Parent engagement in co-design of clinical trials: the PARENT trial.
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ABSTRACT:
SUBMITTER: Vanderloo LM
PROVIDER: S-EPMC8130403 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundEngaging individuals living with disease in drug development and regulatory processes leads to more thoughtful and sensitive trial designs, drives more informative and meaningful outcomes from clinical studies, and builds trust between the public, government, and industry stakeholders. This engagement is especially important in the case of rare diseases, where affected individuals and their families face many difficulties getting information, treatment, and support. Dyne Therapeutics is developing therapeutics for people with genetically-driven muscle diseases. During the development of potential treatments for Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1), Dyne sought the opinions of individuals living with these diseases to inform its clinical trial design and to decrease the difficulties that participants and families might experience participating in them.MethodsDyne engaged individuals and families living with DMD and DM1 as expert partners in its clinical development programs. Dyne convened panels of affected individuals and care partners/parents of individuals living with DMD (n = 8) or DM1 (n = 18). Workshops focused on how affected individuals and their families evaluate and select clinical trials for participation, the importance, quality, and burden associated with individual trial design elements, participation considerations such as site location and the study visit design, patient privacy, the suitability and scope of travel and participant support programs, and the accessibility of content in the informed consent (or assent) forms. Dyne also engaged the DMD Community Advisory Board (CAB) to collect feedback and advice on designing optimal and meaningful clinical trials and measuring relevant outcomes.ResultsThe issues most important to individuals living with DM1 and DMD regarding clinical trials were the ability to participate/access to the trial, perceptions of benefit and risk of trials and potential treatments, the flexibility of participation, clear communication from the sponsor, availability of information from trusted sources, and patient enrollment. In response to the patient advisory workshops and CAB feedback, Dyne refined clinical trial inclusion/exclusion criteria and clinic visit design, developed a travel service program to address the burden of clinical trial travel and enable long-distance and cross-border participation, planned for home visits when feasible, and allowed for adequate rest before clinic visit initiation and between assessments. Additionally, Dyne developed and implemented a transparent and consistent communications plan (including age-appropriate content) for trial participants and community members, and assessed and adjusted procedures to provide maximum participant comfort and lower anxiety, particularly with younger participants.ConclusionsOngoing communication with the Duchenne CAB and with DMD and DM1 patient advisory committee members allows Dyne to stay current with disease community perspectives and feedback on the needs and preferences of those affected and has provided valuable insights into the participant experience thereby helping Dyne initiate clinical trials that better meet the needs of affected individuals and their families.
| S-EPMC10759564 | biostudies-literature
Project description:PurposeTo apply target trial emulation to explore the potential impact of eligibility criteria on the primary outcome of a randomized controlled trial.MethodsSimulations of a real-world explanatory trial of transarterial radioembolization for advanced unresectable hepatocellular carcinoma with portal vein invasion were performed to examine the effects of cohort specification on survival outcomes and patient sample size. Simulations comprised 24 different permutations of the trial varied on three disease nonspecific eligibility parameters. Treatment and control arms for these emulated trials were drawn from the National Cancer Database and matched by treatment propensity. Target trial emulation served as the causal framework for this analysis, allowing the architecture of a true controlled experiment to address forms of bias routinely encountered in comparative effectiveness studies involving real-world observational data.ResultsTwenty-four propensity score-matched cohorts comprising a wider clinical spectrum of patients than specified by the original target trial were successfully generated using the National Cancer Database. The arms for each of the emulated trials demonstrated exchangeability across all eligibility criteria and other clinical covariates. Significant treatment benefits were associated with only a narrow range of eligibility criteria, indicating that the original target trial was well specified.ConclusionThe impact of patient selection on treatment outcomes can be studied using target trial emulation. This analytical framework can furthermore serve to leverage existing real-world data to inform the task of cohort specification for a randomized controlled trial, facilitating a more data-driven approach for this important step in clinical trial design.
| S-EPMC10166475 | biostudies-literature
Project description:Few effective community-based interventions exist for early childhood obesity. Parent mentors have been successful as an intervention for other conditions, but have not been used in childhood obesity. We designed an intervention for early childhood obesity using parent mentors and a positive outlier approach to assess potential efficacy, feasibility, and acceptability.This trial enrolled obese (? 95th BMI percentile for age and gender) 2-5-year-old children in a Head Start program and their parents, with allocation to either parent mentors trained in positively deviant behaviors regarding childhood obesity, or community health workers delivering health education on obesity-related behaviors. The primary outcome is body mass index z-score change at the six-month follow-up assessment. Secondary outcomes include feeding behaviors and practices, health-related quality of life, dietary intake, and participation levels.We enrolled three parent mentors and 60 parent-child dyads. The population is 100% Hispanic; 44% of parents speak Spanish as their primary language and 45% were not high-school graduates. Children had a reported median vegetable and fruit intake of 0.3 and 1.1 cups per day, respectively, at baseline, and a median daily screen time of three hours. There was no intergroup difference in quality-of-life scores at baseline. Retention has been high, at 90% in three months.In this randomized trial of the effects of parent mentors on early childhood obesity, parent-child dyads from an underserved, Hispanic population were successfully enrolled through a partnership with a Head Start organization, with a high retention rate.
| S-EPMC4674310 | biostudies-other
Project description:Digital approaches are increasingly common in clinical trial recruitment, retention, analysis, and dissemination. Community engagement processes have contributed to the successful implementation of clinical trials and are crucial in enhancing equity in trials. However, few studies focus on how digital approaches can be implemented to enhance community engagement in clinical trials. This narrative review examines three key areas for digital approaches to deepen community engagement in clinical trials-the use of digital technology for trial processes to decentralize trials, digital crowdsourcing to develop trial components, and digital qualitative research methods. We highlight how digital approaches enhanced community engagement through a greater diversity of participants, and deepened community engagement through the decentralization of research processes. We discuss new possibilities that digital technologies offer for community engagement, and highlight potential strengths, weaknesses, and practical considerations. We argue that strengthening community engagement using a digital approach can enhance equity and improve health outcomes.
| S-EPMC8956701 | biostudies-literature
Project description:BackgroundGiven the inherent challenges of conducting randomized phase III trials in older cancer patients, single-arm phase II trials which assess the feasibility of a treatment that has already been shown to be effective in a younger population may provide a compelling alternative. Such an approach would need to evaluate treatment feasibility based on a composite endpoint that combines multiple clinical dimensions and to stratify older patients as fit or frail to account for the heterogeneity of the study population to recommend an appropriate treatment approach. In this context, stratified adaptive two-stage designs for binary or composite endpoints, initially developed for biomarker studies, allow to include two subgroups whilst maintaining competitive statistical performances. In practice, heterogeneity may indeed affect more than one dimension and incorporating co-primary endpoints, which independently assess each individual clinical dimension, would therefore appear quite pertinent. The current paper presents a novel phase II design for co-primary endpoints which takes into account the heterogeneity of a population. METHODS: We developed a stratified adaptive Bryant & Day design based on the Jones et al. and Parashar et al. algorithm. This two-stage design allows to jointly assess two dimensions (e.g. activity and toxicity) in two different subgroups. The operating characteristics of this new design were evaluated using examples and simulation comparisons with the Bryant & Day design in the context where the study population is stratified according to a pre-defined criterion.ResultsSimulation results demonstrated that the new design minimized the expected and maximum sample sizes as compared to parallel Bryant & Day designs (one in each subgroup), whilst controlling type I error rates and maintaining a competitive statistical power as well as a high probability of detecting heterogeneity.ConclusionsIn a heterogeneous population, this two-stage stratified adaptive phase II design provides a useful alternative to classical one and allows to identify a subgroup of interest without dramatically increasing sample size. As heterogeneity is not limited to older populations, this new design may also be relevant to other study populations such as children or adolescents and young adults or the development of targeted therapies based on a biomarker.
| S-EPMC9608934 | biostudies-literature
Project description:Randomized clinical trials provide the gold standard evidence base to guide clinical practice. Despite major advances in trial design, pediatric clinical trials are still difficult to perform and pose unique challenges, including the need to consider the impact of developmental changes in trial design. Advances within pediatric rheumatology combined with the need to comply with legislative requirements have driven new approaches to performing pediatric clinical trials such as utilization of large research networks, incorporation of patient and family stakeholders in the planning and implementation of clinical trials, and the development of novel trial designs. The expansion of available biological therapeutics that now includes biosimilar drugs highlights the important and difficult balance of providing new and cost-effective drugs to children while ensuring safety in a vulnerable population. Future advances in juvenile idiopathic arthritis (JIA) clinical trials will likely be the application of precision medicine based on biologic, rather than phenotypic, classification of JIA, with improved understanding of pediatric clinical pharmacology. Clinical trial simulations and comparative effectiveness studies are important supplements to traditional clinical trials, permitting efficient studies and results that are more generalizable.
| S-EPMC6105333 | biostudies-other
Project description:Although adults aged 65 years or older make up a strong majority of cancer patients, their underrepresentation in cancer clinical trials leads to the lack of representative data to guide evidence-based therapeutic decisions in this patient population. The Trial Design Working Group, convened as part of the workshop titled, Engaging Older Adults in the National Cancer Institute Clinical Trials Network: Challenges and Opportunities, recommended study designs and design elements that could improve accrual of older adults in National Cancer Institute-funded clinical trials. These include trials that are specifically designed to enroll older adults, trials that include a cohort of older patients (parallel cohort, stratified cohort, or embedded cohort), and trials with pragmatic design elements to facilitate enrollment of older adults. This manuscript provides brief descriptions of the recommended designs, examples of successful trials, and considerations for implementation of these designs. As with any clinical trial, the scientific questions and trial objectives should drive the study design, the selection of endpoints and intervention, and eligibility criteria. When designing trials that include older adults, the heterogeneity of fitness levels is an important consideration as fitness can influence accrual rates and outcomes. Appropriately incorporating geriatric assessments can help identify the optimal subset of older patients for inclusion and minimize selection bias. Incorporating pragmatic design elements to reduce the burden on trial participants as well as on accruing sites and retaining essential elements to ensure that the main goal of the trial can be accomplished can enhance enrollment without compromising the integrity of trials.
| S-EPMC9949574 | biostudies-literature
Project description:Population heterogeneity is frequently observed among patients' treatment responses in clinical trials because of various factors such as clinical background, environmental, and genetic factors. Different subpopulations defined by those baseline factors can lead to differences in the benefit or safety profile of a therapeutic intervention. Ignoring heterogeneity between subpopulations can substantially impact on medical practice. One approach to address heterogeneity necessitates designs and analysis of clinical trials with subpopulation selection. Several types of designs have been proposed for different circumstances. In this work, we discuss a class of designs that allow selection of a predefined subgroup. Using the selection based on the maximum test statistics as the worst-case scenario, we then investigate the precision and accuracy of the maximum likelihood estimator at the end of the study via simulations. We find that the required sample size is chiefly determined by the subgroup prevalence and show in simulations that the maximum likelihood estimator for these designs can be substantially biased.
| S-EPMC6282861 | biostudies-other
Project description:In 2004 and 2005, the first clinical trials were launched to investigate the use of tenofovir for HIV prevention in Cambodia,Cameroon, Nigeria and Thailand. Controversies erupted over the ethical integrity of the research protocol. We reflect on the events that ledto the controversies and identified that scientific and ethical concerns raised by members of local communities at each of these sites wereerased by trialists, causing crisis that led to premature shut down the early PrEP trials. In the aftermath of these trials, the World HealthOrganisation, UNAIDS, and AVAC developed ethics guidelines intended to recognize the concerns as authentic, and developed guidelines toimprove researchers' engagement of communities in biomedical HIV prevention trial design and implementation. Our findings suggest thatthe ethics guidelines are limited in its ability to address power inequalities that leads to voice erasures and non-recognition of localcompetencies. Rather the ethical documents enabled trialists to gain a new sense of authority through the interpretations of ethical researchconduct enabling trialists regain power that can further entrench inequality and voice erasures. To address concerns with what seems anintractable problem, we suggested models of engagement for off-shored research may be the option.
| S-EPMC7448920 | biostudies-literature
Project description:Randomized, double-blinded, placebo-controlled trials have significant impact on clinical practice. The ultimate goal of a clinical trial of therapy for acute ischemic stroke (AIS) is to compare 2 interventions. Challenges may include interventional therapy standardization, enrollment rate, patient selection, biases, data and safety monitoring, reporting, and financial and logistical support.Selected randomized and single-arm prospective AIS trial designs. Clinical trial elements and their challenges are reviewed. Innovative designs and proposed recommendations to overcome some of the specific challenges and limitations are discussed.AIS therapy trials have specific challenges related to ethical issues, enrollment rate, outcome measures, limited time to treatment, efficacy, safety, and limited or variable operator experience with complex technology in a delicate end organ. Proposed suggestions for improving trial design include the following: incorporation of a lead-in phase; careful patient and outcome measure selection; historical, concurrent, or hybrid controls; open data access; and a Bayesian approach. An open data paradigm may facilitate creation of computerized prediction models for future trials (minimizing cost by decreasing sample size or providing futility analyses and directing resources to other trials). Collaborative, consortium, and network infrastructures may allow more effective and efficient study completion. Self-learning, self-correcting trials with intrinsic flexibility to adapt may help future clinical trial design in AIS.The randomized clinical trial design in AIS endovascular therapy is challenging. Lead-in phases, careful patient selection, use of innovative outcome measures, control groups, and newer clinical trial design may enhance conduct of future trials, their validity, and their results.
| S-EPMC4109233 | biostudies-other