Phase-Based and Lifetime Health System Costs of Care for Patients Diagnosed with Leukemia and Lymphoma: A Population-Based Descriptive Study.

Hematologic cancers, notably leukemias and lymphomas, pose significant challenges to healthcare systems globally, due to rising incidence rates and increasing costs. This study aimed to estimate the phase and lifetime health system total costs (not net costs) of care for patients diagnosed with leukemia and lymphoma in Ontario, Canada. We conducted a population-based study of patients diagnosed between 2005 and 2019, using data from the Ontario Cancer Registry linked with health administrative databases. Costs were estimated using a phase-based approach and stratified by care phase and cancer subtype. Acute lymphocytic leukemia (ALL) patients had the highest mean monthly initial (CAD 19,519) and terminal (CAD 41,901) costs among all cancer subtypes, while acute myeloid leukemia (AML) patients had the highest mean monthly cost (CAD 7185) during the continuing phase. Overall lifetime costs were highest for ALL patients (CAD 778,795), followed by AML patients (CAD 478,516). Comparatively, patients diagnosed with Hodgkin lymphoma (CAD 268,184) and non-Hodgkin lymphoma (CAD 321,834) had lower lifetime costs. Major cost drivers included inpatient care, emergency department visits, same-day surgeries, ambulatory services, and specialized cancer drugs. Since 2005, the cost structure has evolved with rising proportions of interventional drug costs. Additionally, costs were higher among males and younger age groups. Understanding these costs can help guide initiatives to control healthcare spending and improve cancer care quality.

Economic Evaluations of Chimeric Antigen Receptor T-Cell Therapies for Hematologic and Solid Malignancies: A Systematic Review.

OBJECTIVES: This study aimed to systematically review evidence on the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapies for patients with cancer. METHODS: Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments, and economic evaluations that compared costs and effects of CAR-T therapy in patients with cancer were included. Two reviewers independently screened studies, extracted data, synthesized results, and critically appraised studies using the Philips checklist. Cost data were presented in 2022 US dollars. RESULTS: Our search yielded 1809 records, 47 of which were included. Most of included studies were cost-utility analysis, published between 2018 and 2023, and conducted in the United States. Tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, ciltacabtagene autoleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and relmacabtagene autoleucel were compared with various standard of care chemotherapies. The incremental cost-effectiveness ratio (ICER) for CAR-T therapies ranged from $9424 to $4 124 105 per quality-adjusted life-year (QALY) in adults and from $20 784 to $243 177 per QALY in pediatric patients. Incremental cost-effectiveness ratios were found to improve over longer time horizons or when an earlier cure point was assumed. Most studies failed to meet the Philips checklist due to a lack of head-to-head comparisons and uncertainty surrounding CAR-T costs and curative effects. CONCLUSIONS: CAR-T therapies were more expensive and generated more QALYs than comparators, but their cost-effectiveness was uncertain and dependent on patient population, cancer type, and model assumptions. This highlights the need for more nuanced economic evaluations and continued research to better understand the value of CAR-T therapies in diverse patient populations.

Engaging Patients and Caregivers in an Early Health Economic Evaluation: Discerning Treatment Value Based on Lived Experience.

BACKGROUND: Traditionally, economic evaluations have engaged clinicians and policymakers; however, patients and their caregivers have insight that can ensure that the economic evaluation process appropriately reflects disease consequences and adequately addresses their priorities related to treatment. OBJECTIVE: We aimed to identify patient priorities to inform an early economic evaluation of chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia. METHODS: We conducted two online group discussions of four participants each, involving patients with experience of hematological cancer and a caregiver. We used an adapted version of the nominal group technique, a consensus-building discussion approach, to generate focused qualitative data. RESULTS: Patients and a caregiver acknowledged both the costs directly related to clinical care, such as the out-of-pocket cost of drugs, and the indirect treatment costs, such as the cost of transport, accommodation, and food. The emotional and physical toll of treatment and the influence of treatment on employment and education were additional costs emphasized by participants. Treatment benefits prioritized by participants included the efficacy of treatment, manageable side effects, improved quality of life, accessibility of treatment, and short treatment duration. CONCLUSIONS: Engaging patients and caregivers in an early economic evaluation could help identify additional costs and benefits of therapies that are not typically recognized in economic evaluations but have the potential to increase the commercial viability of novel therapies. This research also demonstrates how patients and caregivers can be engaged at different levels in the development of early economic evaluation models.

A cost-utility analysis of the impact of electronic nicotine delivery systems on health care costs and outcomes in Canada. / Analyse coût-utilité de l'incidence des inhalateurs électroniques de nicotine sur les coûts et les résultats des soins de santé au Canada.

INTRODUCTION: We determined the impact of electronic nicotine delivery systems (ENDS) on health outcomes and costs in Canada, based on their effect on smoking cessation and smoking initiation rates. METHODS: We used gender-specific Markov models to estimate lifetime discounted life years, quality-adjusted life years (QALYs) and smoking-related health care costs for cohorts of males and females aged 15 to 19 years, in scenarios in which (1) ENDS are available (status quo); (2) ENDS are completely unavailable; and (3) ENDS are available for smoking cessation through health care provider prescription, in addition to currently recognized smoking cessation tools. Analysis was from the perspective of a publicly funded health care system. RESULTS: Outcomes are expressed per 1000 individuals and based on expected values obtained through a Monte Carlo simulation of 10 000 replications. For males aged 15 to 19 years, life years, QALYs and smoking-related health care costs were 41 553, 35 871 and CAD 79 645 964, respectively, when ENDS were available; 41 568, 35 894 and CAD 79 645 960 when ENDS were unavailable; and 41 570, 35 897 and CAD 79 605 869 when ENDS were available through prescription only. For females, life years, QALYs and smoking-related health care costs were 43 596, 37 416 and CAD 69 242 856, respectively, when ENDS were available; 43 610, 37 438 and CAD 69 085 926 when ENDS were unavailable; and 43 611, 37 438 and CAD 69 076 034 when ENDS were available through prescription only. Thus, situations in which ENDS are unavailable, or available through prescription only are dominant over the status quo. CONCLUSION: These results show that a policy change whereby ENDS were unavailable to the Canadian population or available through prescription only would likely increase population health and reduce health care costs.

Implanted spinal neuromodulation interventions for chronic pain in adults.

BACKGROUND: Implanted spinal neuromodulation (SNMD) techniques are used in the treatment of refractory chronic pain. They involve the implantation of electrodes around the spinal cord (spinal cord stimulation (SCS)) or dorsal root ganglion (dorsal root ganglion stimulation (DRGS)), and a pulse generator unit under the skin. Electrical stimulation is then used with the aim of reducing pain intensity. OBJECTIVES: To evaluate the efficacy, effectiveness, adverse events, and cost-effectiveness of implanted spinal neuromodulation interventions for people with chronic pain. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase Ovid, Web of Science (ISI), Health Technology Assessments, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry from inception to September 2021 without language restrictions, searched the reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing SNMD interventions with placebo (sham) stimulation, no treatment or usual care; or comparing SNMD interventions + another treatment versus that treatment alone. We included participants ≥ 18 years old with non-cancer and non-ischaemic pain of longer than three months duration. Primary outcomes were pain intensity and adverse events. Secondary outcomes were disability, analgesic medication use, health-related quality of life (HRQoL) and health economic outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently screened database searches to determine inclusion, extracted data and evaluated risk of bias for prespecified results using the Risk of Bias 2.0 tool. Outcomes were evaluated at short- (≤ one month), medium- four to eight months) and long-term (≥12 months). Where possible we conducted meta-analyses. We used the GRADE system to assess the certainty of evidence. MAIN RESULTS: We included 15 unique published studies that randomised 908 participants, and 20 unique ongoing studies. All studies evaluated SCS. We found no eligible published studies of DRGS and no studies comparing SCS with no treatment or usual care. We rated all results evaluated as being at high risk of bias overall. For all comparisons and outcomes where we found evidence, we graded the certainty of the evidence as low or very low, downgraded due to limitations of studies, imprecision and in some cases, inconsistency. Active stimulation versus placebo SCS versus placebo (sham) Results were only available at short-term follow-up for this comparison. Pain intensity Six studies (N = 164) demonstrated a small effect in favour of SCS at short-term follow-up (0 to 100 scale, higher scores = worse pain, mean difference (MD) -8.73, 95% confidence interval (CI) -15.67 to -1.78, very low certainty). The point estimate falls below our predetermined threshold for a clinically important effect (≥10 points). No studies reported the proportion of participants experiencing 30% or 50% pain relief for this comparison. Adverse events (AEs) The quality and inconsistency of adverse event reporting in these studies precluded formal analysis. Active stimulation + other intervention versus other intervention alone SCS + other intervention versus other intervention alone (open-label studies) Pain intensity Mean difference Three studies (N = 303) demonstrated a potentially clinically important mean difference in favour of SCS of -37.41 at short term (95% CI -46.39 to -28.42, very low certainty), and medium-term follow-up (5 studies, 635 participants, MD -31.22 95% CI -47.34 to -15.10 low-certainty), and no clear evidence for an effect of SCS at long-term follow-up (1 study, 44 participants, MD -7 (95% CI -24.76 to 10.76, very low-certainty). Proportion of participants reporting ≥50% pain relief We found an effect in favour of SCS at short-term (2 studies, N = 249, RR 15.90, 95% CI 6.70 to 37.74, I2 0% ; risk difference (RD) 0.65 (95% CI 0.57 to 0.74, very low certainty), medium term (5 studies, N = 597, RR 7.08, 95 %CI 3.40 to 14.71, I2 = 43%; RD 0.43, 95% CI 0.14 to 0.73, low-certainty evidence), and long term (1 study, N = 87, RR 15.15, 95% CI 2.11 to 108.91 ; RD 0.35, 95% CI 0.2 to 0.49, very low certainty) follow-up. Adverse events (AEs) Device related No studies specifically reported  device-related adverse events at short-term follow-up. At medium-term follow-up, the incidence of lead failure/displacement (3 studies N = 330) ranged from 0.9 to 14% (RD 0.04, 95% CI -0.04 to 0.11, I2 64%, very low certainty). The incidence of infection (4 studies, N = 548) ranged from 3 to 7% (RD 0.04, 95%CI 0.01, 0.07, I2 0%, very low certainty). The incidence of reoperation/reimplantation (4 studies, N =5 48) ranged from 2% to 31% (RD 0.11, 95% CI 0.02 to 0.21, I2 86%, very low certainty). One study (N = 44) reported a 55% incidence of lead failure/displacement (RD 0.55, 95% CI 0.35, 0 to 75, very low certainty), and a 94% incidence of reoperation/reimplantation (RD 0.94, 95% CI 0.80 to 1.07, very low certainty) at five-year follow-up. No studies provided data on infection rates at long-term follow-up. We found reports of some serious adverse events as a result of the intervention. These included autonomic neuropathy, prolonged hospitalisation, prolonged monoparesis, pulmonary oedema, wound infection, device extrusion and one death resulting from subdural haematoma. Other No studies reported the incidence of other adverse events at short-term follow-up. We found no clear evidence of a difference in otherAEs at medium-term (2 studies, N = 278, RD -0.05, 95% CI -0.16 to 0.06, I2 0%) or long term (1 study, N = 100, RD -0.17, 95% CI -0.37 to 0.02) follow-up. Very limited evidence suggested that SCS increases healthcare costs. It was not clear whether SCS was cost-effective. AUTHORS' CONCLUSIONS: We found very low-certainty evidence that SCS may not provide clinically important benefits on pain intensity compared to placebo stimulation. We found low- to very low-certainty evidence that SNMD interventions may provide clinically important benefits for pain intensity when added to conventional medical management or physical therapy. SCS is associated with complications including infection, electrode lead failure/migration and a need for reoperation/re-implantation. The level of certainty regarding the size of those risks is very low. SNMD may lead to serious adverse events, including death. We found no evidence to support or refute the use of DRGS for chronic pain.

Regional cost effectiveness analyses for increasing radon protection strategies in housing in Canada.

The incremental cost effectiveness ratios for implementing a recent recommendation to install a more radon resistant foundation barrier were modelled for new and existing housing in 2016, for each province and territory in Canada. Cost-utility analyses were conducted, in which the health benefit of an intervention was quantified in quality-adjusted life years, to help guide policymakers considering increasing investment in radon reduction in housing to reduce the associated lung cancer burden shouldered by the health care system. Lung cancer morbidity was modelled using a lifetable analysis that incorporated lung cancer incidence and survival time for localized, regional, and distant stages of diagnoses for both non-small cell and small cell lung cancer. The model accounted for surgical or advanced lung cancer treatment costs avoided, and average health care costs incurred for radon-attributable lung cancer cases prevented by the intervention. The incremental implementation of radon interventions in the housing stock was modelled over a lifetime horizon, and a discount rate of 1.5% was adopted. This radon intervention in new housing was cost effective in all but one region, ranging from $18,075/QALY (15,704; 20,178) for the Yukon to $58,454/QALY (52,045; 65,795) for British Columbia. A sequential analysis was conducted to compare intervention in existing housing for mitigation thresholds of 200 and 100 Bq/m3. This intervention in existing housing was cost effective at a mitigation threshold of 200 Bq/m3 in regions with higher radon levels, ranging from $33,247/QALY (27,699; 39,377) for the Yukon to $61,960/QALY (46,932; 113,737) for Newfoundland, and more cost effective at a threshold of 200 than 100 Bq/m3. More lung cancer deaths can be prevented by intervention in new housing than in existing housing; it was estimated that the proposed intervention in new housing would prevent a mean of 446 (416; 477) lung cancer cases annually. The cost effectiveness of increased radon resistance in foundation barriers in housing varied widely, and would support adopting this intervention in new housing across Canada and in existing housing in higher radon regions. This study provides further evidence that the most cost effective way of responding to the geographically variable radon burden is by implementing specific regional radon reduction policies.

Stakeholder engagement in economic evaluation: Protocol for using the nominal group technique to elicit patient, healthcare provider, and health system stakeholder input in the development of an early economic evaluation model of chimeric antigen receptor T-cell therapy.

INTRODUCTION: Chimeric antigen receptor T-cell (CAR-T) therapy is a class of immunotherapy. An economic evaluation conducted at an early stage of development of CAR-T therapy for treatment of adult relapsed or refractory acute lymphoblastic leukaemia could provide insight into factors contributing to the cost of treatment, the potential clinical benefits, and what the health system can afford. Traditionally, stakeholders are engaged in certain parts of health technology assessment processes, such as in the identification and selection of technologies, formulation of recommendations, and implementation of recommendations; however, little is known about processes for stakeholder engagement during the conduct of the assessment. This is especially the case for economic evaluations. Stakeholders, such as clinicians, policy-makers, patients, and their support networks, have insight into factors that can enhance the validity of an economic evaluation model. This research outlines a specific methodology for stakeholder engagement and represents an avenue to enhance health economic evaluations and support the use of these models to inform decision making for resource allocation. This protocol may inform a tailored framework for stakeholder engagement processes in future economic evaluation model development. METHODS AND ANALYSIS: We will involve clinicians, healthcare researchers, payers, and policy-makers, as well as patients and their support networks in the conduct and verification of an early economic evaluation of a novel health technology to incorporate stakeholder-generated knowledge. Three stakeholder-specific focus groups will be conducted using an online adaptation of the nominal group technique to elicit considerations from each. This study will use CAR-T therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia as a basis for investigating broader stakeholder engagement processes. ETHICS AND DISSEMINATION: This study received ethics approval from the Ottawa Hospital Research Institute Research Ethics Board (REB 20200320-01HT) and the results will be shared via conference presentations, peer-reviewed publications, and ongoing stakeholder engagement.

A Retrospective Cohort Study Investigating the Impact of Maternal Pre-Pregnancy Body Mass Index on Pediatric Health Service Utilization.

OBJECTIVE: Maternal weight during pregnancy impacts the health of both mother and baby. This project investigated associations between maternal pre-pregnancy body mass index (BMI) and the child's future health service utilization. METHODS: The study population comprised all women who delivered a singleton, live infant in Ontario between 2012 and 2014, and was assembled from data contained in the provincial birth registry. Health service utilization in the 24 months following birth was examined by linking data from the registry with other provincial health administrative databases housed at ICES. RESULTS: A total of 258 005 records were available for analysis. After adjusting for infant sex and maternal age, smoking status, income quintile, and pre-existing or gestational diabetes or hypertension, children born to mothers who were overweight or had obesity prior to pregnancy had increased rates of hospitalization (overweight adjusted incidence rate ratio [aIRR] 1.09, 95% confidence interval [CI] 1.06-1.12; obesity aIRR 1.20, 95% CI 1.17-1.24), physician visits (overweight aIRR 1.03, 95% CI 1.03-1.04; obesity aIRR 1.05, 95% CI 1.04-1.05) and emergency department visits (overweight aIRR 1.12, 95% CI 1.10-1.13; obesity aIRR 1.27, 95% CI 1.25-1.29) than infants born to mothers with normal pre-pregnancy BMI. CONCLUSION: Excess maternal weight was associated with greater pediatric health service utilization. Rates of health service utilization appeared to increase with maternal pre-pregnancy BMI. Future study of the reasons behind this increase may allow for early education, diagnosis, and intervention in this at-risk population.

Cost-utility analysis of apixaban compared with usual care for primary thromboprophylaxis in ambulatory patients with cancer.

BACKGROUND: Apixaban (2.5 mg) taken twice daily has been shown to substantially reduce the risk of venous thromboembolism (VTE) compared with placebo for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE. We aimed to compare the health system costs and health benefits associated with primary thromboprophylaxis using apixaban with those associated with the current standard of care (where no primary thromboprophylaxis is given), from the perspective of Canada's publicly funded health care system in this subpopulation of patients with cancer over a lifetime horizon. METHODS: We performed a cost-utility analysis to estimate the incremental cost per quality-adjusted life-year (QALY) gained with primary thromboprophylaxis using apixaban. We obtained baseline event rates and the efficacy of apixaban from the Apixaban for the Prevention of Venous Thromboembolism in High-Risk Ambulatory Cancer Patients (AVERT) trial on apixaban prophylaxis. We estimated relative risk for bleeding, risk of complications associated with VTE treatment, mortality rates, costs and utilities from other published sources. RESULTS: Over a lifetime horizon, apixaban resulted in lower costs to the health system (Can$7902.98 v. Can$14 875.82) and an improvement in QALYs (9.089 v. 9.006). The key driver of cost-effectiveness results was the relative risk of VTE as a result of apixaban. Results from the probabilistic analysis showed that at a willingness to pay of Can$50 000 per QALY, the strategy with the highest probability of being most cost-effective was apixaban, with a probability of 99.87%. INTERPRETATION: We found that apixaban is a cost-saving option for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE.

Outpatient uterine assessment and treatment unit in patients with abnormal uterine bleeding: an economic modelling study.

BACKGROUND: Most often in Canada, the evaluation and management of abnormal uterine bleeding occurs under general anesthesia in the operating room. We aimed to assess the potential cost-effectiveness of an outpatient uterine assessment and treatment unit (UATU) compared with the current standard of care when diagnosing and treating abnormal uterine bleeding in women. METHODS: We performed a cost-effectiveness analysis and developed a probabilistic decision tree model to simulate the total costs and outcomes of women receiving outpatient UATU or usual care over a 1-year time horizon (Apr. 1, 2014, to Mar. 31, 2017) at a tertiary care hospital in Ontario, Canada. Probabilities, resource use and time to diagnosis and treatment were obtained from a retrospective chart review of 200 randomly selected women who presented with abnormal uterine bleeding. Results were expressed as overall cost and time savings per patient. Costs are reported in 2018 Canadian dollars. RESULTS: Compared with usual care, care in the UATU was associated with a decrease in overall cost ($1332, 95% confidence interval [CI] -$1742 to -$1008) and a decrease in overall time to treatment (-75, 95% CI -89 to -63, d). The point at which the UATU would no longer be cost saving is if the additional cost to operate and maintain the UATU is greater than $1600 per patient. INTERPRETATION: From the perspective of Canada's health care system, an outpatient UATU is more cost effective than usual care and saves time. Future studies should focus on the relative efficacy of a UATU and the total budget required to operate and maintain a UATU.

Value of mesenchymal stem cell therapy for patients with septic shock: an early health economic evaluation.

BACKGROUND.: This study estimates the maximum price at which mesenchymal stem cell (MSC) therapy is deemed cost-effective for septic shock patients and identifies parameters that are most important in making treatment decisions. METHODS: We developed a probabilistic Markov model according to the sepsis care trajectory to simulate costs and quality-adjusted life years (QALYs) of septic shock patients receiving either MSC therapy or usual care over their lifetime. We calculated the therapeutic headroom by multiplying the gains attributable to MSCs with willingness-to-pay (WTP) threshold and derived the maximum reimbursable price (MRP) from the expected net monetary benefit and savings attributable to MSCs. We performed scenario analyses to assess the impact of changes to assumptions on the study findings. A value of information analysis is performed to identify parameters with greatest impact on the uncertainty around the cost-effectiveness of MSC therapy. RESULTS: At a WTP threshold of $50,000 per QALY, the therapeutic headroom and MRP of MSC therapy were $20,941 and $16,748, respectively; these estimates increased with the larger WTP values and the greater impact of MSCs on in-hospital mortality and hospital discharge rates. The parameters with greatest information value were MSC's impact on in-hospital mortality and the baseline septic shock in-hospital mortality. CONCLUSION: At a common WTP of $50,000/QALY, MSC therapy is deemed to be economically attractive if its unit cost does not exceed $16,748. This ceiling price can be increased to $101,450 if the therapy significantly reduces both in-hospital mortality and increases hospital discharge rates.

Economic Evaluation of Cannabinoid Oil for Dravet Syndrome: A Cost-Utility Analysis.

INTRODUCTION: Cannabinoid oils are being increasingly used to treat Dravet syndrome, yet the long-term costs and outcomes of this approach are unknown. Thus, we examined the cost effectiveness of cannabinoid oil as an adjunctive treatment (added to clobazam and valproate), compared with adjunctive stiripentol or with clobazam and valproate alone, for the treatment of Dravet syndrome in children. METHODS: We performed a probabilistic cost-utility analysis from the perspective of the Canadian public health care system, comparing cannabinoid oil and stiripentol (both on a background of clobazam and valproate) with clobazam and valproate alone. Costs and quality-adjusted life-years (QALYs) were estimated using a Markov model that followed a cohort of children aged from 5 to 18 years through model states related to seizure frequency. Model inputs were obtained from the literature. The cost effectiveness of adjunctive cannabinoid oil, adjunctive stiripentol, and clobazam/valproate alone was assessed through sequential analysis. The influence of perspective and other assumptions were explored in scenario analyses. All costs are expressed in 2019 Canadian dollars, and costs and QALYs were discounted at a rate of 1.5% per year. RESULTS: The incremental cost per QALY gained with the use of adjunctive cannabinoid oil, from the health care system perspective, was $32,399 compared with clobazam and valproate. Stiripentol was dominated by cannabinoid oil, producing fewer QALYs at higher costs. At a willingness-to-pay threshold of $50,000, cannabinoid oil was the optimal treatment in 76% of replications. From a societal perspective, cannabinoid oil dominated stiripentol and clobazam/valproate. The interpretation of the results was insensitive to model and input assumptions. CONCLUSION: Compared with clobazam/valproate, adjunctive cannabinoid oil may be a cost-effective treatment for Dravet syndrome, if a decision maker is willing to pay at least $32,399 for each QALY gained. The opportunity costs of continuing to fund stiripentol, but not cannabinoid oil, should be considered.

An assessment of uncertainty using two different modelling techniques to estimate the cost effectiveness of mitigating radon in existing housing in Canada.

The burden of lung cancer associated with residential radon in existing housing can be reduced by interventions to screen and mitigate existing housing having radon levels above a mitigation threshold. The objective of this study is to estimate the cost effectiveness of radon interventions for screening and mitigation of existing housing for the 2016 population in Canada and to assess the structural uncertainty associated with the choice of model used in the cost-utility analysis. The incremental cost utility ratios are estimated using both a Markov cohort model and a discrete event simulation model. A societal perspective, a lifetime horizon and a discount rate of 1.5% are adopted. At a radon mitigation threshold of 200 (100) Bq/m3, the discounted ICERs for current rates of screening and mitigation of existing housing are 72,569 (68,758) $/QALY using a Markov cohort model and 84,828 (76,917) $/QALY using discrete event simulation. It appears that minimal structural uncertainty is associated with the choice of model used for this cost-utility analysis, and the cost effectiveness would improve at increased rates of radon testing and mitigation. The mitigation of radon in existing housing is estimated to be a practical policy option for reducing the associated lung cancer burden in Canada.

Liberal Versus Restrictive Red Blood Cell Transfusion Thresholds in Hematopoietic Cell Transplantation: A Randomized, Open Label, Phase III, Noninferiority Trial.

PURPOSE: Evidence regarding red blood cell (RBC) transfusion practices and their impact on hematopoietic cell transplantation (HCT) outcomes are poorly understood. PATIENTS AND METHODS: We performed a noninferiority randomized controlled trial in four different centers that evaluated patients with hematologic malignancies requiring HCT who were randomly assigned to either a restrictive (hemoglobin [Hb] threshold < 70 g/L) or liberal (Hb threshold < 90 g/L) RBC transfusion strategy between day 0 and day 100. The noninferiority margin corresponds to a 12% absolute difference between groups in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) score relative to baseline. The primary outcome was health-related quality of life (HRQOL) measured by FACT-BMT score at day 100. Additional end points were collected: HRQOL by FACT-BMT score at baseline and at days 7, 14, 28, 60, and 100; transplantation-related mortality; length of hospital stay; intensive care unit admissions; acute graft-versus-host disease; Bearman toxicity score; sinusoidal obstruction syndrome; serious infections; WHO Bleeding Scale; transfusion requirements; and reactions to therapy. RESULTS: A total of 300 patients were randomly assigned to either restrictive-strategy or liberal-strategy treatment groups between 2011 and 2016 at four Canadian adult HCT centers. After HCT, mean pre-transfusion Hb levels were 70.9 g/L in the restrictive-strategy group and 84.6 g/L in the liberal-strategy group (P < .0001). The number of RBC units transfused was lower in the restrictive-strategy group than in the liberal-strategy group (mean, 2.73 units [standard deviation, 4.81 units] v 5.02 units [standard deviation, 6.13 units]; P = .0004). After adjusting for transfusion type and baseline FACT-BMT score, the restrictive-strategy group had a higher FACT-BMT score at day 100 (difference of 1.6 points; 95% CI, -2.5 to 5.6 points), which was noninferior compared with that of the liberal-strategy group. There were no significant differences in clinical outcomes between the transfusion strategies. CONCLUSION: In patients undergoing HCT, the use of a restrictive RBC transfusion strategy threshold of 70 g/L was as effective as a threshold of 90 g/L and resulted in similar HRQOL and HCT outcomes with fewer transfusions.

A technique for approximating transition rates from published survival analyses.

BACKGROUND: Quality-adjusted-life-years (QALYs) are used to concurrently quantify morbidity and mortality within a single parameter. For this reason, QALYs can facilitate the discussion of risks and benefits during patient counseling regarding treatment options. QALYs are often calculated using partitioned-survival modelling. Alternatively, QALYs can be calculated using more flexible and informative state-transition models populated with transition rates estimated using multistate modelling (MSM) techniques. Unfortunately the latter approach is considered not possible when only progression-free survival (PFS) and overall survival (OS) analyses are reported. METHODS: We have developed a method that can be used to estimate approximate transition rates from published PFS and OS analyses (we will refer to transition rates estimated using full multistate methods as true transition rates). RESULTS: The approximation method is more accurate for estimating the transition rates out of health than the transition rate out of illness. The method tends to under-estimate true transition rates as censoring increases. CONCLUSIONS: In this article we present the basis for and use of the transition rate approximation method. We then apply the method to a case study and evaluate the method in a simulation study.

A cost effectiveness analysis of interventions to reduce residential radon exposure in Canada.

The objective of this analysis is to estimate the incremental cost effectiveness ratios for the 2012 populations in Canada, each province/territory, and 17 census metropolitan areas, for practical radon mitigation scenarios to reduce residential radon exposures. Sixteen intervention scenarios compare radon mitigation implemented at differing rates in new and existing housing relative to preventive measures installed at construction, using three different radon mitigation thresholds. A period life-table analysis was conducted using data derived from two recent Canadian radon surveys, along with Canadian mortality and quality of life data. Analyses adopted a lifetime horizon and a discount rate of 1.5%. It is practical to reduce residential radon and associated lung cancer mortality in Canada, and the most cost effective scenario at each radon mitigation threshold is the combination of the activation of the preventive measures in new housing and mitigation of existing housing.

A General Population Utility Valuation Study for Metastatic Epidural Spinal Cord Compression Health States.

STUDY DESIGN: General population utility valuation study. OBJECTIVE: This study obtained utility valuations from a Canadian general population perspective for 31 unique metastatic epidural spinal cord compression (MESCC) health states and determined the relative importance of MESCC-related consequences on quality-of-life. SUMMARY OF BACKGROUND DATA: Few prospective studies on the treatment of MESCC have collected quality-adjusted-life-year weights (termed "utilities"). Utilities are an important summative measure which distills health outcomes to a single number that can assist healthcare providers, patients, and policy makers in decision making. METHODS: We recruited a sample of 1138 adult Canadians using a market research company. Quota sampling was used to ensure that the participants were representative of the Canadian population in terms of age, sex, and province of residence. Using the validated MESCC module for the "Self-administered Online Assessment of Preferences" (SOAP) tool, participants were asked to rate six of the 31 MESCC health states, each of which presented varying severities of five MESCC-related dysfunctions (dependent; non-ambulatory; incontinent; pain; other symptoms). RESULTS: Participants equally valued all MESCC-related dysfunctions which followed a pattern of diminishing marginal disutility (each additional consequence resulted in a smaller incremental decrease in utility than the previous). These results demonstrate that the general population values physical function equal to other facets of quality-of-life. CONCLUSION: We provide a comprehensive set of ex ante utility estimates for MESCC health states that can be used to help inform decision making. This is the first study reporting direct utility valuation for a spinal disorder. Our methodology offers a feasible solution for obtaining quality-of-life data without collecting generic health status questionnaire responses from patients. LEVEL OF EVIDENCE: 4.

Decision Models for Assessing the Cost Effectiveness of Treatments for Pediatric Drug-Resistant Epilepsy: A Systematic Review of Economic Evaluations.

BACKGROUND: Drug-resistant epilepsy affects about one-third of children with epilepsy and is associated with high costs to the healthcare system, yet the cost effectiveness of most treatments is unclear. Use of cannabis-based products for epilepsy is increasing, and the cost effectiveness of such strategies relative to conventional pharmacologic treatments must be considered. OBJECTIVE: The objective of this systematic review was to identify economic evaluations of cannabis-based treatments for pediatric drug-resistant epilepsy. We also sought to identify and appraise decision models that have been used in economic evaluations of pharmacologic treatments (i.e., antiepileptic drugs) in this population. METHODS: Electronic searches of MEDLINE, EMBASE, and the Cochrane library, as well as a targeted grey literature search, were undertaken (11 June 2018). Model-based full economic evaluations involving cannabis-based treatments or pharmacologic treatments for drug-resistant epilepsy in children were eligible for inclusion. Two independent reviewers selected studies for inclusion, and study quality was assessed by use of the Drummond and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklists. Study findings, as well as model characteristics, are narratively summarized. RESULTS: Nine economic evaluations involving children with drug-resistant epilepsy were identified; however, none involved cannabis-based treatments. All studies involved pharmacologic treatments compared with other pharmacologic treatments or non-pharmacologic treatments (i.e., ketogenic diet, epilepsy surgery, vagus nerve stimulation). Few studies have assessed the cost effectiveness of pharmacologic treatments in specific drug-resistant epilepsy syndromes, including Dravet and Lennox-Gastaut syndromes. Five included studies involved use of Markov models with a similar structure (i.e., health states based on seizure frequency relative to baseline). There was a wide range of methodological quality, and few studies fully addressed context-specific issues such as weight gain and treatment switching. CONCLUSION: Whether cannabis-based treatments for pediatric drug-resistant epilepsy represent good value for money has yet to be investigated. Economic evaluations of such treatments are needed and should address issues of particular importance in pediatric epilepsy, including weight gain over time, switching or discontinuation of treatments, effectiveness of interventions and comparators, and long-term effectiveness beyond the duration of available clinical studies. PROSPERO REGISTRATION: CRD42018099591.

Back to Bayesian: A strategy to enhance prognostication of metastatic spine disease.

AIMS: Clinicians must consider prognosis when offering treatment to patients with spine metastases. Although several prognostic indices have been developed and validated for this purpose, they may not be applicable in the current era of targeted systemic therapies. Even before the introduction of targeted therapies, these prognostic indices should not have been directly used for individual patient decision making without contextualising with other sources of data. By contextualising, we mean that prognostic estimates should not be based on these scores alone and formally incorporate clinically relevant factors not part of prognostic indices. Contextualisation requires the use of Bayesian statistics which may be unfamiliar to many readers. In this paper we show readers how to correctly apply prognostic scores to individual patients using Bayesian statistics. Through Bayesian analysis, we explore the impact of new targeted therapies on prognostic estimates obtained using the Tokuhashi score. METHODS: We provide a worked calculation for the probability of a patient surviving up to 6 months using dichotomous prognostication. We then demonstrate how to calculate a patient's expected survival using continuous prognostication. Sensitivity of the posterior distribution to prior assumptions is illustrated through effective sample size adjustment. RESULTS: When the predicted prognosis from the Tokuhashi score is contextualised with data on contemporary systemic treatments, patients previously deemed non-surgical candidates may be eligible for surgery. CONCLUSIONS: Bayesian prognostication generates intuitive results and allows multiple data points to be synthesised transparently. These techniques can extend the usefulness of existing prognostic scores in the era of targeted systemic therapies.

The Psychometric Properties of a Self-Administered, Open-Source Module for Valuing Metastatic Epidural Spinal Cord Compression Utilities.

INTRODUCTION: Web surveys are often used for utility valuation. Typically, custom utility valuation tools that have not undergone psychometric evaluation are used. OBJECTIVES: This study aimed to determine the psychometric properties of a metastatic epidural spinal cord compression (MESCC) module run on a customizable open-source, internet-based, self-directed utility valuation platform (Self-directed Online Assessment of Preferences [SOAP]). METHODS: Individuals accompanying patients to the emergency department waiting room in Ottawa, Canada, were recruited. Participants made SOAP MESCC health state valuations in the waiting room and 48 h later at home. Validity, agreement reliability, and responsiveness were measured by logical consistency of responses, smallest detectable change, the interclass correlation coefficient, and Guyatt's responsiveness index, respectively. RESULTS: Of 285 participants who completed utility valuations, only 113 (39.6%) completed the re-test. Of these 113 participants, 92 (81.4%) provided valid responses on the first test and 75 (66.4%) provided valid responses on the test and re-test. Agreement for all groups of health states was adequate, since their smallest detectable change was less than the minimal clinically important difference. The mean interclass correlation coefficients for all health states were > 0.8, indicating at least substantial reliability. Guyatt's responsiveness indices all exceeded 0.80, indicating a high level of responsiveness. CONCLUSIONS: To our knowledge, this is the first validated open-source, web-based, self-directed utility valuation module. We have demonstrated the SOAP MESCC module is valid, reproducible, and responsive for obtaining ex ante utilities. Considering the successful psychometric validation of the SOAP MESCC module, other investigators can consider developing modules for other diseases where direct utility valuation is needed.