Contemporary clinical trials最新文献

Randomized controlled trials commonly employ multiple endpoints to collectively assess the intended effects of the new intervention on multiple aspects of the disease. Focusing on the estimation of the global win probability (WinP), defined as the (weighted) mean of the WinPs across the endpoints that a treated participant would have a better outcome than a control participant, we propose a closed-form sample size formula incorporating pre-specified precision and assurance, with precision denoted by the lower limit of confidence interval and assurance denoted by the probability of achieving that lower limit. We make use of the equivalence of the WinP and the area under the receiver operating characteristic curve (AUC) and adapt a formula originally developed for the difference between two AUCs to handle the global WinP. Unequal variances between treatment groups are allowed. Simulation results suggest that the method performs very well. We illustrate the proposed formula using a Parkinson's disease clinical trial design example.

Background

The opioid epidemic disproportionately affects individuals with co-occurring opioid use and mental health disorders (COD), who often have poor treatment engagement. Multicomponent treatment models are popular solutions to increase treatment access and engagement for those with COD. Maintaining Independence and Sobriety through Systems Integration, Outreach and Networking (MISSION) is a hybrid multicomponent linkage and treatment approach that provides assertive community outreach combined with psychosocial treatment. This protocol paper describes a randomized controlled trial comparing MISSION and medication for opioid use disorder (MOUD), its multicomponent parts along with MOUD, and MOUD treatment as usual (TAU) to assess improvements in health and social outcomes.

Methods

This study will use a half fractional factorial design and randomize 1000 patients with COD to one of five treatment conditions: (1) the full MISSION intervention plus MOUD; (2–4) a combination of two out of three MISSION components plus MOUD; or (5) TAU. Secondary aims include examination of mechanisms of action, economic evaluation of the implementation of MISSION and/or its components plus MOUD versus TAU, and exploratory predictive modeling to match optimal MISSION parts with patient needs.

Discussion

This randomized controlled trial will help determine the effectiveness of MISSION (or its parts) and MOUD compared to TAU to improve engagement in treatment, substance use, and mental health symptoms. This trial is the first to compare MISSION and its parts with MOUD versus TAU in a real-world treatment scenario to determine which components are necessary and sufficient to drive treatment outcomes according to patient needs.

Chen et al. (2022) recently proposed a set of estimating equations that incorporate data from secondary endpoints to improve precision in parameter estimates related to a primary endpoint. We were motivated to translate their methodology to the context of randomized controlled trials to gain precision in treatment effect estimation using data from secondary endpoints. Our results suggest that this estimator cannot gain efficiency in this context because of random treatment assignment, especially when there is a treatment effect on secondary endpoints, and that further methodological work in this area is needed.

Background

Emerging adult (EA) cannabis use is associated with increased risk for health consequences. Just-in-time adaptive interventions (JITAIs) provide potential for preventing the escalation and consequences of cannabis use. Powered by mobile devices, JITAIs use decision rules that take the person's state and context as input, and output a recommended intervention (e.g., alternative activities, coping strategies). The mHealth literature on JITAIs is nascent, with additional research needed to identify what intervention content to deliver when and to whom.

Methods

Herein we describe the protocol for a pilot study testing the feasibility and acceptability of a micro-randomized trial for optimizing MiWaves mobile intervention app for EAs (ages 18–25; target N = 120) with regular cannabis use (≥3 times per week). Micro-randomizations will be determined by a reinforcement learning algorithm that continually learns and improves the decision rules as participants experience the intervention. MiWaves will prompt participants to complete an in-app twice-daily survey over 30 days and participants will be micro-randomized twice daily to either: no message or a message [1 of 6 types varying in length (short, long) and interaction type (acknowledge message, acknowledge message + click additional resources, acknowledge message + fill in the blank/select an option)]. Participants recruited via social media will download the MiWaves app, and complete screening, baseline, weekly, post-intervention, and 2-month follow-up assessments. Primary outcomes include feasibility and acceptability, with additional exploratory behavioral outcomes.

Conclusion

This study represents a critical first step in developing an effective mHealth intervention for reducing cannabis use and associated harms in EAs.

Background

On the Move (OTM), a group exercise program to improve mobility in older adults, is efficacious when delivered by research staff. The next step in the development of OTM as a fully implementable intervention is to conduct an effectiveness study in which the intervention is delivered in community settings by community providers.

Methods

We describe the methods of a hybrid 1 cluster randomized, single-blind, intervention trial to compare the effectiveness of OTM to a delayed intervention control in 502 community-dwelling older adults across 44 sites. OTM classes are taught by certified instructors in the community twice a week for 12 weeks. Control centers receive no intervention for the first 12 weeks followed by 12-weeks of OTM classes. Participants are assessed at baseline, 12 and 24 weeks. The primary outcome is gait speed. Intervention fidelity, measured by adherence and competence in intervention delivery, is assessed by review of instructor intervention diaries and observation. Organizational, instructor, and participant-level factors which may impact fidelity are assessed using questionnaires, focus groups, and structured interviews.

Conclusion

The findings of this trial will 1) establish the effectiveness of OTM on improvements in walking and post-intervention persistence of benefits, 2) assess intervention fidelity and identify the impact of organizational, instructor, and participant level factors on fidelity, and 3) determine the extent to which fidelity moderates the effectiveness of OTM. The information derived from this project will provide valuable insight into the real-world effectiveness of OTM as a health promotion program for improving mobility in older adults.

Background

Mitigating attrition is a key component to reduce selection bias in longitudinal randomized controlled trials (RCTs). Few studies of electronic nicotine delivery systems (ENDS) allow for the examination of long-term retention. This analysis explores the relationship between attrition, baseline measures, and condition assigned for a RCT involving ENDS differing in nicotine delivery over a 24-week intervention period.

Methods

Participants (N = 520) who smoked ≥10 cigarettes per day [CPD] for ≥1 year and reported interest in reducing but not quitting were randomized to 1 of 4 conditions: an ENDS containing 0, 8, or 36 mg/ml liquid nicotine (administered double-blind) or a cigarette-shaped plastic tube. Cox proportional hazards regression models were fit to examine attrition over time and predictors of attrition including baseline characteristics and condition. A stepwise approach was used to determine the final model; alpha was set at 0.05.

Results

Attrition did not differ significantly by condition (223/520), and most (69%) were lost-to-follow-up. Only age, education level, and household income were significantly predictive of attrition. For every additional year of age, attrition risk fell by 3%. Holding a bachelor's degree or higher was associated with reduced attrition risk. Those with the lowest income (<$10 K) were more likely to be withdrawn compared to those earning $10 K–39 K, and those with the highest income ($100 K+) were more likely to be withdrawn compared with the latter bracket and those earning $70-99 K.

Conclusion

ENDS nicotine content did not drive differential attrition in this trial, and targeted retention efforts are needed for specific subgroups.

Trial Registration #: NCT02342795

Background

The term “Overlap Syndrome” (OS) describes the presence of both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) in a single individual. Excessive daytime sleepiness (EDS) is a common symptom of OS shown to be associated with an increased risk of cardiovascular disease (CVD) that could be reduced through exercise. Thus, we propose to investigate a novel exercise intervention in individuals with the EDS-OS phenotype as they are at highest risk of CVD yet have the greatest barriers to exercise.

Methods

We will conduct a single-site, randomized, two-arm, parallel group-controlled exercise trial in individuals with EDS-OS. The Epworth Sleepiness Scale (ESS) will be assessed at baseline. Individuals with OS and the EDS-OS phenotype (ESS >10) (n = 46) will be randomized to a moderate intensity interval training (MIIT, i.e. intervals of 5 min at 50% VO2peak followed by 3 min of active recovery at 10% VO2peak) or a control group of standard of care. We will investigate if MIIT intervention decreases the risk of CVD in EDS-OS, which will be assessed by: 1) quality of life, measured by the 36-Item Short Form Health Survey; 2) physical activity, measured by daily step counts; and 3) cardiovascular health, assessed as VO2peak, flow-mediated dilation and serum high sensitivity C-reactive protein, lipids, and glucose.

Conclusion

Our findings will guide future development and implementation of exercise interventions that could reduce the risk of CVD in the understudied EDS-OS phenotype.

Objective

Sexual minority women (SMW) and transgender and/or nonbinary (TNB) people report more adverse health outcomes (e.g., depression, anxiety, posttraumatic stress, substance use) relative to heterosexual, cisgender people, often due to the additional stress burden from experiencing stigma. Physiological and emotional stress reactivity are mechanisms through which high cumulative stress contributes to adverse health outcomes. The randomized controlled trial (RCT) described in this study protocol examines whether a single-session compassion microintervention may attenuate physiological and emotional stress reactivity to the minority stress Trier Social Stress Test (MS-TSST) among SMW/TNB people. This study will also examine whether the compassion microintervention reduces depression, anxiety, posttraumatic stress symptoms, and substance use from baseline to one-month follow-up, and assess microintervention acceptability.

Methods

This protocol describes a two-arm parallel RCT. Participants are recruited online and at in-person events (e.g., Pride events). Participants complete baseline measures online (e.g., demographics, anxiety symptoms) and then complete an in-person lab visit that includes the compassion microintervention (or no training control). Immediately after the intervention period, participants complete the MS-TSST. Measures of physiological (i.e., blood pressure, cortisol) and emotional (i.e., negative affect, state anxiety) reactivity are collected throughout the lab visit. Participants also complete a one-month follow-up survey. Participants randomized to the microintervention are invited to complete a semi-structured virtual interview about their experiences to assess acceptability.

Conclusion

Findings from this study could provide initial evidence that compassion microinterventions show promise in addressing stigma-related stress reactivity among SMW/TNB people.

ClinicalTrials.govregistration:NCT05949060

Background

Pregnancies conceived within 18 months of a prior delivery (termed short inter-pregnancy interval [IPI]) place mothers and infants at high risk for poor health outcomes. Despite this, nearly one third of U.S. women experience a short IPI.

Objective

To address the gap in the current model of postpartum (PP) contraception care by developing and implementing a novel approach to link (co-schedule) PP contraception care with newborn well-baby care to improve access to timely PP contraception.

Methods

The LINCC Trial will take place in seven clinical locations across five community health centers within the U.S. PP patients (planned n = 3150) who are attending a Well-Baby Visit between 0 and 6 months will be enrolled. The LINCC Trial aims to leverage the Electronic Health Record to prompt providers to ask PP patients attending a Well-Baby Visit about their PP contraception needs and facilitate co-scheduling of PP contraception care with routine newborn care visits. The study includes a cluster randomized, cross-sectional stepped wedge design to roll out the intervention across the seven sites. The outcomes of the study include receipt of most or moderately effective methods of contraception by two and six months PP; and rate of short IPI pregnancies. Implementation outcomes will be assessed at baseline and 6 months after site enters intervention period.

Conclusions

The LINCC Trial seeks to evaluate the effectiveness and feasibility of a linked care model in comparison to usual care.

Introduction

Co-morbid anxiety and depression (distress) in inflammatory bowel disease (IBD) results in poorer outcomes and increased healthcare burden. IBD services require scalable treatment pathways for distress to meet this need. This real-world longitudinal study evaluates the implementation of a new integrated care pathway for distress including: 1) routine mental health screening and 2) therapist-guided, digital CBT tailored to the challenges of living with IBD (compass with adaptations for IBD: COMPASS-IBD) in a UK National Health Service (NHS) large gastroenterology service (∼ 5000 patients).

Methods

We describe a mixed-methods, observational, real-world longitudinal study. Routine mental health screening in the IBD service will identify patients with distress (using pre-defined clinical cut-offs), who will be triaged to determine appropriate treatment pathways (including participation in the COMPASS-IBD study). Participants will receive COMPASS-IBD online for ∼12 weeks (including 6 × 30-min therapist sessions). Key implementation outcomes will assess reach and adoption of the new pathway using aggregate data on uptake of mental health screening, eligibility, and consent rates for COMPASS-IBD, and number of COMPASS-IBD sessions completed. Interviews with patients and healthcare providers will primarily assess acceptability of the new pathway. Potential effectiveness will be assessed using participant questionnaires at pre-intervention, 12-weeks (post-intervention), and 6-month follow-up. The primary effectiveness outcome will be pre-post changes in distress (PHQ-ADS scores). Quantitative data will be summarised using descriptive statistics and qualitative data analysed using reflexive thematic analysis.

Conclusion

Study findings will inform treatment pathways for co-morbid distress in IBD, and highlight adaptations required to increase future scalability and effectiveness.

Trial registration number: NCT05330299 (clinicaltrials.gov).