Browsing by Author "Kelly, Lauren E."

Now showing 1 - 3 of 3
  • Thumbnail Image
    ItemOpen Access
    Adaptive designs in clinical trials: a systematic review-part I
    (2024-10-04) Ben-Eltriki, Mohamed; Rafiq, Aisha; Paul, Arun; Prabhu, Devashree; Afolabi, Michael O. S.; Baslhaw, Robert; Neilson, Christine J.; Driedger, Michelle; Mahmud, Salaheddin M.; Lacaze-Masmonteil, Thierry; Marlin, Susan; Offringa, Martin; Butcher, Nancy; Heath, Anna; Kelly, Lauren E.
    Abstract Background Adaptive designs (ADs) are intended to make clinical trials more flexible, offering efficiency and potentially cost-saving benefits. Despite a large number of statistical methods in the literature on different adaptations to trials, the characteristics, advantages and limitations of such designs remain unfamiliar to large parts of the clinical and research community. This systematic review provides an overview of the use of ADs in published clinical trials (Part I). A follow-up (Part II) will compare the application of AD in trials in adult and pediatric studies, to provide real-world examples and recommendations for the child health community. Methods Published studies from 2010 to April 2020 were searched in the following databases: MEDLINE (Ovid), Embase (Ovid), and International Pharmaceutical Abstracts (Ovid). Clinical trial protocols, reports, and a secondary analyses using AD were included. We excluded trial registrations and interventions other than drugs or vaccines to align with regulatory guidance. Data from the published literature on study characteristics, types of adaptations, statistical analysis, stopping boundaries, logistical challenges, operational considerations and ethical considerations were extracted and summarized herein. Results Out of 23,886 retrieved studies, 317 publications of adaptive trials, 267 (84.2%) trial reports, and 50 (15.8%) study protocols), were included. The most frequent disease was oncology (168/317, 53%). Most trials included only adult participants (265, 83.9%),16 trials (5.4%) were limited to only children and 28 (8.9%) were for both children and adults, 8 trials did not report the ages of the included populations. Some studies reported using more than one adaptation (there were 390 reported adaptations in 317 clinical trial reports). Most trials were early in drug development (phase I, II (276/317, 87%). Dose-finding designs were used in the highest proportion of the included trials (121/317, 38.2 %). Adaptive randomization (53/317, 16.7%), with drop-the-losers (or pick-the-winner) designs specifically reported in 29 trials (9.1%) and seamless phase 2-3 design was reported in 27 trials (8.5%). Continual reassessment methods (60/317, 18.9%) and group sequential design (47/317, 14.8%) were also reported. Approximately two-thirds of trials used frequentist statistical methods (203/309, 64%), while Bayesian methods were reported in 24% (75/309) of included trials. Conclusion This review provides a comprehensive report of methodological features in adaptive clinical trials reported between 2010 and 2020. Adaptation details were not uniformly reported, creating limitations in interpretation and generalizability. Nevertheless, implementation of existing reporting guidelines on ADs and the development of novel educational strategies that address the scientific, operational challenges and ethical considerations can help in the clinical trial community to decide on when and how to implement ADs in clinical trials. Study protocol registration https://doi.org/10.1186/s13063-018-2934-7 .
  • Thumbnail Image
    ItemOpen Access
    Protocol for a randomized control trial of the Building Regulation in Dual Generations Program (BRIDGE): preventing the intergenerational transmission of mental illness in at-risk preschool children
    (2023-09-19) Penner-Goeke, Lara; Belows, Madeline; Kristjanson, Amanda; Andrade, Brendan F.; Cameron, Emily E.; Giuliano, Ryan; Katz, Laurence Y.; Kelly, Lauren E.; Letourneau, Nicole; Mota, Natalie; Reynolds, Kristin; Zalewski, Maureen; Pharazyn, Ashley; Roos, Leslie E.
    Abstract Background Since the onset of the COVID-19 pandemic, the worldwide prevalence of maternal depression has risen sharply; it is now estimated that one quarter of mothers experience clinically significant depression symptoms. Exposure to maternal depression during early childhood increases the risk for the development of childhood mental illness (MI) in offspring, with altered parenting practices mediating the association between maternal depression and child outcomes. Dual-generation interventions, which aim to simultaneously treat parent and child mental health, show promise for improving outcomes for mothers with depression and their young children. The Building Regulation in Dual Generations (BRIDGE) program combines Dialectical Behavior Therapy (DBT) and parenting skills training to concurrently treat maternal depression and improve parenting practices. In pilot within-group studies, BRIDGE has led to large reductions in maternal depression and child MI symptoms. The aim of the current study is to evaluate the efficacy of BRIDGE in reducing maternal depression and child MI symptoms (primary outcomes) as well as parenting stress and harsh parenting (secondary outcomes). Methods A three-armed randomized control trial with equal group sizes will be conducted to compare the efficacy of (1) BRIDGE (DBT + parenting skills), (2) DBT skills training, and (3) services-as-usual. Participants (n = 180) will be mothers of 3- to 5-year-old children who report elevated depression symptoms. Those randomized to BRIDGE or DBT skills training will complete a 16-week group therapy intervention. Assessments will be administered at pre-intervention(T1) post-intervention (T2), and 6-month follow-up (T3). Discussion Dual-generation programs offer an innovative approach to prevent the intergenerational transmission of mental illness. The current study will add to the evidence base for BRIDGE by comparing it to a stand-alone mental health intervention and a services-as-usual group. These comparisons will provide valuable information on the relative efficacy of including parenting support in a mental health intervention for parents. The results will contribute to our understanding of how maternal depression affects children’s development and how intervening at both a mental health and parenting level may affect child and family outcomes. Trial registration Name of registry: Clinical Trials Protocol Registration and Results System; trial registration number: NCT05959538; date of registry: July 24, 2023; available: https://classic.clinicaltrials.gov/ct2/show/NCT05959538
  • Thumbnail Image
    ItemOpen Access
    The Building Emotional Awareness and Mental health (BEAM) program developed with a community partner for mothers of infants: protocol for a feasibility randomized controlled trial
    (2023-03-09) Joyce, Kayla M.; Rioux, Charlie; MacKinnon, Anna L.; Katz, Laurence Y.; Reynolds, Kristin; Kelly, Lauren E.; Klassen, Terry; Afifi, Tracie O.; Mushquash, Aislin R.; Clement, Fiona M.; Chartier, Mariette; Xie, Elisabeth B.; Penner, Kailey E.; Hunter, Sandra; Berard, Lindsay; Tomfohr-Madsen, Lianne; Roos, Leslie E.
    Abstract Background Drastic increases in the rates of maternal depression and anxiety have been reported since the COVID-19 pandemic began. Most programs aim to improve maternal mental health or parenting skills separately, despite it being more effective to target both concurrently. The Building Emotional Awareness and Mental health (BEAM) program was developed to address this gap. BEAM is a mobile health program aiming to mitigate the impacts of pandemic stress on family well-being. Since many family agencies lack infrastructure and personnel to adequately treat maternal mental health concerns, a partnership will occur with Family Dynamics (a local family agency) to address this unmet need. The study’s objective is to examine the feasibility of the BEAM program when delivered with a community partner to inform a larger randomized controlled trial (RCT). Methods A pilot RCT will be conducted with mothers who have depression and/or anxiety with a child 6–18 months old living in Manitoba, Canada. Mothers will be randomized to the 10 weeks of the BEAM program or a standard of care (i.e., MoodMission). Back-end App data (collected via Google Analytics and Firebase) will be used to examine feasibility, engagement, and accessibility of the BEAM program; cost-effectiveness will also be examined. Implementation elements (e.g., maternal depression [Patient Health Questionnaire-9] and anxiety [Generalized Anxiety Disorder-7]) will be piloted to estimate the effect size and variance for future sample size calculations. Discussion In partnership with a local family agency, BEAM holds the potential to promote maternal-child health via a cost-effective and an easily accessible program designed to scale. Results will provide insight into the feasibility of the BEAM program and will inform future RCTs. Trial registration {2a} This trial was retrospectively registered with ClinicalTrial.gov ( NCT05398107 ) on May 31st, 2022.