Trial Implementation Research Articles

Development of Android-Based Interactive Media for History Subjects at SMA Negeri 1 Krueng Barona Jaya

This research is entitled Development of Android-Based Interactive Media for History Subjects at SMA Negeri 1 Krueng Barona Jaya. This research was conducted because there are still many teachers who have not maximized the use of gadgets as learning media in the modern era. This aim of this research is to determine the development of android-based interactive media in history subjects at SMA Negeri 1 Krueng Barona Jaya and to determine the feasibility of android-based interactive media in history subjects at SMA Negeri 1 Krueng Barona Jaya. This research is a type of research and development (RD). This research was developed with five steps of ADDIE model, namely 1) Analysis, 2) Design, 3) Development, 4) Implementation, 5) Evaluation. Data collection techniques use interview, documentation, expert validation sheet. The data analysis technique uses descriptive statistical techniques with percentage formulas. This research produces learning media in the form of android-based interactive media in the form of an application namely History Application (HistoApp)with learning material “The arrival European nations to Indonesia” which contains audio, teks, and images. Based on validation carried out with material experts, a percentage of 88% was obtained in the “very feasible” category. Based on validation carried out with media experts, a percentage of 80% was obtained in the “feasible” category. The expert validation results show that the HistoApp application media product is worthy of being tested in the learning process in class of XI-IIS-1 SMA Negeri 1 Krueng Barona Jaya. The result of the implementation trial before developing android-based interactive media obtained an average students score of 70 and the average students score after developing android-based interactive media was 80. So it can be concluded that the android-based interactive media product for history subjects at SMA Negeri 1 Krueng Barona Jaya with the learning material “The arrival of European nations to Indonesia” which has been developed by researcher is feasible for use in the history learning process.

Abstract 35: Integrating Clinical Trials Into Comprehensive Stroke Education for Inpatient Nurses

Introduction: A major challenge in the implementation of clinical trials is the lack of integration of research into the clinical practice of frontline staff. The University of Minnesota partnered with the M Health Fairview (MHFV) System to incorporate stroke clinical trials into the annual comprehensive stroke education courses. While not required by the stroke accreditation curriculum standards, embedding research topics into ongoing stroke education is a novel practice that broadly increases awareness of clinical research with the frontline staff caring for stroke patients. Methods: In 2019, the comprehensive stroke class was updated to include a section for stroke trials. The research topics include: a brief description of study team roles, an overview of the impact of clinical trials on EBP, results for published trials, updates on current clinical trials, and the impact on nursing workflow. The number of attendees for each session from 2019-June 2023 were recorded along with anonymous comments about the presentation. The total number of subjects enrolled in acute, inpatient, and outpatient stroke trials in MHFV were compiled. Results: The comprehensive stroke class was attended by MHFV nurses 1,667 times. Interest in research was noted 77 times in the comments and research was ranked 3rd “most interesting” topic presented in 2019. A total of 276 patients were enrolled in stroke research in that timeframe. Conclusion: While no direct correlation can be drawn to trial enrollment, the volume of learners demonstrates broad dissemination of stroke trials information to frontline staff caring for stroke patients and the collection of positive feedback shows an interest in the topic. Incorporating clinical trials education into established comprehensive stroke education increases awareness of clinical trials and facilitates integration of research into clinical workflows with a higher acceptance of clinical trial efforts by frontline staff.

Implementing consultation audio recording applications to improve informed decision-making (IDM) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) eligible for docetaxel.

103 Background: Pts with mCRPC have multiple treatment options and face challenges to IDM. This leads some to make poorly informed or goal-discordant decisions. Consultation audio recordings are known to improve IDM by improving recall, but uptake has been limited. It is unclear whether pt-administered apps are an effective, feasible strategy to increase access to recordings and improve IDM. Methods: We conducted a single-site implementation trial. Pts were English-speaking with progressive mCRPC and an upcoming oncology visit in which treatment options including docetaxel would be discussed. Pre-visit, a coordinator sent instructions, provided coaching, and sent text reminders to help pts create recordings using their mobile device. To evaluate change in IDM pre- vs post- the audio-recorded visit, we used an investigator-developed questionnaire testing pt knowledge about docetaxel (19 items, 0-100% correct) and the decisional conflict scale-informed subscale (3 items, 0=feels extremely uninformed to 100=feels extremely informed). Change was evaluated using the Wilcoxon signed-rank test. We also measured implementation: rates of consent, instruction receipt, recording, and listening, as well as pt-reported helpfulness of the app in decision-making. Lastly, we interviewed pts to understand benefits, barriers, and facilitators. Results: Of 78 pts approached, 44 (56%) consented, and 41 (53%) were evaluable. Top reasons for not consenting were too busy (7, 21%), illness (5, 15%), and inadequate devices (4, 12%). Mean age was 75y [56-90], and 34 (83%) were White. Median knowledge about docetaxel increased from 47 to 53 (P=0.048), corresponding to one additional correct response. Median informed subscore increased from 50 to 75 (P=0.011), corresponding to an improvement from feeling neither informed nor uninformed to feeling informed. All pts received instructions, 38 (93%) recorded their visits, and 28 (68%) listened to the recording. Twenty-six pts (63%) found the app helpful in decision-making. In pt interviews, benefits of recording were better recall of treatment options and toxicities, greater decision confidence, and peace of mind. Most frequently reported barriers to use were technology unfamiliarity and disconnected pt portal, telehealth, and recording applications; facilitators were app simplicity and caregiver/coordinator assistance. Conclusions: Implementation of self-administered mobilerecordings was feasible and associated with increased pt knowledge and feeling more informed about treatment with docetaxel in pts with mCRPC. Future efforts should focus on non-White, no/limited-English-speaking populations, and increasing recording/listening rates by addressing barriers and augmenting facilitators (e.g., integrating recordings in electronic pt portals). Clinical trial information: NCT05127850 .

Investigating the Influence of Patient Eligibility Characteristics on the Number of Deferrable Rheumatologist Visits: Planning for a Patient-Initiated Follow-Up Strategy.

Patient-initiated follow-up (PIFU) for rheumatoid arthritis (RA) is a model of care delivery wherein patients contact the clinic when needed instead of having regularly scheduled follow-up. Our objective was to investigate the influence of different patient eligibility characteristics on the number of potentially deferred visits to inform future implementation of a PIFU strategy. We conducted a retrospective chart review of 7 rheumatologists' practices at 2 university-based clinics between March 1, 2021, and February 28, 2022. Data extracted included the type and frequency of visits, disease management, comorbidities, and care complexities. Stable disease was defined as remission or low disease activity with no medication changes at all visits. The influence of patient characteristics on the number of deferrable visits in patients with stable disease was explored in 4 criteria sets that were based on early disease duration, medication prescribed, presence of care complexity elements, and comorbidity burden. Records from 770 visits were reviewed from 365 patients with RA (71.5% female, 70% seropositive). Among all criteria sets, the proportion of visits that could be redirected varied between 2.5% and 20.9%. The highest proportion of deferrable visits was achieved when eligibility criteria included only stable disease activity and patients with RA on conventional synthetic disease-modifying antirheumatic drugs or no medications (n = 161, 20.9%). PIFU may result in a more efficient use of specialist healthcare resources. However, the applicability of such models of care and the number of deferred visits is highly dependent on patient characteristics used to establish eligibility criteria for that model. These findings should be considered when planning implementation trials.

Developing System-based Voice Features for Detecting Parkinson’s Disease Using Machine Learning Algorithms

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a deficit of dopamine in the brain. This condition has the potential to impact individuals of advanced age. The procedure for diagnosing PD is currently not well established. Diagnostics includes a range of methods, including the identification and evaluation of symptoms, the implementation of clinical trials, and the use of laboratory tests. This research work employs a range of machine learning (ML) algorithms, including k-nearest neighbors (k-NN), support vector machines (SVMs), random forest (RF), logistic regression (LR), and AdaBoost boosting approaches, to predict the occurrence of PD and assist healthcare practitioners in recommending tailored treatment plans. To evaluate the suggested ML methods, it is customary to use a standard dataset consisting of various biological voice measures obtained from individuals afflicted with PD as well as healthy individuals. The experimental results demonstrate that the LR model achieves an accuracy of 86%, the k-NN model achieves an accuracy of 92%, the SVM model achieves an accuracy of 95%, the RF model achieves an accuracy of 95%, and the AdaBoost boosting model achieves an accuracy of 93%. SVM and RF are well acknowledged for their high accuracy in classification tasks. Upon conducting a comparative analysis with other studies, it was shown that the proposed intervention yielded outcomes that were either comparable to or superior to those reported in previous research.

Proposal for a new meteotsunami intensity index

Abstract. Atmospherically generated coastal waves labelled as meteotsunami are known to cause destruction, injury, and fatality due to their rapid onset and unexpected nature. Unlike other coastal hazards such as tsunami, there exist no standardised means of quantifying this phenomenon, which is crucial to understand shoreline impacts and to enable researchers to establish a shared language and framework for meteotsunami analysis and comparison. In this study, we present a new five-level Lewis Meteotsunami Intensity Index (LMTI) trialled in the United Kingdom (UK) but designed for global applicability. A comprehensive dataset of meteotsunami events recorded in the UK was utilised, and the index's effectiveness was evaluated, with intensity level and spatial distribution of meteotsunami occurrence derived. Results revealed a predominant occurrence of Level 2 moderate intensity meteotsunami (69 %) in the UK, with distinct hotspots identified in south-western England and Scotland. Further trial implementation of the LMTI in a global capacity revealed its potential adaptability to other meteotsunami-prone regions, facilitating the comparison of events and promoting standardisation of assessment methodologies.

Testing plant growth promoting microorganisms in the field - a proposal for standards.

In the European Union and worldwide there are a burgeoning markets for plant growth promoting microorganisms (PGPM) and other biological agents as soil improvers, bio-fertilizers, plant bio-stimulants, and biological control agents or bio-pesticides. Microbial agents have a major share in this development. The use of such products is often advertised with the promise of contributing to sustainable agricultural practices by increasing crop growth and yield and offering an alternative or substitute to decrease the dependency of agriculture on hazardeous agrochemicals. In contrast to registered microbial plant protection products, PGPM that are marketed in the EU as soil improvers or plant biostimulants, are not strictly required to have proven minimum efficacy levels under field conditions. Manufacturers only have to ensure that these products do not pose unacceptable risks to human, animal or plant health, safety or the environment. Uniform guidelines comparable to the EPPO - standards (European and Mediterranean Plant Protection Organisation) to test the efficacy in field trials are not available. This paper attempts to fill the gap. It proposes guidelines for PGPM field trial design and implementation, as well as recommendations for the type and scope of data collection and evaluation. Selected research papers from literature were evaluated to analyze, whether and to what extent the requirements are already met. The majority of the papers had a clear experimental design followed by proper data evaluation. Frequent deficiencies were the low number of tested environments and crop species, insufficient site and agronomic management description and missing data on soil humidity and temperature. Using the suggested standards is assumed to increase the expressive power of tested microbial products.

Adaptive phase I-II clinical trial designs identifying optimal biological doses for targeted agents and immunotherapies.

Targeted agents and immunotherapies have revolutionized cancer treatment, offering promising options for various cancer types. Unlike traditional therapies the principle of "more is better" is not always applicable to these new therapies due to their unique biomedical mechanisms. As a result, various phase I-II clinical trial designs have been proposed to identify the optimal biological dose that maximizes the therapeutic effect of targeted therapies and immunotherapies by jointly monitoring both efficacy and toxicity outcomes. This review article examines several innovative phase I-II clinical trial designs that utilize accumulated efficacy and toxicity outcomes to adaptively determine doses for subsequent patients and identify the optimal biological dose, maximizing the overall therapeutic effect. Specifically, we highlight three categories of phase I-II designs: efficacy-driven, utility-based, and designs incorporating multiple efficacy endpoints. For each design, we review the dose-outcome model, the definition of the optimal biological dose, the dose-finding algorithm, and the software for trial implementation. To illustrate the concepts, we also present two real phase I-II trial examples utilizing the EffTox and ISO designs. Finally, we provide a classification tree to summarize the designs discussed in this article.

Statistical classification of treatment responses in mouse clinical trials for stratified medicine in oncology drug discovery

Translational oncology research strives to explore a new aspect: identifying subgroups that exhibit treatment response even during pre-clinical phases. In this study, we focus on PDX models and their implementation in mouse clinical trials (MCT). Our primary objective was to identify subgroups with different treatment responses using Latent Class Mixed Model (LCMM).We used a public dataset and focused on one treatment, encorafenib, and two indications, melanoma and colorectal cancer, for which efficacy depends on a specific mutation BRAF V600E. One LCMM per indication was implemented to classify treatment responses at the PDX level, analyzing the growth kinetics of treated tumors and matched controls within the PDX models. A simulation study was carried out to explore the performance of LCMM in this context. For both applications, LCMM identified classes for which the higher the proportion of mutated BRAF V600E PDX models the greater the treatment effect, which is aligned with encorafenib use recommendations. The simulation study showed that LCMM could identify classes with large differences in treatment effects. LCMM is a suitable tool for MCT to explore treatment response subgroups of PDX. Once these subgroups are defined, characterization of their phenotypes/genotypes could be performed to explore treatment response predictors.

Quantifying Site Burden to Optimize Protocol Performance.

The increase in protocol complexity and the resulting rise in the effort required by investigative sites to implement protocols have been well documented, but existing measures of site burden only offer an incomplete view of the burden experienced by site personnel. The introduction of Decentralized Clinical Trials-trials supported by remote and virtual technologies and services-is expected to impact the burden imposed on sites, but this impact has not yet been systematically measured. The Tufts Center for the Study of Drug Development conducted an online survey among clinical research sites worldwide and gathered 355 responses assessing the burden associated with distinct activities and procedures related to the implementation of clinical trial protocols using traditional and decentralized approaches. A high percentage of investigative sites (50.5%) have had no experience with DCT solutions and only a small percentage (6.6%) have participated in fully decentralized clinical trials. Overall, half of respondents view DCT solutions as more burdensome than traditional clinical trials. In general, activities related to operational and managerial aspects of trial implementation were viewed as less burdensome when done remotely, while clinical procedures or elements that require study team-patient interactions were viewed as more burdensome when using DCT approaches versus in-person or traditional methods.

Community health worker training to reduce mental health and substance use stigma towards patients who have disengaged from HIV/TB care in South Africa: protocol for a stepped wedge hybrid type II pilot implementation trial

BackgroundSouth Africa has deployed community health workers (CHWs) to support individuals to enter and stay in HIV/TB care. Although CHWs routinely encounter patients with mental health (particularly depression) and substance use (SU) conditions that impact their engagement in HIV/TB care, CHWs are rarely trained in how to work with these patients. This contributes to mental health and SU stigma among CHWs, a known barrier to patient engagement in care. Mental health and SU training interventions could reduce CHW stigma and potentially improve patient engagement in care, but evidence of the feasibility, acceptability, and preliminary effectiveness of these interventions is scarce. Therefore, we designed a hybrid type 2 effectiveness-implementation pilot trial to evaluate the implementation and preliminary effectiveness of a CHW training intervention for reducing depression and SU stigma in the Western Cape, South Africa.MethodsThis stepped wedge pilot trial will engage CHWs from six primary care clinics offering HIV/TB care. Clinics will be block randomized into three-step cohorts that receive the intervention at varying time points. The Siyakhana intervention involves 3 days of training in depression and SU focused on psychoeducation, evidence-based skills for working with patients, and self-care strategies for promoting CHW wellness. The implementation strategy involves social contact with people with lived experience of depression/SU during training (via patient videos and a peer trainer) and clinical supervision to support CHWs to practice new skills. Both implementation outcomes (acceptability, feasibility, fidelity) and preliminary effectiveness of the intervention on CHW stigma will be assessed using mixed methods at 3- and 6-month follow-up assessments.DiscussionThis trial will advance knowledge of the feasibility, acceptability, and preliminary effectiveness of a CHW training for reducing depression and SU stigma towards patients with HIV and/or TB. Study findings will inform a larger implementation trial to evaluate the longer-term implementation and effectiveness of this intervention for reducing CHW stigma towards patients with depression and SU and improving patient engagement in HIV/TB care.Trial registrationClinicalTrials.gov NCT05282173. Registered on 7 March 2022.

Increasing the uptake of Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) through seasonal malaria chemoprevention channel delivery: protocol of a multicenter cluster randomized implementation trial in Mali and Burkina Faso

BackgroundThe uptake of Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) remains unacceptably low, with more than two-thirds of pregnant women in sub-Saharan Africa still not accessing the three or more doses recommended by the World Health Organisation (WHO). In contrast, the coverage of Seasonal Malaria Chemoprevention (SMC), a more recent strategy recommended by the WHO for malaria prevention in children under five years living in Sahelian countries with seasonal transmission, including Mali and Burkina-Faso, is high (up to 90%). We hypothesized that IPTp-SP delivery to pregnant women through SMC alongside antenatal care (ANC) will increase IPTp-SP coverage, boost ANC attendance, and increase public health impact. This protocol describes the approach to assess acceptability, feasibility, effectiveness, and cost-effectiveness of the integrated strategy.Methods and analysisThis is a multicentre, cluster-randomized, implementation trial of IPTp-SP delivery through ANC + SMC vs ANC alone in 40 health facilities and their catchment populations (20 clusters per arm). The intervention will consist of monthly administration of IPTp-SP through four monthly rounds of SMC during the malaria transmission season (July to October), for two consecutive years. Effectiveness of the strategy to increase coverage of three or more doses of IPTp-SP (IPTp3 +) will be assessed using household surveys and ANC exit interviews. Statistical analysis of IPT3 + and four or more ANC uptake will use a generalized linear mixed model. Feasibility and acceptability will be assessed through in-depth interviews and focus group discussions with health workers, pregnant women, and women with a child < 12 months.DiscussionThis multicentre cluster randomized implementation trial powered to detect a 45% and 22% increase in IPTp-SP3 + uptake in Mali and Burkina-Faso, respectively, will generate evidence on the feasibility, acceptability, effectiveness, and cost-effectiveness of IPTp-SP delivered through the ANC + SMC channel. The intervention is designed to facilitate scalability and translation into policy by leveraging existing resources, while strengthening local capacities in research, health, and community institutions. Findings will inform the local national malaria control policies.Trial registrationRetrospectively registered on August 11th, 2022; registration # PACTR202208844472053.Protocol v4.0 dated September 04, 2023.Trail sponsor: University of Sciences Techniques and Technologies of Bamako (USTTB), Mali.

Cluster-randomized implementation trial of two facilitation strategies to implement a novel information and communications technology at the Veterans Health Administration

BackgroundInformation and communication technologies (ICTs) improve quality and efficiency of healthcare, but effective practices for implementing new ICTs are unknown. From 2019 to 2021, the Veterans Health Administration (VHA) implemented FLOW3, an ICT that facilitates prosthetic limb care. The goal of this study was to compare the impact of two facilitation strategies on FLOW3 adoption, implementation, and sustainment.MethodsFLOW3 is a computerized workflow management system comprised of three applications that facilitate the three steps for prosthesis authorization. During VHA’s implementation of FLOW3, we randomized 60 VHA sites to basic or enhanced facilitation groups. Basic facilitation included a manualized training toolkit and office hours. Enhanced facilitation included basic facilitation plus monthly learning collaboratives and site-specific performance reports. Outcomes included time to adoption of FLOW3 and complete FLOW3 utilization rates during implementation and sustainment periods. We compared outcomes between sites assigned to basic versus enhanced facilitation groups. Results were calculated using both intent-to-treat (ITT) and dose–response analyses. The dose–response analysis used a per-protocol approach and required sites in the enhanced facilitation group to join two of six learning collaboratives; sites that attended fewer were reassigned to the basic group.ResultsRandomization assigned 30 sites to enhanced facilitation and 30 to basic. Eighteen of 30 randomized sites were included in the enhanced facilitation group for dose–response analysis. During the implementation period, enhanced facilitation sites were significantly more likely to completely utilize FLOW3 than basic facilitation sites (HR: 0.17; 95% CI: 1.18, 4.53, p = 0.02) based on ITT analysis. In the dose–response analysis, the enhanced group was 2.32 (95% CI: 1.18, 4.53) times more likely to adopt FLOW3 than basic group (p = 0.014).ConclusionsEnhanced facilitation including a learning collaborative and customized feedback demonstrated greater likelihood for sites to complete a prosthetics consult using FLOW3 throughout our study. We identified statistically significant differences in likelihood of adoption using the dose–response analysis and complete utilization rate using ITT analysis during the implementation period. All sites that implemented FLOW3 demonstrated improvement in completion rate during the sustainment period, but the difference between facilitation groups was not statistically significant. Further study to understand sustainability is warranted.

Are we being equitable enough? Lessons learned from sites lost in an implementation trial.

There is a growing interest in practice-based implementation research, yet too often research prioritizes and is most successful in academic settings. During a national implementation trial to evaluate the effectiveness of Collaborative Care for co-occurring opioid use and mental health disorders, we lost three of our 11 participating implementation sites, all representing community sites. To better understand needed supports for implementation trial participation, we conducted exit interviews (n = 5) with key staff at these community sites. Interview transcripts were double-coded and analyzed using Rapid Assessment Process. Qualitative themes were iteratively reviewed by the study team. Three themes emerged characterizing challenges for community sites, including that: (1) research threatens sites' most precious resource-staff; (2) staff lack comfort with and skills for research; and (3) research participation in its current form does not offer a clear return on investment. Learnings from this work illuminate some of the barriers community sites face when trying to participate in multisite implementation research. An undercurrent of participant perspectives was the belief that community sites like theirs are just not set up to successfully participate in clinical trial research, including population-based implementation trials. Future implementation trials should consider strategies that disrupt traditional approaches, increasing the equitable inclusion of diverse practice settings in implementation research.

Effectiveness of engaging religious leaders in maternal health education for improving maternal health service utilization in Ethiopia: cluster randomized controlled trial.

High mortality rates for pregnant women and their new-borns are one of Africa's most intractable public health issues today, and Ethiopia is one of the countries most afflicted. Behavioral interventions are needed to increase maternal health service utilizations to improve outcomes. Hence, this trial aimed to evaluate effectiveness of trained religious leaders' engagement in maternal health education on maternal health service utilization. The study employed a cluster-randomized controlled community trial that included baseline and end-line measurements. Data on end points were gathered from 593 pregnant mothers, comprising 292 and 301 individuals in the intervention and control groups, respectively. In the intervention group, the trained religious leaders delivered the behavioral change education on maternal health based on intervention protocol. Unlike the other group, the control group only received regular maternal health information and no additional training from religious leaders. Binary generalized estimating equation regression analysis adjusted for baseline factors were used to test effects of the intervention on maternal health service utilization. Following the trial's implementation, the proportion of optimal antenatal care in the intervention arm increased by 21.4% from the baseline (50.90 vs. 72.3, p ≤ 0.001) and the proportion of institutional delivery in the intervention group increased by 20% from the baseline (46.1% vs. 66.1%, p ≤ 0.001). Pregnant mothers in the intervention group significantly showed an increase of proportion of PNC by 22.3% from baseline (26% vs. 48.3%, p ≤ 0.001). A statistically significant difference was observed between in ANC4 (AOR = 2.09, 95% CI: 1.69, 2.57), institutional delivery (AOR = 2.36, 95% CI: 1.94, 2.87) and postnatal care service utilization (AOR = 2.26, 95% CI: 1.79, 2.85) between the intervention and control groups. This research indicated that involving religious leaders who have received training in maternal health education led to positive outcomes in enhancing the utilization of maternal health services. Leveraging the influential position of these religious leaders could be an effective strategy for improving maternal health service utilization. Consequently, promoting maternal health education through religious leaders is advisable to enhance maternal health service utilization.Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT05716178].

Adaptation for sustainability in an implementation trial of team-based collaborative care.

Sustaining healthcare interventions once they have been implemented is a pivotal public health endeavor. Achieving sustainability requires context-sensitive adaptations to evidence-based practices (EBPs) or the implementation strategies used to ensure their adoption. For replicability of adaptations beyond the specific setting in question, the underlying logic needs to be clearly described, and adaptations themselves need to be plainly documented. The goal of this project was to describe the process by which implementation facilitation was adapted to improve the uptake of clinical care practices that are consistent with the collaborative chronic care model (CCM). Quantitative and qualitative data from a prior implementation trial found that CCM-consistent care practices were not fully sustained within outpatient general mental health teams that had received 1 year of implementation facilitation to support uptake. We undertook a multistep consensus process to identify adaptations to implementation facilitation based on these results, with the goal of enhancing the sustainability of CCM-based care in a subsequent trial. The logic for these adaptations, and the resulting adaptations themselves, were documented using two adaptation-oriented implementation frameworks (the iterative decision-making for evaluation of adaptations [IDEA] and the framework for reporting adaptations and modifications to evidence-based implementation strategies [FRAME-IS], respectively). Three adaptations emerged from this process and were documented using the FRAME-IS: (a) increasing the scope of implementation facilitation within the medical center, (b) having the internal facilitator take a greater role in the implementation process, and (c) shortening the implementation timeframe from 12 to 8 months, while increasing the intensity of facilitation support during that time. EBP sustainability may require careful adaptation of EBPs or the implementation strategies used to get them into routine practice. Recently developed frameworks such as the IDEA and FRAME-IS may be used to guide decision-making and document resulting adaptations themselves. An ongoing funded study is investigating the utility of the resulting adaptations for improving healthcare.

ACTIV trials: cross-trial lessons learned for master protocol implementation

Abstract The United States Government (USG) public-private partnership “Accelerating COVID-19 Treatment Interventions and Vaccines” (ACTIV) was launched to identify safe, effective therapeutics to treat patients with Coronavirus Disease 2019 (COVID-19) and prevent hospitalization, progression of disease, and death. Eleven original master protocols were developed by ACTIV, and thirty-seven therapeutic agents entered evaluation for treatment benefit. Challenges encountered during trial implementation led to innovations enabling initiation and enrollment of over 26,000 participants in the trials. While only two ACTIV trials continue to enroll, the recommendations here reflect information from all the trials as of May 2023. We review clinical trial implementation challenges and corresponding lessons learned to inform future therapeutic clinical trials implemented in response to a public health emergency and the conduct of complex clinical trials during “peacetime,” as well.

Home-based high-intensity interval training for people with Parkinson's: Protocol for the HIIT-Home4Parkinson's randomized, controlled feasibility study.

High-intensity interval training (HIIT) is feasible and beneficial for some people with Parkinson's (PwP), although adherence to extended programs may be problematic. PwP face barriers to exercise such as lack of time, expense, and difficulty with travel logistics due to motor symptoms. HIIT based in the home setting if practical, could therefore be apposite for PwP by overcoming these barriers. However, until now, no home-based HIIT program for PwP has been developed. Cocreated by PwP, clinicians, and family members, the HIIT-Home4Parkinson's (HH4P) program is an innovative, 12-week home-based HIIT program for PwP. This protocol describes a feasibility study designed to assess the feasibility and safety of the HH4P program, explore outcomes that may be sensitive to change, and inform the implementation of a potential full trial. Using a randomized controlled parallel group design, 24independently mobile people with Parkinson's of mild to moderate disease severity will be randomized 1:1 to either the HH4P program plus usual care, or usual care alone. Both groups will be assessed at baseline, and upon the completion of the program. Outcomes will include feasibility and safety factors such as recruitment, completion, adverse events, and intervention fidelity with qualitative evaluation along with mechanistic, physiological, and clinical outcomes. Results of this study will inform the rationale and methodological considerations for a full trial with long-term follow-up. Ultimately, further establishing the practicality and utility of home-based HIIT could provide an important exercise option for PwP, potentially leading to extended participation and increased health and well-being for this population.

Primary care-based screening and recruitment for an adolescent depression prevention trial: Contextual considerations during a youth mental health crisis.

Rising rates of adolescent depression in the wake of COVID-19 and a youth mental health crisis highlight the urgent need for accessible mental healthcare and prevention within primary care. Digital mental health interventions (DMHIs) may increase access for underserved populations. However, these interventions are not well studied in adolescents, nor healthcare settings. The purpose of this study was to identify barriers and facilitators to screening and recruitment activities for PATH 2 Purpose (P2P): Primary Care and Community-Based Prevention of Mental Disorders in Adolescents, a multi-site adolescent depression prevention trial comparing two digital prevention programs within four diverse health systems in two U.S. states. This qualitative study is a component of a larger Hybrid Type I trial. We conducted semi-structured key informant interviews with clinical and non-clinical implementers involved with screening and recruitment for the P2P trial. Informed by the Consolidated Framework for Implementation Research (CFIR), interviews were conducted at the midpoint of the trial to identify barriers, facilitators, and needed adaptations, and to gather information on determinants that may affect future implementation. Respondents perceived the P2P trial as valuable, well aligned with the mission of their health systems. However, several barriers were identified, many of which stemmed from influences outside of the healthcare settings. Universal and site-specific outer setting influences (COVID-19 pandemic, youth mental health crisis, local community conditions) interacted with Inner Setting and Innovation domains to create numerous challenges to the implementation of screening and recruitment. Our findings emphasize the need for ongoing, comprehensive assessment of dynamic inner and outer setting contexts prior to and during implementation of clinical trials, as well as flexibility for adaptation to unique clinical contexts. The CFIR is useful for assessing determinants during times of rapid inner and outer setting change, such as those brought on by the COVID-19 pandemic, youth mental health crisis, and the corresponding exacerbation of resource strain within healthcare settings. PATH 2 Purpose: Primary Care and Community-Based Prevention of Mental Disorders in Adolescents https://www.clinicaltrials.gov/study/NCT04290754.

Identification of MGMT promoter methylation as a specific lipid metabolism biomarker, reveals the feasibility of atorvastatin application in glioblastoma

BackgroundGlioblastoma is one of the deadliest tumors, and limited improvement in managing glioblastoma has been achieved in the past decades. The unmethylated promoter area of 6-O-Methylguanine-DNA Methyltransferase (MGMT) is a significant biomarker for recognizing a subset of glioblastoma that is resistant to chemotherapy. Here we identified MGMT methylation can also work as a specific biomarker to classify the lipid metabolism patterns between methylated and unmethylated glioblastoma and verify the potential novel therapeutic strategy for unmethylated MGMT glioblastoma. MethodsLiquid Chromatograph Mass Spectrometer has been applied for non-targeted metabolome and targeted lipidomic profiling to explore the metabolism pattern correlated with MGMT promoter methylation. Transcriptome has been performed to explore the biological differences and the potential mechanism of lipid metabolism in glioblastoma samples. In vivo and ex vivo assays were performed to verify the anti-tumor activity of atorvastatin in the administration of glioblastoma. ResultsMulti-omics assay has described a significant difference in lipid metabolism between MGMT methylated and unmethylated glioblastoma. Longer and unsaturated fatty acyls were found enriched in MGMT-UM tumors. Lipid droplets have been revealed remarkably decreased in MGMT unmethylated glioblastoma. In vivo and ex vivo assays revealed that atorvastatin and also together with temozolomide showed significant anti-tumor activity, and atorvastatin alone was able to achieve better survival and living conditions for tumor-hosting mice. ConclusionsMGMT promoter methylation status might be a well-performed biomarker of lipid metabolism in glioblastoma. The current study can be the basis of further mechanism studies and implementation of clinical trials, and the results provide preclinical evidence of atorvastatin administration in glioblastoma, especially for MGMT unmethylated tumors.