Trials最新文献

A wide range of factors has detrimental impacts upon equity, diversity, and inclusion in clinical trials, amongst which participant burden can be significant. In addition to the potential physical burdens associated with investigational interventions, participants may face onerous demands related to factors like travel, time commitments, psychological, or logistical challenges. Many of these factors have been shown to create barriers that disproportionately affect certain groups like minoritised ethnic groups, people with caring responsibilities, and older adults. One increasingly problematic aspect of participant burden is associated with an excessive volume of data collection, much of which may lack direct relevance to the study's primary objectives and may never be analysed. Although pragmatic and participant-centred trial methodologies have risen in prominence over the past decade, quantitative evidence demonstrates that trial complexity and data volumes are continuing to rise. The widening gap between the notion of participant-centricity and the realities of current trial practice underscores the need for a shift in approach. Reducing unnecessary burden should be regarded as a moral obligation across all clinical trial designs to avoid the systematic exclusion of certain groups. With a focus on data-related aspects, this paper examines the ethical implications of undue burdens upon participants and proposes measures to help minimise and mitigate these burdens. In addressing this issue, researchers contribute to broader efforts to enhance inclusivity and representation in clinical studies.

Background: Exploring barriers and enablers to participant recruitment into trials is a common discussion point in trial methodology. Participant information leaflets (PIL) can be long, have complexity above the average UK reading age, and may discourage engagement with research. This Study Within a Trial (SWAT) explored whether changing the design of a PIL influences recruitment rate and its value in patient decision-making. It was conducted within a host trial taking place in an emergency setting, where time is at a premium, and decisions on trial participation are needed more quickly than in most non-emergency settings.

Methods: We have conducted a randomised SWAT, comparing the standard format PIL with one that has been adapted to be visually appealing, with improved readability and reduced word count. Patients considered eligible for the host trial were provided with a randomly allocated PIL type; consent rates were compared. Those consenting to take part in the host trial were asked to complete a questionnaire to explore the value of the PIL in their decision-making to take part in the trial; responses were compared across the two information sheets. The sample size was dictated by host trial recruitment.

Results: Between September 2019 and September 2022, with a brief pause during the COVID19 pandemic, 271 participants were randomised to receive either the optimised PIL (n = 138) or the conventional PIL (n = 133). The recruitment rates were 47.1% (65/138) in the optimised PIL group and 48.9% (65/133) in the conventional PIL group; this difference was not statistically significant (p = 0.771). There were no significant differences in responses from participants recruited to the host trial who completed the Decision-Making Questionnaire.

Conclusion: Improving the readability and visual presentation of the participant information sheet provided to participants had no effect on recruitment rate, and did not appear to impact decision-making of recruited participants.

Background: Medical cannabis is now commonly prescribed for a range of chronic health conditions. Many medical cannabis products contain delta-9-tetrahydrocannabinol (THC), the intoxicating component in cannabis, though it is unclear whether these products produce impairment when used as prescribed and at therapeutic doses. With current Australian laws prohibiting driving with any amount of THC in one's system, this trial aims to generate novel data on the impact of prescribed medical cannabis on real-world driving performance to inform road safety policy.

Methods: This is a two-phase trial, with the first phase being a semi-naturalistic cohort study involving 72 patients with physician-diagnosed chronic pain, anxiety, or insomnia (n = 24 per group) who will complete repeated on-track driving assessments before and after consuming a standard dose of their medical cannabis prescription. The second phase is a randomised, placebo-controlled, double-blind, and crossover study involving 24 healthy participants who will complete the same repeated on-track driving assessments before and after consuming either alcohol (0.05% blood alcohol concentration) or placebo. Participants in both phases will also complete repeated cognitive assessments and assessments of subjective state and provide biological samples for analysis of cannabinoid (phase 1) and alcohol (phase 2) concentrations. The primary outcome measure is lateral vehicular control. Data will be analysed using a series of mixed-effect and generalised linear mixed models to assess changes in outcome measures over time.

Trial registration numbers: ACTRN 17/09/2024 for 12624001118594 and 24/09/2024 for 12624001163594.

Background: Randomised controlled trials (RCTs) are the gold standard for evaluating treatment effects, with the results informing policy and clinical practice. To ensure appropriate methods are utilised and to avoid misinterpretation of the results of a clinical trial, it is vital that we understand the research question a trial aims to answer. However, there is often ambiguity in how trialists define their research questions. In 2019, an addendum to the international trial regulatory guidelines (ICH E9 (R1)) introduced the estimand framework to combat this. A review of protocols published in 2020 investigated the early adoption of the estimand framework and found no uptake as well as a lack of clarity on key items such as the handling of intercurrent events. The aim of this review was to identify the current application of the estimand framework specifically to trials with an adaptive design.

Methods: The search strategy aimed to identify trial protocols and statistical analysis plans that described RCTs published in two journals (BMJ Open and Trials) in 2023. Articles were eligible if they related to phase 2-4 trials with an adaptive design. A pre-piloted data extract form was used to extract data relating to study details, intercurrent events and estimands.

Results: One thousand five hundred and forty-one articles were identified by the initial search. Following screening, 146 articles were identified as meeting the eligibility criteria. Of the eligible articles, five (3%) stated their primary estimand, and of these, three (2%) stated all five estimand attributes. Ninety-four (64%) articles described one or more intercurrent events; these included a total of two hundred and thirty-two intercurrent events described. Fifty-two (36%) articles did not describe any intercurrent events. No articles specified the estimand for any planned interim analyses or considered the implications of adaptations on the primary estimand.

Conclusions: This review provides evidence that there is still a lack of uptake of the estimand framework in RCTs. Wider application of the estimand framework would ensure clarity in the reporting and interpretation of clinical trial results. In addition, clear guidance on how to implement the estimand framework to trials with an adaptive design is needed.

Background: Attentional function is the basis of cognitive function, and its decline affects the daily lives of older adults. Previous studies have not consistently reported the effects of dual-task training (DTT) on attentional function in community-dwelling older adults. This study aims to verify the effectiveness of DTT by combining "motor tasks" and "cognitive tasks involving motor activity" with a focus on inducing dual-task interference (DTI).

Methods: The study design is a randomized controlled trial. The intervention consists of DTT that combines "motor tasks" involving lower limb movements with "cognitive tasks involving motor activity" incorporating complex finger movements. The program will be implemented in a DTI setting, and tasks will be adjusted individually for each participant. The intervention group will be conducted twice per week for four weeks, with each session lasting one hour. The control group will continue with the participants' usual daily activities for four weeks. Attentional function will be assessed as the primary outcome using the Trail Making Test-Japanese and as secondary outcomes using the digit span test and the Stroop and reverse-Stroop test. Balance function will be measured using the single-leg stance test. All evaluations will be conducted at baseline and post-intervention. In the statistical analysis, paired t-tests will be used to compare pre-intervention and post-intervention changes within each group, and analysis of covariance will be used to compare intervention effects between groups.

Discussion: Based on the study objectives, the maintenance and improvement of attentional function should be promoted to help community-dwelling older adults maintain healthy lives in familiar environments.

Trial registration: UMIN, UMIN000057681. Registered on 30 June 2025. UMIN website https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000065882.

Background: Aggression, substance use, and gambling behaviour often co-occur in a larger pattern of dysregulated behaviour. One of the factors that may underlie this phenomenon is impaired inhibitory control. Inhibitory Control Training (ICT) is an alternative intervention being tested for addressing addictive behaviours by targeting inhibitory control. Given the shared underlying mechanisms of these behaviours, applying ICT to aggression represents a possible extension of this intervention. This research will mark the first implementation of a cognitive bias modification approach to managing aggression among patients with co-occurring substance use disorder and gambling behaviour in the Indian context. A secondary aim of this study will be to assess whether changes in aggression and inhibitory control will be associated with reductions in substance use disorder and gambling behaviour.

Methods: A two-group, parallel randomized controlled trial will be carried out in 130 male in-patients at a tertiary care centre. Participants fulfilling the DSM-5 criteria for substance use disorders, and screening positive for problem (Score ≥ 1) or pathological (Score ≥ 5) gambling on the South Oaks Gambling Screen will be randomly allocated to either experimental (ICT) or control (Sham Training) group. The ICT consists of six 15-min sessions over three days, using a Go/No-Go paradigm with 100% contingency. ST is matched with the active training in terms of both stimulus exposure and response requirements, but reduces the contingency agreement to 50%, thereby preventing the formation of associations between aggressive stimuli and inhibitory responses. Primary and secondary outcome measures will be assessed at baseline, 1-day, 1-month, and 3-months post-intervention.

Discussion: As aggression is frequently observed in individuals with addictive behaviors and is closely linked to deficits in regulatory behaviour, the intervention, if proven efficacious, could offer a cost-effective and time-efficient alternative to traditional cognitive-behavioral and anger management interventions. Conversely, should the intervention prove ineffective, the findings would indicate that this may not be a potential area for further exploration in this population.

Trial registration: The study protocol was registered prospectively with the Clinical Trials Registry of India (CTRI) on August 07, 2024 (Registration Number: CTRI/2024/08/072033) (URL: https://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=113292&EncHid=61291.44954&modid=1&compid=19).

Background: Seated exercises may reduce the need for in-person support during home-based exercise programs in people with balance impairments. However, it is uncertain if these exercises can transfer to improved lower extremity function and mobility. Thus, the objective is to investigate the effects of a remotely delivered 10-week seated exercise intervention on functional mobility, compared with control, in individuals living with a chronic stroke who have balance impairments.

Methods: The study is a multi-site, assessor blinded, randomized controlled trial that will recruit across five provinces in Canada using the CanStroke Recovery Trials platform. A total of 100 adults living with a chronic stroke (≥ 6 months post-stroke) and mobility impairment (using a walking aid) will be recruited. Participants will be randomized (1:1) to the 10-week Virtual Physical Activity Seated Exercise (V-PASE) or control group. All exercise sessions will be delivered one-on-one through videoconferencing by a trained instructor. Sessions will be 60 min in duration and completed 3 times/week at a moderate intensity (40%-60% Heart Rate Reserve). The primary outcome measure is the 30s Sit-To-Stand score at the end of the 10-week intervention. Secondary outcome measures will be mobility, balance, quality of life, stroke-related quality of life, cognition, fatigue, anxiety, depression, and blood profiles (glucose and lipids).

Discussion: Exercises completed in a chair have the potential to transfer to improved functional mobility in people with balance impairments, such as individuals with stroke. The stability of the seated position may improve safety during home-based exercises and thus increase participation.

Trial registration: ClinicalTrials.gov NCT05724823. Registered on February 13th, 2023.

Background: Post-traumatic stress disorder (PTSD) can have detrimental effects for those afflicted and is associated with increased health care utilization and substantial societal costs. Thus, there is a need for accessible, effective, and cost-efficient preventive interventions for post-traumatic psychological sequelae. Research indicates that trauma-focused cognitive-behavioral therapy (CBT-T) could effectively prevent PTSD when applied as an indicated secondary prevention. CIPE is a scalable, low-threshold, therapist-assisted digital CBT-T, which could be readily implemented in services delivering psychosocial support after traumatic incidents if proven effective and cost-effective. The Early Support after Exposure to Trauma (EASE) study evaluates the effectiveness, cost-effectiveness, and implementation of Condensed Internet-delivered Prolonged Exposure (CIPE), applied as an indicated secondary prevention in the context of Norwegian municipal crisis teams.

Methods/design: The EASE study is a hybrid Type 1 effectiveness and implementation trial. The effectiveness trial is a parallel two-armed multicenter randomized controlled add-on superiority trial, enrolling individuals who receive support from psychosocial crisis teams within 7 weeks after trauma. Participants are randomized to CIPE + treatment as usual (TAU) or TAU only. The primary outcome is the level of PTSD symptoms 6 weeks after randomization (10-13 weeks post trauma). Secondary outcomes include symptoms of depression and insomnia, quality of life, and CIPE cost-effectiveness. The implementation trial examines policy-level factors influencing CIPE implementation, using the Exploration, Preparation, Implementation, Sustainment framework.

Discussion: This study will guide further research, policy shaping, and clinical initiatives for implementing preventive interventions aimed at reducing post-traumatic psychological sequelae by integrating evidence-based interventions into routine psychosocial services.

Trial registration: ClinicalTrials.gov NCT06592677. Registered on 10.09.2024.

Background: The Daqing Diabetes Prevention Study II (Daqing DPS-II) builds on the landmark study Daqing Diabetes Prevention Study to develop real-world implementation strategies for preventing type 2 diabetes (T2DM). This study aims to evaluate the effectiveness of digital and complex lifestyle intervention in reducing the incidence of T2DM among adults with increased risk of T2DM, compared to usual care over a 36-month period.

Methods: A three-arm, stratified, cluster-randomized controlled trial will be conducted in eight factories in Daqing, with clusters as the unit of randomization and individual participants as the unit of analysis. Fifty-seven clusters will be randomly allocated (1:1:1) to one of three groups: (1) Digital-based lifestyle intervention, (2) complex lifestyle intervention, or (3) usual care. Eligible participants will be adults aged 25-55 with increased risk of T2DM, defined by IFG, IGT, HbA1c 5.7-6.4%, and/or 1-h PG above 8.6 mmol/L, while not meeting the criteria for diabetes. Exclusion criteria include significant cardiovascular disease (CVD) within 6 months, impaired liver function, renal dysfunction, other significant medical or psychological conditions, or participation in similar studies. The interventions will run for 3 years. The primary outcomes are the 3-year cumulative incidence of T2DM. The study will utilize the RE-AIM framework and Implementation Outcome Framework (IOF) to assess Reach, Adoption, Implementation, Maintenance, Feasibility, Acceptability, and Appropriateness through process measures. Data collection will include plasma glucose (0, 1, and 2 h) and insulin levels (0, 1, and 2 h) based on the oral glucose tolerance test, laboratory tests, blood pressure, body mass index, waist circumference, and dietary and physical activity behaviors, diabetes knowledge, and quality of life. These measures will be assessed by trained doctors or nurses at baseline and at 6-,12-, 24-, and 36-month follow-ups.

Discussion: The study will provide evidence on how population-level strategies of digital and complex lifestyle intervention can be implemented in real-world settings to prevent diabetes. If proven effective, these strategies could be integrated into Workplace Wellness Program in China and other countries to prevent diabetes and other noncommunicable diseases.

Trial registration: Chinese Clinical Trial Registry ChiCTR2400080790. Registered on 7th February 2024 TRIAL ACRONYM: Daqing DPS-II: Daqing Diabetes Prevention Study II.

Background: The use of high-flow oxygen therapy (HFOT) compared with standard low-flow oxygen therapy (LFOT) may improve outcomes in people with oxygen-dependent chronic respiratory failure (CRF). The primary aim of this multicentre trial was to evaluate HFOT in addition to LFOT, compared with regular LFOT in people with CRF due to chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD).

Methods: Registry-based randomised controlled trial (R-RCT) of people on LFOT for CRF due to COPD (n = 270) and ILD (n = 40), at ten Swedish secondary care centres within the Swedish Register for Respiratory Failure (Swedevox). People with ongoing LFOT are randomised in a 1:1 ratio to standard treatment with LFOT (control) or LFOT with added HFOT during nighttime and at the patient's discretion daytime (intervention). HFOT is provided using the ResMed Lumis HFT system and the AcuCare HFNC Cannula. Primary outcome is time to first hospitalisation or death up to 1 year in people with COPD. Secondary outcomes include symptoms, health-related outcomes (HRQL), health-economics, adverse events, and to explore the effects of HFOT in people with CRF due to ILD. Outcome data will be obtained from national registries and from patient questionnaires at 3 and 12 months.

Discussion: This R-RCT will combine the advantages of a prospective randomised trial and large clinical national registries to improve the evidence-based use of long-term oxygen therapy. Recruitment started in June 2024 and is ongoing.

Trial registration: ClinicalTrials.gov, ID: NCT06247397. Registered 2024-02-07.