Application of Multi-Criteria Decision Analysis (MCDA) to Prioritize Real-World Evidence Studies for Health Technology Management: Outcomes and Lessons Learned by the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration.

Multi-criteria decision analysis (MCDA) is a value assessment tool designed to help support complex decision-making by incorporating multiple factors and perspectives in a transparent, structured approach. We developed an MCDA rating tool, consisting of seven criteria evaluating the importance and feasibility of conducting potential real-world evidence (RWE) studies aimed at addressing uncertainties stemming from initial cancer drug funding recommendations. In collaboration with the Canadian Agency for Drugs and Technologies in Health's Provincial Advisory Group, a validation exercise was conducted to further evaluate the application of the rating tool using RWE proposals varying in complexity. Through this exercise, we aimed to gain insight into consensus building and deliberation processes and to identify efficiencies in the application of the rating tool. An experienced facilitator led a multidisciplinary committee, consisting of 11 Canadian experts, through consensus building, deliberation, and prioritization. A total of nine RWE proposals were evaluated and prioritized as low (n = 4), medium (n = 3), or high (n = 2) priority. Through an iterative process, efficiencies and recommendations to improve the rating tool and associated procedures were identified. The refined MCDA rating tool can help decision-makers prioritize important and feasible RWE studies for research and can enable the use of RWE for the life-cycle evaluation of cancer drugs.

Development of a Multi-Criteria Decision Analysis Rating Tool to Prioritize Real-World Evidence Questions for the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration.

The Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration developed an MCDA rating tool to assess and prioritize potential post-market real-world evidence (RWE) questions/uncertainties emerging from public drug funding decisions in Canada. In collaboration with a group of multidisciplinary stakeholders from across Canada, the rating tool was developed following a three-step process: (1) selection of criteria to assess the importance and feasibility of an RWE question; (2) development of rating scales, application of weights and calculating aggregate scores; and (3) validation testing. An initial MCDA rating tool was developed, composed of seven criteria, divided into two groups. Group A criteria assess the importance of an RWE question by examining the (1) drug's perceived clinical benefit, (2) magnitude of uncertainty identified, and (3) relevance of the uncertainty to decision-makers. Group B criteria assess the feasibility of conducting an RWE analysis including the (1) feasibility of identifying a comparator, (2) ability to identify cases, (3) availability of comprehensive data, and (4) availability of necessary expertise and methodology. Future directions include partnering with the Canadian Agency for Drugs and Technology in Health's Provincial Advisory Group for further tool refinement and to gain insight into incorporating the tool into drug funding deliberations.

Cost-effectiveness Analysis of Pertuzumab With Trastuzumab in Patients With Metastatic Breast Cancer.

IMPORTANCE: The initial assessment of pertuzumab use for treatment of metastatic breast cancer by health technology assessment agencies suggested that pertuzumab was not cost-effective. In Ontario, Canada, pertuzumab became funded in November 2013 based on the substantial clinical benefit. To date, there is a paucity of analysis of pertuzumab using real-world data for cost-effectiveness. OBJECTIVE: To assess the cost-effectiveness of pertuzumab, trastuzumab, and chemotherapy vs trastuzumab and chemotherapy for patients with metastatic breast cancer. DESIGN, SETTING, AND PARTICIPANTS: A population-based retrospective economic evaluation was conducted in Ontario, Canada. Patients who received first-line treatments for metastatic breast cancer from January 1, 2008, to March 31, 2018, were identified. Patients were followed up from the start of treatment up to 5 years, with maximum follow-up to March 31, 2019. Patients were identified from the Ontario Cancer Registry and linked to the New Drug Funding Program database to identify receipt of first-line treatment (N = 1158). INTERVENTIONS: Treatment with pertuzumab, trastuzumab, and chemotherapy after public funding (November 25, 2013) compared with treatment with trastuzumab and chemotherapy before funding. MAIN OUTCOMES AND MEASURES: Cost-effectiveness, from a public payer perspective, was estimated from administrative data with a 5-year time horizon, adjusted for censoring, and discounted (1.5%). Incremental cost-effectiveness ratios for life-years gained and quality-adjusted life year (QALY) with bootstrapped 95% CIs were calculated. Sensitivity analysis with price reduction of pertuzumab alone or in combination with trastuzumab was conducted. RESULTS: A total of 579 pairs of matched patients receiving pertuzumab and controls were included. The mean (SD) age of the matched study cohort was 58 (12.97) years; 1151 were women (99.4%). Pertuzumab resulted in 0.61 life-years gained and 0.44 QALYs gained at an incremental cost of $192 139 (all costs measured in Canadian dollar values, CAD) with an incremental cost-effectiveness ratio of $316 203 per life-year gained and $436 679 per QALY. The main factors associated with cost included the cost of pertuzumab (60%), outpatient cancer treatment delivery (24%), and trastuzumab (15%). With 100% price reduction of pertuzumab, the incremental cost-effectiveness ratio was $174 027 per QALY. When the price of pertuzumab and trastuzumab were both reduced by more than 71%, the incremental cost-effectiveness ratio decreased below $100 000 per QALY. CONCLUSIONS AND RELEVANCE: The findings of this population-based study suggest that pertuzumab may increase survival for patients with metastatic breast cancer but would not be considered cost-effective, even after 100% price reduction, under conventional thresholds.

Building a National Reassessment Process for Oncology Drugs: Lessons Learned by the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration through a Simulated Reassessment Exercise.

The CanREValue Collaboration established the Reassessment & Uptake Working Group to develop a preliminary process to reassess funded cancer drugs in Canada. A simulated exercise was conducted to evaluate the proposed reassessment process using a real-world case. We invited 32 attendees including representatives from Health Canada and Health Technology Assessment (HTA) agencies, along with payers, clinicians, academics, and patient representatives. A case was developed using a real-world study on a publicly funded cancer drug. In facilitated group sessions, participants were asked to deliberate upon the evidence presented in the case to issue reassessment recommendations. Several themes were identified through the deliberation discussions. While the generalizability of real-world evidence (RWE) is perceived as a strength, trust in the RWE depends largely on the source of the real-world data. The attendees suggested several improvements to the proposed reassessment process including evidence requirement for reassessment, recommendation categories, and a priori study protocols. This exercise generated important insights on the evidence required for conducting reassessment and considerations for improvements of the proposed reassessment process. Building upon lessons from this exercise, future work would continue to refine the reassessment process as part of the overall CanREValue framework.

Prediction of breast cancer-related outcomes with the Edmonton Symptom Assessment Scale: A literature review.

PURPOSE: The Edmonton Symptom Assessment Scale (ESAS) is a validated tool used in patients with varied cancer diagnoses to measure patient symptoms. The present manuscript will review the literature assessing the ability of the ESAS to predict patient-related outcomes in breast cancer patients. METHODS: A literature search was conducted of Cochrane Central Register of Controlled Trials databases, Ovid MEDLINE, and Embase for English articles that investigated the use of predictive modelling with the ESAS in the breast cancer population. Study type, publication year, sample size, patient demographics, predicted outcomes, and strongest predictive factors/symptoms were summarized for each study. RESULTS: A total of nine articles were included in this review. Five articles used the ESAS in predictive models to determine patient time to death. ESAS was also used to predict emergency department visits, determine symptoms associated with decreased quality of life, and generate a Health Utility Score. Lack of appetite was the most common ESAS symptom, as it was reported in five studies to be associated with decreased survival. In four of the nine articles, an additional survey investigating physical functioning was used in combination with ESAS to strengthen the predictive models. CONCLUSIONS: Included studies support the use of ESAS in predictive models, particularly for predicting survival. Using the ESAS as a predictive tool allows for more accurate time to death predictions, potentially improving symptom management and preventing overtreatment of palliative patients near the end of life.

Impact of rarity on Canadian oncology health technology assessment and funding.

OBJECTIVES: The pan-Canadian Oncology Drug Review (pCODR) evaluates new cancer drugs for public funding recommendations. While pCODR's deliberative framework evaluates overall clinical benefit and includes considerations for exceptional circumstances, rarity of indication is not explicitly addressed. Given the high unmet need that typically accompanies these indications, we explored the impact of rarity on oncology HTA recommendations and funding decisions. METHODS: We examined pCODR submissions with final recommendations from 2012 to 2017. Incidence rates were calculated using pCODR recommendation reports and statistics from the Canadian Cancer Society. Indications were classified as rare if the incidence rate was lower than 1/100,000 diagnoses, a definition referenced by the Canadian Agency for Drugs and Technologies in Health. Each pCODR final report was examined for the funding recommendation/justification, level of supporting evidence (presence of a randomized control trial [RCT]), and time to funding (if applicable). RESULTS: Of the ninety-six pCODR reviews examined, 16.6 percent were classified as rare indications per above criteria. While the frequency of positive funding recommendations were similar between rare and nonrare indication (78.6 vs. 75 percent), rare indications were less likely to be presented with evidence from RCT (50 vs. 90 percent). The average time to funding did not differ significantly across provinces. CONCLUSION: Rare indications appear to be associated with weaker clinical evidence. There appears to be no association between rarity, positive funding recommendations, and time to funding. Further work will evaluate factors associated with positive recommendations and the real-world utilization of funded treatments for rare indications.

Gait Speed vs. VES-13: A Pilot Study Comparing Screening Tools to Determine the Need for a Comprehensive Geriatric Assessment in Senior Women with Breast Cancer.

BACKGROUND/OBJECTIVES: Patients aged 70 years and older may be suboptimally treated with cancer therapy because of the lack of clinical trial data in this population. The Comprehensive Geriatric Assessment can be time consuming, and access to geriatricians is limited. This study aims to determine whether gait speed (GS) analysis is equivalent to the widely accepted Vulnerable Elders Survey 13 (VES-13) in identifying vulnerable or frail patients in need of a Comprehensive Geriatric Assessment. METHODS: A pilot prospective cohort study was carried out at a tertiary cancer centre in Toronto, Canada, in a radiation oncology breast follow-up clinic. GS analysis and VES-13 were completed by each patient at the same clinic visit. GS of <1 meter/second (m/s) and VES-13 score ≥3 were considered abnormal. Sensitivity, specificity, positive and negative predictive values, and Kappa characteristic were calculated for GS compared with VES-13. RESULTS AND DISCUSSION: Twenty-nine participants aged 70 years and older with any stage of breast cancer were included. The GS was 67% sensitive and 95% specific for abnormal VES-13 scores. The GS had an 86% positive predictive value and 86% negative predictive value for abnormal scores on VES-13. Overall, the GS showed a substantial strength of agreement with the VES-13 (kappa 0.66, P < .0001). CONCLUSION: The GS analysis compared very well with VES-13 scores, and this may be a reasonable alternative to VES-13 screening. This pilot data warrant further study in a larger group of patients.

Ambulatory Toxicity Management (AToM) in patients receiving adjuvant or neo-adjuvant chemotherapy for early stage breast cancer - a pragmatic cluster randomized trial protocol.

BACKGROUND: Population-based studies suggest that emergency department visits and hospitalizations are common among patients receiving chemotherapy and that rates in routine practice are higher than expected from clinical trials. Chemotherapy-related toxicities are often predictable and, consequently, acute care visits may be preventable with adequate treatment planning and support between visits to the cancer centre. We will evaluate the impact of proactive telephone-based toxicity management on emergency department visits and hospitalizations in women with early stage breast cancer receiving chemotherapy. METHODS: In this pragmatic covariate constraint-based cluster randomized trial, 20 centres in Ontario, Canada are randomly allocated to either proactive telephone toxicity management (intervention) or routine care (control). The primary outcome is the cluster-level mean number of ED + H visits per patient evaluated using Ontario administrative healthcare data. Participants are all patients with early stage (I-III) breast cancer commencing adjuvant or neo-adjuvant chemotherapy at participating institutions during the intervention period. At least 25 patients at each centre participate in a patient reported outcomes sub-study involving the collection of standardized questionnaires to measure: severity of treatment toxicities, self-care, self-efficacy, quality of life, and coordination of care. Patients participating in the patient reported outcomes (PRO) sub-study are asked to provide written consent to link their PRO data to administrative data. Unit costs will be applied to each per person resource utilized, and a total cost per population and patient will be generated. An incremental cost-effectiveness analysis will be undertaken to compare the incremental costs and outcomes between the intervention and control groups from the health system perspective. DISCUSSION: This study evaluates the effectiveness of a proactive toxicity management intervention in a routine care setting. The use of administrative healthcare data to evaluate the primary outcome enables an evaluation in a real world setting and at a much larger scale than previous studies. TRIAL REGISTRATION: Clinicaltrials.gov , NCT02485678. Registered 30 June 2015.

The impact of pricing strategy on the costs of oral anti-cancer drugs.

BACKGROUND: The soaring costs of anti-cancer drugs pose a threat to the sustainability of cancer care. The pricing strategy chosen by manufacturers can impact the costs of oral anti-cancer drugs during dose modifications, but this issue remains under-recognized in the literature. In general, with the flat pricing strategy, there is a single fixed price for each tablet regardless of dosage strength, whereas with linear pricing, the price of each tablet increases with its dose. We hypothesize that flat pricing will have increased drug costs compared to linear pricing during dose reductions since the cost remains fixed despite decreased dose requirements. This practice may have significant financial implications considering the high costs, extensive utilization, and frequent occurence of dose reductions with anti-cancer drugs.  METHODS: Oral anti-cancer drugs reviewed by the pan-Canadian Oncology Drug Review program between 2011 and 2018 were identified. The cost per mg and cost per 28-day cycle were calculated for dose levels -2 to +2. The percent change in cost per mg and cost per cycle during dose modifications from the standard dose were calculated. We conducted Mann-Whitney U and Fisher-exact tests to compare the association between drug costs during dose reductions and pricing strategy. RESULTS: In this study, 30 oral anti-cancer drugs for use in 41 indications were analyzed; 44% of drugs used linear pricing and 56% used flat pricing. Dose reductions increased the mean cost per mg for drugs with linear pricing by 14.7% (range: 0%-50%) at dose level -1 and 17.2% (range: 0%-50%) at dose level -2 and flat pricing by 60.8% (range: 19%-100%) at dose level -1 and 99.1% (range: 0%-300%) at dose level -2. The cost per mg was significantly increased in drugs using flat pricing compared to linear pricing when dose reduction to either level -1 (P = 0.010) or level -2 (P = 0.006) occurred. The mean cost per cycle was decreased for drugs using linear pricing by 20.9% (range: -40% to 0%) at dose level -1 and 48.7% (range: -60% to -25%) at dose level -2 and flat pricing by 0.8% (range -6% to 0%) at dose level -1 and 11.0% (range: -50% to 100%) at dose level -2. The cost per cycle was significantly decreased in drugs with linear pricing compared to flat pricing when the standard dose is reduced to either dose level -1 (P = 0.005) or dose level -2 (P = 0.026). CONCLUSIONS: Overall, flat pricing had significantly greater costs compared to linear pricing during dose reductions of anti-cancer drugs. While there is a general expectation that the cost of drugs should decrease with dose reduction, drugs with flat pricing were generally found to have increased cost per mg and no change in the cost per cycle. The resultant increased spending on drug acquisition (despite purchasing lower doses) lead to financial wastage, which has significant implications on cost-effectiveness considerations and budgets. Future economic evaluations should take into consideration the hidden costs associated with dose reductions of flat priced drugs.

The impact of cancer drug wastage on economic evaluations.

BACKGROUND: The objective of this study was to determine the impact of modeling cancer drug wastage in economic evaluations because wastage can result from single-dose vials on account of body surface area- or weight-based dosing. METHODS: Intravenous chemotherapy drugs were identified from the pan-Canadian Oncology Drug Review (pCODR) program as of January 2015. Economic evaluations performed by drug manufacturers and pCODR were reviewed. Cost-effectiveness analyses and budget impact analyses were conducted for no-wastage and maximum-wastage scenarios (ie, the entire unused portion of the vial was discarded at each infusion). Sensitivity analyses were performed for a range of body surface areas and weights. RESULTS: Twelve drugs used for 17 indications were analyzed. Wastage was reported (ie, assumptions were explicit) in 71% of the models and was incorporated into 53% by manufacturers; this resulted in a mean incremental cost-effectiveness ratio increase of 6.1% (range, 1.3%-14.6%). pCODR reported and incorporated wastage for 59% of the models, and this resulted in a mean incremental cost-effectiveness ratio increase of 15.0% (range, 2.6%-48.2%). In the maximum-wastage scenario, there was a mean increase in the incremental cost-effectiveness ratio of 24.0% (range, 0.0%-97.2%), a mean increase in the 3-year total incremental budget costs of 26.0% (range, 0.0%-83.1%), and an increase in the 3-year total incremental drug budget cost of approximately CaD $102 million nationally. Changing the mean body surface area or body weight caused 45% of the drugs to have a change in the vial size and/or quantity, and this resulted in increased drug costs. CONCLUSIONS: Cancer drug wastage can increase drug costs but is not uniformly modeled in economic evaluations. Cancer 2017;123:3583-90. © 2017 American Cancer Society.

The Perceptions and Expectations of Older Women in the Establishment of the Senior Women's Breast Cancer Clinic (SWBCC): a Needs Assessment Study.

This study explored older women's perceptions and expectations of the prospective Senior Women's Breast Cancer Clinic (SWBCC) at Sunnybrook Odette Cancer Centre (SOCC) in Toronto, Ontario, Canada. In our previous studies, older breast cancer patients had expressed a greater need for informational, decisional, and post-treatment support. This study also assessed women's perspectives on the involvement of geriatricians and incorporation of geriatric assessment in their cancer care. Twelve breast cancer patients aged 68 years or older who were treated at the SOCC participated in the study. We recorded and transcribed 11 interviews and analyzed them using qualitative thematic analysis methods to identify major themes; one interview was excluded due to recording defect. Eight major themes were identified: transportation issues, service, communication between patient and healthcare professionals, communication between healthcare professionals, support during treatment, support after treatment, informational resources, and patient suggestions. Important issues were raised by participants, such as difficulties in arranging transportation to the clinic, barriers in accessing family physician service, and communication breakdown that result in treatment delay and unaddressed complications. In conclusion, there were important gaps in the cancer care of older women with breast cancer that could be detected earlier and better addressed in the new multidisciplinary SWBCC. The participating women were highly supportive of the initiative and made several suggestions on how the clinic could better accommodate their specific needs during and after breast cancer treatment.

Quantitative ultrasound assessment of breast tumor response to chemotherapy using a multi-parameter approach.

PURPOSE: This study demonstrated the ability of quantitative ultrasound (QUS) parameters in providing an early prediction of tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC). METHODS: Using a 6-MHz array transducer, ultrasound radiofrequency (RF) data were collected from 58 LABC patients prior to NAC treatment and at weeks 1, 4, and 8 of their treatment, and prior to surgery. QUS parameters including midband fit (MBF), spectral slope (SS), spectral intercept (SI), spacing among scatterers (SAS), attenuation coefficient estimate (ACE), average scatterer diameter (ASD), and average acoustic concentration (AAC) were determined from the tumor region of interest. Ultrasound data were compared with the ultimate clinical and pathological response of the patient's tumor to treatment and patient recurrence-free survival. RESULTS: Multi-parameter discriminant analysis using the κ-nearest-neighbor classifier demonstrated that the best response classification could be achieved using the combination of MBF, SS, and SAS, with an accuracy of 60 ± 10% at week 1, 77 ± 8% at week 4 and 75 ± 6% at week 8. Furthermore, when the QUS measurements at each time (week) were combined with pre-treatment (week 0) QUS values, the classification accuracies improved (70 ± 9% at week 1, 80 ± 5% at week 4, and 81 ± 6% at week 8). Finally, the multi-parameter QUS model demonstrated a significant difference in survival rates of responding and non-responding patients at weeks 1 and 4 (p=0.035, and 0.027, respectively). CONCLUSION: This study demonstrated for the first time, using new parameters tested on relatively large patient cohort and leave-one-out classifier evaluation, that a hybrid QUS biomarker including MBF, SS, and SAS could, with relatively high sensitivity and specificity, detect the response of LABC tumors to NAC as early as after 4 weeks of therapy. The findings of this study also suggested that incorporating pre-treatment QUS parameters of a tumor improved the classification results. This work demonstrated the potential of QUS and machine learning methods for the early assessment of breast tumor response to NAC and providing personalized medicine with regards to the treatment planning of refractory patients.

Associations among socioeconomic status, patterns of care and outcomes in breast cancer patients in a universal health care system: Ontario's experience.

BACKGROUND: The Canadian health care system provides equitable access to equivalent standards of care. The authors investigated to determine whether patients with breast cancer who had different socioeconomic status (SES) received different care and had different overall survival (OS) in Ontario, Canada. METHODS: Women who were diagnosed with breast cancer between 2004 and 2009 were identified from the Ontario Cancer Registry and linked to provincial databases to ascertain patient demographics, screening, diagnosis, treatment patterns, and survival. SES was defined as neighborhood income by postal code and was divided into income quintiles (Q1-Q5; with Q5 the highest SES quintile). Univariable and multivariable analyses were used to examine the associations between: 1) SES and mammogram screening and breast cancer treatments, and 2) SES and OS. RESULTS: In total, 34,776 patients with breast cancer who had information on disease stage available at diagnosis were identified. Seventy-six percent of women were aged >50 years. Patients with higher SES were more likely to be diagnosed at an earlier stage (Q5 [44.3%] vs Q1 [37.7%]; odds ratio [OR], 1.31; 95% confidence interval [CI], 1.23-1.41; P < .0001) and also were more likely to receive adjuvant chemotherapy (Q5 vs Q1: OR, 1.18; 95% CI, 1.10-1.26; P < .0001) and radiotherapy (Q5 vs Q1: OR, 1.24; 95% CI, 1.15-1.33; P < .0001). The 5-year OS rates for Q1 through Q5 were 80%, 81%, 82.2%, 83.9%, and 85.7%, respectively (P < .0001). After adjusting for patient demographics, cancer stage at diagnosis, adjuvant chemotherapy, trastuzumab, radiotherapy and surgery types, higher SES remained associated with better OS (P = .0017). CONCLUSIONS: In a universal health care system, higher SES is associated with greater screening and treatments and with better OS after adjusting for screening, cancer stage at diagnosis, and treatments.

Cost-effectiveness of prophylactic granulocyte colony-stimulating factor for febrile neutropenia in breast cancer patients receiving FEC-D.

5-fluorouracil, epirubicin, cyclophosphamide â†’ docetaxel (FEC-D) has been associated with higher-than-expected rates of febrile neutropenia (FN) that meet the current guideline threshold of 20 % for primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF). We examined the cost-effectiveness of FEC-D with varying strategies of G-CSF prophylaxis from the perspective of the public payer in Ontario, Canada. A state-transition model was developed to compare three strategies: FEC-D with secondary prophylaxis (SP) only, PP starting with the first cycle of D, and PP starting with the first cycle of FEC. Analysis was conducted for a hypothetical cohort of 50-year-old early-stage breast cancer patients undergoing adjuvant chemotherapy, at a 10-year horizon. Results were expressed in quality-adjusted life-years (QALYs) and 2013 Canadian dollars. Costs and benefits were discounted at 5 %. Event rates, costs, and utilities were derived from the literature. One-way and probabilistic sensitivity analyses were conducted. Using filgrastim, the incremental cost-effectiveness ratios (ICERs) for starting PP with the first cycle of D and starting PP with the first cycle of FEC, compared to using SP only, were $57,886/QALY and $116,186/QALY, respectively. With pegfilgrastim, the ICERs for the same strategies were $90,735/QALY and $149,483/QALY. Compared to using filgrastim SP only, starting PP with D had a 24 % chance of being cost-effective at a willingness-to-pay (WTP) threshold of $50,000/QALY, and a 99 % chance at a WTP threshold of $100,000/QALY. Results were sensitive to FN-related parameters, such as the risk of FN per cycle with D and the associated mortality, but were robust to uncertainty in parameters related to breast cancer, such as the utilities and hazard of relapse. FEC-D with PP starting with the first cycle of D is most likely to be cost-effective, especially with increased risk of FN and mortality from FN.

Population-based assessment of emergency room visits and hospitalizations among women receiving adjuvant chemotherapy for early breast cancer.

PURPOSE: Adjuvant chemotherapy is considered standard care for patients with lymph node (LN) -positive and high-risk LN-negative early breast cancer (EBC). Although chemotherapy-associated toxicities are documented in clinical trials, the impact of toxicities on emergency room (ER) visits and hospitalizations (ER + Hs) at a population level with contemporary chemotherapy is unknown. We undertook a population-based study of ER + Hs in patients with EBC receiving adjuvant chemotherapy compared with noncancer controls (NCCs). METHODS: All patients diagnosed with EBC between January 2007 and December 2009 in Ontario, Canada, were identified from the Ontario Cancer Registry. Patient records were linked deterministically to provincial health care databases to provide comprehensive medical follow-up. All patients received ≥ one cycle of adjuvant chemotherapy. Patient cases of EBC (n = 8,359) were matched to NCCs (n = 8,359) on age, comorbidity, and geographic location. ER + Hs within 30 days of chemotherapy were identified. If the primary reason for the visit was a common chemotherapy toxicity, the visit was considered chemotherapy associated. All-cause and chemotherapy-associated visits were compared between patient cases and controls. Logistic regression models were used to identify covariates associated with ER + Hs. RESULTS: The proportion of patients with at least one ER + H was significantly higher in patients with EBC undergoing chemotherapy compared with NCCs (43.4% v 9.4%; P < .001). Patients with EBC were also more likely to have multiple ER + Hs (17.9% v 2.4%; P < .001). On multivariable analysis, comorbidity, receiving a regimen containing docetaxel, and certain geographic regions were associated with increased odds of ER + Hs. CONCLUSION: ER + Hs are common among patients with EBC receiving chemotherapy and significantly higher than among controls. This represents a potential opportunity for quality improvement.

Utilization and costs of home care for patients with colorectal cancer: a population-based study.

BACKGROUND: The utilization and costs of home care services provided for people with colorectal cancer is not well-known. We conducted an analysis to determine the utilization and costs of such services associated with each stage of colorectal cancer among patients in the province of Ontario. METHODS: We included cases of colorectal cancer diagnosed in Ontario between Jan. 1, 2005, and Dec. 31, 2009. Data were extracted from the Ontario Cancer Registry and linked to data from a home care administrative database. The types of services used were stratified by stage of disease and by phase of care (initial phase = 180 d after diagnosis, terminal phase = 180 d before death, continuing phase = interval between initial and terminal phases). Overall utilization rates and costs were determined, and regression analysis was used to examine associated factors. RESULTS: A total of 36 195 patients had colorectal cancer diagnosed during the study period; the median age was 71 (interquartile range 61-79) years. Home care services were provided to 24 641 patients (68.1%). The number of services per patient-year was 27.5, at a cost of $2180 per patient-year. The number of services provided per patient-year increased with increasing disease severity at diagnosis (15.5 at stage I, 25.5 at stage II, 32.5 at stage III and 62.5 at stage IV; 22.6 for unstaged disease). The cost of services per patient-year also increased with disease severity at diagnosis ($1170 at stage I, $1995 at stage II, $2727 at stage III and $5541 at stage IV). Publicly funded home care services and associated costs decreased with increasing income group, but they increased among patients who had a history of high health resource utilization. The mean 30-day cost of home care services decreased from the initial phase of care ($323) to the continuing phase ($160) but increased during the terminal phase ($616). INTERPRETATION: More than two-thirds of the patients with colorectal cancer in this study used home care services. Those who received home care services used about 2 services per month in a one-year period, at a cost of about $2000 per year. This information can aid policy-makers in future decisions regarding resource allocations.

Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

BACKGROUND: Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. METHODS: We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). RESULTS: Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. CONCLUSIONS: Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug.

End-of-life home care utilization and costs in patients with advanced colorectal cancer.

OBJECTIVE: To determine overall utilization and costs associated with home care services in Ontario, Canada by linking a home care database to a stage IV colorectal cancer cohort. METHODS: The names of patients with stage IV colorectal cancer at time of diagnosis (diagnosed from 2005 through 2009) were extracted from the Ontario Cancer Registry. The study cohort comprised those who died before the end of the study. The terminal phase of care was the period of time between diagnosis and death, with a maximum value of 180 days (6 months). Patients were linked to home care services datasets. The type, frequency, and cost of home care services were determined. Regression analysis was used to examine factors associated with utilization and cost. RESULTS: In all, 3,613 stage IV colorectal cancer patients (median age, 71 years) were diagnosed and died during the study's time horizon. During the terminal phase, 79.3% received at least 1 home care visit, and 58.0% had at least 1 palliative visit. Terminal metastatic colorectal cancer patients received an average of 8 home care visits at Canadian $800 within a 30-day time horizon. Home care costs were highest in the month before death. Male sex, a history of moderate or high utilization of health care services, and hospitalization were associated with lower home care costs. LIMITATIONS: Administrative data do not reveal the purpose, efficiency, effectiveness/sufficiency, quality, or appropriateness of home care. CONCLUSION: Patients with advanced colorectal cancer who were approaching death required a moderate level of home care support, resulting in costs of about $5,000 over the 6-month time horizon. FUNDING: This study was conducted with the support of the Ontario Institute for Cancer Research and Cancer Care Ontario through funding provided by the government of Ontario. Data were provided by Cancer Care Ontario and the Institute for Clinical Evaluative Sciences. The ICES also provided funding for the study from an annual grant by the Ontario Ministry of Health and Long-term Care.