Contemporary clinical trials最新文献

According to ICH E9(R1), defining the estimand comes before defining the analysis approach, and the strategies for addressing intercurrent events are key components of the estimand. With the composite strategy, the problem of missing data disappears, because it becomes part of the endpoint definition. It is this perspective that we adopt in addressing the problem of missing data. We propose comparing patients in a pairwise manner to determine which patient fared better, one patient from each group, taking into account the reason for and timing of missingness. For purposes of illustration, reasons for missingness are placed into three categories: (1) death or adverse events, (2) administration of rescue medication (treated as missing even if patient continues in the study, or a poor score is assigned), and (3) other reasons such as loss to follow-up or withdrawal of consent. Each pair of patients is compared on the endpoint of interest. The comparison outcomes are determined based on the presence of missing data, its category, and timing. For instance, if both patients in a pair have received rescue medication, the patient with the later time of rescue medication is considered to have fared better. The overall treatment effect is combined across all pairwise comparisons. This method allows the reason and timing of missing data to contribute to the assessment of treatment effects, providing a solution to some limitations of existing methods. Thus, the pairwise comparison approach addresses the missing data problem transparently via the composite strategy.

Background: Despite the association between peer support interventions and improved patient-reported outcomes (PROs) across cancer populations, there is a lack of structured peer support interventions for patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT).

Objective: To test the feasibility, acceptability, and preliminary efficacy of a novel five-session, phone-delivered peer support intervention (STEPP: Supporting Transplant Experiences with Peer Program) for improving quality of life (QOL) and reducing psychological distress in patients undergoing HSCT.

Methods: This single-center pilot randomized clinical trial (RCT) will compare the STEPP intervention to usual transplant care among 90 patients hospitalized for HSCT. Eligible participants include adults (age ≥ 18 years) with hematologic malignancies hospitalized for autologous or allogeneic HSCT. The STEPP intervention provides informational, emotional, and practical support. To test the primary aim of intervention feasibility, we have established a priori benchmarks of 60 % enrollment of eligible patients and 60 % completion of at least 3 out of 5 intervention sessions among those randomized to STEPP. Acceptability will be assessed using the Client Satisfaction Questionnaire, with scores ≥3.0/4.0 indicating greater intervention acceptability. To test the secondary aim of preliminary efficacy, we will examine changes in PROs (e.g., anxiety symptoms and QOL) from pre- to post-intervention.

Discussion: This pilot RCT of a structured, phone-delivered peer support intervention tailored to the needs of patients preparing to undergo HSCT will elucidate the feasibility, acceptability, and preliminary efficacy of the STEPP intervention. We will then be poised to conduct a future, full-scale RCT to establish the efficacy of STEPP on patient outcomes.

Clinicaltrials: gov: NCT06010017.

Older adults with Alzheimer's disease (AD), in addition to significant cognitive disability, have twice the risk of fracture compared to those with normal cognition. Fractures among older adults with AD are associated with substantial morbidity, loss of physical function, and significant mortality. Prior studies have shown a decreased risk of fracture among those taking acetylcholinesterase inhibitors, such as donepezil. With both cognitive and non-cognitive benefits, donepezil would be a valuable component in a fracture prevention program for older adults with AD. Though anti-amyloid therapies are now clinically available, donepezil may still have non-cognitive benefits. However, the specific effects of donepezil on bone metabolism are unknown. We have designed this randomized, double-blind, placebo-controlled clinical trial to investigate the effect of AD treatment with donepezil on bone metabolism. The study will measure the change in bone mineral density, bone turnover markers, and bone quality related to 12-months of donepezil therapy. This will be the first known study of changes in bone metabolism among older adults with AD.

Avoidant/restrictive food intake disorder (ARFID) is a feeding and eating disorder for which there are very few evidence-based treatments. Cognitive-Behavioral Therapy for Avoidant/Restrictive Food Intake Disorder (CBT-AR) is a novel exposure-based treatment which is suitable for people aged ten and older. The primary aims of the study are to undertake a real-world evaluation of the feasibility, acceptability, and preliminary effectiveness of CBT-AR for young people aged 12-25 years old in an outpatient eating disorders service where the patient population has high levels of psychiatric comorbidity. Clinicians, patients, and parents/guardians will be involved in the evaluation. Assessments will be carried out at baseline, during weekly sessions, at the end of each treatment stage, at end of CBT-AR treatment, and at 3-month follow-up. Assessments will measure ARFID symptoms, mood, quality of life, therapeutic alliance, and feedback on the treatment. The study will take place over a 12-month period and will evaluate the use of CBT-AR within real-life clinical practice conditions, noting how and why deviations from the treatment have occurred. The findings of this research will inform future ARFID treatment delivery and the implementation of CBT-AR at outpatient mental health services.

Background: Health-related lifestyle management could improve related symptoms and adverse events in patients with systemic lupus erythematosus (SLE). The phenolic compounds in extra virgin olive oil (EVOO) and physical exercise (PE) have both shown benefits for autoimmune conditions, but no intervention has synergised the two approaches.

Aim: To analyse the effects of an intervention combining EVOO and a multicomponent health promotion and physical exercise programme on disease activity, clinical characteristics, cardiovascular risk, physical fitness, and the molecular level in SLE sufferers.

Methods: Three-arm prospective randomised controlled 24-week clinical trial. 90 participants will be randomised into one of three groups: control; EVOO supplements; or EVOO and multicomponent health promotion and PE programme.

Results: Pre-, mid- and post-intervention assessments will record disease activity, clinical characteristics, nutritional evaluation, cardiovascular risk assessment, physical condition and functioning, and molecular markers.

Conclusions: The proposed trial will help clarify whether a combined intervention adding an EVOO supplement to a Mediterranean diet intake pattern and adherence to an active-healthy lifestyle are beneficial for SLE patients, as well as the need for health and pharmacological care, increasing knowledge of the organic mechanisms mediated by EVOO and PE adherence, allowing new useful biomarkers to be characterised at the diagnostic/prognostic level.

Background: The Diuretic Comparison Project (DCP) was a multi-center, embedded pragmatic trial conducted within the VA healthcare system comparing chlorthalidone and hydrochlorothiazide in preventing major adverse cardiovascular events and non-cancer deaths in hypertensive patients. Study procedures were decentralized, and facility leadership first had to agree and accept study procedures before staff approached participants. Recent evidence suggests facilities that choose and choose not to participate in trials may differ and this study considered such differences within DCP.

Methods: A cross-sectional comparison of facilities participating in DCP was conducted with data from the study start (June 2016) including: 2016 American Community Survey, 2016 Strategic Analytics for Improvement and Learning reports, star ratings, and 2014 hospital complexity. Characteristics of participating and non-participating centers were compared using logistic regression, including county-level socio-economic features and hospital-level performance.

Results: Of 144 VA medical centers, leadership at 75 centers (52 %) initiated participation. Facilities in highly-urban and higher median income counties were more likely to participate, as were higher-complexity facilities. Facilities with research experience were 2.18 times as likely to participate. No other hospital performance metrics or county-level demographics were associated with participation.

Conclusions: Overall, this study suggests research exposure and quality care metrics may impact a facility's decision to participate. These results highlight key considerations for recruitment to multi-site, and particularly pragmatic, clinical trials. Consideration of supporting facilities that have not historically participated in research may be fruitful for recruitment. These results emphasize the importance of education about pragmatic study design and its integration with clinical care.

The NIH Pragmatic Trials Collaboratory supports the design and conduct of 32 embedded pragmatic clinical trials, and many of these trials rely on data from the electronic health record (EHR) to monitor outcomes and/or use functionality provided by the EHR platform to deliver the intervention. Given the complexity and dynamic nature of EHR systems, study teams have encountered challenges in use of the EHR for these purposes, including challenges related to local implementation of trial interventions, rapid technology evolution, EHR updates, and transitions in EHR systems. In this article, we share case examples and lessons learned, and suggest that teams need to be aware of-and perhaps proactively investigate- possible changes to EHR systems and data that will affect the delivery of interventions and the integrity and safety of pragmatic clinical trials.

Background: Somali American individuals have lower cervical cancer screening rates than the U.S. general population. Offering HPV self-sampling in primary care clinics could increase screening rates in Somali American individuals by addressing screening barriers.

Methods: The Isbaar Project is a Hybrid Type 2 effectiveness-implementation study of a patient-centered, culturally tailored HPV self-sampling intervention for Somali American individuals. Guided by the Consolidated Framework for Implementation Research and Social Cognitive Theory, we conducted focus groups with Somali American individuals, and interviews with clinicians and clinic staff to inform refinement and development of implementation strategies. HPV self-sampling was then implemented as a usual care screening option at 3 community-based primary care clinics in Minneapolis, Minnesota in February 2023. The primary objective is to assess the effect of implementing in-clinic HPV self-sampling on screening completion in Somali American individuals. The secondary objective is to assess the effect of implementing HPV self-sampling on screening completion in all patients. Using difference-in-difference methods, we will evaluate changes in screening rates one-year pre and post implementation and compare changes with control clinics followed over the same time period. Using RE-AIM, we will conduct a post-implementation mixed methods analysis of processes and strategies needed to successfully implement HPV self-sampling in primary care.

Conclusions: The study was designed to evaluate a real-world in-clinic HPV self-sampling intervention for Somali American individuals, generating data on both effectiveness and implementation applicable to other community-based clinics in the U.S. The objective of this report is to describe the rationale and design of the study.

Background: Family or friend carers of people with cancer report high levels of depression, anxiety, caregiving strain, and unmet needs. Limited strategies for identification and management of distress have been established among cancer carers. This paper describes the protocol of two linked studies: Study 1a, a distress screening and stepped care pathway feasibility study and Study 1b, a hybrid implementation-effectiveness Randomised Controlled Trial (RCT) to assess the benefit of a comprehensive, carer-centred online Cognitive Behavioural Therapy (iCBT) program for carers with anxiety and depression.

Methods: For Study 1a, 300 cancer carers will be screened for distress. Carers with low distress will be referred to publicly available carer resources. Carers scoring 4 and higher on the distress thermometer will complete depression and anxiety measures. Carers with high anxiety/depression will be recommended psychological therapy. Carers with mild/moderate anxiety and/or depression will be allocated to the Carers iCBT Program, evaluated via a RCT with waitlist control group (Study 1b). For Study 1b, intervention group carers will receive access to a 6-lesson self-directed online iCBT program. Waitlist-controls will access the intervention at 14 weeks. Intervention and control groups will complete baseline, 6 week, and 14 week self-report measures; controls will complete additional measures at 20 and 28 weeks. A sample size of n = 88 carers in the iCBT RCT is needed.

Conclusions: If acceptable, feasible and effective, this pathway and iCBT intervention could offer a sustainable, scalable and low-cost approach to identifying and managing distress in carers, and potentially improving patient and carer outcomes.

Trial registration: Australian and New Zealand Clinical Trial Registry number: ACTRN12623001341617p.

Background: Adolescents and young adults with cancer (AYAs, ages 15-39 at the time of diagnosis) experience significant adverse health and psychosocial outcomes. AYAs live with emotional distress and health care demands that exceed those of their healthy peers but can have difficulty accessing care. Digitally delivered interventions are an attractive option for AYA survivors, a population that routinely utilizes online resources when seeking health information and support.

Aim: By improving access to survivorship resources and support and strengthening health literacy and self-management skills, the INteractive Survivorship Program to Improve Health care REsources [INSPIRE] is designed to improve adherence to AYA health care guidelines and reduce cancer-related distress. We describe the protocol for a two-arm randomized controlled trial (RCT) testing the AYA-adapted INSPIRE program.

Methods/design: The intervention includes an interactive mobile app, study website, and social media platforms, adding telehealth for those with continued distress, lower survivorship health care literacy, or poor engagement with the digital program at 6 weeks. Participants are randomized to INSPIRE or an active control. In the active control arm, survivors receive access to a study website with links to existing AYA survivor resources followed by delayed access to the INSPIRE program. Participants are not blinded; study staff not providing telehealth are blinded. The primary outcomes are cancer-related distress and health care adherence specific to second cancer and cardiometabolic screenings.

Discussion: If effective, the program is positioned for accelerated implementation to improve care for AYA survivors by using a scalable informatics-based administration and largely digital intervention program.