High Compliance With Choosing Wisely Breast Surgical Guidelines at a Safety-Net Hospital.

BACKGROUND: Professional organizations recently set guidelines for avoiding surgeries of low utility and overutilization for the Choosing Wisely campaign. These include re-excision for invasive cancer close to margins, double mastectomy in patients with unilateral breast cancer, axillary lymph node dissection in patients with limited nodal disease, and sentinel lymph node biopsy (SLNB) in patients ≥70 years with early-stage breast cancer. Variable adherence to these recommendations led us to evaluate implementation rates of low-value surgical guidelines at a safety-net hospital. METHODS: We retrospectively analyzed breast cancer patients who underwent surgery from 2015 to 2020. Each patient was assessed for eligibility for omission of the listed surgeries. Trends were evaluated by cohorts before and after a fellowship-trained breast surgeon joined the faculty in 2018. Outcomes were compared using Fisher's exact test. RESULTS: Among 195 patients, none underwent re-excision for close margins of invasive cancer. Only 6.7% of patients (3/45) received contralateral mastectomy and 1.8% of eligible patients (3/169) received axillary lymph node dissection. Overall, 60% of patients ≥ 70 years with stage 1 hormone-positive breast cancer (9/15) received SLNB. There was a downward trend from 71% of eligible patients receiving SLNB in 2015-2018 to 50% in 2019-2020. CONCLUSIONS: De-implementation of traditional surgical practices, deemed as low-value care, toward newer guidelines is achievable even at community hospitals serving a low socioeconomic community. By avoiding overtreatment, hospitals can achieve effective resource allocation which allow for social distributive justice among patients with breast cancer and ensure strategic use of scarce health economic resources while preserving patient outcomes.

End of an era for erythropoiesis-stimulating agents in oncology.

Erythropoiesis-stimulating agents (ESAs) are available to treat chemotherapy-induced anemia (CIA). In 2007-2008, regulatory notifications advised of venous thromboembolism and mortality risks while the Center for Medicare and Medicaid Services' restricted ESA initiation to patients with hemoglobin <10 g/dl. In 2010, a Risk Evaluation and Mitigation Strategies required consent prior to administration. We evaluated ESA utilization from 2003 to 2012 and obtained private health insurer claims data for persons with lung, colorectal, or breast cancer from 2001 to 2012. ESA use for CIA was determined by an ESA claim after chemotherapy, up to 6 months after treatment. We identified 839,948 commercially insured patients, including 24,785 patients with ESA-treated CIA (3.2%). Darbepoetin use increased 3.9-fold from 2003 to 2007 (12.3% to 48.7%) and then decreased 95% to 2.6% by 2012. Epoetin use decreased 90% from 2003 to 2012 (30.3% to 3.1%). Between 2003 and 2012, mean epoetin dosing decreased 0.8-fold (244,979 in 2003 vs. 196,216 units in 2012), but increased 1.8-fold for darbepoetin-treated CIA (262 in 2003 to 467 µg in 2012). Among CIA patients, transfusions were low (4.5%) in 2002-2007, then increased 2.2-fold between 2008 and 2012. Safety initiatives between 2007 and 2010 facilitated reductions in ESA use combined with changes in coverage. These data show the efficacy of regulatory efforts, publication of adverse events and changes in reimbursement in reducing use of ESAs. Future studies are warranted to optimize deimplementation strategies to improve patient safety.

Thrombocytopenia in the intensive care unit.

Thrombocytopenia is a common laboratory finding in critically ill patients admitted to the intensive care unit. Potential etiologies of thrombocytopenia are myriad, ranging from acute disease processes and concomitant conditions to exposures and drugs. The mechanism of decreased platelet counts can also be varied: laboratory measurement may be spurious, platelet production may be decreased, or platelet destruction or sequestration may be increased. In addition to evaluation for the cause of thrombocytopenia, the clinician must also guard against spontaneous bleeding due to thrombocytopenia, prophylax against bleeding resulting from an invasive procedure performed in the setting of thrombocytopenia, and treat active bleeding related to thrombocytopenia.

Factors delaying chemotherapy in patients with breast cancer at a safety-net hospital.

BACKGROUND: Despite advances in healthcare and improved chemotherapy, disparities in breast cancer outcomes continue to persist. Our aim was to evaluate socioeconomic factors that may impact timing of treatment for patients receiving chemotherapy in underserved communities. METHODS: A review of patients with breast cancer who received neoadjuvant or adjuvant chemotherapy from 2015-2019 was conducted at a safety-net hospital. The primary outcomes were times from diagnosis to chemotherapy and surgery. Clinicodemographic factors including race, age, clinical stage, primary language, comorbidities, and median income by zip code were collected. Multivariable regression analysis was performed to evaluate for factors associated with the primary outcomes. RESULTS: One hundred patients were identified. For the neoadjuvant group, median time from diagnosis to chemotherapy and surgery was 52 ± 34 days and 256 ± 59 days, respectively. For the adjuvant group, median time from diagnosis to surgery and chemotherapy was 24.5 ± 18 days and 94.5 ± 53 days, respectively. Non-English language and older age were associated with increased time to chemotherapy in the adjuvant group (p < 0.05). Language and age were not associated with increased time to surgery in both groups. Race, age, comorbidities, and income were not associated with delay in treatment in either groups. CONCLUSIONS: Older age and non-English language were associated with prolonged time from surgery to adjuvant chemotherapy. Targeted interventions directed at patient education and decreasing language barriers especially post-operatively may decrease delays in treatment and subsequently reduce disparities seen in the breast cancer population.

Primary undifferentiated pleomorphic cardiac sarcoma presenting as right heart failure.

Right-sided heart failure is a common sequela of left heart failure and seldom presents as a primary disorder. The differential diagnosis of right heart failure includes a cardiac tumor. Cardiac malignancies are rare tumors with an overall poor prognosis. We evaluated a 69-year-old man who presented with a 3-week history of progressive lower extremity swelling, ascites, and scrotal swelling. Laboratory studies were significant only for mildly elevated liver function tests. CT scan of the abdomen and pelvis showed ascites, hepatic swelling, and a bland clot in the inferior vena cava extending from the level of the kidneys to the right atrium. A large mass originating from the right atrium was identified, and biopsy confirmed an undifferentiated pleomorphic cardiac sarcoma. Given the extensive tumor and clot burden, he was not an operative candidate. He developed portal hypertension with esophageal varices and expired due to variceal bleeding.

Health Equity Within Inequity: Timing of Diagnostic Breast Cancer Care in an Underserved Medical Population.

BACKGROUND/AIM: We evaluated timeliness of care at a safety-net hospital after implementation of a multidisciplinary breast program. PATIENTS AND METHODS: A prospective database of patients with breast cancer was created after multidisciplinary breast program initiation in 2018. Patients were tracked to obtain time to completion of diagnostic imaging, biopsy, and treatment initiation. Patients with breast cancer diagnosed from 2015-2017 were reviewed for comparison. RESULTS: A total of 102 patients were identified. There was no statistical difference in time to completion of imaging, biopsy, and initial treatment between the 2018 and the 2015-2017 cohorts (p>0.05). No statistical difference was observed in time to completion of imaging, biopsy, and initial treatment between different races (p>0.05). CONCLUSION: Within the same socioeconomic status, there was no differential delivery of screening, work-up, and treatment by race. Despite protocol implementations, efficiency of care remained limited in a safety-net hospital with lack of financial resources.

End of an era of administering erythropoiesis stimulating agents among Veterans Administration cancer patients with chemotherapy-induced anemia.

Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003-2012). Epoetin and darbepoetin use were primary outcomes. Segmented linear regression was used to estimate changes in ESA use levels and trends, clinical appropriateness, and adverse events (VTEs) among chemotherapy-treated cancer patients. To estimate changes in level of drug prescription rate after policy actions, model-specific indicator variables as covariates based on specific actions were included. ESA use fell by 95% and 90% from 2005, for epoetin and darbepoetin, from 22% and 11%, respectively, to 1% and 1%, respectively, among cancer patients with CIA, respectively (p<0.01). Following REMS in 2010, mean hematocrit levels at ESA initiation decreased from 30% to 21% (p<0.01). Black box warnings preceded decreased ESA use among VA cancer patients with CIA. REMS was followed by reduced hematocrit levels at ESA initiation. Our findings contrast with privately- insured and Medicaid insured cancer patient data on chemotherapy-induced anemia where ESA use decreased to 3% to 7% by 2010-2012. By 2012, the era of ESA administration to VA to cancer patients had ended but the warnings remain relevant and significant. In 2019, oncology/hematology national guidelines (ASCO/ASH) recommend that cancer patients with chemotherapy-induced anemia should receive ESAs or red blood cell transfusions after risk-benefit evaluation.

Neutropenia-related costs in patients treated with first-line chemotherapy for advanced non-small cell lung cancer.

BACKGROUND: Neutropenia is a major adverse event often associated with chemotherapy administration. Neutropenia-related complications often lead to increased use of costly health care including inpatient and outpatient services. Monitoring and treatment of neutropenia thus place an economic burden on the health care system. OBJECTIVES: To evaluate (a) costs and medical resource use for chemotherapy- related afebrile and febrile neutropenia in an elderly population with Stage IIIB or Stage IV non-small cell lung cancer (NSCLC), and (b) costs unrelated to neutropenia and total all-cause health care costs during first-line chemotherapy. METHODS: Study patients in this retrospective database analysis were aged 65 years or older with a diagnosis of Stage IIIB or Stage IV NSCLC in the Surveillance, Epidemiology and End Results (SEER) cancer registry from 1998 through 2002. Neutropenia was identified by the presence of a primary or secondary diagnosis code for diseases of white blood cells (ICD-9-CM = 288.xx) during a period of first-line chemotherapy treatment. Febrile neutropenia was defined by (a) an inpatient hospitalization with a primary or secondary diagnosis for neutropenia occurring at any time during first-line chemotherapy or (b) intravenous or intramuscular antibiotic administration occurring after the initial neutropenia diagnosis and during first-line chemotherapy. Patients with neutropenia without these events were considered to have afebrile neutropenia. Patients were followed in the SEER-Medicare database to evaluate costs (defined as all Medicare payments, primary insurer payments, and patient copayments and deductibles) and resource use associated with afebrile or febrile neutropenia while on first-line chemotherapy. If a patient switched to second-line chemotherapy, the day prior to the switch was defined as the end of first-line treatment. If a switch to second-line therapy did not occur, then first-line therapy was assumed to end 30 days following administration of the last first-line agent. Costs were summed for 2 main types of cost measures: neutropenia-related costs, defined as costs for claims with either a primary or secondary diagnosis of neutropenia, and costs unrelated to neutropenia. Costs were classified using ICD-9-CM diagnosis and procedure codes appearing on the claims, with confidence intervals [CIs] for cost measures estimated by using nonparametric bootstrapping methods. Group comparisons of patient characteristics, medical utilization, and cost study measures were made using 2-sided Pearson chi-square and t-test statistics for categorical and continuous measures, respectively. The no neutropenia group was used as the reference category for comparisons involving patient characteristic, medical utilization, and total all-cause health care cost study measures. For total neutropenia-related costs, afebrile and febrile neutropenia study groups were compared. RESULTS: Among elderly patients treated first-line for advanced NSCLC, 5,138 met inclusion criteria, of whom 1,228 (23.9%) developed afebrile (n = 740, 14.4%) or febrile neutropenia (n = 488, 9.5%) while on first-line chemotherapy. Mean per patient costs for treating neutropenia during first-line chemotherapy were $12,148 (standard deviation [SD] = $15,432, 95% confidence interval [CI] = $10,915-$13,607) for patients with febrile neutropenia and $3,099 (SD = $4,541, 95% CI = $2,796-$3,431) for patients with afebrile neutropenia (P<0.001), with mean (SD) length of follow-up (duration of first-line chemotherapy) of 4.5 (4.8) and 5.5 (7.0) months, respectively. Expressed as a percentage of total all-cause health care costs during first-line chemotherapy, neutropenia-related costs accounted for 32.2% of total costs for patients with febrile neutropenia (mean [SD] = $37,694 [$26,078]) and 9.1% of total costs for patients with afebrile neutropenia (mean [SD] = $34,204 [$26,317]). Mean neutropenia-related costs per patient per month (PPPM) during first-line chemotherapy were $2,700 for patients with febrile neutropenia and $563 for patients with afebrile neutropenia. PPPM costs unrelated to neutropenia for patients with afebrile neutropenia, febrile neutropenia, and no neutropenia, respectively, were $5,655, $5,677, and $6,146. In sensitivity analyses, results were highly sensitive to the definition of neutropenia (i.e., claims with primary diagnosis only vs. primary or secondary diagnosis) but insensitive to the type of chemotherapy regimen. CONCLUSION: Neutropenia is a major adverse event that places patients at an increased risk of infection and subsequent morbidity and mortality. For elderly patients undergoing first-line chemotherapy for NSCLC, neutropenia, particularly febrile neutropenia, is associated with substantially higher total all-cause health care costs.

An evaluation of reports of ciprofloxacin, levofloxacin, and moxifloxacin-association neuropsychiatric toxicities, long-term disability, and aortic aneurysms/dissections disseminated by the Food and Drug Administration and the European Medicines Agency.

Introduction: Ciprofloxacin, levofloxacin, and moxifloxacin belong to the fluoroquinolone class of antibiotics and are amongst the most commonly prescribed antibiotics. In 2018 and 2019, Food and Drug Administration (FDA) and the European Medicine Agency (EMA) requested that manufacturers harmonize FQ safety information related to neuropsychiatric, aortic dissection, and long-term disability. The authors hypothesize that FDA and EMA epidemiologists support a strong association between these drugs and the three toxicities. Areas covered: Studies of FQ-associated neuropsychiatric toxicity, long-term disability, and aortic ruptures/dissections. Clinical sources include FDA Advisory Committee documents, a 2014 Citizen Petition filed with the FDA requesting safety information additions to FQ labels for neuropsychiatric toxicities (partially granted in 2018), an under-review Citizen Petition under review by the FDA requesting a FQ Risk Evaluation and Mitigation Strategy, and safety notifications from the EMA. Expert opinion: FDA and the EMA report state that neuropsychiatric toxicity, long-term disability, and aortic dissections//aneurysms occur with all FQs. Disability and neuropsychiatric toxicity can occur after one dose or several months after FQs. United States' and European' regulators warn physicians not to prescribe FQs for uncomplicated acute urinary tract infection, sinusitis, or bronchitis, unless other possible choices are tried first, as risks outweigh benefits in these settings.

Quality Initiative in Clinical Practice: A Single-Institution Appraisal of Quality Metrics in the Management of Newly Diagnosed Diffuse Large B-Cell Lymphoma.

OBJECTIVE: To assess our adherence to treatment guidelines for diffuse large B-cell lymphoma (DLBCL) established by the American Society of Hematology in 2014 through implementation of a quality improvement initiative (QII) at our institution in 2015. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL treated from January 1, 2006, through December 31, 2017, were identified. Electronic medical records were reviewed for documentation of American Society of Hematology Practice Improvement Module quality measures (eg, key pathologic features of DLBCL, lymphoma staging, and screening for hepatitis B virus [HBV] infection in patients receiving rituximab-based chemotherapy). We also reviewed assessment of prognosis by revised International Prognostic Index score, testing for hepatitis C virus, HBV, and HIV, chemotherapy education, and the addition of rituximab in the treatment regimen of CD20+ DLBCL. RESULTS: Following QII implementation, we saw improvements in most metrics, including reporting of key molecular features (fluorescence in situ hybridization for c-MYC, BCL2, and BCL6, from 45.5% [75 of 165 patients] before QII to 91.7% [22 of 24 patients] after QII; P<.001), screening for HBV (41.8% [69 of 165 patients] to 91.7% [22 of 24 patients]; P<.001) and HIV infections (33.9% [56 of 165 patients] to 87.5% [21 of 24 patients]; P<.0001), providing chemotherapy education (92.7% [153 of 165 patients] to 100%), and use of rituximab for CD20+ DLBCL (83.6% [138 of 165 patients] to 100%; P=.05). All patients had positron emission tomography-computed tomography for DLBCL staging, and there was significantly lower use of bone marrow biopsy (P=.011). CONCLUSION: Implementating a QII and employing standardized metrics can aid in improving quality of care for patients with newly diagnosed DLBCL and allow opportunities to build and ensure better adherence to evolving patient care guidelines.

Caveat Medicus: Clinician experiences in publishing reports of serious oncology-associated adverse drug reactions.

Oncology-associated adverse drug/device reactions can be fatal. Some clinicians who treat single patients with severe oncology-associated toxicities have researched case series and published this information. We investigated motivations and experiences of select individuals leading such efforts. Clinicians treating individual patients who developed oncology-associated serious adverse drug events were asked to participate. Inclusion criteria included having index patient information, reporting case series, and being collaborative with investigators from two National Institutes of Health funded pharmacovigilance networks. Thirty-minute interviews addressed investigational motivation, feedback from pharmaceutical manufacturers, FDA personnel, and academic leadership, and recommendations for improving pharmacovigilance. Responses were analyzed using constant comparative methods of qualitative analysis. Overall, 18 clinicians met inclusion criteria and 14 interviewees are included. Primary motivations were scientific curiosity, expressed by six clinicians. A less common theme was public health related (three clinicians). Six clinicians received feedback characterized as supportive from academic leaders, while four clinicians received feedback characterized as negative. Three clinicians reported that following the case series publication they were invited to speak at academic institutions worldwide. Responses from pharmaceutical manufacturers were characterized as negative by 12 clinicians. One clinician's wife called the post-reporting time the "Maalox month," while another clinician reported that the manufacturer collaboratively offered to identify additional cases of the toxicity. Responses from FDA employees were characterized as collaborative for two clinicians, neutral for five clinicians, unresponsive for negative by six clinicians. Three clinicians endorsed developing improved reporting mechanisms for individual physicians, while 11 clinicians endorsed safety activities that should be undertaken by persons other than a motivated clinician who personally treats a patient with a severe adverse drug/device reaction. Our study provides some of the first reports of clinician motivations and experiences with reporting serious or potentially fatal oncology-associated adverse drug or device reactions. Overall, it appears that negative feedback from pharmaceutical manufacturers and mixed feedback from the academic community and/or the FDA were reported. Big data, registries, Data Safety Monitoring Boards, and pharmacogenetic studies may facilitate improved pharmacovigilance efforts for oncology-associated adverse drug reactions. These initiatives overcome concerns related to complacency, indifference, ignorance, and system-level problems as barriers to documenting and reporting adverse drug events- barriers that have been previously reported for clinician reporting of serious adverse drug reactions.

Live-cell phenotypic-biomarker microfluidic assay for the risk stratification of cancer patients via machine learning.

The risk stratification of prostate cancer and breast cancer tumours from patients relies on histopathology, selective genomic testing, or on other methods employing fixed formalin tissue samples. However, static biomarker measurements from bulk fixed-tissue samples provide limited accuracy and actionability. Here, we report the development of a live-primary-cell phenotypic-biomarker assay with single-cell resolution, and its validation with prostate cancer and breast cancer tissue samples for the prediction of post-surgical adverse pathology. The assay includes a collagen-I/fibronectin extracellular-matrix formulation, dynamic live-cell biomarkers, a microfluidic device, machine-vision analysis and machine-learning algorithms, and generates predictive scores of adverse pathology at the time of surgery. Predictive scores for the risk stratification of 59 prostate cancer patients and 47 breast cancer patients, with values for area under the curve in receiver-operating-characteristic curves surpassing 80%, support the validation of the assay and its potential clinical applicability for the risk stratification of cancer patients.

Live-single-cell phenotypic cancer biomarkers-future role in precision oncology?

The promise of precision and personalized medicine is rooted in accurate, highly sensitive, and specific disease biomarkers. This is particularly true for cancer-a disease characterized by marked tumor heterogeneity and diverse molecular signatures. Although thousands of biomarkers have been described, only a very small number have been successfully translated into clinical use. Undoubtedly, there is need for rapid, quantitative, and more cost effective biomarkers for tumor diagnosis and prognosis, to allow for better risk stratification and aid clinicians in making personalized treatment decisions. This is particularly true for cancers where specific biomarkers are either not available (e.g., renal cell carcinoma) or where current biomarkers tend to classify individuals into broad risk categories unable to accurately assess individual tumor aggressiveness and adverse pathology potential (e.g., prostate cancer), thereby leading to problems of over-diagnosis and over-treatment of indolent cancer and under-treatment of aggressive cancer. This perspective highlights an emerging class of cancer biomarkers-live-single-cell phenotypic biomarkers, as compared to genomic biomarkers, and their potential application for cancer diagnosis, risk-stratification, and prognosis.

Characteristics and treatment patterns among US patients with hairy cell leukemia: a retrospective claims analysis.

AIM: Describe hairy cell leukemia (HCL) treatment patterns using a large, nationally representative US database. PATIENTS & METHODS: Adults newly diagnosed with HCL (1 January 2006 to 30 June 2014) with continuous health plan enrollment ≥180 days pre- and 90 days post-diagnosis were identified from the QuintilesIMS PharMetrics Plus Health Plan Claims Database. Treatment patterns by line of therapy were assessed over the variable follow-up. RESULTS: Among 749 HCL patients (77.4% male; mean age 55.6; mean 32.3 months follow-up), only 37.7% initiated first-line therapy during the available follow-up in a mean of 4.4 months following diagnosis; the majority (75.5%) received cladribine (mean duration 7.3 days). Thirty-eight patients (5.1%) received second-line treatment. CONCLUSION: Over 2.7 years follow-up, more than a third of patients initiated first-line therapy which appeared to provide a long-lasting response.

Tale of Two Erythropoiesis-Stimulating Agents: Utilization, Dosing, Litigation, and Costs of Darbepoetin and Epoetin Among South Carolina Medicaid-Covered Patients With Cancer and Chemotherapy-Induced Anemia.

PURPOSE: The US Food and Drug Administration (FDA) has approved epoetin and darbepoetin for chemotherapy-induced anemia (CIA). Approved epoetin and darbepoetin dosing schedules were three times per week and weekly, respectively, although off-label, less frequent scheduling was common. In 2004, 2007, and 2008, a US Food and Drug Administration Advisory Committees warned of risks associated with erythropoiesis-stimulating agents. During this period, lawsuits alleging illegal darbepoetin marketing practices have concluded, resulting in $1.1 billion in fines and settlements and one criminal conviction. No prior study, to our knowledge, has reported on the use of darbepoetin versus epoetin for CIA. METHODS: We evaluated the dosing, utilization, and costs of erythropoiesis-stimulating agents among 3,761 South Carolina Medicaid patients with CIA. RESULTS: Epoetin and darbepoetin utilization rates were 22% and 28% in 2003, 10% and 33% in 2007, and 3% and 7% in 2010, respectively. Mean per-patient per-administration epoetin and darbepoetin doses were 40,983 IU and 191 µg, respectively, in 2003 and 47,753 IU and 369 µg, respectively, in 2010. Mean monthly patient costs for epoetin and darbepoetin were $1,030 and $981, respectively, in 2003 and $932 and $1,352, respectively, in 2010. Epoetin use decreased steadily between 2002 and 2010; darbepoetin use increased steadily between 2003 and 2007 and then decreased steadily thereafter. Per-patient dosing of darbepoetin, but not epoetin, increased steadily between 2003 and 2010, and monthly per-patient epoetin costs decreased 3% while the per-patients costs of darbepoetin increased 30% between 2003 and 2010. CONCLUSION: To our knowledge, our findings are the first data reporting on epoetin versus darbepoetin use for CIA and support recently concluded lawsuits involving allegations of illegal marketing practices of the manufacturer of darbepoetin.

Estimating costs of care for patients with newly diagnosed metastatic colorectal cancer.

BACKGROUND: This study examines the resource use patterns and costs of care for patients with incident metastatic colorectal cancer (mCRC) based on analyses of retrospective claims data from selected health plans in the United States. PATIENTS AND METHODS: A case-control analysis was performed using claims from years 1998-2004. Incident mCRC cases were identified based on evidence of a colorectal cancer diagnosis and a metastatic disease diagnosis. Incident mCRC cases could have no other evidence of cancer in the 1-year period before the date of their first mCRC diagnosis. Cases were matched to non-mCRC controls based on age, sex, geographic region, and duration of plan enrollment. Costs were evaluated by phase of disease: diagnosis, treatment, or death phases. Ordinary least squares regressions were performed to evaluate impact of covariates in each phase. RESULTS: Total costs in the follow-up period averaged $97,031 more for mCRC cases than for controls. The main cost drivers for mCRC were hospitalizations ($37,369) and specialist visits ($34,582), which included chemotherapy administration. Approximately 40% of the 672 patients with mCRC who qualified for the phase analysis were identified with a fatal event during follow-up. Monthly costs were similar in the diagnostic phase ($12,205) and death phase ($12,328), but were significantly lower in the treatment phase ($4722). Both mean/median monthly costs increased over time during the study period, regardless of disease phase. CONCLUSION: The economic burden of mCRC is substantial for patients with commercial health plans in the United States, and costs of care have increased substantially in recent years.

Economic Burden of Tyrosine Kinase Inhibitor Treatment Failure in Chronic Myeloid Leukemia.

BACKGROUND: The economic burden of tyrosine kinase inhibitor (TKI) treatment failure in chronic myeloid leukemia (CML) is not well understood. The objective of this study was to quantify the economic burden associated with treatment failure versus successfully remaining on TKI therapy. METHODS: Treatment episodes for adult CML patients initiating a TKI of interest (imatinib, dasatinib, or nilotinib; index TKI) during July 1, 2008, to December 31, 2011, with continuous enrollment for ≥ 120 days before and 1 year after the initiation were identified from the IMS PharMetrics Plus Health Plan Claims Database. Eligible episodes of TKI treatment failure were matched to those without failure using propensity scores based on patients' baseline demographic and clinical characteristics. Treatment failure was defined as a switch to a nonindex TKI or discontinuation (gap in pharmacy claims ≥ 60 days) of index TKI over the 1-year follow-up. Mean all-cause health care resource utilization and costs per episode (in 2012 US dollars) over follow-up were compared between failures and nonfailures. RESULTS: Among 1774 eligible episodes, 547 failures were matched to 547 nonfailures. Failures had fewer TKI prescription fills but higher utilization of all other services versus nonfailures. Consequently, failures incurred lower pharmacy costs ($51,238 vs. $72,450; Δ-$21,212) but higher medical costs ($52,619 vs. $18,180; Δ$34,439) than nonfailures, resulting in higher total costs ($103,857 vs. $90,630; Δ$13,227) (all P < .05). CONCLUSION: Total health care costs are higher for episodes of TKI treatment failure than those of ongoing treatment, largely as a result of costly medical (nonpharmacologic) services. Avoiding treatment failure by optimal CML management may reduce health care costs.