Remote Follow-up in a Heart Failure Pragmatic Trial: Insights From the CONNECT-HF.

BACKGROUND: Randomized controlled trials typically require study-specific visits, which can burden participants and sites. Remote follow-up, such as centralized call centers for participant-reported or site-reported, holds promise for reducing costs and enhancing the pragmatism of trials. In this secondary analysis of the CONNECT-HF (Care Optimization Through Patient and Hospital Engagement For HF) trial, we aimed to evaluate the completeness and validity of the remote follow-up process. METHODS AND RESULTS: The CONNECT-HF trial evaluated the effect of a post-discharge quality-improvement intervention for heart failure compared to usual care for up to 1 year. Suspected events were reported either by participants or by health care proxies through a centralized call center or by sites through medical-record queries. When potential hospitalization events were suspected, additional medical records were collected and adjudicated. Among 5942 potential hospitalizations, 18% were only participant-reported, 28% were reported by both participants and sites, and 50% were only site-reported. Concordance rates between the participant/site reports and adjudication for hospitalization were high: 87% participant-reported, 86% both, and 86% site-reported. Rates of adjudicated heart failure hospitalization events among adjudicated all-cause hospitalization were lower but also consistent: 45% participant-reported, 50% both, and 50% site-reported. CONCLUSIONS: Participant-only and site-only reports missed a substantial number of hospitalization events. We observed similar concordance between participant/site reports and adjudication for hospitalizations. Combining participant-reported and site-reported outcomes data is important to capture and validate hospitalizations effectively in pragmatic heart failure trials.

Comparative Effectiveness of Patient-Driven versus Standardized Diabetes Shared Medical Appointments: A Pragmatic Cluster Randomized Trial.

BACKGROUND: Diabetes self-management education and support can be effectively and efficiently delivered in primary care in the form of shared medical appointments (SMAs). Comparative effectiveness of SMA delivery features such as topic choice, multi-disciplinary care teams, and peer mentor involvement is not known. OBJECTIVE: To compare effects of standardized and patient-driven models of diabetes SMAs on patient-level diabetes outcomes. DESIGN: Pragmatic cluster randomized trial. PARTICIPANTS: A total of 1060 adults with type 2 diabetes in 22 primary care practices. INTERVENTIONS: Practice personnel delivered the 6-session Targeted Training in Illness Management (TTIM) curriculum using either standardized (set content delivered by a health educator) or patient-driven SMAs (patient-selected topic order delivered by health educators, behavioral health providers [BHPs], and peer mentors). MAIN MEASURES: Outcomes included self-reported diabetes distress and diabetes self-care behaviors from baseline and follow-up surveys (assessed at 1st and final SMA session), and HbA1c, BMI, and blood pressure from electronic health records. Analyses used descriptive statistics, linear regression, and linear mixed models. KEY RESULTS: Both standardized and patient-driven SMAs effectively improved diabetes distress, self-care behaviors, BMI (- 0.29 on average), and HbA1c (- 0.45% (mmol/mol) on average, 8.3 to 7.8%). Controlling for covariates, there was a small, significant effect of condition on overall diabetes distress in favor of standardized SMAs (F(1,841) = 4.3, p = .04), attributable to significant effects of condition on emotion and regimen distress subscales. There was a small, significant effect of condition on diastolic blood pressure in favor of standardized SMAs (F(1,5199) = 4.50, p = .03). There were no other differences between conditions. CONCLUSIONS: Both SMA models using the TTIM curriculum yielded significant improvement in diabetes distress, self-care, and HbA1c. Patient-driven diabetes SMAs involving BHPs and peer mentors and topic selection did not lead to better clinical or patient-reported outcomes than standardized diabetes SMAs facilitated by a health educator following a set topic order. NIH TRIAL REGISTRY NUMBER: NCT03590041.

Pragmatic clinical trials to advance research in children and adolescents with eating disorders.

OBJECTIVE: To discuss the utility of pragmatic clinical trials (PCTs) to help advance research in eating disorders (EDs). METHODS: We describe challenges associated with traditional explanatory research trials and examine PCTs as an alternative, including a review of the PRECIS-2 tool. RESULTS: There are many challenges associated with the design and completion of traditional RCTs within the field of EDs. Pragmatic clinical trials are studies that closely align with conditions available in everyday practice and focus on outcomes that are relevant to patients and clinicians. Results of PCTS maximize applicability and generalizability to clinical settings. DISCUSSION: Available therapies established for the treatment of EDs provide remission rates that rarely exceed 50%, implying a need for additional research on new or adjunctive treatments. In addition to a general overview of PCTs, we draw upon published literature and our own experiences involving adjunctive olanzapine for the treatment of children and youth with anorexia nervosa to help highlight challenges associated with randomized controlled trial (RCT) design and implementation, and offer pragmatic suggestions that would allow patients greater choice in treatment trials, while at the same time capturing outcomes that are most likely to advance treatment efforts. CONCLUSIONS: Pragmatic clinical trials provide alternatives to RCT design that can help bolster research in EDs that aims to explore real-world effects of interventions. PUBLIC SIGNIFICANCE: Available therapies established for the treatment of eating disorders (EDs) in children and adolescents provide remission rates that rarely exceed 50%, implying a need for additional research on new or adjunctive treatments. In this article, we discuss the utility of pragmatic trials to help promote research that can help advance knowledge that is relevant to clinical care settings.

Optimizing accrual to a large-scale, clinically integrated randomized trial in anesthesiology: A 2-year analysis of recruitment.

BACKGROUND: Performing large randomized trials in anesthesiology is often challenging and costly. The clinically integrated randomized trial is characterized by simplified logistics embedded into routine clinical practice, enabling ease and efficiency of recruitment, offering an opportunity for clinicians to conduct large, high-quality randomized trials under low cost. Our aims were to (1) demonstrate the feasibility of the clinically integrated trial design in a high-volume anesthesiology practice and (2) assess whether trial quality improvement interventions led to more balanced accrual among study arms and improved trial compliance over time. METHODS: This is an interim analysis of recruitment to a cluster-randomized trial investigating three nerve block approaches for mastectomy with immediate implant-based reconstruction: paravertebral block (arm 1), paravertebral plus interpectoral plane blocks (arm 2), and serratus anterior plane plus interpectoral plane blocks (arm 3). We monitored accrual and consent rates, clinician compliance with the randomized treatment, and availability of outcome data. Assessment after the initial year of implementation showed a slight imbalance in study arms suggesting areas for improvement in trial compliance. Specific improvement interventions included increasing the frequency of communication with the consenting staff and providing direct feedback to clinician investigators about their individual recruitment patterns. We assessed overall accrual rates and tested for differences in accrual, consent, and compliance rates pre- and post-improvement interventions. RESULTS: Overall recruitment was extremely high, accruing close to 90% of the eligible population. In the pre-intervention period, there was evidence of bias in the proportion of patients being accrued and receiving the monthly block, with higher rates in arm 3 (90%) compared to arms 1 (81%) and 2 (79%, p = 0.021). In contrast, in the post-intervention period, there was no statistically significant difference between groups (p = 0.8). Eligible for randomization rate increased from 89% in the pre-intervention period to 95% in the post-intervention period (difference 5.7%; 95% confidence interval = 2.2%-9.4%, p = 0.002). Consent rate increased from 95% to 98% (difference of 3.7%; 95% confidence interval = 1.1%-6.3%; p = 0.004). Compliance with the randomized nerve block approach was maintained at close to 100% and availability of primary outcome data was 100%. CONCLUSION: The clinically integrated randomized trial design enables rapid trial accrual with a high participant compliance rate in a high-volume anesthesiology practice. Continuous monitoring of accrual, consent, and compliance rates is necessary to maintain and improve trial conduct and reduce potential biases. This trial methodology serves as a template for the implementation of other large, low-cost randomized trials in anesthesiology.

Structured Mobilization for Critically Ill Patients: A Pragmatic Cluster-randomized Trial.

Rationale: Small trials and professional recommendations support mobilization interventions to improve recovery among critically ill patients, but their real-world effectiveness is unknown. Objective: To evaluate a low-cost, multifaceted mobilization intervention. Methods: We conducted a stepped-wedge cluster-randomized trial across 12 ICUs with diverse case mixes. The primary and secondary samples included patients mechanically ventilated for ⩾48 hours who were ambulatory before admission, and all patients with ICU stays ⩾48 hours, respectively. The mobilization intervention included 1) designation and posting of daily mobilization goals; 2) interprofessional closed-loop communication coordinated by each ICU's facilitator; and 3) performance feedback. Measurements and Main Results: From March 4, 2019 through March 15, 2020, 848 and 1,069 patients were enrolled in the usual care and intervention phases in the primary sample, respectively. The intervention did not increase the primary outcome, patient's maximal Intensive Care Mobility Scale (range, 0-10) score within 48 hours before ICU discharge (estimated mean difference, 0.16; 95% confidence interval, -0.31 to 0.63; P = 0.51). More patients in the intervention (37.2%) than usual care (30.7%) groups achieved the prespecified secondary outcome of ability to stand before ICU discharge (odds ratio, 1.48; 95% confidence interval, 1.02 to 2.15; P = 0.04). Similar results were observed among the 7,115 patients in the secondary sample. The percentage of days on which patients received physical therapy mediated 90.1% of the intervention effect on standing. ICU mortality (31.5% vs. 29.0%), falls (0.7% vs. 0.4%), and unplanned extubations (2.0% vs. 1.8%) were similar between groups (all P > 0.3). Conclusions: A low-cost, multifaceted mobilization intervention did not improve overall mobility but improved patients' odds of standing and was safe. Clinical trial registered with www.clinicaltrials.gov (NCT03863470).

Long-term Effects of a Collaborative Care Model on Metabolic Outcomes and Depressive Symptoms: 36-Month Outcomes from the INDEPENDENT Intervention.

BACKGROUND: Collaborative care (CC) is a multicomponent team-based approach to providing mental health care with systematic integration into outpatient medical settings. The 12-month INDEPENDENT CC intervention improved joint disease control measures in patients with both depression and diabetes at 12 and 24 months following randomization. OBJECTIVE: This study investigated the durability of intervention effects on patient outcomes at 36 months following randomization. PARTICIPANTS: Adult patients with poorly controlled T2D and depression in India randomized to CC or usual care. DESIGN: Post hoc analyses of between-group differences in patient outcomes at 36 months post-randomization (N = 331) and maintenance of outcomes from 12 to 36 months (N = 314). MAIN MEASURES: We evaluated combined risk factor improvement since baseline, defined as ≥ 50.0% reduction in Symptom Checklist Depression Scale (SCL-20) scores along with reduction of at least 0.5 percentage point hemoglobin A1C, 5 mmHg systolic blood pressure, or 10 mg/dL low-density lipoprotein cholesterol. Improvements in single risk factors were also examined. KEY RESULTS: There were no between-group differences in improvements since baseline in multiple or single risk factors at 36 months. Patients in the CC group with improved outcomes at 12 months were more likely to maintain a ≥ 50.0% reduction since baseline in SCL-20 scores (CC [54.9%] vs. UC [40.9%]; RR: 1.27 [95% CI: 1.04, 1.56]) and 0.5 percentage point reduction since baseline in hemoglobin A1C (CC [31.9%] vs. UC [19.5%]; RR: 1.64 [95% CI: 1.11, 2.41]) at 36 months. CONCLUSIONS: While improvements since baseline in patient outcomes did not differ between the collaborative care and usual care groups at 36 months, patients who received CC were more likely to maintain improvements in depressive symptoms and glucose levels at 36 months if they had achieved these improvements at the end of active intervention. TRIAL REGISTRATION NUMBER: NCT02022111.

Protocol of the Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) study: a pragmatic, prospective multicenter observational cohort study of recurrent high-grade non-muscle invasive bladder cancer.

BACKGROUND: Bladder cancer poses a significant public health burden, with high recurrence and progression rates in patients with non-muscle-invasive bladder cancer (NMIBC). Current treatment options include bladder-sparing therapies (BST) and radical cystectomy, both with associated risks and benefits. However, evidence supporting optimal management decisions for patients with recurrent high-grade NMIBC remains limited, leading to uncertainty for patients and clinicians. The CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options) Study aims to address this critical knowledge gap by comparing outcomes between patients undergoing BST and radical cystectomy. METHODS: The CISTO Study is a pragmatic, prospective observational cohort trial across 36 academic and community urology practices in the US. The study will enroll 572 patients with a diagnosis of recurrent high-grade NMIBC who select management with either BST or radical cystectomy. The primary outcome is health-related quality of life (QOL) at 12 months as measured with the EORTC-QLQ-C30. Secondary outcomes include bladder cancer-specific QOL, progression-free survival, cancer-specific survival, and financial toxicity. The study will also assess patient preferences for treatment outcomes. Statistical analyses will employ targeted maximum likelihood estimation (TMLE) to address treatment selection bias and confounding by indication. DISCUSSION: The CISTO Study is powered to detect clinically important differences in QOL and cancer-specific survival between the two treatment approaches. By including a diverse patient population, the study also aims to assess outcomes across the following patient characteristics: age, gender, race, burden of comorbid health conditions, cancer severity, caregiver status, social determinants of health, and rurality. Treatment outcomes may also vary by patient preferences, health literacy, and baseline QOL. The CISTO Study will fill a crucial evidence gap in the management of recurrent high-grade NMIBC, providing evidence-based guidance for patients and clinicians in choosing between BST and radical cystectomy. The CISTO study will provide an evidence-based approach to identifying the right treatment for the right patient at the right time in the challenging clinical setting of recurrent high-grade NMIBC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03933826. Registered on May 1, 2019.

Overcoming barriers in the design and implementation of clinical trials for acute kidney injury: a report from the 2020 Kidney Disease Clinical Trialists meeting.

Acute kidney injury (AKI) is a growing epidemic and is independently associated with increased risk of death, chronic kidney disease (CKD) and cardiovascular events. Randomized-controlled trials (RCTs) in this domain are notoriously challenging and many clinical studies in AKI have yielded inconclusive findings. Underlying this conundrum is the inherent heterogeneity of AKI in its etiology, presentation and course. AKI is best understood as a syndrome and identification of AKI subphenotypes is needed to elucidate the disease's myriad etiologies and to tailor effective prevention and treatment strategies. Conventional RCTs are logistically cumbersome and often feature highly selected patient populations that limit external generalizability and thus alternative trial designs should be considered when appropriate. In this narrative review of recent developments in AKI trials based on the Kidney Disease Clinical Trialists (KDCT) 2020 meeting, we discuss barriers to and strategies for improved design and implementation of clinical trials for AKI patients, including predictive and prognostic enrichment techniques, the use of pragmatic trials and adaptive trials.

Opportunities to improve quality of care for cancer survivors in primary care: findings from the BETTER WISE study.

PURPOSE: The BETTER WISE (Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Primary Care for Wellness of Cancer Survivors and Patients) intervention is an evidence-based approach to prevention and screening for cancers and chronic diseases in primary care that also includes comprehensive follow-up for breast, prostate and colorectal cancer survivors. We describe the process of harmonizing cancer survivorship guidelines to create a BETTER WISE cancer surveillance algorithm and describe both the quantitative and qualitative findings for BETTER WISE participants who were breast, prostate or colorectal cancer survivors. We describe the results in the context of the COVID-19 pandemic. METHODS: We reviewed high-quality survivorship guidelines to create a cancer surveillance algorithm. We conducted a cluster randomized trial in three Canadian provinces with two composite index outcome measured 12 months after baseline, and also collected qualitative feedback on the intervention. RESULTS: There were 80 cancer survivors for whom we had baseline and follow-up data. Differences between the composite indices in the two study arms were not statistically significant, although a post hoc analysis suggested the COVID-19 pandemic was a key factor in these results. Qualitative finding suggested that participants and stakeholders generally viewed BETTER WISE positively and emphasized the effects of the pandemic. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: BETTER WISE shows promise for providing an evidence-based, patient-centred, comprehensive approach to prevention, screening and cancer surveillance for cancer survivors in the primary care setting. TRIAL REGISTRATION: ISRCTN21333761. Registered on December 19, 2016, http://www.isrctn.com/ISRCTN21333761 .

"We bleed for our community:" A qualitative exploration of the implementation of a pragmatic weight gain prevention trial from the perspectives of community health center professionals.

BACKGROUND: Clinical trial implementation continues to shift toward pragmatic design, with the goal of increasing future adoption in clinical practice. Yet, few pragmatic trials within clinical settings have qualitatively assessed stakeholder input, especially from those most impacted by research implementation and outcomes, i.e., providers and staff. Within this context, we conducted a qualitative study of the implementation of a pragmatic digital health obesity trial with employees at a Federally qualified health center (FQHC) network in central North Carolina. METHODS: Participant recruitment was conducted through purposive sampling of FQHC employees from a variety of backgrounds. Two researchers conducted semi-structured qualitative interviews and collected demographic data. Interviews were digitally recorded, professionally transcribed and double-coded by two independent researchers using NVivo 12. Coding discrepancies were reviewed by a third researcher until intercoder consensus was reached. Responses were compared within and across participants to elucidate emergent themes. RESULTS: Eighteen qualitative interviews were conducted, of whom 39% provided direct medical care to patients and 44% worked at the FQHC for at least seven years. Results illuminated the challenges and successes of a pragmatically designed obesity treatment intervention within the community that serves medically vulnerable patients. Although limited time and staffing shortages may have challenged recruitment processes, respondents described early buy-in from leadership; an alignment of organizational and research goals; and consideration of patient needs as facilitators to implementation. Respondents also described the need for personnel power to sustain novel research interventions and considerations of health center resource constraints. CONCLUSIONS: Results from this study contribute to the limited literature on pragmatic trials utilizing qualitative methods, particularly in community-based obesity treatment. To continue to merge the gaps between research implementation and clinical care, qualitative assessments that solicit stakeholder input are needed within pragmatic trial design. For maximum impact, researchers may wish to solicit input from a variety of professionals at trial onset and ensure that shared common goals and open collaboration between all partners is maintained throughout the trial. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT03003403) on December 28, 2016.

Effects of a shared decision making intervention for older adults with multiple chronic conditions: the DICO study.

BACKGROUND: To evaluate the effects of a shared decision making (SDM) intervention for older adults with multiple chronic conditions (MCCs). METHODS: A pragmatic trial evaluated the effects of the SDMMCC intervention, existing of SDM training for nine geriatricians in two hospitals and a preparatory tool for patients. A prospective pre-intervention post-intervention multi-center clinical study was conducted in which an usual care group of older patients with MCC and their informal caregivers was included before the implementation of the intervention and a new cohort of patients and informal caregivers after the implementation of the intervention. SDM was observed using the OPTIONMCC during video-recorded consultations. Patient- and caregivers reported outcomes regarding their role in SDM, involvement, perceived SDM and decisional conflict were measured. The differences between groups regarding the level of observed SDM (OPTIONMCC) were analyzed with a mixed model analysis. Dichotomous patient-reported outcomes were analyzed with a logistic mixed model. RESULTS: From two outpatient geriatric clinics 216 patients with MCCs participated. The mean age was 77.3 years, and 56.3% of patients were female. No significant difference was found in the overall level of SDM as measured with the OPTIONMCC or in patient-reported outcomes. However, at item level the items discussing 'goals', 'options', and 'decision making' significantly improved after the intervention. The items discussing 'partnership' and 'evaluating the decision-making process' showed a significant decrease. Fifty-two percent of the patients completed the preparatory tool, but the results were only discussed in 12% of the consultations. CONCLUSION: This study provides scope for improvement of SDM in geriatrics. Engaging older adults with MCCs and informal caregivers in the decision making process should be an essential part of SDM training for geriatricians, beyond the SDM steps of explaining options, benefits and harms. More attention should be paid to the integration of preparatory work in the consultation.

Promoting deceased organ and tissue donation registration in family physician waiting rooms (RegisterNow-1): a pragmatic stepped-wedge, cluster randomized controlled registry trial.

BACKGROUND: The shortage of available organs for life-saving transplants persists worldwide. While a majority support donating their organs or tissue when they die, many have not registered their wish to do so. When registered, next of kin are much more likely to follow-through with the decision to donate. In many countries, most people visit their family physician office each year and this setting is a promising, yet underused, site where more people could register for deceased organ donation. Our primary aim was to evaluate the effectiveness of an intervention to promote organ donation registration in family physician's offices. METHODS: We developed an intervention to address barriers and enablers to organ donation registration that involved physician office reception staff inviting patients to register on a tablet in the waiting room while they waited for their appointment. We conducted a cross-sectional stepped-wedge cluster randomized controlled registry trial to evaluate the intervention. We recruited six family physician offices in Canada. All offices began with usual care and then every two weeks, one office (randomly assigned) started the intervention until all offices delivered the intervention. The primary outcome was registration for deceased organ donation in the provincial organ registration registry, assessed within the 7 days of the physician visit. At the end of the trial, we also conducted interviews with clinic staff to assess any barriers and enablers to delivering the intervention. RESULTS: The trial involved 24,616 patient visits by 13,562 unique patients: 12,484 visits in the intervention period and 12,132 in the control period. There was no statistically significant difference in the percentage of patients registered for deceased organ donation in the intervention versus control period (48.0% vs 46.2%; absolute difference after accounting for the secular trend: 0.12%; 95% CI: - 2.30, 2.54; p=0.92). Interviews with clinic staff indicated location of the tablet within a waiting room, patient rapport, existing registration, confidence and motivation to deliver the intervention and competing priorities as barriers and enablers to delivery. CONCLUSIONS: Our intervention did not increase donor registration. Nonetheless, family physician offices may still remain a promising setting to develop and evaluate better interventions to increase organ donation registration. TRIAL REGISTRATION: NCT03213171.

Clinic Factors Associated With Mailed Fecal Immunochemical Test (FIT) Completion: The Difference-Making Role of Support Staff.

PURPOSE: Mailed fecal immunochemical test (FIT) programs can facilitate colorectal cancer (CRC) screening. We sought to identify modifiable, clinic-level factors that distinguish primary care clinics with higher vs lower FIT completion rates in response to a centralized mailed FIT program. METHODS: We used baseline observational data from 15 clinics within a single urban federally qualified health center participating in a pragmatic trial to optimize a mailed FIT program. Clinic-level data included interviews with leadership using a guide informed by the Consolidated Framework for Implementation Research (CFIR) and FIT completion rates. We used template analysis to identify explanatory factors and configurational comparative methods to identify specific combinations of clinic-level conditions that uniquely distinguished clinics with higher and lower FIT completion rates. RESULTS: We interviewed 39 clinic leaders and identified 58 potential explanatory factors representing clinic workflows and the CFIR inner setting domain. Clinic-level FIT completion rates ranged from 30% to 56%. The configurational model for clinics with higher rates (≥37%) featured any 1 of the following 3 factors related to support staff: (1) adding back- or front-office staff in past 12 months, (2) having staff help patients resolve barriers to CRC screening, and (3) having staff hand out FITs/educate patients. The model for clinics with lower rates involved the combined absence of these same 3 factors. CONCLUSIONS: Three factors related to support staff differentiated clinics with higher and lower FIT completion rates. Adding nonphysician support staff and having those staff provide enabling services might help clinics optimize mailed FIT screening programs.

Implementation fidelity in a multifaceted program to foster rational antibiotics use in primary care: an observational study.

BACKGROUND: The ARena study (Sustainable Reduction of Antimicrobial Resistance in German Ambulatory Care) is a three-arm, cluster randomized trial to evaluate a multifaceted implementation program in a German primary care setting. In the context of a prospective process evaluation conducted alongside ARena, this study aimed to document and explore fidelity of the implementation program. METHODS: This observational study is based on data generated in a three-wave survey of 312 participating physicians in the ARena program and attendance documentation. Measures concerned persistence of participation in the ARena program and adherence to intervention components (thematic quality circles, e-learning, basic expenditure reimbursements, additional bonus payments and a computerized decision support system). Participants' views on five domains of the implementation were also measured. Binary logistic and multiple linear regression analyses were used to explore which views on the implementation were associated with participants' adherence to quality circles and use of additional bonus compensation. RESULTS: The analysis of fidelity showed overall high persistence of participation in the intervention components across the three intervention arms (90,1%; 97,9%; 92,9%). 96.4% of planned quality circles were delivered to study participants and, across waves, 30.4% to 93% of practices participated; 56.1% of physicians attended the maximum of four quality circles. 84% of the practices (n = 158) with a minimum of one index patient received a performance-based additional bonus payment at least once. In total, bonus compensation was triggered for 51.8% of affected patients. Participation rate for e-learning (a prerequisite for reimbursement of project-related expenditure) covered 90.8% of practices across all intervention arms, with the highest rate in arm II (96.5%). Uptake of expenditure reimbursement was heterogeneous across study arms, with a mean rate of 86.5% (89.1% in arm I, 96.4% in arm II and 74.1% in arm III). Participants' views regarding participant responsiveness (OR = 2.298) 95% CI [1.598, 3.305] and Context (OR = 2.146) 95% CI [1.135, 4.055] affected additional bonus payment. Participants' views on participant responsiveness (Beta = 0.718) 95% CI [0.479, 0.957], Context (Beta = 0.323) 95% CI [0.055, 0.590] and Culture of shared decision-making (Beta = -0.334) 95% CI [-0.614, -0.053] affected quality circle attendance. CONCLUSION: This study showed an overall high fidelity to the implementation program. Participants' views on the implementation were associated with degree of intervention fidelity. TRIAL REGISTRATION: ISRCTN, ISRCTN58150046.

A pragmatic randomized controlled trial of a group self-management support program versus treatment-as-usual for anxiety disorders: study protocol.

BACKGROUND: The integration of a personal recovery-oriented practice in mental health services is an emerging principle in policy planning. Self-management support (SMS) is an intervention promoting recovery that aims at educating patients on the nature of their mental disorder, improving their strategies to manage their day-to-day symptoms, fostering self-efficacy and empowerment, preventing relapse, and promoting well-being. While SMS is well established for chronic physical conditions, there is a lack of evidence to support the implementation of structured SMS programs for common mental disorders, and particularly for anxiety disorders. This study aims to examine the effectiveness of a group-based self-management support program for anxiety disorders as an add-on to treatment-as-usual in community-based care settings. METHODS/DESIGN: We will conduct a multicentre pragmatic randomized controlled trial with a pre-treatment, post-treatment (4-month post-randomization), and follow-ups at 8, 12 and 24-months. TREATMENT AND CONTROL GROUPS: a) group self-management support (10 weekly 2.5-h group web-based sessions with 10-15 patients with two trained facilitators); b) treatment-as-usual. Participants will include adults meeting DSM-5 criteria for Panic Disorder, Agoraphobia, Social Anxiety Disorder, and/or Generalized Anxiety Disorder. The primary outcome measure will be the Beck Anxiety Inventory; secondary outcome measures will comprise self-reported instruments for anxiety and depressive symptoms, recovery, self-management, quality of life, and service utilisation. STATISTICAL ANALYSIS: Data will be analysed based on intention-to-treat with a mixed effects regression model accounting for between and within-subject variations in the effects of the intervention. DISCUSSION: This study will contribute to the limited knowledge base regarding the effectiveness of structured group self-management support for anxiety disorders. It is expected that changes in patients' self-management behaviour will lead to better anxiety management and, consequently, to improved patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05124639 . Prospectively registered 18 November 2021.

A theory driven, pragmatic trial implementing changes to routine antenatal care that supports recommended pregnancy weight gain.

BACKGROUND: Prevention of weight gain outside recommendations is a challenge for health services, with several barriers to best practice care identified. The aim of this pragmatic implementation study with a historical control was to examine the impact of implementing a service wide education program, and antenatal care pregnancy weight gain chart combined with brief advice on women's knowledge of recommended gestational weight gain (GWG), the advice received and actual GWG. METHODS: The PRECEDE PROCEED Model of Health Program planning guided intervention and evaluation targets and an implementation science approach facilitated service changes. Pregnant women < 22 weeks' gestation attending the antenatal clinic at a metropolitan birthing hospital in Australia were recruited pre (2010, n = 715) and post (2016, n = 478) implementation of service changes. Weight measurements and questionnaires were completed at recruitment and 36 weeks' gestation. Questionnaires assessed advice received from health professionals related to healthy eating, physical activity, GWG, and at recruitment only, pre-pregnancy weight and knowledge of GWG recommendations. RESULTS: Women who correctly reported their recommended GWG increased from 34% (pre) to 53% (post) (p < 0.001). Between pre and post implementation, the advice women received from midwives on recommended GWG was significantly improved at both recruitment- and 36-weeks' gestation. For normal weight women there was a reduction in GWG (14.2 ± 5.3 vs 13.3 ± 4.7 kg, p = 0.04) and clinically important reduction in excess GWG between pre and post implementation (31% vs 24%, p = 0.035) which remained significant after adjustment (AOR 0.53 [95%CI 0.29-0.96]) (p = 0.005). CONCLUSIONS: Service wide changes to routine antenatal care that address identified barriers to supporting recommended GWG are likely to improve the care and advice women receive and prevent excess GWG for normal weight women.

Lessons learned in the Apple Heart Study and implications for the data management of future digital clinical trials.

The digital clinical trial is fast emerging as a pragmatic trial that can improve a trial's design including recruitment and retention, data collection and analytics. To that end, digital platforms such as electronic health records or wearable technologies that enable passive data collection can be leveraged, alleviating burden from the participant and study coordinator. However, there are challenges. For example, many of these data sources not originally intended for research may be noisier than traditionally obtained measures. Further, the secure flow of passively collected data and their integration for analysis is non-trivial. The Apple Heart Study was a prospective, single-arm, site-less digital trial designed to evaluate the ability of an app to detect atrial fibrillation. The study was designed with pragmatic features, such as an app for enrollment, a wearable device (the Apple Watch) for data collection, and electronic surveys for participant-reported outcomes that enabled a high volume of patient enrollment and accompanying data. These elements led to challenges including identifying the number of unique participants, maintaining participant-level linkage of multiple complex data streams, and participant adherence and engagement. Novel solutions were derived that inform future designs with an emphasis on data management. We build upon the excellent framework of the Clinical Trials Transformation Initiative to provide a comprehensive set of guidelines for data management of the digital clinical trial that include an increased role of collaborative data scientists in the design and conduct of the modern digital trial.

Effect of advance care planning video on do-not-hospitalize orders for nursing home residents with advanced illness.

BACKGROUND: The purpose of the study is to evaluate the effect of an Advance Care Planning (ACP) Video Program on documented Do-Not-Hospitalize (DNH) orders among nursing home (NH) residents with advanced illness. METHODS: Secondary analysis on a subset of NHs enrolled in a cluster-randomized controlled trial (41 NHs in treatment arm implemented the ACP Video Program: 69 NHs in control arm employed usual ACP practices). Participants included long (> 100 days) and short (≤ 100 days) stay residents with advanced illness (advanced dementia or cardiopulmonary disease (chronic obstructive pulmonary disease or congestive heart failure)) in NHs from March 1, 2016 to May 31, 2018 without a documented Do-Not-Hospitalize (DNH) order at baseline. Logistic regression with covariate adjustments was used to estimate the impact of the resident being in a treatment versus control NH on: the proportion of residents with new DNH orders during follow-up; and the proportion of residents with any hospitalization during follow-up. Clustering at the facility-level was addressed using hierarchical models. RESULTS: The cohort included 6,117 residents with advanced illness (mean age (SD) = 82.8 (8.4) years, 65% female). Among long-stay residents (n = 3,902), 9.3% (SE, 2.2; 95% CI 5.0-13.6) and 4.2% (SE, 1.1; 95% CI 2.1-6.3) acquired a new DNH order in the treatment and control arms, respectively (average marginal effect, (AME) 5.0; SE, 2.4; 95% CI, 0.3-9.8). Among short-stay residents with advanced illness (n = 2,215), 8.0% (SE, 1.6; 95% CI 4.6-11.3) and 3.5% (SE 1.0; 95% CI 1.5-5.5) acquired a new DNH order in the treatment and control arms, respectively (AME 4.4; SE, 2.0; 95% CI, 0.5-8.3). Proportion of residents with any hospitalizations did not differ between arms in either cohort. CONCLUSIONS: Compared to usual care, an ACP Video Program intervention increased documented DNH orders among NH residents with advanced disease but did not significantly reduce hospitalizations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02612688 .

Effectiveness and implementation success of a co-produced physical activity referral scheme in Germany: study protocol of a pragmatic cluster randomised trial.

BACKGROUND: While effective physical activity referral schemes (PARSs) and related structures for promoting physical activity (PA) already exist in several countries, in Germany, PARSs have not yet been implemented systematically and nationwide. Through a co-production approach with relevant actors in the German healthcare system, a PARS was developed, and an implementation plan was created (e.g. financing). This study protocol aims to evaluate the developed PARS for people with non-communicable diseases (NCDs) in Germany regarding its potential effectiveness and implementation success. METHODS: To evaluate the effectiveness and implementation success of the PARS, we will apply a pragmatic cluster-randomised controlled trial (cRCT) in Hybrid II design by comparing two intervention groups (PARS vs PA advice [PAA]). The trial will take place in the Nürnberg metropolitan region, with 24 physician practices recruiting 567 people with NCDs. Both groups will receive brief PA advice from a physician to initially increase the participants' motivation to change their activity level. Subsequently, the PARS group will be given individualised support from an exercise professional to increase their PA levels and be transferred to local exercise opportunities. In contrast, participants in the PAA group will receive only the brief PA advice as well as information and an overview of regional PA offerings to become more active at their own initiative. After 12 and 24 weeks, changes in moderate to vigorous PA and in physical activity-related health competence (movement competence, control competence, self-regulation competence) will be measured as primary outcomes. Secondary outcomes will include changes in quality of life. To measure implementation success, we refer to the RE-AIM framework and draw on patient documentation, interviews, focus groups and surveys of the participating actors (physicians, exercise professionals). DISCUSSION: Through a between-group comparison, we will investigate whether additional individual support by an exercise professional compared to brief PA advice alone leads to higher PA levels in people with NCDs. The acceptance and feasibility of both interventions in routine care in the German healthcare system will also be evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04947787 . Registered 01 June 2021.

A multi-center, pragmatic, effectiveness-implementation (hybrid I) cluster randomized controlled trial to evaluate a child-oriented goal-setting approach in paediatric rehabilitation (the ENGAGE approach): a study protocol.

BACKGROUND: Child-oriented goal-setting in pediatric rehabilitation may improve child motivation, engagement in therapy, child outcomes related to therapy, and service delivery efficiency. The primary objective of this trial is to determine the effectiveness of a principles-driven, child-focused approach to goal-setting, Enhancing Child Engagement in Goal-Setting (ENGAGE), on pediatric rehabilitation outcomes compared to usual practice. The three secondary objectives are to 1) compare costs and secondary outcomes of the ENGAGE approach to usual practice, 2) determine the influence of child, parent and therapist characteristics on child engagement in therapy and rehabilitation outcomes, and 3) identify barriers and facilitators to the implementation of ENGAGE. METHODS: This research protocol describes a pragmatic, multi-site, cluster, effectiveness-implementation (hybrid type 1 design) randomized controlled trial. Therapists (n = 12 clusters of two therapists) at participating sites (n = 6) will be randomized to 1) the ENGAGE intervention group, or 2) usual care (control) using a computer-generated, permuted-block randomization sequence with site as a stratification variable designed by a statistician (RR). Each therapist will recruit four children 5-12 years old with neurodevelopmental conditions (n = 96), who will receive ENGAGE or usual care, according to therapist group allocation. ENGAGE therapists will be trained to use a 'toolbox' of evidence-driven, theory-informed principles to optimize child and parent motivation, engagement in the goal-setting process, and performance feedback strategies. Outcomes include goal performance (primary outcome), engagement in therapy, functional abilities, participation, and parent and child quality of life. Qualitative interviews with children, parents, ENGAGE therapists, and managers will explore challenges to implementation and potential mitigation strategies. Mixed effects multiple linear regression models will be developed for each outcome to assess group differences adjusted for clustering. A cost-effectiveness analysis will combine cost and a measure of effectiveness into an incremental cost-effectiveness ratio. Qualitative data on implementation will be analyzed inductively (thematic analysis) and deductively using established implementation science frameworks. DISCUSSION: This study will evaluate the effects of collaborative goal-setting in pediatric rehabilitation and inform effective implementation of child-focused goal-setting practices. TRIAL REGISTRATION: NCT05017363 (registered August 23, 2021 on ClinicalTrials.gov).