (including those from ethnic minority backgrounds), carers, multi-disciplinary inpatient clinicians and researchers. Sixty participants with experience of psychosis and in current receipt of acute mental health inpatient care will be recruited. Participants will be randomly allocated to either the crisis-focused CBTp intervention or treatment as usual (TAU).DiscussionFindings of this pilot RCT will indicate whether a larger multi-site RCT is needed to investigate the efficacy of the intervention. If the initial results demonstrate that this trial is feasible and the intervention is acceptable, it will provide evidence that a full-scale effectiveness trial may be warranted.Trial registrationThis trial has been prospectively registered on the ISRCTN registry (ISRCTN59055607) on the 18th of February 2021.

Effect of a tailored upper extremity strength training intervention combined with direct current stimulation in chronic stroke survivors: A Randomized Controlled Trial.

Strengthening exercises are recommended for managing persisting upper limb (UL) weakness following a stroke. Yet, strengthening exercises often lead to variable gains because of their generic nature. For this randomized controlled trial (RCT), we aimed to determine whether tailoring strengthening exercises using a biomarker of corticospinal integrity, as reflected in the amplitude of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS), could optimize training effects in the affected UL. A secondary aim was to determine whether applying anodal transcranial direct current stimulation (tDCS) could enhance exercise-induced training effects. For this multisite RCT, 90 adults at the chronic stage after stroke (>6 months) were recruited. Before training, participants underwent TMS to detect the presence of MEPs in the affected hand. The MEP amplitude was used to stratify participants into three training groups: (1) low-intensity, MEP <50 μV, (2) moderate-intensity, 50 μV < MEP < 120 μV, and (3) high-intensity, MEP>120 μV. Each group trained at a specific intensity based on the one-repetition maximum (1 RM): low-intensity, 35–50% 1RM; moderate-intensity, 50–65% 1RM; high-intensity, 70–85% 1RM. The strength training targeted the affected UL and was delivered 3X/week for four consecutive weeks. In each training group, participants were randomly assigned to receive either real or sham anodal tDCS (2 mA, 20 min) over the primary motor area of the affected hemisphere. Pre-/post-intervention, participants underwent a clinical evaluation of their UL to evaluate motor impairments (Fugl-Meyer Assessment), manual dexterity (Box and Blocks test) and grip strength. Post-intervention, all groups exhibited similar gains in terms of reduced impairments, improved dexterity, and grip strength, which was confirmed by multivariate and univariate analyses. However, no effect of interaction was found for tDCS or training group, indicating that tDCS had no significant impact on outcomes post-intervention. Collectively, these results indicate that adjusting training intensity based on the size of MEPs in the affected extremity provides a useful approach to optimize responses to strengthening exercises in chronic stroke survivors. Also, the lack of add-on effects of tDCS applied to the lesioned hemisphere on exercise-induced improvements in the affected UL raises questions about the relevance of combining such interventions in stroke.Clinical trial registry numberNCT02915185. https://www.clinicaltrials.gov/ct2/show/NCT02915185.

Testing the effectiveness of the Developing Inclusive Youth program: A multisite randomized control trial.

The Developing Inclusive Youth program is a classroom‐based, individually administered video tool that depicts peer‐based social and racial exclusion, combined with teacher‐led discussions. A multisite randomized control trial was implemented with 983 participants (502 females; 58.5% White, 41.5% Ethnic/racial minority; M age = 9.64 years) in 48 third‐, fourth‐, and fifth‐grade classrooms across six schools. Children in the program were more likely to view interracial and same‐race peer exclusion as wrong, associate positive traits with peers of different racial, ethnic, and gender backgrounds, and report play with peers from diverse backgrounds than were children in the control group. Many approaches are necessary to achieve antiracism in schools. This intervention is one component of this goal for developmental science.

Mobile Subthreshold Exercise Program (MSTEP) for concussion: study protocol for a randomized controlled trial

BackgroundSubthreshold exercise, defined as aerobic exercise below the level that causes symptoms, has been utilized as a treatment for youth with persistent postconcussive symptoms (PPCS), but there is currently little evidence to guide use. In addition, prior studies of exercise for PPCS have all required multiple in-person visits. We developed a virtual approach for delivering subthreshold exercise to youth with PPCS called the Mobile Subthreshold Exercise Program (MSTEP), and we have now been funded to conduct a large national randomized controlled trial (RCT) to test its efficacy for reducing concussive symptoms and improving health-related quality of life.MethodsThis investigation is an RCT comparing MSTEP to an active control. We will recruit 200 adolescents 11–18 years old with postconcussive symptoms persisting for at least 1 week but less than 1 year. Youth will be randomized to receive either 6 weeks of subthreshold exercise (MSTEP) or a stretching condition (control). Youth and parents will complete surveys of concussive symptoms at baseline, weekly during the intervention, and at 3 and 6 months. The primary outcomes will be trajectory of concussive symptoms and health-related quality of life over the 6 months of the study. Secondary outcomes will include depression, anxiety, and sleep quality. We will also assess potential mediators of treatment effects including moderate-vigorous physical activity and fear avoidance of concussive symptoms.DiscussionThis multisite RCT of MSTEP will provide vital information regarding the efficacy of a virtually delivered subthreshold exercise program for youth with PPCS, and insight regarding potential mediators of treatment effects, including objectively measured physical activity and fear avoidance of concussive symptoms.Trial registrationClinicalTrials.gov NCT04688255. Registered on December 29, 2020.

Brief Digital Interventions to Support the Psychological Well-being of NHS Staff During the COVID-19 Pandemic: 3-Arm Pilot Randomized Controlled Trial.

BackgroundHealth and social care staff are at high risk of experiencing adverse mental health (MH) outcomes during the COVID-19 pandemic. Hence, there is a need to prioritize and identify ways to effectively support their psychological well-being (PWB). Compared to traditional psychological interventions, digital psychological interventions are cost-effective treatment options that allow for large-scale dissemination and transcend social distancing, overcome rurality, and minimize clinician time.ObjectiveThis study reports MH outcomes of a Consolidated Standards of Reporting Trials (CONSORT)-compliant parallel-arm pilot randomized controlled trial (RCT) examining the potential usefulness of an existing and a novel digital psychological intervention aimed at supporting psychological health among National Health Service (NHS) staff working through the COVID-19 pandemic.MethodsNHS Highland (NHSH) frontline staff volunteers (N=169) were randomly assigned to the newly developed NHSH Staff Wellbeing Project (NHSWBP), an established digital intervention (My Possible Self [MPS]), or a waitlist (WL) group for 4 weeks. Attempts were made to blind participants to which digital intervention they were allocated. The interventions were fully automated, without any human input or guidance. We measured 5 self-reported psychological outcomes over 3 time points: before (baseline), in the middle of (after 2 weeks), and after treatment (4 weeks). The primary outcomes were anxiety (7-item General Anxiety Disorder), depression (Patient Health Questionnaire), and mental well-being (Warwick-Edinburgh Mental Well-being Scale). The secondary outcomes included mental toughness (Mental Toughness Index) and gratitude (Gratitude Questionnaire-6).ResultsRetention rates mid- and postintervention were 77% (n=130) and 63.3% (n=107), respectively. Postintervention, small differences were noted between the WL and the 2 treatment groups on anxiety (vs MPS: Cohen d=0.07, 95% CI –0.20 to 0.33; vs NHSWBP: Cohen d=0.06, 95% CI –0.19 to 0.31), depression (vs MPS: Cohen d=0.37, 95% CI 0.07-0.66; vs NHSWBP: Cohen d=0.18, 95% CI –0.11 to 0.46), and mental well-being (vs MPS: Cohen d=–0.04, 95% CI –0.62 to –0.08; vs NHSWBP: Cohen d=–0.15, 95% CI –0.41 to 0.10). A similar pattern of between-group differences was found for the secondary outcomes. The NHSWBP group generally had larger within-group effects than the other groups and displayed a greater rate of change compared to the other groups on all outcomes, except for gratitude, where the rate of change was greatest for the MPS group.ConclusionsOur analyses provided encouraging results for the use of brief digital psychological interventions in improving PWB among health and social care workers. Future multisite RCTs, with power to reliably detect differences, are needed to determine the efficacy of contextualized interventions relative to existing digital treatments.Trial RegistrationISRCTN Registry (ISRCTN) ISRCTN18107122; https://www.isrctn.com/ISRCTN18107122