The Economic Burden of Recurrence in Triple-Negative Breast Cancer Among Working Age Patients in the United States.

INTRODUCTION: Triple-negative breast cancer (TNBC) is associated with a high recurrence risk. However, the magnitude of direct and indirect costs associated with recurrence is lacking in the literature. METHODS: Adults 18-65 years old diagnosed with TNBC were identified from the OptumHealth Reporting and Insights claims database (1999-2017) and stratified by recurrence. For patients with recurrence, the index date was defined as 30 days before recurrence; for patients without recurrence, it was randomly assigned based on the distribution of time between first treatments and index dates of the recurrence cohort. All-cause and breast cancer-related healthcare resource utilization (HRU), direct and indirect costs, and work loss up to 1 year were compared between cohorts using generalized linear models. Kaplan-Meier analyses and Cox proportional hazards models compared the risk of leaving the workforce. RESULTS: Among the 2340 patients analyzed, mean age was 54 years and > 75% of patients had stage 0-2 cancer. Among the 1170 patients with recurrence, 236 were categorized as having metastatic recurrence and 934 as having locoregional recurrence. Relative to patients without recurrence, those with recurrence had significantly higher all-cause and breast cancer-related HRU. For instance, adjusted incidence rates (IRs) for all-cause inpatient admissions were 3.67 and 10.19 times higher for patients with locoregional and metastatic recurrence, respectively (p < 0.001). Adjusted all-cause healthcare costs were $8575/month higher for metastatic recurrence and $3609/month higher for locoregional recurrence vs. patients without recurrence (p < 0.001). Adjusted IRs for work loss days were approximately two times higher for locoregional and metastatic recurrence vs. without recurrence (p < 0.001). Patients with locoregional recurrence incurred $335/month more indirect costs vs. patients without recurrence; those with metastatic recurrence incurred $769/month more (p < 0.05). Patients with recurrence had a 63% higher rate of leaving the work force (p = 0.003). CONCLUSION: The incremental direct and indirect economic burden associated with recurrent TNBC is substantial relative to non-recurrence.

Real-world treatment patterns and effectiveness outcomes in patients with early-stage triple-negative breast cancer.

Background: This retrospective, observational study examined real-world treatment patterns and effectiveness outcomes in 450 patients with stage II-IIIB early-stage triple-negative breast cancer treated in the community oncology setting. Methods: Kaplan-Meier methods were used to evaluate event-free survival (EFS), time to recurrence and overall survival (OS). Cox regression models were used to evaluate predictors of EFS and OS by pathological complete response (pCR) status. Results: Among patients receiving neoadjuvant systemic therapy only, pCR was a predictor of EFS and OS. Conclusion: These results highlight the unmet need for therapies that improve outcomes for patients with early-stage triple-negative breast cancer including increasing rates of pCR among patients receiving neoadjuvant therapy.

Lay abstract This study included 450 patients with early-stage triple-negative breast cancer treated in the USA at community oncology practices. Patients were female, 18 years or older, diagnosed with stage II, IIIA or IIIB breast cancer between March 2008 and March 2016, and the breast cancer was determined to be triple negative (i.e., negative for estrogen receptors, progesterone receptors and excess HER2 protein). The study looked at the treatments received, whether those treatments worked and the response to treatment at the time of surgery. The study findings align with findings from other studies that complete response in tissue samples is associated with improved clinical outcomes. Triple-negative breast cancer remains challenging to treat, and there is a clear need for innovation in treatment options. Intervening in the early stages of triple-negative breast cancer is critical to improving outcomes.

Healthcare resource utilization and cost among patients treated for early-stage triple-negative breast cancer.

Background: This retrospective, observational study examined real-world healthcare resource utilization (HCRU) and costs in 308 patients diagnosed with early-stage (II-IIIB) triple-negative breast cancer between 1 March 2008 and 31 March 2016. Methods: HCRU and costs were evaluated for two time periods: from neoadjuvant treatment start date to surgery (Time 1) and after surgery to recurrence or death (Time 2). Results: The sample included 236 patients who received neoadjuvant treatment without subsequent adjuvant treatment (Neo) and 72 patients who received neoadjuvant treatment followed by adjuvant treatment (Neo + adj). Mean monthly HCRU events and mean monthly costs per patient were higher in Time 1 compared with Time 2 for both groups. Conclusion: These results demonstrate the economic burden of early-stage triple-negative breast cancer especially during neoadjuvant treatment phase.

Lay abstract This study included 308 patients with early-stage triple-negative breast cancer treated in the USA at community oncology practices. Patients were female, 18 years or older and diagnosed with stage II, IIIA or IIIB breast cancer between March 2008 and March 2016, and the breast cancer was determined to be triple negative (i.e., negative for estrogen receptors, progesterone receptors and excess HER2 protein). There were 236 patients who received neoadjuvant treatment without subsequent adjuvant treatment (the Neo group) and 72 patients who received neoadjuvant treatment followed by adjuvant treatment (the Neo + adj group). The study looked at healthcare resource use and costs of care during two time periods: from neoadjuvant treatment start date to surgery (Time 1) and after surgery to recurrence or death (Time 2). Average monthly healthcare resource use and average monthly costs of care per patient were higher in Time 1 compared with Time 2 for both groups. These results demonstrate the economic and resource burden of early-stage triple-negative breast cancer especially in the time from neoadjuvant treatment initiation until surgery.

Systemic therapy, survival and end-of-life costs for metastatic triple-negative breast cancer: retrospective SEER-Medicare study of women age ≥65 years.

Aim: To analyze therapy for metastatic triple-negative breast cancer (mTNBC), factors contributing to survival and costs. Patients & methods: Using 2010-2016 SEER-Medicare data, we identified women (≥65 years) with mTNBC. Results: Of 302 eligible patients, 152 (50%) received systemic therapy. In multivariable regression analyses, only age <75 years was associated with therapy receipt (odds ratio: 2.91; 95% CI: 1.79-4.74); and only systemic therapy significantly reduced risk of death (hazard ratio: 0.34; 95% CI: 0.26-0.44). Median overall survival was 13.4 (95% CI: 11.3-15.1) vs 3.3 months (95% CI: 2.7-3.9) in therapy vs no-therapy cohorts. Mean per-patient-per-month costs <30 days before end-of-life/follow-up were $14,100 and $15,600 (2019 USD), respectively. Conclusion: Poor outcomes and high costs indicate need for more effective mTNBC therapy.

Estimated Costs and Long-term Outcomes of Patients With High-Risk Non-Muscle-Invasive Bladder Cancer Treated With Bacillus Calmette-Guérin in the Veterans Affairs Health System.

Importance: Management of high-risk non-muscle-invasive bladder cancer (NMIBC) represents a clinical challenge due to high failure rates despite prior bacillus Calmette-Guérin (BCG) therapy. Objective: To describe real-world patient characteristics, long-term outcomes, and the economic burden in a population with high-risk NMIBC treated with BCG therapy. Design, Setting, and Participants: This retrospective cohort study identified 412 patients with high-risk NMIBC from 63 139 patients diagnosed with bladder cancer who received at least 1 dose of BCG within Department of Veterans Affairs (VA) centers across the US from January 1, 2000, to December 31, 2015. Adequate induction BCG therapy was defined as at least 5 installations, and adequate maintenance BCG therapy was defined as at least 7 installations. Data were analyzed from January 2, 2020, to January 20, 2021. Exposures: Intravesical BCG therapy, including adequate induction BCG therapy, was defined as at least 5 intravesical instillations of BCG within 70 days from BCG therapy start date. Adequate maintenance BCG therapy was defined as at least 7 installations of BCG within 274 days of the start (the first instillation) of adequate induction BCG therapy (ie, adequate induction BCG plus some form of additional BCG). Main Outcomes and Measures: The Kaplan-Meier method was used to estimate outcomes, including event-free survival. All-cause expenditures were summarized as medians with corresponding interquartile ranges (IQRs) and adjusted to 2019 USD. Results: Of the 412 patients who met inclusion criteria, 335 (81%) were male and 77 (19%) were female, with a median age of 67 (IQR, 61-74) years. Follow-up was 2694 person-years. A total of 392 patients (95%) received adequate induction BCG therapy, and 152 (37%) received adequate BCG therapy. For all patients with high-risk NMIBC, the 10-year progression-free survival rate and disease-specific death rate were 78% and 92%, respectively. Patients with carcinoma in situ (Cis) had worse disease-free survival than those without Cis (hazard ratio [HR], 1.85; 95% CI, 1.34-2.56). Total median costs at 1 year were $29 459 (IQR, $14 991-$52 060); at 2 years, $55 267 (IQR, $28 667-$99 846); and at 5 years, $117 361 (IQR, $59 680-$211 298). Patients with progressive disease had significantly higher median 5-year costs ($232 729 [IQR, $151 321-$341 195] vs $94 879 [IQR, $52 498-$172 631]; P < .001), with outpatient care, pharmacy, and surgery-related costs contributing. Conclusions and Relevance: Despite adequate induction BCG therapy, only 37% of patients received adequate BCG therapy. Patients with Cis had increased risk of progression, and progression regardless of Cis was associated with significantly increased costs relative to patients without progression. Extrapolating cost figures, regardless of progression, resulted in nationwide costs at 1 year of $373 million for patients diagnosed with high-risk NMIBC in 2019.

Early triple-negative breast cancer in women aged ≥65: retrospective study of outcomes, resource use and costs, 2010-2016.

Aim: To examine real-world treatment patterns and outcomes in neoadjuvant and adjuvant settings for early-stage triple-negative breast cancer (TNBC). Patients & methods: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients (≥65 years) with newly diagnosed stage II/III TNBC in 2010-2015 who had surgery plus neoadjuvant and/or adjuvant (systemic and/or radiation) therapy. Treatment, survival, healthcare resource use and costs were assessed through 2016. Results: Of 1569 patients (>99% women), 6%/74%/20% received neoadjuvant-only/adjuvant-only/both (neo + adj) therapies, respectively. Median overall survival was 23 months/not reached (NR)/78 months, with longer survival at stage II (NR/NR/78 months) than stage III (22/43/38 months). Mean per patient per month costs were $10,620 and $17,872 in neoadjuvant and adjuvant periods. Conclusion: These findings provide insights into clinical and economic outcomes for early-stage TNBC in 2010-2016.

Limitations and Challenges of Conducting Budget Impact Analyses in Rare Diseases: A Case Study of Alpha-1 Antitrypsin Deficiency.

OBJECTIVES: There are challenges in conducting a budget impact analysis (BIA) for rare disorders. Through this case study, we present some challenges and limitations of a BIA of managing patients affected with alpha-1 antitrypsin deficiency (AATD). We explored a conceptual basis and barriers for health services researchers interested in quantifying budget impacts of rare disease management program (DMP). METHODS: We developed a static budget impact cost calculator model in Microsoft Excel, obtaining the clinical impact of a DMP from the literature and translating it into costs using OLDW. Cost inputs and resource use was obtained from 2010 to 2015 claims data using the OLDW. Insurers' payments were calculated and categorized into the following cost buckets: physician visits, emergency room visits, inpatients stays, augmentation therapy, other prescription drugs costs, and other costs. RESULTS: Data were based on 6832 patients with alpha-1 antitrypsin deficiency identified among over 21 million OLDW enrollees observed between January 1, 2010, and December 31, 2015. The introduction of a DMP was estimated to decrease costs of the management of patients with alpha-1 antitrypsin deficiency by $13.5 million over 5 years. The savings attributed to the program over the 5-year time horizon are due to 2555 exacerbations, 5180 emergency room visits, 9342 specialist visits, and 105 358 general practitioner visits avoided. CONCLUSIONS: A comprehensive DMP for a rare condition might provide cost savings to a health plan. BIAs for rare disease may be more informative if they focus on DMPs rather than on individual drugs.

Medical costs of Alpha-1 antitrypsin deficiency-associated COPD in the United States.

BACKGROUND: There are limited data on economic aspects of the genetic variant of chronic obstructive pulmonary disease (COPD) in the context of the more prevalent form of COPD. The objective of this study was to isolate the healthcare resource utilization and economic burden attributable to the presence of a genetic factor among COPD patients with and without Alpha-1 Antitrypsin Deficiency (AATD), twelve months before and after their initial COPD diagnosis. METHODS: Retrospective analysis of OptumLabs® Data Warehouse claims (OLDW; 2000-2017). The OLDW is a comprehensive, longitudinal real-world data asset with de-identified lives across claims and clinical information. AATD-associated COPD cases were matched with up to 10 unique non-AATD-associated COPD controls. Healthcare resource use and costs were assigned into the following categories: office (OV), outpatient (OP), and emergency room visits (ER), inpatients stays (IP), prescription drugs (RX), and other services (OTH). A generalized linear model was used to estimate total pre- and post-index (initial COPD diagnosis) costs from a third-party payer's perspective (2018 USD) controlling for confounders. Healthcare resource utilization was estimated using a negative binomial regression. RESULTS: The study population consisted of 8881 patients (953 cases matched with 7928 controls). The AATD-associated COPD cohort had higher expenditures and use of office visits (OV) and other (OTH) services, as well as OV, outpatient (OP), emergency room (ER), and prescription drugs (RX) before and after the index date, respectively. Adjusted total all-healthcare cost ratios for AATD-associated COPD patients as compared to controls were 2.04 [95% CI: 1.60-2.59] and 1.98 [95% CI: 1.55-2.52] while the incremental cost difference totaled $6861 [95% CI: $3025 - $10,698] and $5772 [95% CI: $1940 - $9604] per patient before and after the index date, respectively. CONCLUSIONS: Twelve months before and after their initial COPD diagnosis, patients with AATD incur higher healthcare utilization costs that are double the cost of similar COPD patients without AATD. This study also suggests that increased costs of AATD-associated COPD are not solely attributable to augmentation therapy use. Future studies should further explore the relationship between augmentation therapy, healthcare resource use, and other AATD-associated COPD expenditures.

The possible harms of statins: What do product labels, patient package inserts, and pharmacy leaflets tell us?

OBJECTIVES: To evaluate the degree to which health care professionals and patients receive consistent messages regarding the possible harms of statins. DESIGN: Cross-sectional study of prescribing information (PI), patient package inserts (PPIs), and pharmacy leaflets for 8 statins approved by the U.S. Food and Drug Adminstration. SETTING: Not applicable. PARTICIPANTS: Not applicable. MAIN OUTCOME MEASURES: All passages describing 7 adverse events (diarrhea, arthralgia, dyspepsia, confusion, memory loss, rhabdomyolysis, and kidney failure) were extracted from PIs, PPIs, and pharmacy leaflets. For each type of information source and adverse event (drug-harm pair), 2 reviewers independently judged passages as indicating either a confirmed, unconfirmed, or mixed causal relationship between statin and adverse event (drug-harm pair). Disagreements were resolved through consensus, and the consistency between information sources was calculated. RESULTS: PI and PPI consistently conveyed the relationship between a given statin and given adverse event (either both "confirmed" or both "unconfirmed") in 12 of 17 evaluable drug-harm pairs. PPIs and pharmacy leaflets were consistent in 10 of 10 evaluable drug-harm pairs. PIs indicated a confirmed, causal relationship in 15 drug-harm pairs that were not mentioned in pharmacy leaflets. Likewise, PPIs indicated a confirmed, causal relationship in 7 drug-harm pairs that were not listed in pharmacy leaflets. CONCLUSION: Despite the widespread use of statins, we discovered considerable ambiguity in language used to describe the evidence concerning their possible harms and variable consistency between PIs, PPIs, and pharmacy leaflets. Further study is needed to understand the reason why pharmacy leaflets did not list, in 15 cases, adverse events that PIs indicated were causally related to the statin.

Costs of Medical Care Among Augmentation Therapy Users and Non-Users with Alpha-1 Antitrypsin Deficiency in the United States.

Background: This study is the first to utilize a large claims database to estimate medical costs of patients with alpha-1 antitrypsin deficiency (AATD) in the United States. Methods: Adult AATD patients were identified from the OptumLabs™ Data Warehouse. Insurer and patient out-of-pocket costs were categorized into the following cost buckets, stratified by augmentation therapy use: physician visits (PV), emergency department visits (ED), inpatient stays (IP), augmentation therapy (AUG), other prescription drug costs (RX), and other costs (OTH). Costs were weighted and adjusted to 2017 U.S. dollars using the medical care component of the consumer price index. Results: The study cohort consisted of9117 AATD patients followed for 53,872 person years observed between 1993 and 2015. The annual costs among AATD patients totaled $127,537 among augmentation therapy users and $15,874 among non-users. The major drivers of annual costs to the insurer among the 7975 patients not on augmentation therapy were: PV: $5352 (37.7%) and IP: $4506 (31.8%). Among the 1142 augmentation users, major annual cost drivers to the insurer were PV: $15,064 (12.3%) and AUG: $82,002 (66.7%). Annual patient out-of-pocket costs were $4601 (AUG: $2084 [45.3%]; RX: $940 [20.4%]) and $1689 (PV: $727 [43.0%]; RX: $589 [34.9%]) among augmentation therapy users and non-users, respectively. Averaged across the entire cohort, the average annual costs per AATD patient were $22,975, paid by insurers ($21,100) and patients ($1875). Conclusions: Annual medical costs among patients with AATD are $127,537 and $15,874 among augmentation therapy users and non-users, respectively, with 75.3% of the cost difference attributable to AUG.

ADHD medications and cardiovascular adverse events in children and adolescents: cross-national comparison of risk communication in drug labeling.

PURPOSE: Regulators approve written medical information for healthcare professionals and consumers, but the consistency of these sources has not been studied. We investigated the consistency of information regarding four cardiovascular risks of attention-deficit/hyperactivity disorder (ADHD) medications approved in four countries. METHODS: Professional and consumer product labeling for five ADHD medications approved in Australia, Canada, the UK, and the USA were obtained in March/April 2016. Language describing the relationship between medication and elevated blood pressure and/or heart rate, myocardial infarction, stroke, and sudden death was extracted verbatim and classified into one of four categories based on the described relationship between medication and adverse event: "confirmed," "unconfirmed," "mixed," and "not mentioned." We judged the consistency of messages delivered to healthcare professionals and consumers as either "consistent" or "inconsistent." RESULTS: We obtained 20 healthcare professional labels and 20 corresponding consumer labels for the five ADHD medications registered in all four countries. Not all professional and consumer labeling contained language regarding all four adverse events. Of the 80 theoretically evaluable drug-risk pairs, 38 (48%) were not evaluable because of absence of mention of the adverse event in the consumer label. For the remaining 42, the potential causal relationship was expressed consistently in professional and consumer labeling in 25 (60%) cases. The cardiovascular risk profile was not described consistently across all four countries for any of the five drugs. CONCLUSIONS: Product labeling provides healthcare professionals and consumers with inconsistent messages regarding the potential causal relationship between stimulant use and specific cardiovascular risks in children and adolescents. Copyright © 2017 John Wiley & Sons, Ltd.