Browsing by Author "Tomlinson, George"

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    A Novel Semi-Automated Approach for Trial Identification and Evaluation of the Certainty of Evidence from Network Meta-Analyses
    (2024-09-09) Kamso, Mohammed Mujaab; Hazlewood, Glen; Deardon, Rob; Sajobi, Tolulope; Tomlinson, George
    This thesis introduces an innovative approach for the rapid identification of randomized controlled trials (RCTs) and evaluation of the certainty of evidence within the context of a living systematic review and network meta-analysis. The first paper (Chapter 4) describes a living systematic review methodology that incorporates crowd-sourcing, machine learning and a web-based tool to streamline the identification and classification of RCTs, introducing a novel "studification" process to enhance review maintenance. The second paper (Chapter 5) presents a semi-automated method for evaluating the certainty of evidence derived from direct estimates within a Bayesian network meta-analysis framework, adhering to GRADE guidance. The study also addresses the assessment of indirectness at the study-specific level using online tools. The final paper (Chapter 6) extends this methodology to assess the certainty of evidence for indirect and mixed evidence separately. This is achieved through a semi-automated process that utilizes the concept of the contribution matrix to identify the first-order loop, highlighting the primary contributors to indirect estimate. Additionally, in accordance with GRADE recommendations, an automated approach for evaluating imprecision is developed. Overall, this thesis may enhance the efficiency of maintaining a living systematic review, offering a novel approach to semi-automate the evaluation of evidence certainty from Bayesian network meta-analysis models while adhering to GRADE guidelines. Applied to the context of early rheumatoid arthritis, the findings potentially have positive policy implications such as how fast reviews can be done for clinical practice guideline development.
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    A phase II randomized controlled trial of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy
    (2019-01-03) Alibhai, Shabbir M H; Santa Mina, Daniel; Ritvo, Paul; Tomlinson, George; Sabiston, Catherine; Krahn, Murray; Durbano, Sara; Matthew, Andrew; Warde, Padraig; O’Neill, Meagan; Timilshina, Narhari; Segal, Roanne; Culos-Reed, Nicole
    Abstract Background Existing evidence demonstrates that 1:1 personal training (PT) improves many adverse effects of androgen deprivation therapy (ADT). Whether less resource-intensive exercise delivery models are as effective remains to be established. We determined the feasibility of conducting a multi-center non-inferiority randomized controlled trial comparing PT with supervised group (GROUP) and home-based (HOME) exercise programs, and obtained preliminary efficacy estimates for GROUP and HOME compared to PT on quality of life (QOL) and physical fitness. Methods Men with prostate cancer on ADT were recruited from one of two experienced Canadian centres and randomized 1:1:1 to PT, GROUP, or HOME. Randomization was stratified by length of ADT use and site. Participants completed moderate intensity aerobic and resistance exercises 4–5 days per week for 6 months with a target 150 min per week of exercise. Exercise prescriptions were individualized and progressed throughout the trial. Feasibility endpoints included recruitment, retention, adherence, and participant satisfaction. The efficacy endpoints QOL, fatigue, and fitness (VO2 peak, grip strength, and timed chair stands) in GROUP and HOME were compared for non-inferiority to PT. Descriptive analyses were used for feasibility endpoints. Between-group differences for efficacy endpoints were examined using Bayesian linear mixed effects models. Results Fifty-nine participants (mean age 69.9 years) were enrolled. The recruitment rate was 25.4% and recruitment was slower than projected. Retention was 71.2%. Exercise adherence as measured through attendance was high for supervised sessions but under 50% by self-report and accelerometry. Satisfaction was high and there was no difference in this measure between all three groups. Between-group differences (comparing both GROUP and HOME to PT) were smaller than the minimum clinically important difference on most measures of QOL, fatigue, and fitness. However, two of six outcomes for GROUP and four of six outcomes for HOME had a > 20% probability of being inferior for GROUP. Conclusions Feasibility endpoints were generally met. Both GROUP and HOME interventions in men with PC on ADT appeared to be similar to PT for multiple efficacy outcomes, although conclusions are limited by a small sample size and cost considerations have not been incorporated. Efforts need to be targeted to improving recruitment and adherence. A larger trial is warranted. Trial registration ClinicalTrials.gov: NCT02046837 . Date of registration: January 20, 2014.
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    Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial
    (2024-05-22) Khan, James S.; Gilron, Ian; Devereaux, P. J.; Clarke, Hance; Ayach, Nour; Tomlinson, George; Quan, May L.; Ladha, Karim S.; Choi, Stephen; Munro, Allana; Brull, Richard; Lim, David W.; Avramescu, Sinziana; Richebé, Philippe; Hodgson, Nicole; Paul, James; McIsaac, Daniel I.; Derzi, Simone; Zbitnew, Geoff L.; Easson, Alexandra M.; Siddiqui, Naveed T.; Miles, Sarah J.; Karkouti, Keyvan
    Abstract Background Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. Methods PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1–3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. Discussion This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. Trial registration This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).
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    Protocol for a phase III RCT and economic analysis of two exercise delivery methods in men with PC on ADT
    (2018-10-23) Alibhai, Shabbir M H; Ritvo, Paul; Santa Mina, Daniel; Sabiston, Catherine; Krahn, Murray; Tomlinson, George; Matthew, Andrew; Lukka, Himu; Warde, Padraig; Durbano, Sara; O’Neill, Meagan; Culos-Reed, S. N
    Abstract Background Androgen deprivation therapy (ADT) is commonly used to treat prostate cancer. However, side effects of ADT often lead to reduced quality of life and physical function. Existing evidence demonstrates that exercise can ameliorate multiple treatment-related side effects for men on ADT, yet adherence rates are often low. The method of exercise delivery (e.g., supervised group in-centre vs. individual home-based) may be important from clinical and economic perspectives; however, few studies have compared different delivery models. Additionally, long-term exercise adherence and an understanding of predictors of adherence are critical to achieving sustained benefits, but such data are lacking. The primary aim of this multi-centre phase III non-inferiority randomized controlled trial is to determine whether a home-based delivery model is non-inferior to a group-based delivery model in terms of benefits in fatigue and fitness in this population. Two other key aims include examining cost-effectiveness and long-term adherence. Methods Men diagnosed with prostate cancer of any stage, starting or continuing on ADT for at least 6 months, fluent in English, and living close to a study centre are eligible. Participants complete five assessments over 12 months (baseline and every 3 months during the 6-month intervention and 6-month follow-up phases), including a fitness assessment and self-report questionnaires. Biological outcomes are collected at baseline, 6, and 12 months. A total of 200 participants will be randomized in a 1:1 fashion to supervised group training or home-based training supported by smartphones, health coaches, and Fitbit technology. Participants are asked to complete 4 to 5 exercise sessions per week, incorporating aerobic, resistance and flexibility training. Outcomes include fatigue, quality of life, fitness measures, body composition, biological outcomes, and program adherence. Cost information will be obtained using patient diary-based self-report and utilities via the EQ-5D. Discussion To disseminate publicly funded exercise programs widely, clinical efficacy and cost-effectiveness have to be demonstrated. The goals of this trial are to provide these data along with an increased understanding of adherence to exercise among men with prostate cancer receiving ADT. Trial registration The trial has been registered at clinicaltrials.gov (Registration # NCT02834416 ). Registration date was June 2, 2016.