Cost-Effectiveness of Using a Molecular Diagnostic Test to Improve Preoperative Diagnosis of Thyroid Cancer

AbstractObjectiveFine-needle aspiration biopsy (FNAB) is a safe and inexpensive diagnostic procedure for evaluating thyroid nodules.Up to 25% of the results from an FNAB, however, may not be diagnostic or may be indeterminate, leading to a subsequent diagnostic thyroid surgery. A new molecularly based diagnostic test could potentially reduce indeterminate cytological results and, with high accuracy, provide a definitive diagnosis for cancer in thyroid nodules. The aim of the study was to estimate the cost-effectiveness of utilizing a molecular diagnostic (DX) test as an adjunct to FNAB, compared with NoDX, to improve the preoperative diagnosis of thyroid nodules.MethodsWe constructed a patient-level simulation model to estimate the clinical and economic outcomes of using a DX test compared with current practice (NoDX) for the diagnosis of thyroid nodules. By using a cost-effectiveness framework, we measured incremental clinical benefits in terms of quality-adjusted life-years and incremental costs over a 10-year time horizon.ResultsAssuming 95% sensitivity and specificity of the Dx test when used as an adjunct to FNAB, the utilization of the DX test resulted in a gain of 0.046 quality-adjusted life-years (95% confidence interval 0.019–0.078) and a saving of $1087 (95$691–$1533) in direct costs per patient. If the cost of the Dx test is less than$1087 per test, we expect to save quality-adjusted life-years and reduce costs when it is utilized. Sensitivity of the DX test, compared with specificity, had a larger influence on the overall outcomes

Future Impact of Various Interventions on the Burden of COPD in Canada: A Dynamic Population Model

Background: Chronic obstructive pulmonary disease (COPD) is a growing economic burden worldwide. Smoking cessation is thought to be the single most effective way of reducing the economic burden of COPD. The impact of other strategies such as interventions that predict risk of disease, reduce progression of disease, or reduce exacerbations has not been systematically studied. Objectives: We estimated the economic and clinical burden of COPD over the next 25 years in Canada and the impact of three potential interventions (screening test for predisposition to COPD, new drugs to avoid progression into more severe disease stages, and predictive test for exacerbations) on COPD burden. Methods Using a dynamic simulation model, we projected the total burden of COPD (cost, morbidity, and mortality) from 2011 to 2035 using the population of Canada as a case study. The model stratified population based on sex, age, smoking status, respiratory symptoms, and their COPD stage. The cost and quality adjusted life years (QALYs) associated with each intervention were estimated. Results: The model indicates that annual societal cost of COPD is $4.52 billion (B) Canadian dollars in 2011 and will reach$3.61B ($7.33B undiscounted) per year in 2035. Over the next 25 years, COPD will be responsible for approximately$101.4B in societal costs ($147.5B undiscounted) and 12.9 million QALYs lost (19.0 million undiscounted). Our results suggested that the best strategy to reduce the financial burden of COPD is by reducing exacerbations. Smoking cessation, while it is the cornerstone of COPD prevention, has only a modest effect in attenuating the financial burden of COPD over the next 25 years in Western countries such as Canada. Conclusion: Our data suggest that any intervention that can reduce the number of exacerbations has a substantial impact on morbidity and costs of COPD and should be considered in conjunction with the ongoing efforts to reduce smoking rates

Comparison of Benefit-Risk Assessment Methods for Prospective Monitoring of Newly Marketed Drugs: A Simulation Study

AbstractObjectivesTo compare benefit-risk assessment (BRA) methods for determining whether and when sufficient evidence exists to indicate that one drug is favorable over another in prospective monitoring.MethodsWe simulated prospective monitoring of a new drug (A) versus an alternative drug (B) with respect to two beneficial and three harmful outcomes. We generated data for 1000 iterations of six scenarios and applied four BRA metrics: number needed to treat and number needed to harm (NNT|NNH), incremental net benefit (INB) with maximum acceptable risk, INB with relative-value–adjusted life-years, and INB with quality-adjusted life-years. We determined the proportion of iterations in which the 99% confidence interval for each metric included and excluded the null and we calculated mean time to alerting.ResultsWith no true difference in any outcome between drugs A and B, the proportion of iterations including the null was lowest for INB with relative-value–adjusted life-years (64%) and highest for INB with quality-adjusted life-years (76%). When drug A was more effective and the drugs were equally safe, all metrics indicated net favorability of A in more than 70% of the iterations. When drug A was safer than drug B, NNT|NNH had the highest proportion of iterations indicating net favorability of drug A (65%). Mean time to alerting was similar among methods across the six scenarios.ConclusionsBRA metrics can be useful for identifying net favorability when applied to prospective monitoring of a new drug versus an alternative drug. INB-based approaches similarly outperform unweighted NNT|NNH approaches. Time to alerting was similar across approaches

Using the Incremental Net Benefit Framework for Quantitative Benefit–Risk Analysis in Regulatory Decision-Making—A Case Study of Alosetron in Irritable Bowel Syndrome

AbstractObjectiveThere is consensus that a more transparent, explicit, and rigorous approach to benefit–risk evaluation is required. The objective of this study is to evaluate the incremental net benefit (INB) framework for undertaking quantitative benefit–risk assessment by performing a quantitative benefit–risk analysis of alosetron for the treatment of irritable bowel syndrome from the patients’ perspective.MethodsA discrete event simulation model was developed to determine the INB of alosetron relative to placebo, calculated as “relative value-adjusted life-years (RVALYs).”ResultsIn the base case analysis, alosetron resulted in a mean INB of 34.1 RVALYs per 1000 patients treated relative to placebo over 52 weeks of treatment. Incorporating parameter uncertainty into the model, probabilistic sensitivity analysis revealed a mean INB of 30.4 (95% confidence interval 15.9–45.4) RVALYs per 1000 patients treated relative to placebo over 52 weeks of treatment. Overall, there was >99% chance that both the incremental benefit and incremental risk associated with alosetron are greater than placebo. As hypothesized, the INB of alosetron was greatest in patients with the worst quality of life experienced at baseline. The mean INB associated with alosetron in patients with mild, moderate, and severe symptoms at baseline was 17.97 (−0.55 to 36.23), 29.98 (17.05–43.37), and 35.98 (23.49–48.77) RVALYs per 1000 patients treated, respectively.ConclusionsThis study demonstrates the potential utility of applying the INB framework to real-life decision-making, and the ability to use simulation modeling incorporating outcomes data from different sources as a benefit–risk decision aid

Parents and adolescents preferences for asthma control: a best-worst scaling choice experiment using an orthogonal main effects design

Background: The preferences of parents and children with asthma influence their ability to manage a child’s asthma and achieve good control. Potential differences between parents and adolescents with respect to specific parameters of asthma control are not considered in clinical asthma guidelines. The objective was to measure and compare the preferences of parents and adolescents with asthma with regard to asthma control parameters using best worst scaling (BWS). Methods: Fifty-two parents of children with asthma and 44 adolescents with asthma participated in a BWS study to quantify preferences regarding night-time symptoms, wheezing/chest tightening, changes in asthma medications, emergency visits and physical activity limitations. Conditional logit regression was used to determine each group’s utility for each level of each asthma control parameter. Results: Parents displayed the strongest positive preference for the absence of night-time symptoms (β = 2.09, p < 0.00001) and the strongest negative preference for 10 emergency room visits per year (β = −2.15, p < 0.00001). Adolescents displayed the strongest positive preference for the absence of physical activity limitations (β = 2.17, p < 0.00001) and the strongest negative preference for ten physical activity limitations per month (β = −1.97). Both groups were least concerned with changes to medications. Conclusion: Parents and adolescents placed different weights on the importance of asthma control parameters and each group displayed unique preferences. Understanding the relative importance placed on each parameter by parents and adolescents is essential for designing effective patient-focused disease management plans. Electronic supplementary material The online version of this article (doi:10.1186/s12890-015-0141-9) contains supplementary material, which is available to authorized users

Integration of genomics into clinical care : methods for economic evaluation

Background: As genomic technologies become more affordable, the demand for having these data will increase. Decision-makers must anticipate the increasing influence of genomics on heath care systems and take into account the expectations of patients, the public, health care providers, and industry in this regard. This thesis demonstrates applications of several methods for evaluation of genomic technologies in medicine. Using four case studies, I have highlighted the advantages that each method can offer given the nature and scope of the research question in each case study. Objectives: My specific objectives in the case studies were: 1) To elicit the preferences of cancer patients as well as the public for a hypothetical, genetically-guided treatment for cancer (a discrete choice experiment ); 2) To estimate the relative importance of attributes which influence physicians’ decisions for using personalized medicine in their practice (a Best Worst Scaling choice experiment); 3) To evaluate the impact of three potential genomic/proteomic tests on the long term burden of COPD in Canada (a system dynamics model); 4) To measure the cost-effectiveness of adding a new molecular diagnostic test (DX) to the current diagnostic strategy for thyroid cancer (using a discrete event simulation). Methods: Through these case studies, I have demonstrated the particular advantages of using discrete choice experiment (DCE), best-worst scaling (BWS) experiment, system dynamics simulation, and discrete event simulation (DES) for evaluations of genomic technologies. Results: Using four case studies I exemplified the questions that emerge in the process of integrating genomics into clinical care. In addition to bridging the methodological gaps by incorporating several novel methods (BWS, dynamic systems, and DES), the selected case studies illustrated the practical issues regarding the integration of genomics into clinical care from the perspective of patients, the public, health care providers, and decisionmakers. Conclusion: Although the methods previously developed for health technology assessment can be applied to the evaluation of genomic technologies as well, methodological challenges in the evaluation of genomic applications entail utilizing more diverse and more sophisticated analytical tools.Pharmaceutical Sciences, Faculty ofGraduat

Increasing incidence associated with herpes zoster infection in British Columbia, Canada

Background: Recent studies have shown an increasing incidence of herpes zoster (HZ) infection, which may be related to the introduction of varicella vaccination programs in children. We examined the epidemiology and treatment costs of HZ and post-herpetic neuralgia (PHN) over time in British Columbia, Canada. Methods The cohort consisted of all cases with HZ infection from January 1, 1997 and December 31, 2012. Incident zoster was defined as a case (ICD-9 053 or ICD-10 B02) without a previous episode of HZ or PHN in the previous 12 months. We determined the incidence for HZ and PHN and the age-sex standardized rate for the overall population. We determined the association between the varicella vaccination program and increased HZ rates by evaluating the rate ratios in the publicly-funded varicella vaccine period compared to the non-publicly funded period in a regression model. We evaluated the hospitalization rates, treatment by GPs and their associated yearly costs for HZ and PHN. Results HZ incidence increased for the entire study period from 3.2 per 1000 population in 1997 to 4.5 in 2012. HZ rates were higher for females than males and all age groups had an increased incidence rate, except the 0–9 year olds, where the rate decreased. Crude and age-sex standardized incidence rates of PHN demonstrated very similar patterns to HZ incidence. Based on the regression model, rates of HZ were higher in the older individuals. No significant increase with HZ incidence was seen during the publically funded varicella vaccination program compared to the non-publicly funded period. From 1997 to 2012, the annual HZ-related costs associated with hospitalizations and GP visits were over $CDN4.9 million and$CDN537,286, respectively; treatment costs for hospitalizations have increased significantly over time. Majority of PHN-related cases are managed by GPs, with a steady increase over time in number of cases and associated annual costs. Conclusions The incidence of zoster and PHN is increasing with time, particularly in the elderly population and the risk is greater in the over 65 year olds. Treatment costs for both HZ and PHN represent a significant burden on the Canadian healthcare system.Medicine, Faculty ofNon UBCInfectious Diseases, Division ofMedicine, Department ofReviewedFacult