Nick Bansback

Background: Pregnancy hypertension is a common, potentially fatal condition. New guidance recommends ‘tight’ control of pregnancy hypertension over ‘less-tight’ control. However, guidance also suggests that treatment recommendations consider patient preferences. This dissertation aims to understand how to support patients and providers to make preference-congruent and informed decisions about pregnancy hypertension management.Methods: First, a mixed-methods study, including a best-worst scaling task, of patient preferences for pregnancy hypertension management was conducted. Next, a systematic review built upon ancillary findings by assessing emotion in patient decision aids (PtDAs) for decisions during pregnancy. Using results from the preferences study, the subsequent study re-analyzed the Control of Hypertension in Pregnancy Study (CHIPS) trial using a patient-oriented composite endpoint. A PtDA was developed and assessed for quality and effectiveness. Lastly, a preliminary study explored emotion-regulation in patient decision-making.Results: The mixed-methods preference study (n=210) found that individuals prioritised seven outcomes when choosing how to manage pregnancy hypertension. Latent class analysis identified three preference profiles (a profile comprises participants with similar preferences). Each profile placed different importance on each outcome: 1) ‘equal prioritisers’ valued the outcomes equally; 2) ‘early delivery avoiders’ prioritised avoiding delivery before 34 weeks; and 3) ‘medication minimisers’ prioritised avoiding medication. A systematic review of 39 PtDAs found that most did not address emotion. Reanalysis of the CHIPS trial using a weighted patient-oriented composite endpoint found that while both strategies yielded equal outcomes for equal prioritisers; ‘tight’ control produced better outcomes for early delivery avoiders; and ‘less-tight’ control produced better outcomes for medication minimisers. A prototype PtDA that incorporated these profiles was assessed (n=99) as very acceptable and clear, and significantly improved knowledge. The preliminary emotion study (n=107) found that individuals’ beliefs about their own ability to regulate emotions may limit the benefit of a PtDA. Conclusions: Patient preferences for management of pregnancy hypertension can be broadly described by three profiles. ‘Tight control’ is well-suited to only two of these profiles, emphasizing the importance of shared decision-making in reaching treatment decisions. A PtDA for pregnancy hypertension may help patients make more informed decisions. Future work should explore how to include emotion in PtDAs.

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Since 2008, efavirenz+tenofovir+emtricitabine (EFV+TDF+XTC) has been the preferred first-line antiretroviral therapy (ART) regimen for treating HIV throughout most countries. With an expanding choice of ART, should a newer treatment be preferred? The therapeutic landscape was assessed for efficacy, safety and tolerability through a systematic literature review (SLR) and network meta-analysis (NMA). Data were analyzed using aggregate data (AgD) from publications for each population of interest. Ninety eligible trials were identified in the principal SLR and 65 were included in analyses. There was high certainty that dolutegravir (DTG) was superior to EFV with respect to viral suppression, change in CD4 cell counts, discontinuation, and adverse events. DTG and EFV were comparable among TB-HIV co-infected patients. Among pregnant women initiating DTG, there appeared to be fewer adverse events than with EFV. To determine whether the inclusion of individual patient data (IPD) would impact decision-making and to explore the impact of integrating IPD in varying ways, the SLR and NMA were expanded through the addition of IPD obtained for three critical trials: SINGLE, FLAMINGO and SPRING-2. Use of IPD did not alter the conclusions. In the few cases where IPD-based analyses were selected, the impact on estimates did not meaningfully impact their utility towards the development of clinical guidelines. A simulation study was conducted to determine how network size, density, proportion of IPD, and nature of effect-modification could predict impact of IPD on NMA results. The inclusion of IPD may be most impactful among small and/or sparse networks of evidence. Having a higher proportion of treatment comparisons with IPD also improves the NMA estimates, particularly among larger networks of evidences. Similarly, these simulations suggested while inclusion of IPD led to improvements with respect to both bias and precision of estimates, these improvements decreased within larger and more dense networks – such as those used in the HIV analyses. In conclusion, the findings support the use of DTG+TDF+XTC as the preferred first-line regimen, supporting the change in HIV guidelines by the World Health Organization in late 2018. The analyses provide important insights into the types of networks where IPD would influence results of NMA.

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Whole Disease Models (WDMs) are decision analytic models characterized by their ability to reflect the policy changes that occur at multiple points within the entire clinical trajectory of a given disease. They differ from conventional ‘piecewise’ modeling approaches in their ability to reflect processes that occur ‘upstream’ and ‘downstream’ from a technology decision of interest. This dissertation describes the development of a WDM of oral cancer, and its application in generating evidence to inform Health Technology Management (HTM).The dissertation reviews the available scientific literature concerning health economic decision analytic modeling in oral cancer, and argues that a Whole Disease Model approach is appropriate for economic evaluation in this disease. A conventional piecewise Markov model is used to evaluate the cost-effectiveness of risk-guided management of oral premalignancy, and the limitations of that approach are discussed. The dissertation then describes the development and validation of the Whole Disease Model of Oral Cancer (WDMOC). The WDMOC is used to re-evaluate the risk-guided management policy, and how the cost-effectiveness of such a policy is influenced by upstream (tobacco/alcohol cessation, improved screening) and downstream (improved surgical treatment for early-stage disease, improved systemic therapy for late-stage disease) policy changes, including the hypothetical effect of a population HPV vaccination program. The WDMOC found that risk-guided management was cost saving compared to current standard practice, but was not expected to produce gains in quality-adjusted life years (QALYs). The cost-effectiveness of a risk-guided management approach was affected by upstream factors that influence malignant progression and downstream factors that prolonged survival among advanced cancers. Scenario analysis was used to estimate the impact of multiple simultaneous policy changes on the cost-effectiveness of a risk-guided approach. The WDMOC contributes a useful platform for economic evaluation that can inform HTM. Results of the analysis suggest that a risk-guided approach is cost-effective, particularly among patients with regular access to a dentist that regularly performs oral cancer screenings and in the presence of improved options for managing late-stage disease. The WDMOC was developed using an open source approach so that it can readily incorporate new information and have users in multiple policy jurisdictions.

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Background: Supporting shared decision-making (SDM) between patients and providers is a key health care objective. SDM-interventions can help encourage SDM but may require investment. This thesis used a case study of treatment decision-making for advanced osteoarthritis to quantify the economic value of SDM-interventions in health care. Methods: A trial-based cost-effectiveness analysis and a longer-term cost analysis using administrative data was undertaken to estimate the value of a SDM-intervention in adults considering total joint arthroplasty. Limitations of conventional cost-effectiveness analysis in assessing the consequences of SDM-interventions were outlined, and methods for valuing the process of SDM presented. A systematic review of discrete choice experiments (DCEs) that have valued the process of SDM was undertaken. A two-step chained valuation technique which included a DCE was completed to estimate the health state utility value of the process of SDM.Results: The trial-based cost-effectiveness and administrative data analyses suggested that SDM-interventions for total joint arthroplasty provided value, resulting in lower costs at two and seven-years follow-up and similar quality-adjusted life-years (QALYs) over the two-year trial period. QALYs may fail to capture the consequences of SDM-interventions, such as the value of being informed and involved in decision-making. To reflect the opportunity cost of allocating scarce resources toward these non-health benefits, Canadian guidelines suggest that their value be ascertained through the trade-off with health outcomes using societal preferences. The systematic review found 25 studies that have valued SDM using a DCE. No studies valued SDM in advanced osteoarthritis, and most did not include a health outcome attribute or elicit societal preferences. Analysis of the data from the DCE completed by nearly 1,500 Canadians aged 60 and older revealed that respondents were willing to sacrifice health outcomes for greater SDM and estimated the value of SDM.Conclusions: Evidence suggests that SDM-interventions for adults with advanced osteoarthritis are a cost-effective use of resources. Results from the trial-based cost-effectiveness analysis, systematic review, and DCE suggest that policy-makers may be justified in allocating scarce resources toward SDM-interventions at the expense of other interventions that provide health benefits. Future research is required to quantify the value of SDM-interventions in other contexts.

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Background: Shared decision-making (SDM) has been suggested as a means to improve communication between patients and their healthcare providers, with the purposes of improving multiple asthma-related health outcomes. Despite mounting evidence that suggests potential benefits attributable to SDM, clinical uptake has been slow. Objectives: The purpose of this dissertation is to ascertain the role of SDM in asthma management, to determine the extent to which SDM is currently being implemented into regular asthma care, and to suggest clinical implementation strategies that may facilitate SDM implementation in BC.Methods: This project consists of a) a systematic review of physician attitudes toward SDM, b) a comprehensive narrative literature review to describe the proposed role of SDM in asthma, c) a population level analysis to explore variation in adherence to controller medication, as well as d) an online survey of 117 adult asthma patients living in BC. Results: Results of this work show that in general a) physicians support the use of SDM in various clinical practice scenarios, b) there is a clear role for SDM in treating asthma patients with the goal of reducing the burden of controller medication non-adherence, and c) adherence to controller medications is sub-optimal, with little variation being explained at the population level. The patient survey (d) provided additional insight into this research agenda by showing that while patients prefer to be actively involved in treatment decision-making, there is substantial variation in the extent to which asthma patients are being engaged in their care. Furthermore, multiple predictors of adherence that can be addressed during the clinical encounter (e.g. medication-related concerns) were shown to impact self-reported treatment adherence. Conclusions: The results of this project provide further support for the use of SDM in regular care of asthma patients. I conclude by highlighting the importance of addressing issues related to adherence in an individual and ongoing basis, the value of increasing awareness about the use of SDM, and the potentially valuable role of engaging non-physician caregivers in future SDM implementation efforts. These findings may guide future research investigations regarding SDM uptake and efforts to reduce the disease burden of asthma.

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