Browsing by Author "Thabane, Lehana"

Now showing 1 - 8 of 8
  • Thumbnail Image
    ItemOpen Access
    A comparison of meta-analytic methods for synthesizing evidence from explanatory and pragmatic trials
    (2018-01-25) Sajobi, Tolulope T; Li, Guowei; Awosoga, Oluwagbohunmi; Wang, Meng; Menon, Bijoy K; Hill, Michael D; Thabane, Lehana
    Abstract Background The pragmatic–explanatory continuum indicator summary version 2 (PRECIS-2) tool has recently been developed to classify randomized clinical trials (RCTs) as pragmatic or explanatory based on their design characteristics. Given that treatment effects in explanatory trials may be greater than those obtained in pragmatic trials, conventional meta-analytic approaches may not accurately account for the heterogeneity among the studies and may result in biased treatment effect estimates. This study investigates if the incorporation of PRECIS-2 classification of published trials can improve the estimation of overall intervention effects in meta-analysis. Methods Using data from 31 published trials of intervention aimed at reducing obesity in children, we evaluated the utility of incorporating PRECIS-2 ratings of published trials into meta-analysis of intervention effects in clinical trials. Specifically, we compared random-effects meta-analysis, stratified meta-analysis, random-effects meta-regression, and mixture random-effects meta-regression methods for estimating overall pooled intervention effects. Results Our analyses revealed that mixture meta-regression models that incorporate PRECIS-2 classification as covariate resulted in a larger pooled effect size (ES) estimate (ES = − 1.01, 95%CI = [− 1.52, − 0.43]) than conventional random-effects meta-analysis (ES = − 0.15, 95%CI = [− 0.23, − 0.08]). Conclusions In addition to the original intent of PRECIS-2 tool of aiding researchers in their choice of trial design, PRECIS-2 tool is useful for explaining between study variations in systematic review and meta-analysis of published trials. We recommend that researchers adopt mixture meta-regression methods when synthesizing evidence from explanatory and pragmatic trials.
  • Thumbnail Image
    ItemOpen Access
    Effectiveness of a community program for older adults with type 2 diabetes and multimorbidity: a pragmatic randomized controlled trial
    (2020-05-13) Miklavcic, John J; Fraser, Kimberly D; Ploeg, Jenny; Markle-Reid, Maureen; Fisher, Kathryn; Gafni, Amiram; Griffith, Lauren E; Hirst, Sandra; Sadowski, Cheryl A; Thabane, Lehana; Triscott, Jean A C; Upshur, Ross
    Abstract Background Type II diabetes mellitus (T2DM) affects upwards of 25% of Canadian older adults and is associated with high comorbidity and burden. Studies show that lifestyle factors and self-management are associated with improved health outcomes, but many studies lack rigour or exclude older adults, particularly those with multimorbidity. More evidence is needed on the effectiveness of community-based self-management programs in older adults with T2DM and multimorbidity. The study purpose is to evaluate the effect of a community-based intervention versus usual care on physical functioning, mental health, depressive symptoms, anxiety, self-efficacy, self-management, and healthcare costs in older adults with T2DM and 2 or more comorbidities. Methods Community-living older adults with T2DM and two or more chronic conditions were recruited from three Primary Care Networks (PCNs) in Alberta, Canada. Participants were randomly allocated to the intervention or control group in this pragmatic randomized controlled trial comparing the intervention to usual care. The intervention involved up to three in-home visits, a monthly group wellness program, monthly case conferencing, and care coordination. The primary outcome was physical functioning. Secondary outcomes included mental functioning, anxiety, depressive symptoms, self-efficacy, self-management, and the cost of healthcare service use. Intention-to-treat analysis was performed using ANCOVA modeling. Results Of 132 enrolled participants (70-Intervention, 62-Control), 42% were 75 years or older, 55% were female, and over 75% had at least six chronic conditions (in addition to T2DM). No significant group differences were seen for the baseline to six-month change in physical functioning (mean difference: -0.74; 95% CI: − 3.22, 1.74; p-value: 0.56), mental functioning (mean difference: 1.24; 95% CI: − 1.12, 3.60; p-value: 0.30), or other secondary outcomes.. Conclusion No significant group differences were seen for the primary outcome, physical functioning (PCS). Program implementation, baseline differences between study arms and chronic disease management services that are part of usual care may have contributed to the modest study results. Fruitful areas for future research include capturing clinical outcome measures and exploring the impact of varying the type and intensity of key intervention components such as exercise and diet. Trial registration NCT02158741 Date of registration: June 9, 2014.
  • Thumbnail Image
    ItemOpen Access
    Erratum to: Pediatric intensive care stress ulcer prevention (PIC-UP): a protocol for a pilot randomized trial
    (2017-08-18) Duffett, Mark; Choong, Karen; Foster, Jennifer; Gilfoyle, Elaine; Lacroix, Jacques; Pai, Nikhil; Thabane, Lehana; Cook, Deborah J
  • Thumbnail Image
    ItemOpen Access
    Pediatric intensive care stress ulcer prevention (PIC-UP): a protocol for a pilot randomized trial
    (2017-05-19) Duffett, Mark; Choong, Karen; Foster, Jennifer; Gilfoyle, Elaine; Lacroix, Jacques; Pai, Nikhil; Thabane, Lehana; Cook, Deborah J
    Abstract Background Despite sparse pediatric data on effectiveness, the majority of critically ill children receive medications to prevent gastrointestinal (GI) bleeding. Stress ulcer prophylaxis may have unintended consequences—increasing the risk of nosocomial infections—which may be more serious and common than the bleeding which these drugs are prescribed to prevent. Randomized controlled trials (RCTs) in pediatric critical care are exceptionally challenging to complete, thus a rigorous pilot RCT is crucial. The objective of this pilot RCT is to assess the feasibility of a large multicentre RCT of stress ulcer prophylaxis with pantoprazole to prevent upper GI bleeding vs. placebo. Methods A multi-centre blinded pilot RCT of 120 children in six Canadian PICUs. Children expected to require mechanical ventilation for more than 48 h will be randomized to receive intravenous pantoprazole 1 mg/kg or identical placebo once daily until they no longer need mechanical ventilation. We have four feasibility outcomes and will consider the trial successful if we achieve: 1. Effective screening: If >80% of eligible patients are approached for consent. 2. Timely enrollment: if >80% of participants receive their first dose of the assigned study drug within 1 day of becoming eligible. 3. Participant accrual: If the average monthly enrolment is two or more participants per centre per month. 4. Protocol adherence: if >90% of doses are administered according to the protocol. Discussion There are many uncertainties about the risks and benefits of stress ulcer prophylaxis. In an era of widespread use—where clinicians prescribe prophylaxis to the more severely ill—a large, rigorous RCT is required. A trial to determine if a strategy of withholding stress ulcer prophylaxis is not inferior to a strategy of routine stress ulcer prophylaxis will be challenging. A carefully designed and implemented pilot trial is essential. Trial registration ClinicalTrials.gov: NCT02929563 (Registered October 3, 2016).
  • Thumbnail Image
    ItemEmbargo
    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.
  • Thumbnail Image
    ItemOpen Access
    The ACHRU-CPP versus usual care for older adults with type-2 diabetes and multiple chronic conditions and their family caregivers: study protocol for a randomized controlled trial
    (2017-02-06) Markle-Reid, Maureen; Ploeg, Jenny; Fraser, Kimberly D; Fisher, Kathryn A; Akhtar-Danesh, Noori; Bartholomew, Amy; Gafni, Amiram; Gruneir, Andrea; Hirst, Sandra P; Kaasalainen, Sharon; Stradiotto, Caralyn K; Miklavcic, John; Rojas-Fernandez, Carlos; Sadowski, Cheryl A; Thabane, Lehana; Triscott, Jean A C; Upshur, Ross
    Abstract Background Many community-based self-management programs have been developed for older adults with type-2 diabetes mellitus (T2DM), bolstered by evidence from randomized controlled trials (RCTs) that T2DM can be prevented and managed through lifestyle modifications. However, the evidence for their effectiveness is contradictory and weakened by reliance on single-group designs and/or small samples. Additionally, older adults with multiple chronic conditions (MCC) are often excluded because of recruiting and retention challenges. This paper presents a protocol for a two-armed, multisite, pragmatic, mixed-methods RCT examining the effectiveness and implementation of the Aging, Community and Health Research Unit-Community Partnership Program (ACHRU-CPP), a new 6-month interprofessional, nurse-led program to promote self-management in older adults (aged 65 years or older) with T2DM and MCC and support their caregivers (including family and friends). Methods/design The study will enroll 160 participants in two Canadian provinces, Ontario and Alberta. Participants will be randomly assigned to the control (usual care) or program study arm. The program will be delivered by registered nurses (RNs) and registered dietitians (RDs) from participating diabetes education centers (Ontario) or primary care networks (Alberta) and program coordinators from partnering community-based organizations. The 6-month program includes three in-home visits, monthly group sessions, monthly team meetings for providers, and nurse-led care coordination. The primary outcome is the change in physical functioning as measured by the Physical Component Summary (PCS-12) score from the short form-12v2 health survey (SF-12). Secondary client outcomes include changes in mental functioning, depressive symptoms, anxiety, and self-efficacy. Caregiver outcomes include health-related quality of life and depressive symptoms. The study includes a comparison of health care service costs for the intervention and control groups, and a subgroup analysis to determine which clients benefit the most from the program. Descriptive and qualitative data will be collected to examine implementation of the program and effects on interprofessional/team collaboration. Discussion This study will provide evidence of the effectiveness of a community-based self-management program for a complex target population. By studying both implementation and effectiveness, we hope to improve the uptake of the program within the existing community-based structures, and reduce the research-to-practice gap. Trial registration ClinicalTrials.gov, Identifier: NCT02158741 . Registered on 3 June 2014.
  • Thumbnail Image
    ItemOpen Access
    The CANadian Pediatric Weight management Registry (CANPWR): lessons learned from developing and initiating a national, multi-centre study embedded in pediatric clinical practice
    (2018-07-19) Morrison, Katherine M; Ball, Geoff D C; Ho, Josephine; Mackie, Pam; Buchholz, Annick; Chanoine, Jean-Pierre; Hamilton, Jill; Laberge, Anne-Marie; Legault, Laurent; Thabane, Lehana; Tremblay, Mark; Zenlea, Ian
    Abstract Background There is increasing recognition of the value of “real-world evidence” in evaluating health care services. Registry-based, observational studies conducted in clinical settings represent a relevant model to achieve this directive. Starting in 2010, we undertook a longitudinal, observational study (the CANadian Pediatric Weight management Registry [CANPWR]), which is embedded in 10 multidisciplinary, pediatric weight management clinics across Canada. The objective of this paper was to share the lessons our team learned from this multi-centre project. Methods Data sources included a retrospective review of minutes from 120 teleconferences with research staff and investigators, notes taken during clinical site visits made by project leaders, information from quality control processes to ensure data accuracy and completeness, and a study-specific survey that was sent to all sites to solicit feedback from research team members (n = 9). Through an iterative process, the writing group identified key themes that surfaced during review of these information sources and final lessons learned were developed. Results Several key lessons emerged from our research, including the (1) value of pilot studies and central research coordination, (2) need for effective and regular communication, (3) importance of consensus on determining outcome measures, (4) challenge of embedding research within clinical practice, and (5) difficulty in recruiting and retaining participants. The sites were, in spite of these challenges, enthusiastic about the benefits of participating in multi-centre collaborative studies. Conclusion Despite some challenges, multi-centre observational studies embedded in pediatric weight management clinics are feasible and can contribute important, practical insights into the effectiveness of health services for managing pediatric obesity in real-world settings.
  • Thumbnail Image
    ItemOpen Access
    Vital sign monitoring with continuous pulse oximetry and wireless clinical notification after surgery (the VIGILANCE pilot study)—a randomized controlled pilot trial
    (2019-02-26) Paul, James E; Chong, Matthew A; Buckley, Norman; Harsha, Prathiba; Shanthanna, Harsha; Tidy, Antonella; Buckley, Diane; Clarke, Anne; Young, Christopher; Wong, Timothy; Vanniyasingam, Thuvaraha; Thabane, Lehana
    Abstract Background Respiratory depression is a serious perioperative complication associated with morbidity and mortality. Recently, technology has become available to wirelessly monitor patients on regular surgical wards with continuous pulse oximetry and wireless clinician notification with alarms. When a patient’s SpO2 falls below a set threshold, the clinician is notified via a pager and may intervene earlier to prevent further clinical deterioration. To date, the technology has not been evaluated with a randomized controlled trial (RCT). Methods We designed a parallel-group unblinded pilot RCT of a wireless monitoring system on two surgical wards in an academic teaching hospital. Postsurgical patients with an anticipated length of stay of at least 1 day were included and randomized to standard care or standard care plus wireless respiratory monitoring for up to a 72-h period. The primary outcomes were feasibility outcomes: average patients recruited per week and tolerability of the system by patients. Secondary outcomes included (1) respiratory events (naloxone administration for respiratory depression, ICU transfers, and cardiac arrest team activation) and (2) system alarm types and details. The analysis of the outcomes was based on descriptive statistics and estimates reported using point (95% confidence intervals). Criteria for success of feasibility were recruitment of an average of 15 patients/week and 90% of the patients tolerating the system. Results The pilot trial enrolled 250 of the 335 patients screened for eligibility, with 126 and 124 patients entering the standard monitoring and wireless groups, respectively. Baseline demographics were similar between groups, except for slightly more women in the wireless group. Average patient recruitment per week was 14 95% CI [12, 16] patients. The wireless monitoring was quite tolerable with 86.6% (95% CI 78.2–92.7%) of patients completing the full course, and there were no other adverse events directly attributable to the monitoring. With regard to secondary outcomes, the respiratory event rate was low with only 1 event in the wireless group and none in the control group. The average number of alarms per week was 4.0 (95% CI, 1.6–6.4). Conclusions This pilot study demonstrated adequate patient recruitment and high tolerability of the wireless monitoring system. A full RCT that is powered to detect patient important outcomes such as respiratory depression is now underway. Trial registration ClinicalTrials.gov, Registration number NCT02907255 , registered 7 September 2016—retrospectively registered.