Wilson, Matthew G;
(2024)
Digital Clinically-Integrated Trials for
Comparative Effectiveness Research
in Learning Health Systems.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Evidence-based medicine has become the accepted model for clinical decision making in healthcare systems, driven by the use of Randomised Controlled Trials. However, despite being effective at discerning treatment efficacy, classical trial designs do not represent the optimal mechanism for conducting pragmatic investigations of treatments used in the routine delivery of clinical care. As a result, clinicians continue to act without guiding evidence, resulting in variation in the treatment patients receive, which may influence outcomes. Whether associated with a positive or negative outcome, this variation remains unobserved, unstudied and unlearned from. New approaches for integrating Comparative Effectiveness Research into everyday clinical practice have been proposed, and Learning Health Systems offer a framework to connect the key elements of data collection, knowledge generation and clinician feedback. This thesis investigates the feasibility of a research pipeline for the conduct of digital clinically-integrated randomised trials for routine treatment comparative effectiveness research. Specifically, whether electronic point-of-care randomisation prompts, delivered through an existing electronic health record system may allow clinicians to randomise treatment where they have clinical equipoise. A retrospective, observational, electronic health record cohort study was conducted to investigate the boundaries of existing variation in practice for routine magnesium supplementation in a mixed critical care population. Multilevel modelling was used to predict magnesium supplementation, estimating the amount of variation attributable to the individual clinician to be 13%. Clinician preferences for magnesium supplementation were then used in a natural experiment to estimate the association between supplementation and risk of developing atrial fibrillation. A 3% relative risk reduction in atrial fibrillation was observed amongst patients managed by a clinician with a liberal approach to magnesium supplementation. Boundaries in existing variation identified in the observational study were then used to define testable treatment arms for a prospective, randomised, mixed methods feasibility study. The PROSPECTOR-critical care study was conducted between February and November 2022. The study aimed to evaluate overall feasibility of the concept, but also directly compare two designs of electronic point-of-care randomisation prompt. 23 patients were recruited to the study, of which 11 were randomised to receive either nudge or preference prompt design, and either liberal or restrictive magnesium supplementation strategy. In a parallel qualitative study, 21 clinicians undertook semi-structured interviews exploring the study concepts, intervention design and to map the current clinical workflow for magnesium supplementation. The study demonstrated that whilst recruitment under a standard, pre-emptive consent model was challenging, patients found the study principles and research question acceptable. The technical design and implementation of the electronic randomisation prompts were both successful within the proscribed limits of the electronic health record system used, however key elements required for integrating the prompts into a clinical workflow were not achieved. Clinician concordance with randomisation was 61% for the nudge design and 86% in the preference design arm, giving an overall concordance rate of 68%. However, the small sample numbers for each treatment arm means these results should be interpreted with caution. Additionally, accompanying qualitative data suggest that the prompts were not sufficiently integrated within the clinical workflow. Overall, this thesis advances the development of modern Learning Health Systems by investigating new methods for integrating research conduct into clinical practice using existing electronic health record systems. Further work will focus on three areas: 1) investigating the acceptability of alternative consent approaches to patients and the public to address issues with recruitment encountered in the feasibility study, 2) optimisation of the study design including randomisation prompts and alternative methods such as cluster randomisation per clinician, and 3) “closing the loop” by returning knowledge derived from the study to clinicians to improve future patient care.
Type: | Thesis (Doctoral) |
---|---|
Qualification: | Ph.D |
Title: | Digital Clinically-Integrated Trials for Comparative Effectiveness Research in Learning Health Systems |
Language: | English |
Additional information: | Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
Keywords: | Clinically integrated trials, digital trials, electronic health record systems, nudge randomisation |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology |
URI: | https://discovery.ucl.ac.uk/id/eprint/10189219 |
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