Associations between clinical pathway concordance, cost, and survival outcomes for stage II colon cancer: a population-based study.

This study measures patient's concordance between clinical reference pathways with survival or cost among a population-based cohort of colon cancer patients applying a continuous measure of concordance. The primary hypothesis is that a higher concordance score with the clinical pathway is significantly associated with longer survival or lower cost. The study informs whether patient's adherence to a defined clinical pathway is beneficial to patients' outcomes or health system. An externally determined clinical pathway for colon cancer was used to identify treatment nodes in colon cancer care. Using observational data up to 2019, the study generated a continuous measure of pathway concordance. The study measured whether incremental improvements in pathway concordance were associated with survival and treatment costs. Concordance between patients' reference pathways and their observed trajectories of care was highly statistically associated with survivorship [hazard ratio: 0.95 (95% confidence interval, CI, 0.95-0.96)], showing that adherence to the clinical pathway was associated with a lower mortality rate. An increase in concordance was statistically significantly associated with a decrease in health system cost. When patients' care followed the clinical pathway, survival outcomes were better and total health system costs were lower in this cohort. This finding creates a compelling case for further research into understanding the barriers to pathway concordance and developing interventions to improve outcomes and help providers implement best practice care where appropriate.

Development of population-level colon cancer pathway concordance measures and association with survival.

Clinical cancer pathways help standardize healthcare delivery to optimize patient outcomes and health system costs. However, population-level measurement of concordance between standardized pathways and actual care received is lacking. Two measures of pathway concordance were developed for a simplified colon cancer pathway map for Stage II-III colon cancer patients in Ontario, Canada: a cumulative count of concordant events (CCCE) and the Levenshtein algorithm. Associations of concordance with patient survival were estimated using Cox proportional hazards models adjusted for patient characteristics and time-dependent cancer-related activities. Models were compared and the impact of including concordance scores was quantified using the likelihood ratio chi-squared test. The ability of the measures to discriminate between survivors and decedents was compared using the C-index. Normalized concordance scores were significantly associated with patient survival in models for cancer stage-a 10% increase in concordance for Stage II patients resulted in a CCCE score adjusted hazard ratio (aHR) of death of 0.93, 95% CI 0.88-0.98 and a Levenshtein score aHR of 0.64, 95% CI 0.60-0.67. A similar relationship was found for Stage III patients-a 10% increase in concordance resulted in a CCCE aHR of 0.85, 95% CI 0.81-0.88 and a Levenshtein aHR of 0.78, 95% CI, 0.74-0.81. Pathway concordance can be used as a tool for health systems to monitor deviations from established clinical pathways. The Levenshtein score better characterized differences between actual care and clinical pathways in a population, was more strongly associated with survival and demonstrated better patient discrimination.

Trends of Dementia among Community-Dwelling Adults in Ontario, Canada, 2010-2015.

BACKGROUND: There are increasing numbers of people living with dementia (PLWD) and most reside in community settings. Characterizing the number of individuals affected with dementia and their transitions are important to understand in order to plan for their healthcare needs. Using administrative health data in Ontario, Canada, we examined recent trends in the prevalence and incidence of dementia among the community-dwelling population, described their characteristics, and investigated admissions to long-term care (LTC) and overall survival. METHODS: Using a validated case ascertainment algorithm, we performed a population-based retrospective cohort study of community-dwelling PLWD aged 40-105 years old between 2010 and 2015. We assessed crude and age- and sex-adjusted prevalence and incidence, cohort characteristics, and time to LTC admission and survival. RESULTS: Between 2010 and 2015, the adjusted community prevalence increased by 9.5% (p < 0.001), while the incidence decreased by 15.8% (p < 0.001). Demographic and socioeconomic characteristics remained similar over time, while the prevalence of comorbidities increased significantly from 2010 to 2015. There was no difference in the time to LTC admission for individuals diagnosed in 2014 when compared to 2010 (p = 0.06). A lower risk of 2-year mortality was observed for individuals diagnosed in 2015 compared to 2010 (HR 0.93, 95% CI 0.90-0.97, p < 0.001). CONCLUSION: There was an increase in the prevalence of dementia despite decreasing incidence among community-dwelling PLWD. Lower rates of mortality indicate that PLWD are surviving longer following diagnosis. Adequate resources and planning are required to support this growing population, considering the changing population size and characteristics.

Clearing the surgical backlog caused by COVID-19 in Ontario: a time series modelling study.

BACKGROUND: To mitigate the effects of coronavirus disease 2019 (COVID-19), jurisdictions worldwide ramped down nonemergent surgeries, creating a global surgical backlog. We sought to estimate the size of the nonemergent surgical backlog during COVID-19 in Ontario, Canada, and the time and resources required to clear the backlog. METHODS: We used 6 Ontario or Canadian population administrative sources to obtain data covering part or all of the period between Jan. 1, 2017, and June 13, 2020, on historical volumes and operating room throughput distributions by surgery type and region, and lengths of stay in ward and intensive care unit (ICU) beds. We used time series forecasting, queuing models and probabilistic sensitivity analysis to estimate the size of the backlog and clearance time for a +10% (+1 day per week at 50% capacity) surge scenario. RESULTS: Between Mar. 15 and June 13, 2020, the estimated backlog in Ontario was 148 364 surgeries (95% prediction interval 124 508-174 589), an average weekly increase of 11 413 surgeries. Estimated backlog clearance time is 84 weeks (95% confidence interval [CI] 46-145), with an estimated weekly throughput of 717 patients (95% CI 326-1367) requiring 719 operating room hours (95% CI 431-1038), 265 ward beds (95% CI 87-678) and 9 ICU beds (95% CI 4-20) per week. INTERPRETATION: The magnitude of the surgical backlog from COVID-19 raises serious implications for the recovery phase in Ontario. Our framework for modelling surgical backlog recovery can be adapted to other jurisdictions, using local data to assist with planning.

Estimation of high-dimensional propensity scores with multiple exposure levels.

PURPOSE: Little information is available on the performance of high-dimensional propensity scores (HDPS) in settings with more than two exposure levels. Our objective was to adapt the HDPS algorithm to allow for the inclusion of multilevel treatments and compare estimates obtained via this approach with those obtained via pairwise comparisons in a case study using real-world data. METHODS: We conducted a retrospective cohort study of cardiovascular events associated with three smoking cessation drugs (varenicline, bupropion, nicotine replacement therapy [NRT]) using the Clinical Practice Research Datalink. We applied the binary HDPS algorithm adjusted for pre-specified and empirically-selected covariates to cohorts formed by each treatment pair. We then constructed multinomial HDPS models on a cohort of new users of any of the three drugs, adjusting for predefined covariates and different combinations of empirically-selected covariates. After trimming the area of non-overlap of the HDPS distributions, the effects of the study drugs on cardiovascular events were estimated with the Cox proportional hazards models adjusted for propensity score category. RESULTS: Outcome models adjusted for multinomial HDPS estimated treatment effects that were slightly more protective than those estimated in pairwise comparisons (varenicline vs NRT: HRMultinomial = 0.60-0.62, HRPairwise = 0.64; bupropion vs NRT: HRMultinomial = 0.70-0.72, HRPairwise = 0.76). Trimming rates were similar between the two approaches. CONCLUSIONS: The extension of HDPS to multilevel exposures is a valid and practical approach to confounder control that may be useful when comparing different classes of drugs prescribed for the same indication or different molecules within a given drug class.

Effect of PET/CT on the Management and Outcomes of Participants with Hodgkin and Aggressive Non-Hodgkin Lymphoma: A Multicenter Registry.

Purpose To determine the relationship of PET/CT staging to the management and outcomes of participants with apparent limited-stage (LS) Hodgkin lymphoma (HL) or aggressive non-HL (ANHL) treated with curative intent. Materials and Methods This prospective multicenter registry included 850 participants (467 men and 383 women; median age, 54.1 years) from nine centers who had LS HL or ANHL on the basis of clinical data and CT, or with equivocal CT for advanced stage, who were considered for curative-intent first-line therapy. Participants were recruited between May 1, 2013, and December 31, 2015. Pre-PET/CT treatment plan was compared with treatment provided. Survival and second-line therapy initiation were compared with an historical control pool staged by using CT alone. Administrative data sources were used to control for baseline characteristics. Outcomes were assessed by using adjusted Cox proportional hazards regression and propensity score matching. Results PET/CT helped to upstage 150 of 850 participants (17.6%). There was a change in planned therapy in 224 of 580 (38.6%) of participants after PET/CT. There was a lower 1-year mortality for participants with ANHL in the PET/CT versus CT cohort (hazard ratio, 0.63; 95% confidence interval: 0.40, 1.0; P < .05) and for those with LS at PET/CT compared with those with LS at CT (hazard ratio, 0.40; 95% confidence interval: 0.21, 0.74; P = .004). For participants with HL, no 1-year outcome difference was found (P = .16). Conclusion PET/CT helped to upstage approximately 18% of participants and planned management was frequently altered. Participants with aggressive non-Hodgkin lymphoma whose first-line therapy was guided by PET/CT had significantly better survival compared with participants whose treatment was guided by CT. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Scott in this issue.

The Estimation of Gestational Age at Birth in Database Studies.

BACKGROUND: Studies on the safety of prenatal medication use require valid estimation of the pregnancy duration. However, gestational age is often incompletely recorded in administrative and clinical databases. Our objective was to compare different approaches to estimating the pregnancy duration. METHODS: Using data from the Clinical Practice Research Datalink and Hospital Episode Statistics, we examined the following four approaches to estimating missing gestational age: (1) generalized estimating equations for longitudinal data; (2) multiple imputation; (3) estimation based on fetal birth weight and sex; and (4) conventional approaches that assigned a fixed value (39 weeks for all or 39 weeks for full term and 35 weeks for preterm). The gestational age recorded in Hospital Episode Statistics was considered the gold standard. We conducted a simulation study comparing the described approaches in terms of estimated bias and mean square error. RESULTS: A total of 25,929 infants from 22,774 mothers were included in our "gold standard" cohort. The smallest average absolute bias was observed for the generalized estimating equation that included birth weight, while the largest absolute bias occurred when assigning 39-week gestation to all those with missing values. The smallest mean square errors were detected with generalized estimating equations while multiple imputation had the highest mean square errors. CONCLUSIONS: The use of generalized estimating equations resulted in the most accurate estimation of missing gestational age when birth weight information was available. In the absence of birth weight, assignment of fixed gestational age based on term/preterm status may be the optimal approach.

Statin potency and the risk of hospitalization for community-acquired pneumonia.

AIM: Previous studies suggest that statins may have beneficial respiratory effects. However, it is unclear if these purported benefits vary with statin potency. Our objective was to determine if higher potency statins, compared with lower potency statins, were associated with a reduced risk of hospitalization for community-acquired pneumonia (HCAP). METHODS: We conducted a nested case-control analysis of a retrospective, population-based cohort of new users of statins using data extracted from the UK's Clinical Practice Research Datalink and Hospital Episode Statistics. For each HCAP case, we used risk set sampling to randomly select up to 10 controls, matched on sex, age, cohort entry date and follow-up duration. We used conditional logistic regression with high-dimensional propensity scores to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for HCAP with current use of higher potency statin vs. lower potency statins. RESULTS: A total of 217 721 patients entered the cohort on a lower potency statin and 130 707 entered on a higher potency statin; these patients resulted in 2251 cases of HCAP during 561 886 person-years of observation (rate: 4.0 HCAP per 1000 persons per year, 95% CI: 3.8-4.2). The analysis included 22 178 matched controls. Compared with lower potency statins, higher potency statins were associated with an increased rate of HCAP (HR: 1.14, 95% CI: 1.03-1.27). Higher potency statins were also associated with an increased rate of fatal HCAP (HR: 1.29, 95% CI: 1.04-1.59). CONCLUSIONS: Higher potency statins were not associated with a decreased risk of HCAP compared with lower potency statins.

Hypertensive Disorders in Pregnancy and the Risk of Subsequent Cardiovascular Disease.

BACKGROUND: Hypertensive disorders in pregnancy (HDP) have been shown to predict later risk of cardiovascular disease (CVD). However, previous studies have not accounted for subsequent pregnancies and their complications, which are potential confounders and intermediates of this association. METHODS: A cohort of 146 748 women with a first pregnancy was constructed using the Clinical Practice Research Datalink. HDP was defined using diagnostic codes, elevated blood pressure readings, or new use of an anti-hypertensive drug between 18 weeks' gestation and 6 weeks post-partum. The study outcomes were incident CVD and hypertension. Marginal structural Cox models (MSM) were used to account for time-varying confounders and intermediates. Time-fixed exposure defined at the first pregnancy was used in secondary analyses. RESULTS: A total of 997 women were diagnosed with incident CVD, and 6812 women were diagnosed with hypertension or received a new anti-hypertensive medication during the follow-up period. Compared with women without HDP, those with HDP had a substantially higher rate of CVD (hazard ratio (HR) 2.2, 95% confidence interval (CI) 1.7, 2.7). In women with HDP, the rate of hypertension was five times that of women without a HDP (HR 5.6, 95% CI 5.1, 6.3). With overlapping 95% CIs, the time-fixed analysis and the MSM produced consistent results for both outcomes. CONCLUSIONS: Women with HDP are at increased risk of developing subsequent CVD and hypertension. Similar estimates obtained with the MSM and the time-fixed analysis suggests that subsequent pregnancies do not confound a first episode of HDP and later CVD.

Targeted Maximum Likelihood Estimation for Pharmacoepidemiologic Research.

BACKGROUND: Targeted maximum likelihood estimation has been proposed for estimating marginal causal effects, and is robust to misspecification of either the treatment or outcome model. However, due perhaps to its novelty, targeted maximum likelihood estimation has not been widely used in pharmacoepidemiology. The objective of this study was to demonstrate targeted maximum likelihood estimation in a pharmacoepidemiological study with a high-dimensional covariate space, to incorporate the use of high-dimensional propensity scores into this method, and to compare the results to those of inverse probability weighting. METHODS: We implemented the targeted maximum likelihood estimation procedure in a single-point exposure study of the use of statins and the 1-year risk of all-cause mortality postmyocardial infarction using data from the UK Clinical Practice Research Datalink. A range of known potential confounders were considered, and empirical covariates were selected using the high-dimensional propensity scores algorithm. We estimated odds ratios using targeted maximum likelihood estimation and inverse probability weighting with a variety of covariate selection strategies. RESULTS: Through a real example, we demonstrated the double robustness of targeted maximum likelihood estimation. We showed that results with this method and inverse probability weighting differed when a large number of covariates were included in the treatment model. CONCLUSIONS: Targeted maximum likelihood can be used in high-dimensional covariate settings. In high-dimensional covariate settings, differences in results between targeted maximum likelihood and inverse probability weighted estimation are likely due to sensitivity to (near) positivity violations. Further investigations are needed to gain better understanding of the advantages and limitations of this method in pharmacoepidemiological studies.

Reprise du retard en chirurgie causé par la COVID-19 en Ontario : étude de modélisation de séries chronologiques.

CONTEXTE: Pour limiter la propagation de la maladie à coronavirus 2019 (COVID-19), de nombreux pays ont décidé de réduire le nombre d'interventions chirurgicales non urgentes, ce qui a créé des retards en chirurgie partout dans le monde. Notre objectif était d'évaluer l'ampleur du retard pour ce type d'interventions en Ontario, au Canada, ainsi que le temps et les ressources nécessaires pour y remédier. MÉTHODES: Nous avons consulté 6 bases de données administratives décrivant la population ontarienne et canadienne pour dégager la distribution du volume chirurgical et de la cadence des salles d'opération pour chaque type d'interventions et chaque région, et connaître la durée d'occupation d'un lit d'hôpital et d'un lit de soins intensifs. Les données utilisées concernent l'ensemble ou une partie de la période du 1er janvier 2017 au 13 juin 2020. Nous avons estimé l'ampleur du retard accumulé et prédit le temps nécessaire pour le reprendre dans un scénario avec capacité d'appoint de + 10 % (ajout d'un jour à 50 % de la capacité par semaine) à l'aide de modèles de séries chronologiques, de modèles de files d'attente et d'une analyse de sensibilité probabiliste. RÉSULTATS: Entre le 15 mars et le 13 juin 2020, le retard en chirurgie à l'échelle de l'Ontario s'est accru de 148 364 opérations (intervalle de prévision à 95 % 124 508­174 589) au total, et en moyenne de 11 413 opérations par semaine. Pour reprendre le retard accumulé, il faudra environ 84 semaines (intervalle de confiance [IC] à 95 % 46­145) et une cadence hebdomadaire de 717 patients (IC à 95 % 326­1367), qui elle demande 719 heures passées au bloc opératoire (IC à 95 % 431­1038), 265 lits d'hôpital (IC à 95 % 87­678) et 9 lits de soins intensifs (IC à 95 % 4­20) par semaine. INTERPRÉTATION: L'ampleur du retard en chirurgie dû à la COVID-19 laisse entrevoir de graves conséquences pour la phase de reprise en Ontario. Le cadre qui nous a servi à modéliser la reprise du retard peut être adapté ailleurs, avec des données locales, pour faciliter la planification.

Confounding by drug formulary restriction in pharmacoepidemiologic research.

PURPOSE: The potential consequences of confounding due to drug formulary restrictions in pharmacoepidemiologic research remain incompletely understood. Our objective was to illustrate this potential bias using the example of fluticasone/salmeterol combination therapy, an oral inhaler used to treat asthma and chronic obstructive pulmonary disease, whose use is restricted in the province of Quebec, Canada. METHODS: We identified all new users of fluticasone/salmeterol in Quebec's administrative databases and classified those who received their initial dispensing of fluticasone/salmeterol between 1 September 1999 and 30 September 2003 as users from the liberal period and those who received it between 1 January 2004 and 31 October 2006 as users from the restricted period. The primary outcome was time to first hospitalization for respiratory causes within 12 months of cohort entry. RESULTS: Our cohort included 72 154 new users from the liberal period and 5058 from the restricted period. Compared with use during the liberal period, use during the restricted period was associated with an increased rate of hospitalization for respiratory causes (crude hazard ratio [HR] = 1.41, 95% confidence interval [CI] = 1.32, 1.51). Subsequent adjustment for age, sex, and hospitalization for respiratory causes in the previous year attenuated the association (HR = 1.05, 95%CI = 0.98, 1.12). Further adjustment for other potential confounders resulted in a lower rate during the restricted period (HR = 0.78, 95%CI = 0.73, 0.83). CONCLUSIONS: Formulary restrictions can result in substantial and unexpected confounding and should be considered during the design and analysis of pharmacoepidemiologic studies.

High-sensitivity cardiac troponin T and the risk of incident atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) study.

INTRODUCTION: Structural changes in the heart are known risk factors for atrial fibrillation (AF). An association between high-sensitivity cardiac troponin T (hs-cTnT), a marker of myocardial cell damage measured with a high-sensitivity assay, and the risk of AF could have implications for AF risk stratification. OBJECTIVE: To estimate the association between hs-cTnT and the risk of incident AF in the ARIC study, a prospective cohort of middle-aged adults from 4 US communities. METHODS: Study included 10,584 participants (mean age 62.7 years) free of AF in 1996 to 1998 and followed through 2008. Atrial fibrillation was defined using International Classification of Diseases codes from hospitalizations and death certificates. Participants with undetectable hs-cTnT levels (58%) were assigned the lower limit of measurement (5 ng/L). Net reclassification improvement was used to examine the discriminative ability of hs-cTnT for 10-year AF risk prediction (categories: <5%, 5%-15%, and >15%). RESULTS: A total of 920 incident AF cases were observed for 109,227 person-years. After adjustment, a 1-SD difference in ln(hs-cTnT) was associated with a hazard ratio of 1.16 (95% CI 1.10-1.23). Compared with those with undetectable levels, participants with hs-cTnT ≥14 ng/L had a hazard ratio of 1.78 (95% CI 1.43-2.24). Addition of hs-cTnT to known AF predictors did not increase the c statistic appreciably (0.756 vs 0.758) or improve risk stratification (net reclassification improvement 0.4%, 95% CI -1.4% to 2.3%). CONCLUSIONS: High-sensitivity cTnT level is associated with an increased incidence rate of AF but did not improve risk stratification.

Real-world effectiveness and safety of ustekinumab in bio-naive patients with moderate-to-severe Crohn's disease: A Canadian multi-center study.

BACKGROUND: Clinical practice guidelines recommend ustekinumab as a first-line biological treatment option for moderately-to-severely active Crohn's disease (CD). However, there is limited real-world effectiveness and safety data in bio-naïve patients. AIMS: To assess ustekinumab effectiveness and safety in bio-naïve CD patients. METHODS: Medical charts were reviewed retrospectively at seven Canadian centers. The primary outcome was the proportion of patients achieving clinical remission at Month 6 following ustekinumab initiation. Secondary outcomes included clinical, biochemical, and endoscopic response, and remission at Months 4, 6 and 12. Ustekinumab safety was assessed over the one-year follow-up period. RESULTS: 158 charts were reviewed. Clinical remission was achieved by 50.0% (36/72), 67.7% (105/155), and 73.7% (84/114) of patients at Months 4, 6, and 12, respectively. At these study timepoints, biochemical remission was observed in 65.2% (43/66), 71.6% (63/88), and 73.9% (68/92) of patients. At Months 6 and 12, endoscopic remission was observed in 40.5% (15/37) and 56.3% (27/48) of patients, respectively. Most participants (93.5%; 145/155) persisted on ustekinumab through Month 12. No serious adverse drug reactions were reported. CONCLUSION: In this real-world study, ustekinumab presents as an effective first-line biologic for induction and maintenance of remission among bio-naïve Canadian patients with moderately-to-severely active CD.

Healthcare resource utilization following ustekinumab initiation among bio-naïve Canadian patients with moderately-to-severely active Crohn's disease.

BACKGROUND/AIMS: Real-world healthcare resource utilization (HCRU) of bio-naïve patients with Crohn's disease (CD) receiving ustekinumab was assessed. METHODS: A multicentre, retrospective chart review study of bio-naïve Canadian adult patients with moderately-to-severely active CD treated with ustekinumab was conducted. CD-related HCRU (i.e., surgery, hospitalization, or emergency room [ER] visits) was evaluated at Months 4, 6, and 12 post-ustekinumab initiation, and associated costs were sourced from a provincial database. Proportion of patients with HCRU events and ustekinumab persistence were summarized at each timepoint. Paired analysis compared HCRU events and associated costs incurred by the same patient whilst in remission vs. when not in remission. RESULTS: By Month 12, 11.1 % (17/153) of patients had record(s) of any CD-related HCRU event, with ER visits being the most common (7.7 %; 12/155). Hospitalization had the highest average cost (CAD $436.10; SD $2,089.25) across all patients, accounting for 82.2 % of the mean total annual cost/patient (CAD $530.47; SD $2,229.92). While in remission, ≤5 % of patients experienced some healthcare encounter, compared with 7 % when not in remission (P = 0.289). Finally, 93.5 % of patients persisted on ustekinumab at Month 12. CONCLUSIONS: HCRU rates and associated total annual costs were lower for bio-naïve CD patients receiving ustekinumab, and when patients were in remission. Most patients continued with ustekinumab at Month 12.

Real-World Safety and Effectiveness of a Bevacizumab Biosimilar (ABP 215) in Metastatic Colorectal Cancer Patients in Canada.

BACKGROUND: ABP 215 is a biosimilar to the reference product, bevacizumab, and was one of the first biosimilars approved by Health Canada for the first-line treatment of metastatic colorectal cancer (mCRC). This study aimed to address gaps in real-world evidence (RWE) including patient characteristics, treatment safety (primary objective), and effectiveness (secondary objective) for first-line ABP 215 therapy in Canadian patients with mCRC. MATERIALS AND METHODS: Retrospective data were collected in 2 waves, at least 1 year (Wave 1) or 2 years (Wave 2) after commercial availability of ABP 215 at each participating site. RESULTS: A total of 75 patients from Wave 1 and 164 patients from Wave 2 treated with a minimum of 1 cycle of ABP 215 were included. At least one safety event of interest (EOI) was recorded for 34.7% of Wave 1 and 42.7% of Wave 2 patients. The median progression free survival (PFS) for Wave 1 and 2 patients were 9.47 (95% confidence interval [CI]: 6.71, 11.90) and 21.38 (95% CI: 15.82, not estimable) months, respectively. Median overall survival was not estimable for Wave 1 and was 26.45 months for Wave 2. CONCLUSION: The safety and effectiveness of ABP 215 observed in this real-world study were comparable to clinical trial findings and to other RWE with longer PFS in the current study.

Estimating the Burden of Illness of Relapsed Follicular Lymphoma and Marginal Zone Lymphoma in Ontario, Canada.

BACKGROUND: Many patients with advanced follicular lymphoma (FL) and marginal zone lymphoma (MZL) relapse after first-line chemotherapy. OBJECTIVE: To examine healthcare resource utilization (HCRU) and cost, treatment patterns, progression, and survival of patients with FL and MZL who relapse after first-line treatment, in Ontario, Canada. METHODS: A retrospective, administrative data study identified patients with relapsed FL and MZL (1 January 2005-31 December 2018). Patients were followed for up to three years post relapse to assess HCRU, healthcare costs, time to next treatment (TTNT), and overall survival (OS), stratified by first- and second-line treatment. RESULTS: The study identified 285 FL and 68 MZL cases who relapsed after first-line treatment. Average duration of first-line treatment was 12.4 and 13.4 months for FL and MZL patients, respectively. Drug (35.9%) and cancer clinic costs (28.1%) were major contributors to higher costs in year 1. Three-year OS was 83.9% after FL and 74.2% after MZL relapse. No statistically significant differences were observed in TTNT and OS between patients with FL who received R-CHOP/R-CVP/BR in the first line only versus both the first- and second- line. A total of 31% of FL and 34% of MZL patients progressed to third-line treatment within three years of initial relapse. CONCLUSION: Relapsing and remitting nature of FL and MZL in a subset of patients results in substantial burden to patients and the healthcare system.

Estimating the Associated Burden of Illness and Healthcare Utilization of Newly Diagnosed Patients Aged ≥65 with Mantle Cell Lymphoma (MCL) in Ontario, Canada.

BACKGROUND: With the emergence of therapies for mantle cell lymphoma (MCL), understanding the treatment patterns and burden of illness among older patients with MCL in Canada is essential to inform decision making. METHODS: A retrospective study using administrative data matched individuals aged ≥65 who were newly diagnosed with MCL between 1 January 2013 and 31 December 2016 with general population controls. Cases were followed for up to 3 years in order to assess healthcare resource utilization (HCRU), healthcare costs, time to next treatment or death (TTNTD), and overall survival (OS); all were stratified according to first-line treatment. RESULTS: This study matched 159 MCL patients to 636 controls. Direct healthcare costs were highest among MCL patients in the first year following diagnosis (Y1: CAD 77,555 ± 40,789), decreased subsequently (Y2: CAD 40,093 ± 28,720; Y3: CAD 36,059 ± 36,303), and were consistently higher than the costs for controls. The 3-year OS after MCL diagnosis was 68.6%, with patients receiving bendamustine + rituximab (BR) experiencing a significantly higher OS compared to patients treated with other regimens (72.4% vs. 55.6%, p = 0.041). Approximately 40.9% of MCL patients initiated a second-line therapy or died within 3 years. CONCLUSION: Newly diagnosed MCL presents a substantial burden to the healthcare system, with almost half of all patients progressing to a second-line therapy or death within 3 years.

Identifying Breast Cancer Recurrence in Administrative Data: Algorithm Development and Validation.

Breast cancer recurrence is an important outcome for patients and healthcare systems, but it is not routinely reported in cancer registries. We developed an algorithm to identify patients who experienced recurrence or a second case of primary breast cancer (combined as a "second breast cancer event") using administrative data from the population of Ontario, Canada. A retrospective cohort study design was used including patients diagnosed with stage 0-III breast cancer in the Ontario Cancer Registry between 1 January 2009 and 31 December 2012 and alive six months post-diagnosis. We applied the algorithm to healthcare utilization data from six months post-diagnosis until death or 31 December 2013, whichever came first. We validated the algorithm's diagnostic accuracy against a manual patient record review (n = 2245 patients). The algorithm had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 67%, a negative predictive value of 98%, an accuracy of 93%, a kappa value of 71%, and a prevalence-adjusted bias-adjusted kappa value of 85%. The second breast cancer event rate was 16.5% according to the algorithm and 13.0% according to manual review. Our algorithm's performance was comparable to previously published algorithms and is sufficient for healthcare system monitoring. Administrative data from a population can, therefore, be interpreted using new methods to identify new outcome measures.