Randomized control trial Archives - Implementation Science at UW

✪ Feasibility and Implementation of INTERVAL-GAP4: A Global Randomised Controlled Trial of Intense Hybrid-supervised/Self-managed Versus Self-directed Exercise for Metastatic Prostate Cancer

Authors:

Stacey A Kenfield, Nicolas H Hart, Kerry S Courneya, Rosemary Greenwood , June M Chan, Jennette Sison, Li Zhang, Sarah RudmaN, Leah Ung, Moritz Schumann, Erin L Van Blarigan, Sam McKeown, Charles J Ryan, James Catto, Daniel A Galvão, Robert U Newton, Fred Saad; INTERVAL-GAP4 Site Investigators and INTERVAL-GAP4 Steering and Management Committees (Stephen R. Plymate, Committee Member

^{University of Washington affiliated authors are displayed in bold.}

✪ Open Access

Published: December 2025

Read the full text in the open access journal European Urology Open Science

Abstract:

Background and objective

Physical activity is associated with a lower risk of mortality in men with prostate cancer (PC); yet, randomised controlled trials with survival endpoints are nonexistent. INTense ExeRcise for surviVAL-Global Action Plan 4 (INTERVAL-GAP4) was a global phase 3 trial designed to test whether structured, hybrid-supervised/self-managed exercise improves survival in men with metastatic PC. The trial was stopped early due to poor accrual. This paper reports feasibility and implementation outcomes.

Methods

Men with metastatic PC were randomised (1:1) to a supervised/self-managed moderate- to high-intensity resistance and aerobic programme (three sessions per week for 2 yr) or to self-directed exercise. We evaluated site activation, recruitment, year 1 adherence, adverse events, and barriers to global trial feasibility. Efficacy outcomes—including survival, physical fitness, and biomarker results—will be reported separately.

Key findings and limitations

Of 21 activated sites across seven countries, 13 (62%) randomised patients. Of 938 patients approached, 232 (25%) consented and 145 (15%) were randomised (75 in the intervention and 70 in the control group) between April 2016 and February 2023. The median age was 70 yr (range: 44–89 yr). The study closed early after reaching 17% of the intended target. The median adherence in the intervention arm was 84% (interquartile range: 61–95%), with no difference between metastatic castrate-resistant and hormone-sensitive PC. At 12 mo, 58% of intervention participants met exercise guidelines versus 24% of controls. In year 1, 162 adverse events occurred in the intervention group and 109 in the control group; 19 adverse events were study related, all in the intervention arm. The major feasibility challenges included administrative burden, infrastructure limitations, logistics of supervised exercise delivery, and coronavirus disease 2019 disruptions.

Conclusions and clinical implications

While high adherence to a demanding exercise programme was achieved in selected metastatic PC patients, global recruitment proved difficult. Future large-scale exercise-oncology trials require streamlined protocols, realistic timelines, and greater alignment with site resources. Implementation science research is needed to support integration of exercise into routine advanced cancer care. A forthcoming paper will present the trial’s survival and physical fitness efficacy outcomes.

^{**This abstract is posted with permission under the Creative Commons Attribution 4.0 International License**}

✪ A randomized controlled trial testing supervision strategies in community mental health

Abstract:

Background

Clinicians need supports beyond training to deliver evidence-based treatments with fidelity. Workplace-based clinical supervision often is a commonly provided support in community mental health, yet too few studies have empirically examined supervision and its impact on clinician fidelity and treatment delivery.

Method

Building on a Washington State-funded evidence-based treatment initiative (CBT+), we conducted a randomized controlled trial (RCT), testing two supervision conditions delivered by workplace-based supervisors (supervisors employed by community mental health organizations). The RCT followed a supervision-as-usual (SAU) phase for comparison. The treatment of focus was trauma-focused cognitive behavioral therapy (TF-CBT). Clinicians (N = 238) from 25 organizations participated in the study across the SAU baseline and RCT phases. In the RCT phase, clinicians were randomized to either symptom and fidelity monitoring (SFM) or SFM and behavioral rehearsal (SFM + BR). For BR, clinicians engaged in a short role play of an upcoming treatment element. Supervisors delivered both conditions, with regular study monitoring for drift. Clinicians audiorecorded therapy sessions with enrolled clients, and masked coders coded a subset of recordings for adherence to TF-CBT. One hundred and thirty-three clinicians had recorded TF-CBT session data for 258 youth. We examined six adherence outcomes, including potential moderators.

Results

Results of generalized estimating equations indicated that there were no real differences on adherence outcomes for experimental conditions (SFM, SFM + BR) compared to SAU. Adherence scores in the baseline SAU phase and the RCT conditions were high. Only one interaction was significant.

Conclusions

Contrary to our hypotheses, we did not see improvements in adherence with the RCT conditions. However, nonsignificant findings seem best explained by clinicians’ acceptable/high adherence in SAU. This study was conducted within the context of a long-standing, state-funded EBT initiative, in which clinicians and their supervisors receive training and support, and in which participating community mental health organizations have adopted and supported TF-CBT.

Trial Registration

ClinicalTrials.gov ID: NCT01800266

Plain Language Summary

Clinicians often receive training in evidence-based treatments (EBTs), but training alone is not enough for clinicians to deliver EBTs well. They need other supports. One of the necessary supports is clinical supervision. In public community mental health organizations, which are often resource-constrained, routine clinical supervision is a commonly available support. However, its potential for supporting high-quality EBT delivery is not well understood. This study looked at supervision and clinicians’ delivery of trauma-focused cognitive behavioral therapy (TF-CBT), an EBT for youth who have mental health problems subsequent to trauma. We found that clinicians who received workplace-based supervision on TF-CBT from TF-CBT-trained supervisors, within the context of a state-funded EBT initiative, delivered TF-CBT well. This initiative supported delivery by providing training and supervisor-specific supports. In a second phase of the study, we rigorously tested supervisors’ use of two specific technique packages. These packages included having supervisors review: (a) graphed client mental health symptoms across treatment and clinicians’ report of TF-CBT elements delivered each session or (b) these plus having clinicians do a brief demonstration of how they would deliver an upcoming TF-CBT element to their client, so supervisors could “see” clinicians’ skill and provide feedback. Contrary to expectations, we did not see important differences in clinicians’ TF-CBT delivery. This may be because the clinicians enrolled in our study were already delivering TF-CBT well and, therefore, there was less opportunity for changes. Future studies should explore if these techniques are more helpful for specific situations or clinicians.

^{**This abstract is posted with permission under the Creative Commons Attribution 4.0 International License**}

✪ Formative evaluation of the implementation of digital therapeutics for opioids and other substance use disorders in primary care (DIGITS trial)

Abstract:

Background

Substance use disorders (SUDs) result in individual and societal burden. However, most individuals with SUD receive no treatment. Implementing SUD interventions in primary care could address this population's treatment needs. In the USA, reSET® and reSET-O® were the first prescription digital therapeutics (PDTs) for SUDs and opioid use disorder (OUD), respectively. The Digital Treatments for Substance Use Disorder (DIGITS) study tested the effectiveness of practice facilitation and health coaching strategies to support reSET and reSET-O implementation into primary care. A formative evaluation was conducted to monitor implementation, inform adaptations, and learn what promotes PDT sustainment.

Method

The Dynamic Sustainability Framework and the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies guided the evaluation. Using rapid qualitative methods, we collected and analyzed observational fieldnotes, key informant interviews, and document sources (e.g., meeting minutes) for synthesis and dissemination to clinical partners and the study team via formative reports. We analyzed the reports to generate evaluation results.

Results

Twenty-four primary care clinics participated. Evaluation data included 98 observational fieldnotes, 16 interviews, and 253 document sources. We produced nine formative reports. The study encountered barriers and facilitators in each DSF domain (ecological system, practice setting, and intervention). In the ecological system, the PDT vendor enabled the study, but the COVID-19 pandemic, laws, regulations, and contracting delayed implementation. In the practice setting, staff shortages and low clinic capacity were implementation challenges, while electronic health record capabilities were both barriers and facilitators. At the intervention level, non-routine workflows, clinician burden, and low patient engagement were barriers despite clinicians’ efforts.

Conclusions

Digital therapeutics are promising SUD and OUD treatments, but integration into primary care requires conducive laws and regulations, organizational capacity, and patient and clinician engagement. Formative evaluation identified important lessons for future PDT implementation.

Plain Language Summary

Evaluation of the integration of digital treatments for opioid and other substance use disorders in primary care

Most people with substance use disorders (SUDs) receive no treatment. In the USA, two smartphone app-based digital treatments for SUD and opioid use disorders (OUDs) became available by prescription. The Digital Treatments for Substance Use Disorder (DIGITS) study, a randomized implementation trial, tested how best to integrate these digital treatments for SUD and OUD into primary care. Throughout the study, we conducted a formative evaluation to observe progress, recommend implementation improvements, and understand how digital treatments could be offered to patients after the study ended. For this evaluation, we collected qualitative data through observing study meetings and interviewing primary care leaders, clinicians, and clinical and study staff. The data were regularly summarized and reported to our clinical partners and the study team. We used two implementation frameworks to interpret the data: the Dynamic Sustainability Framework and the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies. The evaluation revealed factors that helped and hindered implementation. Obstacles from outside the health care system included the COVID-19 pandemic, laws, regulations, and delays in setting up contractual agreements, whereas a partnership with the digital treatment vendor proved helpful. Clinics had difficulties with clinician burden, staff shortages, lack of time and available appointments, and performing new and unfamiliar tasks. The electronic health record system both supported and impended implementation. Last, few patients accepted the offered digital treatment, or used it persistently. Formative evaluation results suggest that digital treatments for SUD and OUD in primary care are promising, however their successful use requires supportive laws and regulations, health system resources, and increased patient and clinician engagement.

^{**This abstract is posted with permission under the Creative Commons Attribution 4.0 International License**}

✪ Digital communication between mothers and community health workers to support neonatal health (CHV-NEO): study protocol for a randomized controlled trial

Authors:

Keshet Ronen, Lincoln C. Pothan, Violet Apondi, Felix A. Otieno, Daniel Mwakanema, Felix O. Otieno, Lusi Osborn, Julia C. Dettinger, Priyanka Shrestha, Helena Manguerra, Ferdinand Mukumbang, Millicent Masinde, Evelyn Waweru, Mercy Amulele, Christine Were, Beatrice Wasunna, Grace John-Stewart, Bryan Weiner, Arianna Rubin Means, Barbra A. Richardson, Anna B. Hedstrom, Jennifer A. Unger & John Kinuthia

^{University of Washington affiliated authors are displayed in bold.}

✪ Open Access

Published: October 2024

Read the full text in the open access journal Trials

Abstract:

Background

Provision of essential newborn care at home, rapid identification of illness, and care-seeking by caregivers can prevent neonatal mortality. Mobile technology can connect caregivers with information and healthcare worker advice more rapidly and frequently than healthcare visits. Community health workers (CHWs) are well-suited to deliver such interventions. We developed an interactive short message service (SMS) intervention for neonatal health in Kenya, named CHV-NEO. CHV-NEO sends automated, theory-based, actionable, messages throughout the peripartum period that guide mothers to evaluate maternal and neonatal danger signs and facilitate real-time dialogue with a CHW via SMS. We integrated this intervention into Kenya’s national electronic community health information system (eCHIS), which is currently used at scale to support CHW workflow.

Methods

The effect of CHV-NEO on clinical and implementation outcomes will be evaluated through a non-blinded cluster randomized controlled trial. Twenty sites across Kisumu County in Western Kenya were randomized 1:1 to provide either the national eCHIS with integrated CHV-NEO messaging (intervention) or standard of care using eCHIS without CHV-NEO (control). We will compare neonatal mortality between arms based on abstracted eCHIS data from 7200 pregnant women. Secondary outcomes include self-reported provision of essential newborn care (appropriate cord care, thermal care, and timely initiation of breastfeeding), knowledge of neonatal danger signs, and care-seeking for neonatal illness, compared between arms based on questionnaires with a subgroup of 2000 women attending study visits at enrollment in pregnancy and 6 weeks postpartum. We will also determine CHV-NEO’s effect on CHW workflows and evaluate determinants of intervention acceptability, adoption, and fidelity of use through questionnaires, individual interviews, and messaging data.

Discussion

We hypothesize that the CHV-NEO direct-to-client communication strategy can be successfully integrated within existing CHW workflows and infrastructure, improve the provision of at-home essential newborn care, increase timely referral of neonatal illness to facilities, and reduce neonatal mortality. The intervention’s integration into the national eCHIS tool will facilitate rapid scale-up if it is clinically effective and successfully implemented.

Trial registration

ClinicalTrials.gov, NCT05187897. The CHV-NEO study was registered on January 12, 2022.

^{**This abstract is posted with permission under the Creative Commons Attribution 4.0 International License**}

✪ Virtual versus usual in-office care for multiple sclerosis: The VIRTUAL-MS multi-site randomized clinical trial study protocol

Abstract:

Background

Multiple sclerosis (MS) affects nearly 1 million people and is estimated to cost $85.4 billion in the United States annually. People with MS have significant barriers to receiving care and telemedicine could substantially improve access to specialized, comprehensive care. In cross-sectional analyses, telemedicine has been shown to be feasible, have high patient and clinician satisfaction, reduce patient costs and burden, and enable a reasonable assessment of disability. However, no studies exist evaluating the longitudinal impact of telemedicine care for MS. Here we describe the study protocol for VIRtual versus UsuAL In-office care for Multiple Sclerosis (VIRTUAL-MS). The main objective of the study is to evaluate the impact of telemedicine for MS care on: patient clinical outcomes, economic costs, patient, and clinician experience.

Methods

This two-site randomized clinical trial will enroll 120 adults with a recent diagnosis of MS and randomize 1:1 to receive in-clinic vs. telemedicine care for 24 months. The primary outcome of the study is worsening in any one of the four Multiple Sclerosis Functional Composite 4 (MSFC4) measures at 24 months. Other study outcomes include patient and clinician satisfaction, major healthcare costs, Expanded Disability Status Scale, treatment adherence, and digital outcomes.

Conclusion

The results of this study will directly address the key gaps in knowledge about longitudinal telemedicine-enabled care in an MS population. It will inform clinical care implementation as well as design of trials in MS and other chronic conditions.

^{**This abstract is posted with permission under the Creative Commons Attribution 4.0 International License**}

Organize and mobilize for implementation effectiveness to improve overdose education and naloxone distribution from syringe services programs: A randomized controlled trial

Abstract:

Background

The United States (US) continues to face decades-long increases in opioid overdose fatalities. As an opioid overdose reversal medication, naloxone can dramatically reduce opioid overdose mortality rates when distributed to people likely to experience or witness an opioid overdose and packaged with education on its use, known as overdose education and naloxone distribution (OEND). Syringe services programs (SSPs) are ideal venues for OEND with staff who are culturally competent in providing services for people who are at risk of experiencing or observing an opioid overdose. We carried out a randomized controlled trial of SSPs to understand the effectiveness of the organize and mobilize for implementation effectiveness (OMIE) approach at improving OEND implementation effectiveness within SSPs

Methods

Using simple randomization, 105 SSPs were enrolled into the trial and assigned to one of two study arms — (1) dissemination of OEND best practice recommendations (Control SSPs) or the OMIE approach along with dissemination of the OEND best practice recommendations (i.e., OMIE SSPs). OMIE SSPs could participate in 60-min OMIE sessions once a month for up to 12 months. At 12-month post-baseline, 102 of 105 SSPs (97%) responded to the follow-up survey.

Results

The median number of sessions completed by OMIE SSPs was 10. Comparing OMIE SSPs to control SSPs, we observed significant increases in the number of participants receiving naloxone (incidence rate ratio: 2.15; 95% CI: 1.42, 3.25; p < 0.01) and the rate of naloxone doses distributed per SSP participant (adjusted incidence rate ratio: 1.97; 95% CI: 1.18, 3.30; p = 0.01). We observed no statistically significant difference in the number of adopted best practices between conditions (difference in means 0.2, 95% CI: − 0.7, 1.0; p = 0.68). We also observed a threshold effect where SSPs receiving a higher OMIE dose had greater effect sizes with regard to the number of people given naloxone and the number of naloxone doses distributed.

Conclusions

In conclusion, the multifaceted OMIE approach was effective at increasing naloxone distribution from SSPs, despite substantial external shocks during the trial. These findings have major implications for addressing the overdose crisis, which has continued unabated for decades.

^{**This abstract is posted with permission under the Creative Commons Attribution 4.0 International License**}

✪ Recruiting Community Health Centers for Implementation Research: Challenges, Implications, and Potential Solutions

✪ Assessment of implementation methods in sepsis: study protocol for a cluster-randomized hybrid type 2 trial

Abstract:

Background

Sepsis is the leading cause of intensive care unit (ICU) admission and ICU death. In recognition of the burden of sepsis, the Surviving Sepsis Campaign (SSC) and the Institute for Healthcare Improvement developed sepsis “bundles” (goals to accomplish over a specific time period) to facilitate SSC guideline implementation in clinical practice. Using the SSC 3-h bundle as a base, the Centers for Medicare and Medicaid Services developed a 3-h sepsis bundle that has become the national standard for early management of sepsis. Emerging observational data, from an analysis conducted for the AIMS grant application, suggest there may be additional mortality benefit from even earlier implementation of the 3-h bundle, i.e., the 1-h bundle.

Method

The primary aims of this randomized controlled trial are to: (1) examine the effect on clinical outcomes of Emergency Department initiation of the elements of the 3-h bundle within the traditional 3 h versus initiating within 1 h of sepsis recognition and (2) examine the extent to which a rigorous implementation strategy will improve implementation and compliance with both the 1-h bundle and the 3-h bundle. This study will be entirely conducted in the Emergency Department at 18 sites. A secondary aim is to identify clinical sepsis phenotypes and their impact on treatment outcomes.

Discussion

This cluster-randomized trial, employing implementation science methodology, is timely and important to the field. The hybrid effectiveness-implementation design is likely to have an impact on clinical practice in sepsis management by providing a rigorous evaluation of the 1- and 3-h bundles.

^{**This abstract is posted with permission under the Creative Commons Attribution 4.0 International License**}

✪ Promoting alcohol treatment engagement post-hospitalization with brief intervention, medications and CBT4CBT: protocol for a randomized clinical trial in a diverse patient population

Abstract:

Background

Alcohol use disorder (AUD) commonly causes hospitalization, particularly for individuals disproportionately impacted by structural racism and other forms of marginalization. The optimal approach for engaging hospitalized patients with AUD in treatment post-hospital discharge is unknown. We describe the rationale, aims, and protocol for Project ENHANCE (ENhancing Hospital-initiated Alcohol TreatmeNt to InCrease Engagement), a clinical trial testing increasingly intensive approaches using a hybrid type 1 effectiveness-implementation approach.

Methods

We are randomizing English and/or Spanish-speaking individuals with untreated AUD (n = 450) from a large, urban, academic hospital in New Haven, CT to: (1) Brief Negotiation Interview (with referral and telephone booster) alone (BNI), (2) BNI plus facilitated initiation of medications for alcohol use disorder (BNI + MAUD), or (3) BNI + MAUD + initiation of computer-based training for cognitive behavioral therapy (CBT4CBT, BNI + MAUD + CBT4CBT). Interventions are delivered by Health Promotion Advocates. The primary outcome is AUD treatment engagement 34 days post-hospital discharge. Secondary outcomes include AUD treatment engagement 90 days post-discharge and changes in self-reported alcohol use and phosphatidylethanol. Exploratory outcomes include health care utilization. We will explore whether the effectiveness of the interventions on AUD treatment engagement and alcohol use outcomes differ across and within racialized and ethnic groups, consistent with disproportionate impacts of AUD. Lastly, we will conduct an implementation-focused process evaluation, including individual-level collection and statistical comparisons between the three conditions of costs to providers and to patients, cost-effectiveness indices (effectiveness/cost ratios), and cost–benefit indices (benefit/cost ratios, net benefit [benefits minus costs). Graphs of individual- and group-level effectiveness x cost, and benefits x costs, will portray relationships between costs and effectiveness and between costs and benefits for the three conditions, in a manner that community representatives also should be able to understand and use.

Conclusions

Project ENHANCE is expected to generate novel findings to inform future hospital-based efforts to promote AUD treatment engagement among diverse patient populations, including those most impacted by AUD.

^{**This abstract is posted with permission under the Creative Commons Attribution 4.0 International License**}

Prevention of Opioid Use and Disorder Among Youth Involved in the Legal System: Innovation and Implementation of Four Studies Funded by the NIDA HEAL Initiative

Authors:

✪ Open Access

Read the full text in the open access journal European Urology Open Science

Abstract:

Background and objective

Methods

Key findings and limitations

Conclusions and clinical implications

Authors:

✪ Open Access

Read the full text in the open access journal Implementation Research and Practice

Abstract:

Background

Method

Results

Conclusions

Trial Registration

Plain Language Summary

Authors:

✪ Open Access

Read the full text in the open access journal Implementation Research and Practice

Abstract:

Background

Method

Results

Conclusions

Plain Language Summary

Evaluation of the integration of digital treatments for opioid and other substance use disorders in primary care

Authors:

✪ Open Access

Read the full text in the open access journal Trials

Abstract:

Background

Methods

Discussion

Trial registration

Authors:

✪ Open Access

Read the full text in the open access journal Contemporary Clinical Trials

Abstract:

Background

Methods

Conclusion

Authors:

✪ Open Access

Read the full text in the open access journal Implementation Science

Abstract:

Background

Methods

Results

Conclusions

Authors:

✪ Open Access

Read the full text open access in the journal Health Equity

Authors:

✪ Open Access

Read the full text in the open access journal Trials

Abstract:

Abstract:

Background

Method

Discussion

Authors:

✪ Open Access

Read the full text open access in the journal Addiction Science and Clinical Practice

Abstract:

Background

Methods

Conclusions

Authors:

Subscription Required for Full Text Access

Read the full text in the subscription access journal Prevention Science