Browsing by Author "Ademola, Ayoola"

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    PrEvention of posttraumatic contractuRes with Ketotifen 2 (PERK 2) – protocol for a multicenter randomized clinical trial
    (2020-02-24) Ademola, Ayoola; Hildebrand, Kevin A; Schneider, Prism S; Mohtadi, Nicholas G H; White, Neil J; Bosse, Michael J; Garven, Alexandra; Walker, Richard E A; Sajobi, Tolulope T
    Abstract Background Injuries and resulting stiffness around joints, especially the elbow, have huge psychological effects by reducing quality of life through interference with normal daily activities such as feeding, dressing, grooming, and reaching for objects. Over the last several years and through numerous research results, the myofibroblast-mast cell-neuropeptide axis of fibrosis had been implicated in post-traumatic joint contractures. Pre-clinical models and a pilot randomized clinical trial (RCT) demonstrated the feasibility and safety of using Ketotifen Fumarate (KF), a mast cell stabilizer to prevent elbow joint contractures. This study aims to evaluate the efficacy of KF in reducing joint contracture severity in adult participants with operately treated elbow fractures and/or dislocations. Methods/design A Phase III randomized, controlled, double-blinded multicentre trial with 3 parallel groups (KF 2 mg or 5 mg or lactose placebo twice daily orally for 6 weeks). The study population consist of adults who are at least 18 years old and within 7 days of injury. The types of injuries are distal humerus (AO/OTA type 13) and/or proximal ulna and/or proximal radius fractures (AO/OTA type 2 U1 and/or 2R1) and/or elbow dislocations (open fractures with or without nerve injury may be included). A stratified randomization scheme by hospital site will be used to assign eligible participants to the groups in a 1:1:1 ratio. The primary outcome is change in elbow flexion-extension range of motion (ROM) arc from baseline to 12 weeks post-randomization. The secondary outcomes are changes in ROM from baseline to 6, 24 & 52 weeks, PROMs at 2, 6, 12, 24 & 52 weeks and impact of KF on safety including serious adverse events and fracture healing. Descriptive analysis for all outcomes will be reported and ANCOVA be used to evaluate the efficacy KF over lactose placebo with respect to the improvement in ROM. Discussion The results of this study will provide evidence for the use of KF in reducing post-traumatic joint contractures and improving quality of life after joint injuries. Trial registration This study was prospectively registered (July 10, 2018) with ClinicalTrials.gov reference: NCT03582176.
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    Some Contributions to Understanding the Heterogeneity of Treatment Effects in Stroke Trials
    (2024-06-20) Ademola, Ayoola; Sajobi, Tolulope; Hildebrand, Kevin A.; Hill, Michael D.; Thabane, Lehana
    Background: Stroke is a neurological disease that is the third leading cause of death and the tenth-largest known cause of disability-adjusted life years in Canada. Fortunately, clinical trial evidence has identified a few treatments that improve patients’ outcomes, resulting in faster reperfusion, better functional outcomes, lower mortality rates, and improved quality of life. Despite the overall positive benefits of these interventions, there remain differences in the impact of the treatment at the individual level, with some patients experiencing positive benefits and others showing neutral or adverse effects of interventions. Such heterogeneity of treatment effects (HTE) could be attributed to differences in patients’ socio-demographic or clinical characteristics, study designs, inclusion/exclusion criteria, and geographic or regional healthcare systems. Conventional statistical approaches for accounting for within-study and between-study HTE have primarily relied on within-trial subgroup analysis and meta-analysis. However, these approaches are limited because they are based on restrictive distributional assumptions, which may only be tenable in some clinical trials. Methods: This dissertation investigates relevant methodologies for characterizing and accommodating treatment effects within- and between-study heterogeneity in stroke trials. The specific objectives of this dissertation are to: 1) assess the credibility of subgroup analyses reported in published stroke trials; 2) investigate the comparative performance of methods for subgroup identification in clinical trials with binary endpoints when there is no a priori knowledge of patients’ characteristics associated with HTE, and 3) examine the performance of random-effects models when synthesizing evidence from trials with different study design characteristics. This study uses a combination of knowledge synthesis methodology and computer simulations to address these objectives. For objective 1, we conducted a systematic review to examine the credibility of reported subgroups in stroke trials. We used the Instrument for Assessing the Credibility of Effect Modification Analyses (ICEMAN) checklist to evaluate the quality of the subgroup analyses conducted for each study. For Objectives 2 and 3, computer simulations were used to examine the comparative performance of subgroup identification methods for identifying relevant variables/biomarkers associated with HTE in clinical trials of binary endpoints and meta-analytic methods for synthesizing treatment effects obtained from explanatory and pragmatic trials, respectively. Results: The systematic review of reporting quality of subgroup analyses in stroke trials revealed that the credibility of reported subgroup analyses is poor, with most studies not providing a priori rationale for the type and number of subgroup analyses conducted. Among all the subgroup identification methods investigated, the model-based recursive partitioning (MOB) method had the best control of Type I and higher statistical power to detect HTE. The random-effects model based on t-distribution (robustRE) and the mixture random-effects model (mixRE) are more appropriate for meta-analysis data with substantial HTE. However, the conventional random-effects model (RE model) remains reliable for estimating pooled treatment effects in data with moderate HTE. Conclusion: Understanding and capturing treatment effect heterogeneity is critical for generating evidence about treatment effectiveness in clinical trials. More statistical methods that account for heterogeneity in the study population and design characteristics are recommended to analyze and synthesize evidence from clinical trials.
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    Systematic review of economic evaluations investigating education, exercise, and dietary weight management to manage hip and knee osteoarthritis: protocol
    (2020-10-06) Mazzei, Darren R; Ademola, Ayoola; Abbott, J. H; Sajobi, Tolulpe; Hildebrand, Kevin; Marshall, Deborah A
    Abstract Background International guidelines recommend education, exercise, and dietary weight management as core treatments to manage osteoarthritis (OA) regardless of disease severity or co-morbidity. Evidence supports the clinical effectiveness of OA management programs, but the cost-effectiveness of core treatments remains unclear. We will systematically review, synthesize, and assess the literature in economic evaluations of core treatments (education, exercise, and dietary weight management) for the management of hip and/or knee OA. Methods We will search the following elecftronic databases (from inception onwards): MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), National Health Services Economic Evaluation Database, and EconLit. Economic evaluations alongside randomized or nonrandomized clinical trials investigating OA education, exercise, and dietary weight management interventions will be included. Title, abstract, and full text of relevant publications will be screened independently by two reviewers. A content matter expert will resolve any conflicts between two reviewers. Key information from relevant papers will be extracted and tabulated to provide an overview of the published literature. Methodological quality will be evaluated using the Consensus on Health Economic Criteria list. A narrative synthesis without meta-analysis will be conducted. Subgroup analysis will attempt to find trends between research methods, intervention characteristics, and results. Discussion The findings of this review will evaluate the breadth and quality of economic evaluations conducted alongside clinical trials for core treatments in OA management. Systematic review registration PROSPERO CRD42020155964