Larry Lynd


Relevant Degree Programs


Great Supervisor Week Mentions

Each year graduate students are encouraged to give kudos to their supervisors through social media and our website as part of #GreatSupervisorWeek. Below are students who mentioned this supervisor since the initiative was started in 2017.


#GreatSupervisor Week @UBC: Can't forget @ldlynd, also know as "Uncle Larry." Term of endearment for a great supervisor and @CORE_UBC director.

Nicole Tsao (2017)


Graduate Student Supervision

Doctoral Student Supervision (Jan 2008 - Nov 2020)
Safety of perinatal biologic use in autoimmune diseases: population-based studies of maternal and infant outcomes (2018)

Objectives: To examine biologic use before or during pregnancy among women with autoimmune inflammatory disease by: 1) Describing the patterns of use, discontinuation, and 10-year secular trends; 2) Evaluating the association between biologic exposure before or during pregnancy and adverse maternal and infant outcomes including: preterm deliveries, small-for-gestational-age (SGA) births, congenital anomalies, and serious infections; and 3) Reviewing existing literature and meta-analyzing my findings with published results. Methods: Using provincial population-based administrative health data linked with the perinatal registry and prescription dispensations database, a cohort of women with autoimmune inflammatory disease who had at least one pregnancy during 2002-2012 was identified. Descriptive statistics, multivariable modeling, and high-dimensional propensity score (HDPS) methods were used to describe the patterns of perinatal biologic prescriptions and assess associations with outcomes of interest. Results were meta-analyzed with findings from existing literature.Findings: 1) Perinatal biologic use has increased significantly over 10 years, comprising 5.7% of all pregnancies in this population by 2012. Most often women discontinued their biologic in the first (31%), or second (38%) trimesters, while 98% of those on treatment during the second trimester continued through to delivery. Only disease type was associated with discontinuation. 2) After applying HDPS matching, there were no associations observed between biologic use before or during pregnancy and risk of preterm deliveries (OR 1.13, 95% CI 0.67 to 1.90); SGA (OR 0.91, 95% CI 0.46 to 1.78); or congenital anomalies (OR 1.06, 95% CI 0.46 to 2.47). The theoretical concern of serious infections due to immunomodulatory effects of biologics was not observed. 3) Meta-analysis of unadjusted risk estimates showed significantly increased risks of congenital anomalies, preterm deliveries, and low birth weight babies associated with biologic exposure. However, pooled adjusted risk estimates showed no significant associations. Conclusions: Using novel methods to address potential confounding and pooling existing evidence, the findings from this thesis demonstrated that treatment with biologics before or during pregnancy are not associated with a number of important perinatal outcomes. These findings help patients and clinicians weigh risks and benefits of treatment options in pregnancy, and support difficult decision making around using biologics in a vulnerable population.

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A population-based cohort study evaluating the association between inhaled corticosteroid use and statin use with lung cancer risk in chronic obstructive pulmonary disease patients (2017)

Background: Lung cancer incidence is elevated in patients with chronic obstructive pulmonary disease (COPD), often due to smoking, but potentially also resulting from inflammation. COPD patients are also often diagnosed with comorbidities, the most prominent being cardiovascular disease (CVD). Statins, due to the increased prevalence of CVD, and inhaled corticosteroids (ICS), are two commonly prescribed medications for COPD patients that may reduce lung cancer risk.Objective: To evaluate the association between lung cancer risk with ICS and statin use inCOPD patients. A priori, the hypothesis of this study was that use of these medications would be associated with a reduction in lung cancer risk.Methods: This study used population-based data for the province of British Columbia to identify a cohort COPD patients. To be included, patients were to have filled three prescriptions for COPD-related medications within a twelve-month period. To evaluate the association between statin and ICS use with lung cancer risk, an array of methods of defining medication exposure were used, including a novel recency-weighed approach.Results: In the analysis evaluating the association between ICS use and lung cancer diagnosis, time-dependent ICS exposure was associated with a 30% reduction in lung cancer risk. The recency-weighted duration of use exposure metric also demonstrated a protective effect from ICS exposure (HR: 0.74 (95% CI: 0.66-0.82). This protective effect was consistent over all exposure metrics. Evaluation of the association between statin use and lung cancer risk produced less consistent results. However, the best-fitting model which incorporated the recency-weighted duration of use exposure metric indicated a protective effect from statin exposure (HR: 0.85 (95% CI: 0.77-0.93). Statin exposure in patients 65 or over was protective against lung cancer diagnosis consistently for all exposure metrics. An interaction term between ICS and statin use was also explored, but was not found to be statistically significant.Conclusions: These results suggest that the benefits of ICS and statin use might extend beyond their primary indication. The results also underscore the importance of using appropriate methods for measuring medication exposure in observational studies, particularly those using administrative data. Finally, this work highlights the importance of ‘real-world’ evidence.

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The value of weekly short message service interventions targeting medication adherence: A multi-national economic evaluation in HIV and tuberculosis infection (2017)

Introduction: The World Health Organization has ambitious goals to eliminate AIDS and TB globally. However, the plan is expensive and financial commitment to achieve this goal is uncertain. Mobile phone-based short message service (SMS) interventions have demonstrated the ability to improve HIV drug therapy adherence. My objective was to evaluate the cost-effectiveness of SMS-based adherence interventions in three settings, which have unique epidemics and health systems, yet struggle with similar adherence barriers. In this thesis, I also consider the value of conducting a cost-effectiveness evaluation before, during and after a randomized trial.Method: This thesis has three parts. First, I evaluated the cost-effectiveness of SMS-based HIV drug adherence interventions in Kenya, where the interventions were first developed. Second, I evaluated the burden of non-adherence and cost sensitivity of SMS-based adherence interventions for latent tuberculosis infection (LTBI) drug therapy in British Columbia, where a trial of an SMS-based adherence intervention is underway. Finally, I evaluated 5,836 combinations of 15 HIV interventions, to understand the role of SMS interventions as part of a combination HIV intervention in India where a trial was being planned. Value was expressed in terms of incremental cost-effectiveness ratios (ICERs), which were a function of incremental costs and quality-adjusted life years (QALYs).Results: In Kenya, the SMS interventions were highly cost-effective in the base case (ICER=$1,389/QALY), and remained cost-effective across most sensitivity analyses. In British Columbia, hypothetical interventions that brought the population to full adherence to LTBI drug therapy could cost up to $450 per person per year and remain cost-effective. SMS interventions were least sensitive to cost and would likely be cost-effective if their efficacy were confirmed. Finally, in India, the SMS interventions were cost saving and were part of 4 of the 5 most efficient combination interventions out of 5,836 possible combinations.Conclusion: The SMS interventions are cost-effective or cost saving when compared to the standard of care in multiple settings. Findings support the implementation of SMS interventions as part of HIV and TB care and suggest they could play an essential role in global containment of these diseases.

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Longitudinal Studies of Disease Progression, Health Care Costs and Health-Related Quality of Life in Patients with Asthma (2016)

This thesis examines the burden of asthma and its determinants though a series of longitudinal observational studies. Objectives: 1) To quantify the natural history of severe asthma and the impact of early risk factors; 2) To examine the influence of socioeconomic status (SES) on excess direct medical costs of moderate-to-severe asthma and guideline-based asthma care; 3) To estimate excess costs of asthma and the economic implications of comorbidities; 4) To assess the joint influences of asthma control and comorbidity on health-related quality of life. Methods: For the first three objectives, administrative health data (for the period of 1997-2013) were obtained from British Columbia (BC) Ministry of Health, and for the last objective data were obtained from the Economic Burden of Asthma (EBA) study in BC. Various models for longitudinal data were applied for each objective. Findings: 1) Most patients (83%) with incident severe asthma transitioned to milder states after 10 years. Low SES and comorbidity at disease onset led to worse long-term prognosis. 2) Across both individual- and neighborhood-levels, there was evidence that low-SES asthma patients and/or their care providers did not follow guideline-based asthma care and subsequently incurred substantially greater excess costs of asthma. 3) Excess costs in patients with asthma were $1187/year (95%CI $1130─$1243) overall, with comorbidity-attributable costs five times higher than asthma-attributable costs, all of which greatly increased with age. 4) Changes in asthma control had a greater effect on disease-specific (AQ5D) than generic (EQ5D) utilities, whereas changes in comorbidity burden had a larger impact on EQ5D than AQ5D utilities. Conclusions: With several novel methodology techniques, this thesis provided evidence for the first-time on the long-term trajectory and burden of asthma. Projection of cost and effectiveness of decisions and policies in asthma care requires a robust understanding of the natural history of asthma, effect of risk factors on this trajectory, and estimates of costs and health-related quality of life associated with asthma. This thesis provides new evidence on all such parameters. These findings have direct relevance to estimating cost-effectiveness of health technologies in asthma and can result in more informed decision-making in health policy and clinical practice.

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Master's Student Supervision (2010 - 2018)
Assessment of atrial fibrillation patients' education needs (2018)

Introduction: Education facilitates construction of a correct illness representation, corrects beliefs about medications and improves patients’ illness-treatment coherence. There is no consensus on the best education strategy for atrial fibrillation (AF) patients. Identifying patients’ education needs is the first step towards development of an effective education program.Purpose: The overall aim of this thesis was to provide insights into AF patients’ education needs from patient and clinician viewpoints, and to inform the design of AF patient education programs and initiatives.Methods: The current evidence on AF patients’ knowledge gaps was summarized through a literature review. This was followed by a qualitative descriptive study utilizing semi-structured interviews with patients and clinicians who were recruited through purposive sampling. All interviews were conducted by a Master of science student. The interviews were conducted in English, in a private room or over the phone, without the presence of any non-participants. Each interview lasted approximately 30 minutes and was audio-recorded. Verbatim transcripts were generated within three days of the interview. The reporting of this qualitative study conforms to the Standards for Reporting Qualitative Research (SQRQ) and the Consolidated Criteria for Reporting Qualitative Research (COREQ).Analysis: The analysis of the data was iterative, occurring as interviews proceeded. The interview guides were revised frequently based on the emerging data. The data collected were analyzed through inductive qualitative thematic analysis. Data from patients and clinicians were analyzed independently.Results: Eleven clinicians and ten patients were interviewed. Clinician and patient interviews led to emergence of three and four themes, respectively. This research went beyond identification of knowledge gaps by offering a rich description on patients’ misconceptions, information seeking behavior, education style preferences, attitudes towards online education, expectations of an education program, emotional education needs, preferences for risk communication, and clinicians’ views on the topic. A key finding of my study was the identification of patients’ emotional education needs: the need for education that addresses patients’ concerns and relieves their anxiety. Summarizing my study findings, I offered a set of recommendations that can be used by those involved in educating AF patients.

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Validation of a diabetes model: a process to select and assess the validity of an existing model for economic evaluation of type 2 diabetes in British Columbia (2017)

The growing burden of chronic disease like Type 2 Diabetes Mellitus (T2DM) raises concern about the sustainability of Canada’s health system. Consequently, greater emphasis is being placed on economic evaluation using computer simulation models to enhance decision making in health care. This research was initiated to assess if model output for a cost-effectiveness analysis (CEA) in T2DM would be generalizable to a diverse BC population.The thesis outline is as follows:• Chapter 1 overviews the epidemiology, risk factors and complications of T2DM, the role of model based economic evaluation and knowledge gaps used to guide the thesis objectives.• Chapter 2 assesses the methods of existing T2DM models and utilizes criteria to select a model for validation.• Chapter 3 describes an internal validation of a T2DM model by comparing the expected versus actual impact of changes to input parameters on output.• Chapter 4 describes an external validation comparing the predicted rate of vascular events to the observed rate by gender, age and ethnic sub-cohorts from a BC population based on the coefficient of determination (R²) and a 95% confidence interval (CI). • Chapter 5 summarizes the results, discusses limitations, and highlights future research to enhance the credibility of T2DM models.Results: The Ontario Diabetes Economic Model (ODEM) was selected and an internal validation demonstrated the simulated rate of vascular events responded as expected to changes in baseline variables in a 10 year simulation. The external validation in cohorts with no history of complications had a modest positive correlation (R² = 0.68) and a tendency to over predict vascular events in older adults. Adding individuals with previous events improved the correlation (R² > 0.99) and statistical accuracy of the ODEM. A higher correlation was observed in those of younger age, male gender (R² = 0.71) and SA ethnicity (R² = 0.77). Conclusion:The ODEM was demonstrated to be a functional model with output considered generalizable for the economic evaluation of a diverse BC T2DM population. There were trends in model to overestimate complications in cohorts with no previous vascular events and those of older age that require further research to validate.

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Evaluating the implementation of the emergency, triage, assessment and treatment plus admission care intervention in Rwanda (2015)

Background: Emergency, Triage, Assessment and Treatment plus Admission care (ETAT+) intervention – a locally adapted pediatric advanced life support program – introduced in Rwanda in 2010 to facilitate the achievement of the fourth Millennium Development Goal. The current thesis was undertaken as part of a larger program of research that aims to evaluate the ETAT+ implementation in Rwanda. Methods: Data were gathered during a cross-sectional study in 8 district hospitals across Rwanda; an audit in these hospitals was undertaken to establish a baseline description of the availability of essential resources and process of care related to the leading causes of under-five mortality in Rwanda. To determine changes in participating healthcare providers’ knowledge and practical skills (n=374) between pre- and post ETAT+ implementation, a one group pre-posttest design was used. Paired t-test was used to assess the effect of ETAT+ training on knowledge improvement; and, linear and logistic regression models were fitted to examine factors associated with healthcare providers’ performance on ETAT+ knowledge and skills assessments in Rwanda. Results: Baseline assessment reveals some deficiencies in processes of care (i.e. assessment, treatment and follow-up care), poor organization of some hospital services (e.g., triage), and poor uptake of current pediatric clinical practice guidelines (e.g., dehydration). Post ETAT+, participants’ knowledge scores improved on average by 22.8% (95% CI 20.5, 25.1). Compared to participants who identified as proficient in French, those who identified as proficient in both English and French had on average a higher improvement in knowledge (least square mean=6.64; 95% CI 3.79, 9.49) and were more likely to pass the practical skills assessment (adjusted odds ratio=2.58; 95% CI 1.28, 5.48).Conclusions: The audit of medical records reveals gaps in the process of pediatric care; and these gaps were found to be consistent with knowledge gaps among healthcare providers, as assessed through the ETAT+ pre-assessment. Improvements in post-ETAT+ performance were significant and a number of factors (e.g., language barriers) were identified as important influences on ETAT+ training outcomes. These factors need to be taken in account when implementing ETAT+ and other continuing medical education interventions within the Rwandan context.

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An evaluation of Canadians' values and attitudes towards expensive drugs for rare diseases (2014)

Background: Expensive drugs for rare diseases pose a great challenge for decision-makers involved in determining their funding status due to their extremely high treatment costs, the small patient populations, the uncertainty of evidence for treatment effectiveness and a moral obligation to provide treatment where there is no alternative. The decision to fund a medication is traditionally and primarily guided by two factors: the drug’s cost and its effectiveness. This efficiency-based method is useful in guiding funding decisions for common medications, however is insufficient for rare diseases as they are unlikely to meet current cost-effectiveness thresholds, and moreover does not consider values associated with rarity including disease severity, unmet need and equity. Decision-makers are using values to determine rare disease funding status; however, it is unknown whether these decisions reflect societal priorities. Should society value rarity, this may provide decision-makers with the justification for the funding of expensive drugs which serve a disproportionately small population. Objectives: Identify the public values on health technologies, and the criteria society feels are most important for guiding priority-setting for health technology assessment and drug-reimbursement; Determine the relative importance of rarity; Determine whether society values rarity and accepts the opportunity costs associated with funding high-cost medications. Methods: We conducted an online survey of 2211 Canadians where multiple methodologies including simple ranking with an analytic hierarchy process, measures of attitudes towards equity statements, and trade-off questions were employed. Results: The values most important to Canadians for drug-reimbursement prioritization are drug safety, effect on quality and quantity of life, and certainty of efficacy. Factors related to rare diseases such as severity and equity are important factors to Canadians; however, rarity alone was of relatively low importance for the priority-setting of orphan drug treatment. Although society was not found to be willing to accept the opportunity cost for funding a rare disease if it is at the cost of a common condition, they prefer funding of a rare disease over a non-health benefit. Equity and equal access to drug treatments are important factors to Canadians, though rarity alone is not justification for prioritizing a drug treatment for funding.

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Physician and patient preferences for stroke prophylaxis in atrial fibrillation (2014)

Purpose. To derive and compare relative preferences of physicians and patients for selecting oral antithrombotics in atrial fibrillation (AF). Methods. Elicitation task: Time trade-off (TTO) and best worst scaling (BWS) choice experiments were constructed from literature review and expert opinion, reflecting four attributes relevant to oral antithrombotic selection in the setting of stroke prevention in AF – frequency of laboratory monitoring, annual risk of stroke, annual risk of major bleed, availability of reversal agent. Analysis. Utilities based on the patient TTO data were derived and analyzed for subgroup differences. Relative utilities based on the BWS choice data were derived using the conditional logit model and latent class analysis. The Wilcoxon signed-rank test was performed to assess the difference in preference for each attribute level between the Best-Worst score for the two groups. Results. 33 physicians and 58 patients completed the choice experiment. Both groups favoured “annual stroke risk of 0%” as the most valued attribute-level, and “annual stroke risk of 10%” was the least favourable attribute-level. Significant preference differences between the two perspectives for several of the attribute levels were also found. The results points out that while both groups had strong positive preferences for “annual stroke 0%”, the physicians valued this attribute level to be much more desirable than the patients. Similar observation applies to “annual stroke 10%”, where physicians had much stronger negative preferences for the attribute level compared to the patients as well as the range of annual bleeding rates, suggesting that physicians in general, were more stroke and bleed averse than the patients. Conclusions. There is a general congruence in physician and patient preferences for stroke prophylaxis, however, the strength of preferences differ for several attributes differ between the two groups. Using a BWS choice experiment, a preference elicitation method based on the random utility theory, this is the first study that quantitatively evaluated the preferences of physicians and patients for stroke prophylaxis in atrial fibrillation and provides important insights into clinical decision-making in a patient-centered care model.

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Deriving health utility weights for infants with respiratory syncytial virus (RSV) (2013)

Background: RSV infects the majority of infants under one year, and is a leading cause of bronchiolitis-related hospitalization, incurring significant cost on the health care system. Economic evaluation guidelines require the use of quality-adjusted life years (QALYs) – a single measure of health outcome that incorporates both quality of life and length of life; however, there is no established standard for eliciting health utilities in children. Measuring utility in infant RSV presents significant methodological challenges related to proxy response, perspective of the elicitation task, and the temporary nature of the health condition combined with potential long-term outcomes. Objectives: The objectives of this thesis were to: 1) review the methodological literature surrounding infant utility derivation using a proxy respondent and in temporary health states; 2) derive the health utility for different severities of Respiratory Syncytial Virus (RSV) infection; and 3) determine relative preferences of health state attributes for RSV in infants.Methods: Using results from a literature review and qualitative study, time trade-off (TTO) and best-worst scaling (BWS) experiments were constructed reflecting four RSV severity levels, using two perspectives – child and adult. Administered online, respondents randomly received either a questionnaire from either the adult or child perspective, completing both TTO and BWS tasks, allowing elicitation and comparison of both health state utilities and relative preferences for health state attributes from two perspectives Results: Respondents were willing to trade off more time to avoid more severe health states, indicating greater disutility associated with severe RSV, and suggests respondents understood the task. Responses differed between the adult and child perspectives, with disutilities from the child perspective being slightly greater. BWS revealed that respondents most often chose breathing failure as the worst attribute and 0% risk of wheeze as the best from both perspectives.Conclusion: Responses differ between adult and child perspectives. This is the first study known to explore utilities for RSV in infants, and can be utilized for the further utility research and economic evaluation of any current or potential treatment for RSV, or other temporary health states in infants.

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Risk-benefit tradeoffs for NSAIDs for the management of rheumatoid arthritis (RA)- a discrete choice experiment (DCE) (2011)

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are drugs that are used to reduce pain and inflammation in those with rheumatoid arthritis (RA). There are two types of NSAID drugs available for treating those with RA, nonselective NSAIDs and coxibs. Rofecoxib, is a coxib that was taken off the market due to evidence of an increased risk of cardiovascular events from the use of this drug relative to placebo. However, there are those who benefited from this drug and were willing to take the risk. ObjectiveThe primary objective of this study is to use a DCE to quantify the risk preferences of those with RA, i.e., how much potential risk they are willing to accept in order to gain a specified potential benefit. It is hypothesized that given greater potential benefit, those with RA will be willing to accept greater risk of AEs, in particular myocardial infarction and stroke, than what they are currently exposed to in their NSAIDs.MethodologyThe DCE requires the creation of a questionnaire-based survey that was administered online to a sample of RA patients. Discrete choice experimentation allows the elicitation of patients’ preference for different treatment attributes through paired choice scenarios where respondents are required to choose between treatment options based on the risks of adverse events and benefits associated with each treatment.ConclusionsFor those with RA, the benefits outweigh the risks. In particular, given greater chance of benefit with improvement in pain and function, RA patients are willing to accept a greater risk of ulcers, dyspepsia, myocardial infarction, and stroke than what is present in current and past NSAIDs. Increased knowledge of the risk preferences of those with RA may aid decision-makers in better-informed drug approval and withdrawal decisions, thereby preventing patients from losing access to potentially beneficial drugs.

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Outcomes evaluation in knee arthroplasty for the treatment of osteoarthritis (2010)

Objectives: The primary objective was to evaluate differences in outcome between unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) with respect to total WOMAC and OKS scores. In order to properly evaluate outcomes following both UKA and TKA valid and responsive instruments are needed. Therefore the second objective was to assess the construct validity and responsiveness of the SF-6D and the WOMAC derived HUI3 in patients undergoing either UKA or TKA. Lastly, the third objective was to evaluate any differences in the effect of socioeconomic status in outcomes following UKA compared to TKA.Methods: A retrospective analysis was conducted to evaluate outcomes following knee arthroplasty on data collected between July 2000 and December 2008 on all patients requiring either UKA or TKA. Patients completed the WOMAC, OKS and SF-12 preoperatively and then subsequently at 3 and 6 months post-surgery. The Pearson correlation coefficient and intraclass correlation coefficient (ICC) were used to measure the correlation between the OKS, WOMAC, SF-6D and HUI3. Responsiveness was evaluated using a distribution based evaluation and an anchor-based method. A three level hierarchical linear model was used to model the total WOMAC scores and OKS as a function of group (UKA or TKA) and time. A similar model was used to investigate whether differences in total WOMAC or OKS between UKA and TKA occur across socioeconomic groups.Results: The WOMAC derived HUI3 and SF-6D appear to be valid measures of HRQL in this patient sample. The SF-6D was not as responsive as the HUI3 but demonstrated a good ability to identify patients who had improved. There were no significant differences in HRQL between UKA and TKA and socioeconomic status did not have a significant effect on HRQL following knee arthroplasty.Conclusions: Both the HUI3 and SF-6D appeared to be valid and responsive measures in this patient sample. However, further study looking at the interchangeability of the WOMAC derived HUI3 with the HUI3 itself is needed. No differences in HRQL between UKA and TKA were noted and there were no differences in outcome between UKA and TKA across SES groups.

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News Releases

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