Trials最新文献

Background: There are numerous approaches available to analyse data from cluster randomised trials. These include cluster-level summary methods and individual-level methods accounting for clustering, such as generalised estimating equations and generalised linear mixed models. There has been much methodological work showing that estimates of treatment effects can vary depending on the choice of approach, particularly when estimating odds ratios, essentially because the different approaches target different estimands.

Methods: In this manuscript, we describe the protocol for a planned re-analysis of data from a large number of cluster randomised trials. Our main objective is to examine empirically whether and how odds ratios estimated using different approaches (for both primary and secondary binary outcomes) vary in cluster randomised trials. We describe the methods that will be used to identify the datasets for inclusion and how they will be analysed and reported.

Discussion: There have been a number of small comparisons of empirical differences between the different approaches to analysis for CRTs. The systematic approach outlined in this protocol will allow a much deeper understanding of when there are important choices around the model approach and in which settings. This will be of importance given the heightened awareness of the importance of estimands and the specification of statistical analysis plans.

Background: Primary dental care settings are strategically important locations where randomised controlled trials (RCTs) of behaviour change interventions (BCIs) can be tested to tackle oral diseases. Findings have so far produced equivocal results. Improving treatment fidelity is posed as a mechanism to improve scientific rigour, consistency and implementation of BCIs. The National Institutes of Health Behaviour Change Consortium (NIH BCC) developed a tool to assess and evaluate treatment fidelity in health behaviour change interventions, which has yet to be applied to the primary dental care BCI literature.

Method: We conducted a scoping review of RCTs delivered in primary dental care by dental team members (in real-world settings) between 1980 and 2023. Eligible studies were coded using the NIH BCC checklist to determine the presence of reported fidelity strategies across domains: design, training, delivery, receipt and enactment.

Results: We included 34 eligible articles, reporting 21 RCTs. Fidelity reporting variations were found both between and within NIH BCC domains: strategy reporting ranged from 9.5 to 85.7% in design, 9.5 to 57.1% in training, 0 to 66.7% in delivery, 14.3 to 36.8% in receipt and 13.3 to 33.3% in enactment. The most reported domain was design (M = 0.45), and the least reported domain was delivery (M = 0.21). Only one study reported over 50% of the recommended strategies in every domain.

Conclusions: This review revealed inconsistencies in fidelity reporting with no evidence that fidelity guidelines or frameworks were being used within primary dental care trials. This has highlighted issues with interpretability, reliability and reproducibility of research findings. Recommendations are proposed to assist primary dental care trialists with embedding fidelity strategies into future research.

Background: Exposure with Response Prevention (ERP) is a first-line treatment for OCD, but even when combined with first-line medications it is insufficiently effective for approximately half of patients. Compulsivity in OCD is thought to arise from an imbalance of two distinct neural circuits associated with specific subregions of striatum. Targeted modulation of these circuits via key cortical nodes (dorsolateral prefrontal cortex [dlPFC] or presupplementary motor area [pSMA]) has the potential to improve ERP efficacy by decreasing compulsions during therapy.

Methods: The NExT (Neuromodulation + Exposure Therapy) trial is a two-phase, multisite early-stage randomized controlled trial designed to examine whether TMS augmentation of ERP alters activity in dlPFC and/or pSMA-associated circuitry and reduces compulsions during therapy in youth with OCD age 12-21 years. Phase 1 (N = 60) will compare two different active TMS regimens with sham: A. continuous theta burst stimulation (cTBS) to pSMA vs. B. intermittent theta burst stimulation (iTBS) to dlPFC. A priori "Go/No-Go" criteria will inform a decision to proceed to Phase 2 and the choice of TMS regimen. Phase 2 (N = 60) will compare the selected TMS regimen vs. sham in a new sample.

Discussion: This trial is the first to test TMS augmentation of ERP in youth with OCD. Results will inform the potential of TMS to enhance ERP efficacy and enhance knowledge about mechanisms of change.

Trial registration: ClinicalTrials.gov NCT05931913. Registered prospectively on July 5, 2023.

Background: The treatment of all-trans retinoic acid (ATRA) and arsenical agent has revolutionarily improved the prognosis of acute promyelocytic leukemia (APL) both in adults and children. Nevertheless, coagulation disorder and differentiation syndrome (DS) are the main causes of early death in APL patients. Early chemotherapy to reduce leukocytes during induction is an important measure to reduce complications and mortality. However, the incidence of hyperleukocytosis (WBC > 10 × 10⁹/L) was significantly higher in pediatric patients without chemotherapy than in adults. Although ATRA plus arsenic is the standard therapy for non-high-risk adult patients, it remains controversial whether chemotherapy is necessary for induction therapy in pediatric APL.

Methods: This study was designed as a multicenter randomized controlled trial. Children with APL were randomly assigned into experimental group (ATRA-RIF plus chemotherapy) and control group (ATRA-RIF). The experimental group was treated with ATRA-RIF plus chemotherapy for induction, while the control group was treated with ATRA-RIF alone. In addition, both groups received the same regimen of ATRA-RIF plus chemotherapy for consolidation and maintenance.

Discussion: This trial aims to compare the efficacy of ATRA-RIF plus chemotherapy versus ATRA-RIF in pediatric non-high-risk patients with APL to demonstrate that chemotherapy during induction therapy can reduce the incidence of complications such as hyperleukocytosis and DS, thereby reducing mortality.

Trial registration: Chinese Clinical Trials Registry, ID: ChiCTR2000038877. Registered on October 8, 2020, https://www.chictr.org.cn/showproj.html?proj=60733 . V1.0 date 08/01/2020.

Background: Although the challenges of recruiting to randomised controlled trials (RCTs) are well documented, few studies have focused on the impact that the communication between recruiters and patients has on patients' participation decisions. Recruiters are thought to influence patient decision-making, but the mechanisms by which this occurs are unclear. The aim of this research was to investigate how patients interpret and use the information conveyed to them by healthcare professionals (HCPs) in trial participation decisions.

Methods: Three pragmatic UK-based multicentre RCTs were purposively sampled to provide contrasting clinical specialities. Data collection was integrated into each RCT, including audio-recordings of patient recruitment consultations and interviews with patients. Where possible, consultation audio-recordings were linked to interviews to explore how information communicated by recruiters was interpreted and used by patients during their decision-making. Data were analysed thematically, using the constant comparison approach.

Results: Twenty audio-recorded recruitment consultations were obtained across the 3 RCTs, combined with 42 interviews with patients who had consented to or declined RCT participation. Consultation and interview data were 'linked' for 17 individual patients. Throughout the patient's clinical pathway, HCPs (both those involved in the RCT and not) influenced patients' perceptions of treatment need and benefit by indicating that they preferred a particular treatment option for the patient as an individual. Whilst patients valued and were influenced by information conveyed by HCPs, they also drew on support from other sources and ultimately framed RCT participation decisions as their own. Patients' willingness to be randomised hinged on perceptions of whether they stood to benefit from a particular treatment and the availability of those treatments outside of the trial.

Conclusion: This study supports the need for training and support for healthcare professionals involved throughout the clinical pathway of patients eligible for RCTs, as all healthcare professionals who interact with patients have the potential to influence their perceptions of treatments being compared in the trial.

Trial registration: OPTIMA ISRCTN42400492. Prospectively registered on 26 June 2012. Prepare for Kidney Care ISRCTN17133653. Prospectively registered on 31 May 2017. MARS 2 ISRCTN44351742. Retrospectively registered on 5 September 2018.

Background: Around 40% of people with major depressive disorder (MDD) experience moderate remission, with the remainder meeting the criteria for resistant major depression (RMD). It has been shown that exercise has a low-to-moderate effect on MDD, but there is a lack of evidence on exercise interventions in RMD patients. The primary purpose of the proposed study will be to investigate the effect of a 12-week supervised combined exercise program on depressive symptoms in people with RMD compared to a treatment-as-usual (TAU) group.

Method: This randomised, single-blind, controlled experimental trial will include 70 adults (≥ 18 years old) with RMD. Participants randomised to an exercise intervention, or a TAU group will be assessed at baseline and after a three-month intervention period. The primary variable will be participants' depressive symptoms measured with the Montgomery-Asberg Depression Rating Scale. Secondary outcome variables will include cardiorespiratory fitness (peak oxygen uptake through peak cardiopulmonary exercise test), body composition (bioimpedance and anthropometric variables), physical activity level (the International Physical Activity Questionnaire), health-related quality of life (the Short Form-36 Health Survey), functional outcome (the Sheehan Disability Scale and Quality of Life in Depression Scale), overall disease severity (the Clinical Global Impression Scale-Severity of Illness), and biochemical variables (a fasting blood sample).

Discussion: This study will try to answer whether a supervised co-adjuvant combined (aerobic and resistance training) exercise program will help the prognosis of this population with RMD.

Trial registration: ClinicalTrials.gov NCT05136027. Last public release on 12/13/2023.

Background: Lower-than-expected recruitment continues to be one of the major causes of trial delays, and trials to improve mental health are no exception. Indeed, recruitment challenges in trials of vulnerable populations, such as those living with mental health illness, can even be exacerbated. To address this, researchers are turning to digital and online recruitment strategies, e.g. web-based approaches and multi-media in order to (1) increase recruitment efficiency (recruit to target and on time) and (2) improve diversity in mental health clinical trials to be more inclusive and reduce health inequity. There is, however, inconclusive evidence on the success of digital and online recruitment strategies in mental health clinical trials. The RE-MIND study comprised a scoping review to assess the impact of using such recruitment strategies in mental health clinical trials to inform a more systematic scoping review.

Methods: A cohort of 191 recently published RCTs and randomised feasibility studies were identified from the NIHR Journals Library and top two mental health journals (based on citation metrics), Lancet Psychiatry and JAMA Psychiatry. Population characteristics including gender, ethnicity and age were summarised for inclusivity using descriptive statistics, and recruitment strategies were compared to examine differences in their success in recruiting to target.

Results: After screening, 97 articles were included for review. The review findings showed no evidence that offline or mixed strategies were superior for achieving recruitment targets in mental health trials. However, there was a suggestion that trials using a mixed recruitment strategy improved inclusivity and tended to recruit closer to the target.

Conclusions: The key finding was that consideration should be given to a mixed methods approach to recruitment not only to enable wider and more diverse participation in mental health trials but also to realize greater efficiency.

Current guidelines tend to focus on a p-value threshold of a pre-specified primary endpoint tested in randomized controlled clinical trials to determine a treatment effect for a specific drug. However, a p-value does not always provide evidence on the treatment effect of a drug, especially when stratification of the data does not account for unforeseen variables introduced into the analysis. We report and discuss a rare case in which investigational site stratification in the pre-specified analysis method of a primary endpoint results in a loss of statistical power in the evaluation of the treatment effect due to data attrition of almost 17% of outcome data in the phase III randomized, controlled PANAMO study in critically ill COVID-19 patients. Other analyses utilizing no or different stratification (e.g., stratifying by country, region, pooling low enrollment clinical sites) evaluates 100% of patient data resulting in p-values suggesting a positive treatment effect (p < 0.05). We demonstrate how this technical artifact occurs by adjustment for site stratification within the Cox regression analysis for survival outcomes and how alternative stratification corrects this discrepancy.

Background: Appropriate management of fractures is crucial for restoring natural bone function and preventing long-term complications. Previous research on animal models indicates that trehalose can improve bone fracture healing by inhibiting the inflammatory cascade. We hope that trehalose can accelerate bone fracture healing in humans, alleviate pain, and ultimately enhance the individual's quality of life.

Methods: This randomized, double-blind clinical trial will be conducted at Taleghani Hospital in Tehran, Iran. Sixty-four patients admitted to the orthopedic ward will be enrolled based on eligibility criteria. The participants will be randomly allocated based on the permuted block randomization into two groups: those receiving trehalose (32 patients) or placebo (32 patients). The patients in the trehalose and placebo groups will receive 3.3 g of trehalose or placebo for 12 weeks, respectively. A consent form, general questionnaire, as well as the Visual Analog Scale (VAS), Harris Hip Score (HHS), and radiological analyses will be used to assess fracture healing quality. The intention-to-treat principle will form the basis of the statistical analysis.

Discussion: The trial results may provide a convenient and safe adjuvant treatment option for the Pertrochanteric Fractures population.

Trial registration: Iranian Registry of Clinical Trials. IRCT20240605062013N1. URL of the trial registry record: https://irct.behdasht.gov.ir/trial/77212 . Registration date: 16 June 2024.

Background: A large proportion of older adults suffer from chronic diseases. Health coaching is a promising intervention that enhances individuals' health knowledge and supports changes in health behaviours. Even though health professionals usually conduct health coaching interventions, lay health workers from different backgrounds account for a growing segment of health coaches over the years. The planned study's main objective is to investigate whether health coaching by lay health workers is as effective as that by health professionals.

Methods: The effects of health coaching intervention by lay health workers will be examined in comparison with that by health professionals within a single-blind, multi-centre, randomised controlled trial with a follow-up assessment after 3 months. A total of 380 community-dwelling older adults with chronic diseases will be recruited and randomly assigned using a 1:1 ratio into the intervention and control groups. The intervention group will receive a 3-month health coaching intervention delivered by lay health workers, whereas the control group will receive the intervention delivered by health professionals. Primary outcomes include patient activation, physical activity and nutrition behaviours.

Discussion: The expected findings of this study will advance the health coaching literature, research and practice by determining whether health coaching by lay health workers is as effective as that by health professionals in enhancing older adults' knowledge, skills and confidence in chronic disease self-management and promoting changes in health behaviours. If proven effective, the inclusion of lay health workers in delivering effective self-management interventions should be advocated to reduce the over-reliance on health professionals in the primary healthcare system.

Trial registration: ISRCTN, ISRCTN73836238 . Registered 8 November 2023.