CAR T-cell Therapy for Diffuse Large B-cell Lymphoma in Canada: A Cost-Utility Analysis.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is a novel cell therapy for treating non-Hodgkin lymphoma. The development of CAR T-cell therapy has transformed oncology treatment by offering a potential cure. However, due to the high cost of these therapies, and the large number of eligible patients, decision makers are faced with difficult funding decisions. Our objective was to assess the cost-effectiveness of tisagenlecleucel for adults with relapsed/refractory diffuse large B-cell lymphoma in Canada using updated survival data from the recent JULIET trial. METHODS: We developed an individual-simulated discrete event simulation model to assess the costs and quality-adjusted life-years (QALY) of tisagenlecleucel compared with salvage chemotherapy. Survival estimates were obtained from a published clinical trial and retrospective analysis. If patients remained progression free for 5 y, they were assumed to be in long-term remission. Costing and utility data were obtained from reports and published sources. A Canadian health care payer perspective was used, and outcomes were modeled over a lifetime horizon. Costs and outcomes were discounted at 1.5% annually, with costs reported in 2021 Canadian dollars. A probabilistic analysis was used, and model parameters were varied in 1-way sensitivity analyses and scenario analyses. RESULTS: After we incorporated the latest clinical evidence, tisagenlecleucel led to an additional cost of $503,417 and additional effectiveness of 2.48 QALYs, with an incremental cost-effectiveness ratio of $202,991 compared with salvage chemotherapy. At a willingness-to-pay threshold of $100,000/QALY, tisagenlecleucel had a 0% likelihood of being cost-effective. CONCLUSIONS: At the current drug price, tisagenlecleucel was not found to be a cost-effective option. These results heavily depend on assumptions regarding long-term survival and the price of CAR T. Real-world evidence is needed to reduce uncertainty. HIGHLIGHTS: For patients with diffuse large B-cell lymphoma who failed 2 or more lines of systemic therapy, CAR T was not found to be a cost-effective treatment option at a willingness-to-pay threshold of $100,000.These results heavily depend on the expected long-term survival. The uncertainty in the model may be improved using real-world evidence reported in the future.

Pharmacotherapy vs surgery as initial therapy for patients with moderate-to-severe benign prostate hyperplasia: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of using a surgery, such as transurethral resection of the prostate (TURP) or photoselective vaporisation of the prostate using greenlight laser (GL-PVP), as initial treatment for men with moderate-to-severe benign prostate hyperplasia (BPH) compared to the standard practice of using pharmacotherapy as initial treatment followed by surgery if symptoms do not resolve. PATIENTS AND METHODS: We compared a combination of eight strategies involving upfront pharmacotherapy (i.e., α-blocker, 5α-reductase inhibitor, or combination) followed by surgery (e.g. TURP or GL-PVP) upon failure vs TURP or GL-PVP as initial treatment, for a target population of men with moderate-to-severe BPH symptoms, with a mean age of 65 years and no contraindications for treatment. A microsimulation decision-analytic model was developed to project the costs and quality-adjusted life years (QALYs) of the target population over the lifetime. The model was populated and validated using published literature. Incremental cost-effectiveness ratios (ICERs) were determined. Cost-effectiveness was evaluated using a public payer perspective, a lifetime horizon, a discount rate of 1.5%, and a cost-effectiveness threshold of $50 000 (Canadian dollars)/QALY. Sensitivity and probabilistic analyses were performed. RESULTS: All options involving an upfront pharmacotherapy followed by TURP for those who fail were economically unattractive compared to strategies involving a GL-PVP for those who fail, and compared to using either BPH surgery as initial treatment. Overall, upfront TURP was the most costly and effective option, followed closely by upfront GL-PVP. On average, upfront TURP costs $1015 more and resulted in a small gain of 0.03 QALYs compared to upfront GL-PVP, translating to an incremental cost per QALY gained of $29 066. Results were robust to probabilistic analysis. CONCLUSIONS: Surgery is cost-effective as initial therapy for BPH. However, the health and economic evidence should be considered concurrently with patient preferences and risk attitudes towards different therapy options.

Economic evaluation of smoking cessation in Ontario's regional cancer programs.

Quitting smoking after a diagnosis of cancer results in greater response to treatment and decreased risk of disease recurrence and second primary cancers. The objective of this study was to evaluate the potential cost-effectiveness of two smoking cessation approaches: the current basic smoking cessation program consisting of screening for tobacco use, advice, and referral; and a best practice smoking cessation program that includes the current basic program with the addition of pharmacological therapy, counseling, and follow-up. A Markov model was constructed that followed 65-year-old smokers with cancer over a lifetime horizon. Transition probabilities and mortality estimates were obtained from the published literature. Costs were obtained from standard costing sources in Ontario and reports. Probabilistic and deterministic sensitivity analyses were conducted to address parameter uncertainties. For smokers with cancer, the best practice smoking cessation program was more effective and more costly than the basic smoking cessation program. The incremental cost-effectiveness ratio of the best practice smoking cessation program compared to the basic smoking cessation program was $3367 per QALY gained and $5050 per LY gained for males, and $2050 per QALY gained and $4100 per LY gained for females. Results were most sensitive to the hazard ratio of mortality for former and current smokers, the probability of quitting smoking through participation in the program and smoking-attributable costs. The study results suggested that a best practice smoking cessation program could be a cost-effective option. These findings can support and guide implementation of smoking cessation programs.

Cost analysis of Greenlight photoselective vaporization of the prostate compared to transurethral resection of the prostate for benign prostatic hyperplasia.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a non-cancerous enlargement of the prostate gland, which results in the development of lower urinary tract symptoms that can interfere with a patient's daily activities and negatively impact their quality of life. The gold standard treatment for moderate to severe BPH has been transurethral resection of the prostate (TURP), however, this procedure is associated with prolonged hospitalizations and increased complications. An alternative to TURP is Greenlight photoselective vaporization of the prostate (PVP), which is associated with better perioperative safety. The objectives of the research were to 1) assess the cost of Greenlight PVP compared to TURP and bipolar TURP; and 2) assess the predictors of total cost. METHODS: We conducted a descriptive costing study from the hospital perspective. We evaluated perioperative costs of patients who underwent each procedure from 2013-2015 at a tertiary academic medical centre. A multiple linear regression was performed to identify predictors of total cost. The variables included in regression analysis were patient age, type of procedure, Charlson Comorbidity Index, and distance to clinic. RESULTS: A total of 202 patients received one of the three procedures over the study period. The total cost of Greenlight PVP was $3836 per patient compared to $4963 for TURP and $4978 for bipolar TURP. The linear regression showed that the Charlson Comorbidity Index and type of procedure were independent predictors of total cost. CONCLUSIONS: The procedure costs and readmission rates are lower for Greenlight PVP compared to TURP and bipolar TURP, making it a preferable option for hospitals.

Province-wide Biliary Atresia Home Screening Program in British Columbia: Evaluation of First 2 Years.

BACKGROUND AND OBJECTIVES: Biliary atresia (BA), a rare newborn liver disease, is the leading cause of liver-related death in children. Early disease recognition and timely surgical Kasai hepatoportoenterostomy (KP) offers long-term survival without liver transplant. Universal BA screening in Taiwan using infant stool color cards (ISCCs) has proven effectiveness. We report our experience with infant stool color card (ISCC) BA screening in a province-wide program in British Columbia (BC). The objective of this study is to assess program performance and cost from launch April 1, 2014 to March 31, 2016. METHODS: ISCCs distributed to families upon maternity ward discharge. Parents were instructed to monitor their infant's stool color for 1 month and contacted the screening center with concerns. The number of live births, ISCC distribution, BA cases, and costs were recorded. Cases with Program screen success had both acholic stool recognition (ISCC screen success) and timely referral for BA. RESULTS: All 126 maternity units received ISCCs. Of 87,583 live births there were 6 BA cases. Of the 5 cases with ISCC Screen Success 3 had Program Screen Success. The median KP age in the program screen success and failure groups was 49 (42-52) and 116 (49-184) days, respectively. Program sensitivity was 50%, specificity 99%, positive predictive value 4%, and negative predictive value 99%. A random sample of 1054 charts at BC Children's Hospital found an ISCC distribution rate of 94%. After a phase-in period, the annual program cost was $30,033.82, and the ISCC cost per birth was $0.68. CONCLUSIONS: The screening program has high specificity and distribution with low cost. Successful program case identification had earlier age at KP. Program modifications aim to improve sensitivity. Longer-term studies will determine program impact on health outcomes.

Cost-Utility Analysis of Extending Public Health Insurance Coverage to Include Diabetic Retinopathy Screening by Optometrists.

BACKGROUND: Diabetic retinopathy (DR) is one of the leading causes of vision loss and blindness in Canada. Eye examinations play an important role in early detection. However, DR screening by optometrists is not always universally covered by public or private health insurance plans. This study assessed whether expanding public health coverage to include diabetic eye examinations for retinopathy by optometrists is cost-effective from the perspective of the health care system. METHODS: We conducted a cost-utility analysis of extended coverage for diabetic eye examinations in Prince Edward Island to include examinations by optometrists, not currently publicly covered. We used a Markov chain to simulate disease burden based on eye examination rates and DR progression over a 30-year time horizon. Results were presented as an incremental cost per quality-adjusted life year (QALY) gained. A series of one-way and probabilistic sensitivity analyses were performed. RESULTS: Extending public health coverage to eye examinations by optometrists was associated with higher costs ($9,908,543.32) and improved QALYs (156,862.44), over 30 years, resulting in an incremental cost-effectiveness ratio of $1668.43/QALY gained. Sensitivity analysis showed that the most influential determinants of the results were the cost of optometric screening and selected utility scores. At the commonly used threshold of $50,000/QALY, the probability that the new policy was cost-effective was 99.99%. CONCLUSIONS: Extending public health coverage to eye examinations by optometrists is cost-effective based on a commonly used threshold of $50,000/QALY. Findings from this study can inform the decision to expand public-insured optometric services for patients with diabetes.

Methodological Issues in Economic Evaluations Submitted to the Pan-Canadian Oncology Drug Review (pCODR).

BACKGROUND: Public drug plans are faced with increasingly difficult funding decisions. In Canada, the pan-Canadian Oncology Drug Review (pCODR) makes funding recommendations to the provincial and territorial drug plans responsible for cancer drugs. Assessments of the economic models submitted by pharmaceutical manufacturers are publicly reported. OBJECTIVES: The main objective of this research was to identify recurring methodological issues in economic models submitted to pCODR for funding reviews. The secondary objective was to explore whether there exists any observed relationships between reported methodological issues and funding recommendations made by pCODR's expert review committee. METHODS: Publicly available Economic Guidance Reports from July 2011 (inception) until June 2014 for drug reviews with a final funding recommendation (N = 34) were independently examined by two authors. Major methodological issues from each review were abstracted and grouped into nine main categories. Each issue was also categorized based on perception of the reviewer's actions to manage it. RESULTS: The most commonly reported issues involved costing (59% of reviews), time horizon (56%), and model structure (36%). Several types of issues were identified that usually could not be resolved, such as quality of clinical data or uncertainty with indirect comparisons. Issues with costing or choice of utility estimates could usually be addressed or explored by reviewers. No statistically significant relationship was found between any methodological issue and funding recommendations from the expert review committee. CONCLUSIONS: The findings provide insights that can be used by parties who submit or review economic evidence for continuous improvement and consistency in economic modeling, reporting, and decision making.

Harmonization of HTA--based reimbursement and regulatory approval activities: a qualitative study.

BACKGROUND: Regulatory approval and reimbursement are necessary to bring health technologies to market. As both are distinct processes, the lack of interaction between regulators and payers has been criticized for resulting in health system inefficiencies. OBJECTIVES: This study describes the experiences of health system stakeholders on the development and implementation of initiatives to better harmonize HTA-reimbursement and regulatory activities, as well as Canadian perceptions on such initiatives. METHODS: Thematic analysis of semi-structured interviews was conducted. Participants represented those whom have published or worked actively in this area or who held positions in HTA and/or reimbursement agencies that gave them insight into the Canadian healthcare system. Interviews were recorded, transcribed and analyzed to identify emerging themes and relationships. RESULTS: Fourteen individuals from twelve organizations participated, including representatives from Canada, US, UK and Netherlands. Harmonization was identified as either a means to: (i) develop economies of scale in the generation of clinical data; and/or (ii) align the lifecycle of a health technology. For such initiatives to be successfully implemented, the following key issues emerged: (i) fostering healthy relationships; (ii) promoting well-intentions; (iii) defining governance and leadership clearly; and (iv) securing organizational infrastructure. CONCLUSIONS: Attempts to harmonize reimbursement and regulatory activities is in its infancy; although, much can be learned from current Canadian and international experiences. Within Canada there is much interest, although concerns have been raised on the extent to which harmonization is possible. Successful policy implementation would require inter-agency collaborations, with particular attention towards capacity building and strong leadership.

Home-based screening for biliary atresia using infant stool colour cards: a large-scale prospective cohort study and cost-effectiveness analysis.

OBJECTIVE: Biliary atresia (BA), a leading cause of paediatric liver failure and liver transplantation, manifests by three weeks of life as jaundice with acholic stools. Poor outcomes due to delayed diagnosis remain a problem worldwide. We evaluated and assessed the cost-effectiveness of methods of introducing a BA Infant Stool Colour Card (ISCC) screening programme in Canada. SETTING AND METHODS: A prospective study at BC Women's Hospital recruited consecutive healthy newborns through six incrementally more intensive screening approaches. Under the baseline "passive" strategy, families received ISCCs at maternity, with instructions to monitor infant stool colour daily and return the ISCC by mail at age 30 days. Additional strategies were: ISCC mailed to family physician; reminder letters or telephone calls to families or physicians. Random telephone surveys of ISCC non-returners assessed total card utilization. Primary outcome was ISCC utilization rate expressed as a composite outcome of the ISCC return rate and non-returned ISCC use. Markov modelling was used to predict incremental costs and life years gained from screening (passive and reminder), compared with no screening, over a 10-year time horizon. RESULTS: 6,187 families were enrolled. Card utilization rates in the passive screening strategy were estimated at 60-94%. For a Canadian population, the increase in cost for passive screening, compared with no screening, is $213,584 and the gain in life years is 9.7 ($22,000 per life-year gained). CONCLUSIONS: A BA ISCC screening programme targeting families of newborns is feasible in Canada. Passive distribution of ISCC at maternity is potentially effective and highly cost-effective.

Harmonization of reimbursement and regulatory approval processes: a systematic review of international experiences.

A considerable degree of overlap exists between reimbursement and regulatory approval of health technologies, and harmonization of certain aspects is both possible and feasible. Various models to harmonization have been suggested in which a number of practical attempts have been drawn from. Based on a review of the literature, approaches can be categorized into those focused on reducing uncertainty and developing economies of scale in the evidentiary requirements; and/or aligning timeframes and logistical aspects of the review process. These strategies can further be classified based on the expected level of structural and organizational change required to implement them into the existing processes. Passive processes require less modification, whereas active processes are associated with greater restructuring. Attempts so far at harmonization have raised numerous legal and practical issues and these must be considered when introducing a more harmonized framework into the existing regulatory and reimbursement arrangements.

Predictors of health service use over the palliative care trajectory.

BACKGROUND: Health system restructuring coupled with the preference of patients to be cared for at home has altered the setting for the provision of palliative care. Accordingly, there has been emphasis on the provision of home-based palliative care by multidisciplinary teams of health care providers. Evidence suggests that these teams are better able to identify and deal with the needs of patients and their family members. Currently there is a lack of literature examining the predictors of palliative care service use for various professional service categories. OBJECTIVE: The purpose of this study was to examine the predictors of the propensity and intensity of five main health service categories in the last three months of life for home-based palliative care patients. DESIGN: This was a prospective cohort study. The predictors of service use were assessed using a two-part model, which treats the decision to use a service (propensity) and the amount of service use (intensity) as two distinct processes. Propensity was modeled using a logistic regression and intensity was modeled using ordinary least squares regression. RESULTS: The results indicate that each service category emerged with a different set of predictor variables. Common predictors of health service use across service categories were patient age and functional status. The results suggest that a consistent set of predictors across service categories does not exist, and thus the determinants of access to each service category are unique. CONCLUSION: These findings will help case managers, health administrators, and policy decision makers better allocate human resources to palliative patients.

Innovations in health service organization and delivery in northern rural and remote regions: a review of the literature.

OBJECTIVES: To identify and review innovations relevant to improving access, quality, efficiency and/or effectiveness in the organization and delivery of health care services in rural and remote areas. STUDY DESIGN: Literature review. METHODS: Key bibliographic databases that index health research were searched: MEDLINE, EMBASE and CINAHL. Other databases relevant to Arctic health were also accessed. Abstracts were assessed for relevancy and full articles were reviewed and categorized according to emergent themes. RESULTS: Many innovations in delivering services to rural and remote areas were identified, particularly in the public health realm. These innovations were grouped into 4 key themes: organizational structure of health services; utilization of telehealth and ehealth; medical transportation; and public health challenges. CONCLUSIONS: Despite the challenges facing rural and remote regions, there is a distinctly positive message from this broad literature review. Evidence-based initiatives exist across a range of areas - which include operational efficiency and integration, access to care, organizational structure, public health, continuing education and workforce composition - that have the potential to positively impact health care quality and health-related outcomes.

Cost variations in ambulatory and home-based palliative care.

Restructuring health care in Canada has emphasized the provision of ambulatory and home-based palliative care. Acquiring economic evidence is critical given this trend and its tremendous demands on family caregivers. The purposes of this study were: 1) to comprehensively assess the societal costs of home-based palliative care; and 2) to examine the socio-demographic and clinical factors that account for variations in costs over the course of the palliative trajectory. One hundred and thirty-six family caregivers were interviewed every two weeks from time of palliative referral until death. Information regarding appointments, travel and out-of-pocket expenses, time devoted to caregiving, as well as demographic and clinical characteristics were measured. The mean monthly cost of care per patient was $24,549 (2008 CDN$). Family caregivers' time costs comprised most costs (70%). Multivariable linear regression indicated that costs were greater for patients who: had lower physical functioning (p < 0.001); lived with someone (p = 0.007); and when the patients approached death (p = 0.021). Information highlighting the variation in costs across individuals may aid policy makers and mangers in deciding how to allocate resources. Greater clarity regarding costs over the course of the palliative trajectory may improve access to care.

Determinants of place of death for recipients of home-based palliative care.

INTRODUCTION: Health system restructuring combined with the preferences of many terminally ill care recipients and their caregivers has led to an increase in home-based palliative care, yet many care recipients die within institutional settings such as hospitals. This study sought to determine the place of death and its predictors among palliative care patients with cancer. METHODS: Study participants were recruited from the Temmy Latner Centre for Palliative Care, a regional palliative care program based in Toronto, Canada. A total of 137 patients and their family caregivers participated in the study; application of various exclusion criteria restricted analysis to a sub-sample of 110. Bivariate (chi-square) and multivariate (logistic regression) analyses were conducted. RESULTS: 66 percent of participants died at home. Chi-square analysis indicated that women were more likely to die at home than men; multivariate analysis indicated that women and those living with others were significantly more likely to die at home than men or those who lived alone. CONCLUSION: Place of death is influenced by the socio-demographic characteristics of patients, the characteristics of their caregivers, and health service factors. Palliative care programs need to tailor services to men and those living alone in order to reduce institutional deaths.