Contemporary clinical trials最新文献

Background

As part of the IMPACT Consortium of three effectiveness-implementation trials, the NU IMPACT trial was designed to evaluate implementation and effectiveness outcomes for an electronic health record (EHR)-embedded symptom monitoring and management program for outpatient cancer care. NU IMPACT uses a unique stepped-wedge cluster randomized design, involving six clusters of 26 clinics, for evaluation of implementation outcomes with an embedded patient-level randomized trial to evaluate effectiveness outcomes. Collaborative, consortium-wide efforts to ensure use of the most robust and recent analytic methodologies for stepped-wedge trials motivated updates to the statistical analysis plan for implementation outcomes in the NU IMPACT trial.

Methods

In the updated statistical analysis plan for NU IMPACT, the primary implementation outcome patient adoption, as measured by clinic-level monthly proportions of patient engagement with the EHR-based cancer symptom monitoring system, will be analyzed using generalized least squares linear regression with auto-regressive errors and adjustment for cluster and time effects (underlying secular trends). A similar strategy will be used for secondary patient and provider implementation outcomes.

Discussion

The analytic updates described here resulted from highly iterative, collaborative efforts among statisticians, implementation scientists, and trial leads in the IMPACT Consortium. This updated statistical analysis plan will serve as the a priori specified approach for analyzing implementation outcomes for the NU IMPACT trial.

Background

Food insecurity is associated with poor glycemic control and increased risk for diabetes-related complications. The clinical benefit of addressing these challenges through a medically supportive grocery prescription (GRx) program in patients with type 2 diabetes mellitus (T2D) remains unclear. We report the aims and design of a randomized clinical trial to evaluate the effectiveness of a 6-month GRx intervention on hemoglobin A1c (HbA1c) levels among low-income adults with T2D.

Methods

The Kaiser Permanente Evaluating Nutritional Interventions in Food-Insecure High-Risk Adults (KP ENRICH) Study is a pragmatic randomized trial enrolling 1100 participants within Kaiser Permanente Northern California and Southern California, two integrated health care delivery systems serving >9 million members. Medicaid-insured adults with T2D and baseline HbA1c ≥7.5% will be randomized at a 1:1 ratio to either GRx, delivered as $100 per month for select items from among a curated list of healthful food groups in an online grocery ordering and home-delivery platform along with biweekly digital nutrition educational materials, or control, consisting of free membership and deliveries from the online grocery platform but without curated food groups or purchasing dollars. The primary outcome is 6-month change in HbA1c. Secondary outcomes include 12-month change in HbA1c, and 6- and 12-month change in medical resource utilization, food security, nutrition security, dietary habits, diabetes-related quality of life, and dietary self-efficacy.

Conclusions

The results of this large randomized clinical trial of GRx will help inform future policy and health system-based initiatives to improve food and nutrition security, disease management, and health equity among patients with T2D.

Background

In the United States, over 1.2 million people are living with HIV. This disease disproportionately affects men who have sex with men (MSM), people of color, youth and young adults, and transgender individuals. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention method. Barriers exist for both primary care providers (PCPs) to prescribe PrEP and prevent patients from initiating PrEP.

Methods

This study, MOST: PrEP, follows the multiphase optimization strategy (MOST) framework. The purpose is to identify a multi-level intervention among patients and PCPs to increase PrEP prescriptions in primary care. First, feedback will be obtained from providers and patients via focus groups, then, suggestions related to the context-specific (provider and individual level) factors of intervention component delivery will be incorporated. Subsequently, a rigorous experiment will be conducted using a 2⁴ factorial design focusing on priority populations for PrEP initiation. Provider components include computer-based simulation training and a best practice alert. Patient components include a tailored PrEP educational video and HIV risk assessment. Finally, the facilitators and barriers to implementing the intervention components will be qualitatively examined.

Conclusion

In this protocol paper, we describe the one of the first known multilevel MOST optimization trial in healthcare. Intervention components are to be delivered to patients and providers in a large healthcare system, based in an HIV Ending the Epidemic priority jurisdiction. If effective, this multi-level approach could be disseminated to providers and patients in other large healthcare systems to make a significant impact on HIV prevention.

Background

African Americans (AAs) face cardiovascular health (CVH) disparities linked to systemic racism. The 2020 police killing of Mr. George Floyd in Minneapolis, Minnesota, alongside the COVID-19 pandemic, exacerbated adverse psychosocial factors affecting CVH outcomes among AAs. This manuscript describes the study protocol and participant characteristics in an ancillary study exploring the relationship between biopsychosocial factors and CVH among AAs.

Methods

Using a community-based participatory approach, a mixed-methods ancillary study of 58 AA participants from an overarching randomized control trial (RCT) was conducted. Baseline RCT health assessments (November 2020) provided sociodemographic, medical, and clinical data. Subsequent health assessments (February–December 2022) measured sleep quality, psychosocial factors (e.g., high-effort coping), biomarkers (e.g., cortisol), and cardiovascular diagnostics (e.g., cardio-ankle vascular index). CVH was assessed using the American Heart Association Life's Simple 7 (LS7) (range 0 to 14, poor to ideal) and Life's Essential 8 (LE8) scores (range 0 to 100, low to high). Correlations between these scores will be examined. Focus group discussions via videoconferencing (March to April 2022) assessed psychosocial and structural barriers, along with the impact of COVID-19 and George Floyd's killing on daily life.

Results

Participants were predominantly female (67%), with a mean age of 54.6 [11.9] years, high cardiometabolic risk (93% had overweight/obesity and 70% hypertension), and moderate LE8 scores (mean 57.4, SD 11.5).

Conclusion

This study will enhance understanding of the associations between biopsychosocial factors and CVH among AAs in Minnesota. Findings may inform risk estimation, patient care, and healthcare policies to address CVD disparities in marginalized populations.

Background

Black and brown birthing people experience persistent disparities in adverse maternal health outcomes, partially due to inadequate perinatal care. The goal of this study is to design and evaluate a patient-centered intervention for obstetric patients with one or more cardiometabolic risk factors for severe maternal morbidity [gestational diabetes, diabetes mellitus, hypertensive disorders of pregnancy (chronic hypertension, preeclampsia, eclampsia, or gestational hypertension), or preconception obesity (BMI > 30)] to promote postpartum visit attendance.

Methods

To address identified unmet needs for postpartum support and barriers to postpartum care, we developed 20 thematic postpartum planning modules, each with corresponding patient educational materials, community resources, care coordination protocols, and clinician support tools (decision aids, electronic medical record prompts and fields). During prenatal care encounters, a research coordinator delivers the educational content (in English or Spanish), facilitates the participant's planning and shared decision-making, provides the participant with resources, and documents decisions in the electronic medical record. We will randomize 320 eligible patients with a 1:1 ratio to the intervention or standard prenatal care and evaluate the impact on postpartum visit attendance at 4–12 weeks and secondary outcomes (postpartum mental health, perceived future maternal and cardiometabolic risk, contraceptive use, primary care use, readmission, and patient satisfaction with care).

Discussion

Through engagement with patients and community stakeholders, we developed a guideline-based, locally tailored intervention to address drivers of engagement with postpartum care for high-risk obstetric patients. If demonstrated to be effective, the educational materials and electronic medical record based-tool can be adapted to other settings.

Trial registration

This trial was registered on ClinicalTrials.gov (NCT05430815) on June 23, 2022.

Background and aims

To determine the effect of a multimodal intervention (nutritional behavior change and physical exercise) on quality of life, chemotherapy response rate and tolerance, histopathological level of the tumor, body composition, and biochemical parameters, in patients diagnosed with breast cancer during neoadjuvant chemotherapy treatment, and to compare them with the control group.

Methods

Anticipated 80 patients diagnosed with breast cancer aged 18–70 years will be recruited for this randomized, unblinded clinical trial based on a nutritional behavior change and physical exercise in patients during the approximately 6 months in which the patient receives neoadjuvant treatment. Participants will be randomly allocated (1:1) to one of two groups (intervention or control). Primary and secondary outcomes will be assessed before the beginning and after the neoadjuvant treatment (before surgery). The primary outcome is quality of life, whereas secondary outcomes include chemotherapy response rate and tolerance, histopathological level of the tumor and body composition (i.e., visceral adipose tissue activity, bone, lean and fat masses). We will analyze blood parameters (i.e., biochemical, inflammatory, and tumor markers) as exploratory outcomes.

Conclusion

This study will address the influence of a practical and viable multimodal intervention (i.e., nutritional behavior change and physical exercise) on breast cancer patients undergoing neoadjuvant chemotherapy. Given the practical viability of the intervention in real-world settings, our study holds promise for significant scientific and clinical implications.

Background

To improve the site selection process for clinical trials, we expanded a site survey to include standardized assessments of site commitment time, team experience, feasibility of tight timelines, and local medical community equipoise as factors that might better predict performance. We also collected contact information about institutional research services ahead of site onboarding.

Aim

As a first step, we wanted to confirm that an expanded survey could be feasible and generalizable—that asking site teams for more details upfront was acceptable and that the survey could be completed in a reasonable amount of time, despite the assessment length.

Methods

A standardized, two-part Site Assessment Survey Instrument (SASI), examining qualitative components and with multiple contact list sections, was developed using a publicly accessible dashboard and later transferred to a REDCap platform. After multiple rounds of internal testing, the SASI was deployed 11 times for multicenter trials. Follow-up questionnaires were sent to site teams to confirm that an expanded survey instrument is acceptable to the research community and could be completed during a brief work shift.

Results

Respondents thought the SASI collected useful and relevant information about their sites (100%). Sites were “comfortable” (90%) supplying detailed information early in the site selection process and 57% completed the SASI in one to two hours.

Conclusions

Coordinating centers and sites found the SASI tool to be acceptable and helpful when collecting data in consideration of multicenter trial site selection.

Background

Pilot trials indicate that both a low glycemic load (GL) diet and calorie restriction (CR) can be implemented successfully in people with multiple sclerosis (pMS) and may improve MS symptoms and physical function, but large randomized clinical trials (RCTs) have not yet been conducted. The purpose of this study is to test these interventions alone and in combination to determine their efficacy for improving clinical and patient reported outcomes (PROs) in pMS.

Methods

This 32-week, two-arm, RCT at two centers will randomly assign 100 adults with relapsing-remitting or secondary progressive MS to a low GL diet (n = 50) or a standard GL diet (n = 50). Both diet groups will complete two study phases: a eucaloric phase (16 weeks) and a CR phase (16 weeks). Groceries for the study meal plans will be delivered to participants' homes weekly. The primary outcome is physical function, measured by timed 25-ft walk test. Secondary outcomes are pain, fatigue, mood, and anxiety.

Discussion

This will be the most rigorous intervention trial to date of a low GL diet and CR in adults with MS, and among the first to assess the impact of intentional weight loss on MS symptoms. Results will provide valuable insight for recommending dietary change, weight loss, or both to adults with MS. These non-drug interventions pose few risks and have potential to yield significant improvements in MS symptoms.

Trial registration ID: NCT05327322

Background/Aims

COVID-19 necessitated a shift to virtual data collection for many research projects, providing the opportunity for novel approaches to carrying out multi-site clinical trials. Virtual multiteam systems (VMTS) are a type of team structure in which multiple geographically dispersed teams collaborate using technology-mediated communication. The article presents a case study of our use of VMTS, in response to COVID-19, to carry out a multisite randomized hybrid effectiveness-implementation trial of a caregiver-implemented intervention.

Methods

We describe how we modified our team structure from predominantly site-specific, co-located teams to predominantly cross-site, virtual teams. We then present examples of how we have conducted the two primary data collection activities virtually. To demonstrate the feasibility of this approach, we present participant demographic information, the percent of cross-site data collection activities, and fidelity data.

Results

In the first 20 months of data collection, we have enrolled 108 EI providers and 132 families, with 17% and 9% attrition respectively. The family sample is highly diverse in terms of race/ethnicity, parent education, and household income. The majority of provider training activities and roughly 50% of family assessment activities have been conducted cross-site. Fidelity is high, with no differences across site.

Conclusions

Our data illustrate the feasibility of using virtual teams, training, and assessment in a multisite clinical trial in the Part C system. We discuss the strengths and challenges of this approach, as well as lessons learned to facilitate the planning of future multisite randomized clinical trials which may benefit from this approach.

Clinical Trials

NCT05114538

Background

Clinical trial monitoring is evolving from labor-intensive to targeted approaches. The traditional 100% Source Data Monitoring (SDM) approach fails to prioritize data by significance, diverting attention from critical elements. Despite regulatory guidance on Risk-Based Monitoring (RBM), its widespread implementation has been slow.

Methods

Our study teams assess the study's overall risk, document heightened and critical risks, and create a study-specific risk-based monitoring plan, integrating SDM and Central Data Monitoring (CDM). SDM combines a fixed list of pre-identified variables and a list of randomly identified variables to monitor. Identifying variables follows a two-step approach: first, a random sample of participants is selected, second, a random set of variables for each participant selected is identified. Sampling weights prioritize critical variables. Regular team meetings are held to discuss and compile significant findings into a Study Monitoring Report.

Results

We present a random SDM sample and a Study Monitoring Report. The random SDM output includes a look-up table for selected database elements. The report provides a holistic view of the study issues and overall health.

Conclusions

The proposed random sampling method is used to monitor a representative set of critical variables, while the Study Monitoring Report is written to summarize significant monitoring findings and data trends. The report allows the sponsor to assess the current status of the study and data effectively. Communicating and sharing emerging insights facilitates timely adjustments of future monitoring activities, optimizing efficiencies, and study outcomes.