Financial toxicity among adolescent and young adult cancer survivors: A systematic review of educational attainment, employment, and income.

PURPOSE: To identify, evaluate and summarize the evidence on educational attainment, employment status and income of AYAs surviving cancer. METHODS: A search of six databases for articles published between 01/01/2010 and 03/31/2022 was performed. Articles with an AYA survivorship population, quantitative design and a cancer-free comparator group were included. Data extraction was conducted, and quality appraisal was completed using ROBINS-I. Results were summarized using a narrative synthesis. RESULTS: A total of 2801 articles were identified, of which 12 were included. Among the limited evidence, educational attainment did not differ from cancer-free peers. Survivors were more likely to be unemployed, have lower incomes and require social security for income supplementation. Evidence suggested that females, diagnosis of brain cancer and the presence of late-effects were among the risk factors for severe outcomes. CONCLUSIONS: Limited socioeconomic evidence exists for AYAs surviving cancer. Long-lasting financial toxicities occur and highlights a need for further investigation.

Healthcare utilization and costs associated with acute lymphoblastic leukemia in children with and without Down syndrome.

BACKGROUND: Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) are at increased risk of treatment-related morbidity and mortality compared to non-DS-ALL, requiring increased supportive care. We examined the healthcare utilization and costs in DS-ALL patients to inform future evaluations of novel therapies. METHODS: A provincial registry identified all children (1-17 years) diagnosed with B-lineage ALL in Ontario, Canada between 2002 and 2012. Detailed demographic, disease, treatment, and outcome data were abstracted. Linkage to population-based health services databases identified all outpatient and emergency department (ED) visits, hospitalizations, and physician billings. Healthcare utilization costs were available for patients diagnosed during 2006-2012 using validated algorithms (2018 Canadian dollars). Healthcare utilization rates and costs were compared between DS and non-DS patients using regression models, adjusting for all covariates. RESULTS: Of 711 patients, 28 (3.9%) had DS. Adjusting for all covariates, children with DS-ALL experienced substantially higher rates of ED visits (rate ratio [RR] 1.5, 95% confidence interval [95% CI]: 1.2-2.0; p = .001) and inpatient days (RR 2.5, 95% CI: 1.4-4.5; p = .002) compared to non-DS children. Outpatient visit rates were similar (RR 1.1, 95% CI: 0.9-1.3; p = .41). Among patients with available cost data (N = 533, DS = 19), median 5-year healthcare utilization cost was $247,700 among DS patients (interquartile range [IQR]: 200,900-354,500) and $196,200 among non-DS patients (IQR: 148,900-280,300; p = .02). In adjusted analyses, DS-associated costs were 50% higher (RR 1.5, 95% CI: 1.2-1.9; p < .002). CONCLUSIONS: Healthcare utilization and treatment costs of DS-ALL patients are substantially higher than those of non-DS-ALL. Our data provide a baseline for future DS-specific cost-effectiveness studies.

Health care utilisation and costs associated with different treatment protocols for newly diagnosed childhood acute lymphoblastic leukaemia: A population-based study in Ontario, Canada.

BACKGROUND: Although different treatment protocols for childhood acute lymphoblastic leukaemia (ALL) all achieve high cure rates, their health care utilisation and costs have not been rigorously compared. METHODS: Disease, treatment, and outcome data were chart abstracted for all children with ALL in Ontario, Canada, diagnosed 2002-2012. Linkage to population-based databases identified health care utilisation. Utilisation-associated costs were determined through validated algorithms. Chemotherapy-associated costs were calculated separately. Health care utilisation and costs were compared between patients receiving Children's Oncology Group (COG) versus Dana-Farber Cancer Institute (DFCI)-based treatment. FINDINGS: Of 802 patients, 146 (18.2%) were treated on DFCI-based protocols. COG patients experienced significantly higher rates of emergency department (ED) visits (adjusted rate ratio [aRR]: 1.3, 95% confidence interval [CI]: 1.1-1.5; p = 0·01), whereas outpatient visit rates were 60% higher among DFCI patients (aRR: 1.6, 95% CI: 1.5-1.7, p < 0.0001). In adjusted analyses, DFCI-associated cost intensity was 70% higher (aRR: 1.7, 95% CI: 1.5-1.9; p < 0.0001), mainly attributable to outpatient visit costs. Total chemotherapy costs were higher among COG-treated patients ($39,400 ± $1100 versus $33,400 ± $2800; p = 0.02). Among PEG-ASNase-treated patients, total chemotherapy costs were highest among DFCI patients (median $54,200 ± $7400; p = 0.003 versus COG patients). INTERPRETATION: COG and DFCI treatments were associated with higher ED visit rates and higher outpatient visit rates, respectively. Overall utilisation-associated costs were increased in DFCI-treated patients. Administration of some intravenous chemotherapy at home and decreases in PEG-ASNase cost would decrease health care utilisation and costs for all patients and mitigate differences between COG and DFCI protocols. FUNDING: C17 Research Network.

Cost-effectiveness of Tisagenlecleucel vs Standard Care in High-risk Relapsed Pediatric Acute Lymphoblastic Leukemia in Canada.

Importance: Tisagenlecleucel, a chimeric antigen receptor T-cell therapy for relapsed or refractory pediatric acute lymphoblastic leukemia, has been approved for use in multiple jurisdictions. The public list price is US $475 000, or more than CaD $600 000. Assessing the cost-effectiveness of tisagenlecleucel is necessary to inform policy makers on the economic value of this treatment. Objective: To assess the value for money of tisagenlecleucel compared with current standard care for tisagenlecleucel-eligible pediatric patients with acute lymphoblastic leukemia under unknown long-term effectiveness. Design, Setting, and Participants: A cost-utility analysis of tisagenlecleucel compared with current standard care using a Canadian population-based registry of pediatric patients with acute lymphoblastic leukemia was performed. Results from 3 pooled single-arm tisagenlecleucel clinical trials and a provincial pediatric cancer registry were combined to create treatment and control arms, respectively. The population-based control arm consisted of patients meeting clinical trial inclusion and exclusion criteria, starting at second relapse. Multistate and individual-level simulation modeling were combined to predict patient lifetime health trajectories by treatment strategy. Tisagenlecleucel efficacy was modeled across long-term cure rates, from 10% to 40%, to account for limited information on its long-term effectiveness. Uncertainty was tested with 1-way and probabilistic sensitivity analysis. Data were collected in September 2017, and analysis began in December 2017. Exposures: Tisagenlecleucel compared with current standard care for tisagenlecleucel-eligible patients. Main Outcomes and Measures: Relative health care costs, survival gains, and quality-adjusted life-years (QALYs) between tisagenlecleucel and current standard care. Results: The treatment and control arms were modeled on 192 and 118 patients, respectively. The mean (SD) age of control individuals was 10 (4.25) years, and the mean (SD) age of the pooled clinical trial sample was 11 (6) years. The control individuals had 78 boys (66%), and the pooled clinical trial sample had 102 boys (53%). Treatment with tisagenlecleucel was associated with an additional 2.14 to 9.85 life years or 1.68 to 6.61 QALYs, compared with current care. The average additional cost of tisagenlecleucel was CaD $470 013 (US $357 031). Accounting for the total discounted cost over the patient lifetime resulted in an incremental cost of CaD $71 000 (US $53 933) to CaD $281 000 (US $213 453) per QALY gain. Conclusions and Relevance: To our knowledge, this study offers the first cost-effectiveness analysis of tisagenlecleucel compared with current standard care for pediatric patients with acute lymphoblastic leukemia using a constructed population-based control arm. At a willingness-to-pay threshold of $150 000/QALY, tisagenlecleucel had a 32% likelihood of being cost-effective. Tisagenlecleucel cost-effectiveness would fall below $50 000/QALY with a long-term cure rate of over 0.40 or a price discount of 49% at its currently known effectiveness.

Development of System Performance Indicators for Adolescent and Young Adult Cancer Care and Control in Canada.

OBJECTIVES: To develop an expert-group, consensus-based list of system performance indicators to be used for monitoring, evaluating, and benchmarking progress for cancer care and control in adolescents and young adults (AYAs) in Canada. METHODS: A national multidisciplinary panel of AYA oncology experts was convened; they prepared a literature review and undertook a brainstorming exercise to create a comprehensive list of indicators based on a previously defined framework for AYA cancer care and control in Canada. A modified Delphi process was then undertaken to cull the list based on 3 quick screen criteria. Three rounds of ranking were required. The fourth stage employed a face-to-face meeting, and the final stage utilized a survey to rank the indicators on the basis of importance and feasibility. RESULTS: Nineteen participants contributed to the 5-stage process. From an initial list of 114 indicators, 14 were ultimately endorsed, representing 5 themes: active care, survivorship, psychosocial issues, palliative care, and research. The 5 highest ranked indicators were assessed as very to moderately feasible, with only a single indicator (clinical trial enrollment) in the top 5 assigned a least feasible ranking. CONCLUSION: The 14 indicators provide a starting point for the development of a standard set of metrics for AYA cancer care and control in Canada and have potential for international utility.

Use of physician billing claims to identify infections in children.

While medical records have detailed information, they are limited in reach to the availability and accessibility of those records. On the other hand, administrative data while limited in scope, have a much further reach in coverage of an entire population. However, few studies have validated the use of administrative data for identifying infections in pediatric populations. Pediatric patients from Ontario, Canada aged <18 years were randomly sampled from the Electronic Medical Record Administrative data Linked Database (EMRALD). Using physician diagnoses from the electronic medical record (EMR) as the reference standard, we determined the criterion validity of physician billing claims in administrative data for identifying infectious disease syndromes from 2012 to 2014. Diagnosis codes were assessed by infection category (respiratory, skin and soft tissue, gastrointestinal, urinary tract and otitis externa) and for all infections combined. Sensitivity analyses assessed the performance if patients had more than one reason to visit the physician. We analysed 2,139 patients and found 33.3% of all visits were for an infection, and respiratory infections accounted for 67.6% of the infections. When we combined all infection categories, sensitivity was 0.74 (95% CI 0.70-0.77), specificity was 0.95 (95% CI 0.93-0.96), positive predictive value (PPV) was 0.87 (95% CI 0.84-0.90), and negative predictive value (NPV) was 0.88 (95% CI 0.86-0.89). For respiratory infections, sensitivity was 0.77 (95% CI 0.73-0.81), specificity was 0.96 (95% CI 0.95-0.97), PPV was 0.85 (95% CI 0.81-0.88), and NPV was 0.94 (95% CI 0.92-0.95). Similar performance was observed for skin and soft tissue, gastrointestinal, urinary tract, and otitis externa infections, but with lower sensitivity. Performance measures were highest when the patient visited the physician with only one health complaint. We found when using linked EMR data as the reference standard, administrative billing codes are reasonably accurate in identifying infections in a pediatric population.

Choice of relative or cause-specific approach to cancer survival analysis impacts estimates differentially by cancer type, population, and application: evidence from a Canadian population-based cohort study.

BACKGROUND: Cause-specific (CS) and net survival in a relative survival framework (RS) are two of the most common methods for estimating cancer survival. In this paper, we assess the differences in results produced by two permutations of cause-specific and relative survival applied to estimating cancer survival and disparities in cancer survival, using data from First Nations and non-Aboriginal populations in Canada. METHODS: Subjects were members of the 1991 Canadian Census Mortality Cohort, a population-based cohort of adult respondents to the 1991 Long Form Census who have been followed up for incident cancers and death through linkage to administrative databases. We compared four methods: relative survival analyses with ethnicity-specific life tables (RS-ELT); relative survival with general population life tables (RS-GLT); cause-specific survival with a broad definition of cancer death (CS-Broad); and cause-specific survival with a narrow definition of cause of death (CS-Narrow) and applied these to the nine most common cancers among First Nations. RESULTS: Apart from breast and prostate cancers, RS-ELT, RS-GLT, and CS-Broad tended to produce similar estimates of age-standardized five-year survival, whereas CS-Narrow yielded higher estimates of survival. CS-Narrow estimates were particularly unlike those based on the other methods for cancers of the digestive and respiratory tracts. Estimates of disparities in survival were generally comparable across the four methods except for breast and prostate cancers. CONCLUSIONS: Cancer surveillance efforts in sub-populations defined by race, ethnicity, geography, socioeconomic status, or similar factors are necessary for identifying disparities and monitoring progress toward reducing them. In the absence of routine monitoring of cancer survival and cancer survival disparities in these populations, estimates generated by different methods will inevitably be compared over time and across populations. In this study, we demonstrate that caution should be exercised in making these comparisons, particularly in interpreting cause-specific survival rates with an unknown or narrow definition of cancer death and in estimates of breast and prostate cancer survival and/or disparities in survival generated by different methods.

Classification of treatment-related mortality in children with cancer: a systematic assessment.

Treatment-related mortality is an important outcome in paediatric cancer clinical trials. An international group of experts in supportive care in paediatric cancer developed a consensus-based definition of treatment-related mortality and a cause-of-death attribution system. The reliability and validity of the system was tested in 30 deaths, which were independently assessed by two clinical research associates and two paediatric oncologists. We defined treatment-related mortality as death occurring in the absence of progressive cancer. Of the 30 reviewed deaths, the reliability of classification for treatment-related mortality was noted as excellent by clinical research associates (κ=0·83, 95% CI 0·60-1·00) and paediatric oncologists (0·84, 0·63-1·00). Criterion validity was established because agreement between the consensus classifications by clinical research associates and paediatric oncologists was almost perfect (0·92, 0·78-1·00). Our approach should allow comparison of treatment-related mortality across trials and across time.

Inferior survival among Aboriginal children with cancer in Ontario.

BACKGROUND: Pediatric cancer distribution and outcomes have not been examined in Canadian Aboriginal children. The objective of this study was to describe the distribution, event-free survival, and overall survival of Aboriginal children with malignancies who reside in Ontario compared with non-Aboriginal children. METHODS: This population-based study included 10,520 Ontario children (aged <18 years) who were diagnosed with cancer between 1985 and 2011. Patients were identified from the Pediatric Oncology Group of Ontario Networked Information System database. Aboriginal children were identified by self-reported ethnicity or postal code on a Native reserve at diagnosis. Descriptive statistics of the patients were presented and compared using the Fisher exact test. Event-free and overall survival probabilities were calculated for Aboriginal and non-Aboriginal children, described using Kaplan-Meier curves, and compared using log-rank tests. RESULTS: In total, 65 Aboriginal children and 10,364 non-Aboriginal children with malignancy were identified. The distribution of malignancy type was similar between the 2 groups. There were no significant differences in baseline characteristics, presence of metastatic disease, or treatment approach (clinical trial, standard of care, or individualized protocol) between the groups. The 5e-year event-free survival rate (± standard error) was 56.3% ± 6.2% among Aboriginal children versus 72.8% ± 0.4% among non-Aboriginal children (P = .0042), and the 5-year overall survival rate was 64% ± 6.0% versus 79.3 ± 0.4% (P = .0017), respectively. The cause of death did not vary according to Aboriginal ethnicity. CONCLUSIONS: Survival was significantly inferior among Aboriginal children who had cancer compared with non-Aboriginal children who had cancer in Ontario. Future studies are required to define the etiology of this disparity, evaluate the issue nationally, and create interventions to improve outcomes for Aboriginal children.

Low socioeconomic status is associated with worse survival in children with cancer: a systematic review.

BACKGROUND: While low socioeconomic status (SES) has been associated with inferior cancer outcome among adults, its impact in pediatric oncology is unclear. Our objective was therefore to conduct a systematic review to determine the impact of SES upon outcome in children with cancer. METHODS: We searched Ovid Medline, EMBASE and CINAHL from inception to December 2012. Studies for which survival-related outcomes were reported by socioeconomic subgroups were eligible for inclusion. Two reviewers independently assessed articles and extracted data. Given anticipated heterogeneity, no quantitative meta-analyses were planned a priori. RESULTS: Of 7,737 publications, 527 in ten languages met criteria for full review; 36 studies met final inclusion criteria. In low- and middle-income countries (LMIC), lower SES was uniformly associated with inferior survival, regardless of the measure chosen. The majority of associations were statistically significant. Of 52 associations between socioeconomic variables and outcome among high-income country (HIC) children, 38 (73.1%) found low SES to be associated with worse survival, 15 of which were statistically significant. Of the remaining 14 (no association or high SES associated with worse survival), only one was statistically significant. Both HIC studies examining the effect of insurance found uninsured status to be statistically associated with inferior survival. CONCLUSIONS: Socioeconomic gradients in which low SES is associated with inferior childhood cancer survival are ubiquitous in LMIC and common in HIC. Future studies should elucidate mechanisms underlying these gradients, allowing the design of interventions mediating socioeconomic effects. Targeting the effect of low SES will allow for further improvements in childhood cancer survival.

The association between socioeconomic status and survival among children with Hodgkin and non-Hodgkin lymphomas in a universal health care system.

BACKGROUND: The association between socioeconomic status (SES) and cancer survival has been studied extensively in adults. However, little is known about this relationship in the pediatric population, specifically in jurisdictions with universal health care insurance programs. Our aim was to determine whether lower SES is associated with poorer survival in pediatric Hodgkin (HL) and non-Hodgkin lymphoma (NHL) patients in Ontario. PROCEDURE: All incident cases of HL and NHL in children between 0 and 14 years old diagnosed in Ontario between January 1st, 1985 and December 31st, 2006 were identified through the Pediatric Oncology Group of Ontario Networked Information System. Neighborhood income quintile and material deprivation quintile at diagnosis were used as proxies for SES. Cox proportional hazards regressions were used to assess the association between SES and the risk of event-free or overall survival. RESULTS: A total of 692 patients were included in the analysis: 302 HL and 390 NHL. SES was not associated with survival (overall or event-free) among HL and NHL patients (P > 0.05 for all four comparisons, i.e., HL/NHL, EFS/OS) after adjustment for age, sex, period of diagnosis, and disease stage. There were no differences in the distribution of disease stage across SES strata at the time of diagnosis. Similarly, the distribution of deaths among long-term survivors (survived ≥5 years from diagnosis) did not differ across SES strata (P > 0.05). CONCLUSIONS: SES was not associated with risk of death among pediatric HL and NHL patients in Ontario. This was consistent through the cancer trajectory, including diagnosis, treatment, and survivorship.

Survey design from the ground up: collaboratively creating the Toronto Teen Survey.

The Toronto Teen Survey is a community-based participatory research study whose aim is to gather information on the accessibility and relevance of sexual health services for diverse groups of urban youth (13 to 17 years of age). This information will be used to develop a proactive, citywide strategy to improve sexual health outcomes for Toronto adolescents. In this article, the authors focus on the processes of collaboratively developing a survey tool with youth, academics, and community stakeholders. An overview of the project and examples from the design stage are provided. In addition, recommendations are given toward developing best practices when working with young people on research and survey design.

Work disability absence among young workers with respect to earnings losses in the following year.

OBJECTIVES: The primary objective of this study was to evaluate the earnings losses that young workers experience in the year after a work disability absence. METHODS: The sample consisted of workers aged 16 to 24 years from a longitudinal survey of a representative sample of Canadians. Young workers who lost > or =5 days of work due to work disability or illness (ie, work disability absence) were matched to uninjured controls on the basis of age, gender, preabsence earnings, and student status. This matching procedure resulted in 173 cases and 795 controls. The outcome measure was the difference in earnings the year after the work disability episode between injured cases and their uninjured controls. RESULTS: An analysis of variance indicated that young workers experiencing a work disability absence had significantly fewer earnings than their controls in the year after the absence (P<0.05). This earnings loss was not due to between-group differences in school activity or workhours in the year after the work absence. CONCLUSIONS: No study to date has estimated the impact of work-related disability on earnings trajectories among young workers. The findings of the present study indicate that earnings losses can occur among young workers even during their transition into the labor market. Documenting the economic impacts of work injuries early in one's worklife can provide information for policy debates on the allocation of resources to control workplace hazards where teenagers and young adults work and debates on the determination of fair and adequate benefits for young workers.

The impact of work-related musculoskeletal disorders on workers' caregiving activities.

BACKGROUND: The purpose of the study was to describe and quantify the impact of work-related musculoskeletal disorders on workers' caregiving activities. METHODS: A cross-sectional study was conducted in which a telephone survey was administered to 187 lost-time workers' compensation claimants from Ontario, of whom 49.2% were women. Forty-eight percent of the injured workers were providing unpaid care prior to the injury. RESULTS: Injured workers providing caregiving reported an average reduction in time spent in caregiving activities of 5.5 hr/week, 8 months post-injury. A Sex X Return-to-work status ANCOVA was conducted with difference in caregiving hours as the dependent variable, and with the following covariates: Mean number of caregiving hours, comorbidities, site of injury, and education. Independent of weekly hours of caregiving, decreases in caregiving hours were significantly higher if the worker was a woman or had not returned to work. CONCLUSIONS: Work-related musculoskeletal disorders have a significant impact on workers' time spent in unpaid caregiving activities, an example of the social consequences of occupational injuries. Occupational and caregiving roles are limited by work-related disorders in a parallel fashion.

Duration of work disability: a comparison of self-report and administrative data.

BACKGROUND: Studies have used insurer-reported compensable days absent as an outcome measure when studying work-related injury or illness. Compared to self-reported days absent, insurer data are less expensive to collect. Previous work has identified that insurer-claims data consistently underestimate the duration of days absent when compared to self-report. The objective of this study was to examine the agreement between the number of self-reported days absent from work following a compensable work-related injury and the number of insurer-reported compensation days paid, and to examine factors associated with the magnitude of the discrepancy between the number of self-reported days absent and the number of insurer-reported compensated days paid. METHODS: One hundred sixty six respondents who experienced a work-related injury were interviewed approximately 200 days post-injury to assess the number of days absent from work. The number of days compensated by the insurer was compared to self-report using descriptive statistics and linear regression. RESULTS: Respondents who had yet to experience a return-to-work (RTW) had the largest median discrepancy followed by respondents with an unsustained RTW and finally sustained RTW. Respondents with upper extremity injuries, lower education, and lower RTW self-efficacy showed greater discrepancy between self-reported and compensated days absent. Among respondents who self-reported fewer days absent than insurer-compensated days absent an inverse relationship between firm size and discrepancy was noted. CONCLUSIONS: Researchers should be aware of the discrepancies between self-reported and compensated days absent. Future studies planning to incorporate days absent as an outcome variable should carefully consider what measure would be more appropriate and potentially collect both self-report and administrative data to assess the discrepancy.