Time to diagnosis among young patients with cancer.

BACKGROUND: Sociodemographic and clinical factors associated with diagnostic delays in pediatric, adolescent, and young adult cancers are poorly understood. METHODS: Using the Optum Labs Data Warehouse's de-identified claims data for commercial health plan enrollees, we identified children (0-14 years) and adolescents/young adults (AYAs) (15-39 years) diagnosed with one of 10 common cancers from 2001 to 2017, who were continuously enrolled for 6 months preceding diagnosis. Time to diagnosis was calculated as days between first medical encounter with possible cancer symptoms and cancer diagnosis date. Median times from first symptom to diagnosis were compared using Wilcoxon rank sum test. Multivariable unconditional logistic regression identified sociodemographic factors associated with longer time (>3 months) to cancer diagnosis (from symptom onset). RESULTS: Of 47,296 patients, 87% presented prior to diagnosis with symptoms. Patients with central nervous system (CNS) tumors were most likely to present with symptoms (93%), whereas patients with cervical cancer were least likely (70%). Symptoms varied by malignancy. Of patients with symptoms, thyroid (105 days [range: 50-154]) and cervical (104 days [range: 41-151]) cancer had the longest median time to diagnosis. Females and patients at either end of the age spectrum were more likely to experience diagnosis delays of more than 3 months. CONCLUSION: In a commercially insured population, time to diagnosis varies by cancer type, age, and sex. Further work is needed to understand the patient, provider, and health system-level factors contributing to time from symptom onset to diagnosis, specifically in the very young children and the young adult patient population going forward.

Idiopathic pulmonary fibrosis in the United States: time to diagnosis and treatment.

OBJECTIVE: Create a timeline of diagnosis and treatment for IPF in the US. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was performed in collaboration with the OptumLabs Data Warehouse using an administrative claims database of Medicare Fee for Service beneficiaries. Adults 50 and over with IPF were included (2014 to 2019). EXPOSURE: To focus on IPF, the following diagnoses were excluded: post-inflammatory fibrosis, hypersensitivity pneumonitis, rheumatoid arthritis, sarcoidosis, scleroderma, and connective tissue disease. MAIN OUTCOMES AND MEASURES: Data were collected from periods prior, during, and following initial clinical diagnosis of IPF. This included prior respiratory diagnoses, number of respiratory-related hospitalizations, anti-fibrotic and oxygen use, and survival. RESULTS: A total of 44,891 with IPF were identified. The most common diagnoses prior to diagnosis of IPF were upper respiratory infections (47%), acute bronchitis (13%), other respiratory disease (10%), chronic obstructive pulmonary disease and bronchiectasis (7%), and pneumonia (6%). The average time to a diagnosis of IPF was 2.7 years after initial respiratory diagnosis. Half of patients had two or more respiratory-related hospitalizations prior to IPF diagnosis. Also, 37% of patients were prescribed oxygen prior to diagnosis of IPF. These observations suggest delayed diagnosis. We also observed only 10.4% were treated with anti-fibrotics. Overall survival declined each year after diagnosis with median survival of 2.80 years. CONCLUSIONS AND RELEVANCE: Our retrospective cohort demonstrates that IPF is often diagnosed late, usually preceded by other respiratory diagnoses and hospitalizations. Use of available therapies is low and outcomes remain poor.

Expenditures among young adults with acute lymphoblastic leukemia by site of care.

BACKGROUND: Individuals diagnosed with acute lymphoblastic leukemia (ALL) between the ages of 22 and 39 years experience worse outcomes than those diagnosed when they are 21 years old or younger. Treatment at National Cancer Institute-designated Comprehensive Cancer Centers (CCC) mitigates these disparities but may be associated with higher expenditures. METHODS: Using deidentified administrative claims data (OptumLabs Data Warehouse), the cancer-related expenditures were examined among patients with ALL diagnosed between 2001 and 2014. Multivariable generalized linear model with log-link modeled average monthly health-plan-paid (HPP) expenditures and amount owed by the patient (out-of-pocket [OOP]). Cost ratios were used to calculate excess expenditures (CCC vs non-CCC). Incidence rate ratios (IRRs) compared CCC and non-CCC monthly visit rates. Models adjusted for sociodemographics, comorbidities, adverse events, and months enrolled. RESULTS: Clinical and sociodemographic characteristics were comparable between CCC (n = 160) and non-CCC (n = 139) patients. Higher monthly outpatient expenditures in CCC patients ($15,792 vs $6404; P < .001) were driven by outpatient hospital HPP expenditures. Monthly visit rates and per visit expenditures for nonchemotherapy visits (IRR = 1.6; P = .001; CCC = $8247, non-CCC = $1191) drove higher outpatient hospital expenditures among CCCs. Monthly OOP expenditures were higher at CCCs for outpatient care (P = .02). Inpatient HPP expenditures were significantly higher at CCCs ($25,918 vs $13,881; ꞵ = 0.9; P < .001) before accounting for adverse events but were no longer significant after adjusting for adverse events (ꞵ = 0.4; P = .1). Hospitalizations and length of stay were comparable. CONCLUSIONS: Young adults with ALL at CCCs have higher expenditures, likely reflecting differences in facility structure, billing practices, and comprehensive patient care. It would be reasonable to consider CCCs comparable to the oncology care model and incentivize the framework to achieve superior outcomes and long-term cost savings. LAY SUMMARY: Health care expenditures in young adults (aged 22-39 years) with acute lymphoblastic leukemia (ALL) are higher among patients at National Cancer Institute-designated Comprehensive Cancer Centers (CCC) than those at non-CCCs. The CCC/non-CCC differences are significant among outpatient expenditures, which are driven by higher rates of outpatient hospital visits and outpatient hospital expenditures per visit at CCCs. Higher expenditures and visit rates of outpatient hospital visits among CCCs may also reflect how facility structure and billing patterns influence spending or comprehensive care. Young adults at CCCs face higher inpatient HPP expenditures; these are driven by serious adverse events.

Sexually Transmitted Infection Testing and Prevalence Before and After Preexposure Prophylaxis Initiation Among Men Aged ≥18 Years in US Private Settings.

BACKGROUND: The Centers for Disease Control and Prevention recommends initial and follow-up sexually transmitted infection (STI) and HIV testing when taking HIV preexposure prophylaxis (PrEP). We assessed frequencies of STIs and HIV testing and rates of STIs before and after PrEP initiation among men aged ≥18 years. METHODS: We used the OptumLabs database for this cohort study. We measured STI/HIV testing rates and prevalence in 2 time intervals: (1) within 90 days before and on the date of PrEP initiation and (2) within 45 days of the 180th day after the date of PrEP initiation. RESULTS: Of 4210 men who initiated PrEP in 2016 to 2017 and continuously used PrEP for ≥180 days, 45.7%, 45.7%, and 56.0% were tested for chlamydia, gonorrhea, and HIV, respectively, at the second time interval. These percentages were significantly lower than those at the first time interval (58.3%, 57.9%, and 73.5%, respectively; P < 0.01). Chlamydia and gonorrhea prevalence rates at the second time interval were 6.5% and 6.2%, respectively, versus 5.0% and 4.7%, respectively, at the first time interval. Most gonorrhea or chlamydia infections at the second time intervals seem to be new infections new infections. CONCLUSIONS: Sexually transmitted infection/HIV testing for PrEP users in the real-world private settings is much lower than in clinical trials. High STI prevalence before and after PrEP initiation in this study suggests that patients taking PrEP have an increased risk of acquiring STI. Interventions to improve provider adherence for PrEP users are urgently needed.

Estimating Recommended Gonorrhea and Chlamydia Treatment Rate Using Linked Medical Claims, Prescription, and Laboratory Data in US Private Settings.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) recommends specific regimens for chlamydia and dual therapy for gonorrhea to mitigate antimicrobial-resistant gonorrhea in the CDC 2015 sexually transmitted disease treatment guidelines. Only limited studies examining adherence to these recommendations have been conducted at private practices in the United States. METHODS: We used the OptumLabs Data Warehouse, a comprehensive, longitudinal data asset with deidentified persons with linked commercial insurance claims and clinical information, to identify persons aged 15 to 60 years who had valid nucleic acid amplification testing results demonstrating urogenital or extragenital gonorrhea or chlamydia in 2016 to 2018. We defined valid laboratory results as positive or negative. We then assessed the time of their first positive test result and the type of treatment within 30 days to determine if there was evidence in the claims record that the CDC-recommended treatment was provided. We defined presumed treatment if the date of treatment was before the date of the positive test result within 30 days. RESULTS: Among 6476 patients with positive gonorrhea test results and 26,847 patients with positive chlamydia test results only, 34.8% and 64.2% had evidence of receiving the CDC-recommended therapy, respectively. Approximately 11.6% of patients with positive gonorrhea test results with recommended dual treatment and 7.1% of patients with positive chlamydia test results only with recommended chlamydia treatment were presumptively treated. CONCLUSION: Analysis of treatment claims and medical records from private settings indicated low rates of recommended gonorrhea and chlamydia treatment. Validation of treatment claims is needed to support further quality of care interventions based on these data.

Opioid Prescribing for Opioid-Naive Patients in Emergency Departments and Other Settings: Characteristics of Prescriptions and Association With Long-Term Use.

STUDY OBJECTIVE: We explore the emergency department (ED) contribution to prescription opioid use for opioid-naive patients by comparing the guideline concordance of ED prescriptions with those attributed to other settings and the risk of patients' continuing long-term opioid use. METHODS: We used analysis of administrative claims data (OptumLabs Data Warehouse 2009 to 2015) of opioid-naive privately insured and Medicare Advantage (aged and disabled) beneficiaries to compare characteristics of opioid prescriptions attributed to the ED with those attributed to other settings. Concordance with Centers for Disease Control and Prevention (CDC) guidelines and rate of progression to long-term opioid use are reported. RESULTS: We identified 5.2 million opioid prescription fills that met inclusion criteria. Opioid prescriptions from the ED were more likely to adhere to CDC guidelines for dose, days' supply, and formulation than those attributed to non-ED settings. Disabled Medicare beneficiaries were the most likely to progress to long-term use, with 13.4% of their fills resulting in long-term use compared with 6.2% of aged Medicare and 1.8% of commercial beneficiaries' fills. Compared with patients in non-ED settings, commercial beneficiaries receiving opioid prescriptions in the ED were 46% less likely, aged Medicare patients 56% less likely, and disabled Medicare patients 58% less likely to progress to long-term opioid use. CONCLUSION: Compared with non-ED settings, opioid prescriptions provided to opioid-naive patients in the ED were more likely to align with CDC recommendations. They were shorter, written for lower daily doses, and less likely to be for long-acting formulations. Prescriptions from the ED are associated with a lower risk of progression to long-term use.

Characteristics and outcomes of patients with type 2 diabetes mellitus treated with canagliflozin: a real-world analysis.

BACKGROUND: Canagliflozin, an oral agent that inhibits sodium glucose co-transporter 2, improves glycemic control, body weight, and blood pressure and is generally well tolerated in patients with type 2 diabetes mellitus (T2DM). This study extends the scope of previous analyses by evaluating outcomes associated with the use of canagliflozin over a 6-month period in a real-world setting. METHODS: This retrospective cohort study used data obtained from a large health plan database for patients (≥18 years) with a diagnosis of T2DM who filled at least one canagliflozin prescription between April 1, 2013 and October 30, 2013 (first 7 months canagliflozin was commercially available in the USA) and were continuously enrolled in the health plan for 6 months prior to (baseline) and 6 months following the first canagliflozin prescription claim (follow-up). Changes in glycemic control were evaluated, along with characteristics of enrolled patients and changes in treatment patterns. RESULTS: 4017 patients (mean age 56 years, 43 % female) met the study inclusion criteria. Of these, at the time of first canagliflozin claim, 21 % used canagliflozin concomitantly with three or more other antihyperglycemic agents (AHAs), 29 % with two other AHAs, 30 % with one other AHA, and 20 % without other AHAs. During follow-up, patients received 3.4 (average) canagliflozin prescription fills and a mean of 148 total days of supply; median adherence (interquartile range [IQR]) was 86 % (66-98 %) for patients with ≥2 fills. Among patients with available glycated hemoglobin (A1C) measurements at baseline and follow-up (n = 826, baseline A1C 8.59 %), mean A1C reduction was 0.81 % (P < 0.001). Mean A1C reduction during the follow-up period was greatest in patients with the highest baseline A1C levels. Of the patients who used canagliflozin concomitantly with other AHAs, 20 % were observed to discontinue one or more other AHAs during follow-up. The most commonly discontinued baseline AHAs were: glucagon-like peptide-1 receptor agonists (16 %), dipeptidyl peptidase-4 inhibitors (15 %), insulin (13 %), sulfonylureas (13 %), and metformin (11 %). CONCLUSIONS: This real-world study on canagliflozin use in a range of patients with T2DM demonstrated significant improvements in mean A1C from baseline following the first canagliflozin prescription. In patients concomitantly using one or more additional AHAs at baseline, there appears to be a trend toward lower other AHA use after canagliflozin initiation.

Health care costs and resource utilization, including patient burden, associated with novel-agent-based treatment versus other therapies for multiple myeloma: findings using real-world claims data.

BACKGROUND: . Treatment of multiple myeloma has dramatically improved with the introduction of bortezomib (BOR), thalidomide (THAL), and lenalidomide (LEN). Studies assessing health care costs, particularly economic burden on patients, are limited. We conducted a claims-based, retrospective analysis of total health care costs as well as patient burden (patient out-of-pocket costs and number of ambulatory/hospital visits) associated with BOR/THAL/LEN treatment versus other therapies (OTHER). METHODS. Treatment episodes starting between January 1, 2005 and September 30, 2010 were identified from the claims database of a large U.S. health plan. Health care costs and utilization were measured during 1 year after initiation and analyzed per treatment episode. Multivariate analyses were used to adjust for patient characteristics, comorbidities, and line of treatment. RESULTS: A total of 4,836 treatment episodes were identified. Mean adjusted total costs were similar between BOR ($112,889) and OTHER ($111,820), but higher with THAL ($129,412) and LEN ($158,428). Mean adjusted patient out-of-pocket costs were also similar for BOR ($3,846) and OTHER ($3,900) but remained higher with THAL ($4,666) and LEN ($4,483). Mean adjusted rates of ambulatory visits were similar across therapies (BOR: 69.67; THAL: 66.31; LEN: 65.60; OTHER: 69.42). CONCLUSIONS: Adjusted analyses of real-world claims data show that total health care costs, as well as patient out-of-pocket costs, are higher with THAL/LEN treatment episodes than with BOR/OTHER therapies. Additionally, similar rates of ambulatory visits suggest that any perceived advantage in patient convenience of the orally administered drugs THAL/LEN is not supported by these data.

Pegfilgrastim prophylaxis is associated with a lower risk of hospitalization of cancer patients than filgrastim prophylaxis: a retrospective United States claims analysis of granulocyte colony-stimulating factors (G-CSF).

BACKGROUND: Myelosuppressive chemotherapy can lead to dose-limiting febrile neutropenia. Prophylactic use of recombinant human G-CSF such as daily filgrastim and once-per-cycle pegfilgrastim may reduce the incidence of febrile neutropenia. This comparative study examined the effect of pegfilgrastim versus daily filgrastim on the risk of hospitalization. METHODS: This retrospective United States claims analysis utilized 2004-2009 data for filgrastim- and pegfilgrastim-treated patients receiving chemotherapy for non-Hodgkin's lymphoma (NHL) or breast, lung, ovarian, or colorectal cancers. Cycles in which pegfilgrastim or filgrastim was administered within 5 days from initiation of chemotherapy (considered to represent prophylaxis) were pooled for analysis. Neutropenia-related hospitalization and other healthcare encounters were defined with a "narrow" criterion for claims with an ICD-9 code for neutropenia and with a "broad" criterion for claims with an ICD-9 code for neutropenia, fever, or infection. Odds ratios (OR) for hospitalization and 95% confidence intervals (CI) were estimated by generalized estimating equation (GEE) models and adjusted for patient, tumor, and treatment characteristics. Per-cycle healthcare utilization and costs were examined for cycles with pegfilgrastim or filgrastim prophylaxis. RESULTS: We identified 3,535 patients receiving G-CSF prophylaxis, representing 12,056 chemotherapy cycles (11,683 pegfilgrastim, 373 filgrastim). The mean duration of filgrastim prophylaxis in the sample was 4.8 days. The mean duration of pegfilgrastim prophylaxis in the sample was 1.0 day, consistent with the recommended dosage of pegfilgrastim - a single injection once per chemotherapy cycle. Cycles with prophylactic pegfilgrastim were associated with a decreased risk of neutropenia-related hospitalization (narrow definition: OR = 0.43, 95% CI: 0.16-1.13; broad definition: OR = 0.38, 95% CI: 0.24-0.59) and all-cause hospitalization (OR = 0.50, 95% CI: 0.35-0.72) versus cycles with prophylactic filgrastim. For neutropenia-related utilization by setting of care, there were more ambulatory visits and hospitalizations per cycle associated with filgrastim prophylaxis than with pegfilgrastim prophylaxis. Mean per-cycle neutropenia-related costs were also higher with prophylactic filgrastim than with prophylactic pegfilgrastim. CONCLUSIONS: In this comparative effectiveness study, pegfilgrastim prophylaxis was associated with a reduced risk of neutropenia-related or all-cause hospitalization relative to filgrastim prophylaxis.

Persistency with zoledronic acid is associated with clinical benefit in patients with multiple myeloma.

Zoledronic acid (ZOL), an intravenous bisphosphonate, has been shown to reduce and delay the incidence of skeletal-related events (SREs) in multiple myeloma (MM) patients with bone disease. A retrospective claims-based analysis was conducted that used two distinct US managed care databases to examine the relationship between persistency with ZOL and clinical benefit. Patients >18 years, diagnosed with MM, and with at least one claim for ZOL (or a claim for malignant bone disease and ZOL initiation within 30 days) between 1/1/2001 and 12/31/2006 were included. Patients were evaluated for incidence of SREs and for mortality. Treatment persistency was defined as the absence of a >45 day gap between ZOL administrations. Of 1,655 patients in this analysis, 1,060 received ZOL and 595 received no intravenous bisphosphonate therapy. Compared with patients not receiving bisphosphonate therapy, ZOL-treated patients had lower incidences of SREs (P < 0.0001) and death (P = 0.0001). Longer persistency with ZOL was associated with lower risks of SREs (P = 0.001), fracture (P = 0.003), and death (P = 0.002) versus shorter persistency. Patients who were persistent with ZOL for ≥1.5 years had an incidence of 15.0 SREs and 6.2 fractures per 100 person-years. Patients who were persistent for 31-90 days had an incidence of 24.6 SREs and 14.0 fractures per 100 person-years, and patients not receiving intravenous bisphosphonates had an incidence of 32.2 SREs and 16.9 fractures per 100 person-years. These data from a real-world setting indicate that among MM patients, longer persistency with ZOL was associated with a lower risk of SREs and fracture.

Methods and Study Design for Cancer Health Economics Research: Summary of Discussions From a Breakout Session.

The legitimacy of findings from cancer health economics research depends on study design and methods. A breakout session, Methods and Study Design for Cancer Health Economics Research, was convened at the Future of Cancer Health Economics Research Conference to discuss 2 commonly used analytic tools for cancer health economics research: observational studies and decision-analytic modeling. Observational studies include analysis of data collected with the primary purpose of supporting economic evaluation or secondary use of data collected for another purpose. Modeling studies develop a parametrized structure, such as a decision tree, to estimate hypothetical impact. Whereas observational studies focus on what has happened and why, modeling studies address what may happen. We summarize the discussion at this breakout session, focusing on 3 key elements of high-quality cancer health economics research: study design, analytical methods, and addressing uncertainty.

Long-term antimüllerian hormone patterns differ by cancer treatment exposures in young breast cancer survivors.

OBJECTIVE: To compare antimüllerian hormone (AMH) patterns by cancer status and treatment exposures across 6 years after incident breast cancer using administrative data. DESIGN: In a cross-sectional design, AMH levels in patients who developed incident breast cancer between ages 15-39 years during 2005-2019 were matched 1:10 to levels in females without cancer in the OptumLabs Data Warehouse. Modeled AMH patterns were compared among cyclophosphamide-based chemotherapy, non-cyclophosphamide-based chemotherapy, no chemotherapy, and no breast cancer groups. SETTING: Commercially insured females in the United States. PATIENT(S): Females with and without breast cancer. EXPOSURE(S): Breast cancer, cyclophosphamide- and non-cyclophosphamide-based chemotherapy. MAIN OUTCOME MEASURE(S): AMH levels. RESULT(S): A total of 233 patients with breast cancer (mean age, 34 years; standard deviation, 3.7 years) contributed 278 AMH levels over a median of 2 years (range, 0-6.7 years) after diagnosis; 52% received cyclophosphamide-based chemotherapy, 17% received non-cyclophosphamide-based chemotherapy (80% platinum-based), and 31% received no chemotherapy. A total of 2,777 matched females without cancer contributed 2,780 AMH levels. The pattern of AMH levels differed among the 4 groups. Among females without cancer and breast cancer survivors who did not undergo chemotherapy, AMH declined linearly over time. In contrast, among those who received cyclophosphamide-based and noncyclophosphamide-based chemotherapy, a nonlinear pattern of AMH level of initial fall during chemotherapy, followed by an increase over 2-4 years, and then by a plateau over 1-2 years before a decline was observed. CONCLUSION(S): In breast cancer survivors, AMH levels from administrative data supported ovarian toxicity of non-cyclophosphamide-based chemotherapy in breast cancer and efficiently depicted the timing and duration of changes in ovarian reserve to reflect the residual reproductive lifespan.

Expenditures in Young Adults with Hodgkin Lymphoma: NCI-Designated Comprehensive Cancer Centers versus Other Sites.

BACKGROUND: Outcomes among Hodgkin lymphoma (HL) patients diagnosed between 22 and 39 years are worse than among those diagnosed <21 years, and have not seen the same improvement over time. Treatment at an NCI-designated Comprehensive Cancer Center (CCC) mitigates outcome disparities, but may be associated with higher expenditures. METHODS: We examined cancer-related expenditures among 22- to 39-year-old HL patients diagnosed between 2001 and 2016 using deidentified administrative claims data (OptumLabs Data Warehouse; CCC: n = 1,154; non-CCC: n = 643). Adjusting for sociodemographics, clinical characteristics, and months enrolled, multivariable general linear models modeled average monthly health-plan paid (HPP) expenditures, and incidence rate ratios compared CCC/non-CCC monthly visit rates. RESULTS: In the year following diagnosis, CCC patients had higher HPP expenditures ($12,869 vs. $10,688, P = 0.001), driven by higher monthly rates of CCC nontreatment outpatient hospital visits (P = 0.001) and per-visit expenditures for outpatient hospital chemotherapy ($632 vs. $259); higher CCC inpatient expenditures ($1,813 vs. $1,091, P = 0.001) were driven by 3.1 times higher rates of chemotherapy admissions (P = 0.001). Out-of-pocket expenditures were comparable (P = 0.3). CONCLUSIONS: Young adults with HL at CCCs saw higher health-plan expenditures, but comparable out-of-pocket expenditures. Drivers of CCC expenditures included outpatient hospital utilization (monthly rates of non-therapy visits and per-visit expenditures for chemotherapy). IMPACT: Higher HPP expenditures at CCCs in the year following HL diagnosis likely reflect differences in facility structure and comprehensive care. For young adults, it is plausible to consider incentivizing CCC care to achieve superior outcomes while developing approaches to achieve long-term savings.

Percutaneous Left Atrial Appendage Occlusion in Comparison to Non-Vitamin K Antagonist Oral Anticoagulant Among Patients With Atrial Fibrillation.

Background This study aimed to compare percutaneous left atrial appendage occlusion (LAAO) with non-vitamin K antagonist oral anticoagulants among patients with atrial fibrillation. Methods and Results Using a US administrative database, 562 850 patients with atrial fibrillation were identified, among whom 8397 were treated with LAAO and 554 453 were treated with non-vitamin K antagonist oral anticoagulants between March 13, 2015 and December 31, 2018. Propensity score overlap weighting was used to balance baseline characteristics. The primary outcome was a composite end point of ischemic stroke or systemic embolism, major bleeding, and all-cause mortality. The mean age was 76.4±7.6 years; 280 097 (49.8%) were female. Mean follow-up was 1.5±1.0 years. LAAO was associated with no significant difference in the risk of the primary composite end point (hazard ratio [HR], 0.93 [0.84-1.03]), or the secondary outcomes including ischemic stroke/systemic embolism (HR, 1.07 [0.81-1.41]), and intracranial bleeding (HR, 1.08 [0.72-1.61]). LAAO was associated with a higher risk of major bleeding (HR, 1.22 [1.05-1.42], P=0.01) and a lower risk of mortality (HR, 0.73 [0.64-0.84], P<0.001). The lower risk of mortality associated with LAAO was most pronounced in patients with a prior history of intracranial bleeding. Conclusions In comparison to non-vitamin K antagonist oral anticoagulants, LAAO was associated with no significant difference in the risk of the composite outcome and a lower risk of mortality, which suggests LAAO might be a reasonable option in select patients with atrial fibrillation. The observation of higher bleeding risk associated with LAAO highlights the need to optimize postprocedural antithrombotic regimens as well as systematic efforts to assess and address bleeding predispositions.

The Friends of Cancer Research Real-World Data Collaboration Pilot 2.0: Methodological Recommendations from Oncology Case Studies.

The purpose of this study was to evaluate the potential collective opportunities and challenges of transforming real-world data (RWD) to real-world evidence for clinical effectiveness by focusing on aligning analytic definitions of oncology end points. Patients treated with a qualifying therapy for advanced non-small cell lung cancer in the frontline setting meeting broad eligibility criteria were included to reflect the real-world population. Although a trend toward improved outcomes in patients receiving PD-(L)1 therapy over standard chemotherapy was observed in RWD analyses, the magnitude and consistency of treatment effect was more heterogeneous than previously observed in controlled clinical trials. The study design and analysis process highlighted the identification of pertinent methodological issues and potential innovative approaches that could inform the development of high-quality RWD studies.

Some cautions on the use of instrumental variables estimators in outcomes research: how bias in instrumental variables estimators is affected by instrument strength, instrument contamination, and sample size.

OBJECTIVES: To examine the performance of instrumental variables (IV) and ordinary least squares (OLS) regression under a range of conditions likely to be encountered in empirical research. METHODS: A series of simulation analyses are carried out to compare estimation error between OLS and IV when the independent variable of interest is endogenous. The simulations account for a range of situations that may be encountered by researchers in actual practice-varying degrees of endogeneity, instrument strength, instrument contamination, and sample size. The intent of this article is to provide researchers with more intuition with respect to how important these factors are from an empirical standpoint. RESULTS: Notably, the simulations indicate a greater potential for inferential error when using IV than OLS in all but the most ideal circumstances. CONCLUSIONS: Researchers should be cautious when using IV methods. These methods are valuable in testing for the presence of endogeneity but only under the most ideal circumstances are they likely to produce estimates with less estimation error than OLS.

Patterns of biologic agent utilization among patients with rheumatoid arthritis: a retrospective cohort study.

BACKGROUND: The role of biologic therapies in the treatment of rheumatoid arthritis has expanded, but dosing patterns in the first versus subsequent lines of therapy have not been thoroughly explored. METHODS: In order to describe patterns of biologic agent utilization among patients with rheumatoid arthritis, health care claims data on use of abatacept, rituximab, or the anti-tumor necrosis factor (TNF) agents etanercept, adalimumab, and infliximab in first- or subsequent-line settings were used to form patient cohorts. Variables included: starting dose (first administration or fill), maintenance dose (third administration or fill), average dose, dose escalation, inter-infusion interval, and discontinuation (gap in therapy > 60 days or switch). Time to discontinuation was assessed with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Over 1 year, average (SD) doses of first-line etanercept (N = 1593; 45.4 [8.8] mg/week), adalimumab (N = 1040; 40.7 [10.4] mg/2 weeks), and abatacept (N = 360; 715.4 [214.5] mg/4 weeks) were similar to the starting and maintenance doses; the average infliximab dose (N = 538; 441.0 [209.2] mg/8 weeks) was greater than the starting and maintenance doses. Trends in the subsequent-line anti-TNF cohorts were similar. The percentages with a dose escalation or discontinuation were greater in the subsequent-line anti-TNF cohorts. The proportion with a dose escalation was greatest for the infliximab cohorts (61.2% first-line and 80.2% subsequent-line). The average period between abatacept infusions was 4.8 [1.4] weeks (4-week approved schedule); and 6.8 [2.6] months between rituximab courses (currently approved schedule is 6 months). Time to discontinuation was significantly shorter for subsequent-line than first-line anti-TNF therapy (median 9.7 vs. 12.5 mo; p < 0.001). The hazard ratio for discontinuing subsequent-line versus first-line anti-TNF therapy was 1.177 (p < 0.001). CONCLUSIONS: Subsequent-line anti-TNF therapy cohorts had higher rates of discontinuation, dose escalation, and shorter time to discontinuation than first-line anti-TNF cohorts.

Health Care Cost Associated With Contemporary Chronic Myelogenous Leukemia Therapy Compared With That of Other Hematologic Malignancies.

PURPOSE: Given the widespread introduction of tyrosine kinase inhibitors (TKIs), we evaluated the cost associated with chronic myelogenous leukemia (CML) care compared with the cost of care for patients with hematologic malignancies (HEM) and for patients without cancer (GEN), to aid with resource allocation and clinical decision making. METHODS: A retrospective cohort was constructed from the OptumLabs Data Warehouse using claims from 2000 to 2016. Eligible patients had ≥ 2 CML claims and were enrolled continuously for ≥ 6 months before diagnosis and ≥ 1 year afterward (n = 1,909). Patients with CML were frequency matched 4:1 with HEM and GEN cohorts and were observed through October 2017. We used generalized linear models to assess the variation in total mean annualized health care costs in the 3 cohorts and to examine the influence of factors associated with costs. RESULTS: Mean annualized costs for CML were $82,054 (ie, $25,471 [95% CI, $20,808 to $30,133] more than those for HEM and $74,993 [95% CI, $70,818 to $79,167] more than those for GEN); these differences were driven by pharmacy costs in the CML group. The cost of CML care exceeded that for HEM and GEN for all index years in this study and increased over each diagnostic interval until 2015, peaking at $91,990. The mean annual cost of all TKIs increased. Imatinib's mean annualized cost was $41,546 in the period 2000-2004 but increased to $105,069 in the period 2015-2017. In multivariable analysis, percent days on TKIs had the greatest influence on cost: ≥ 75% of the time versus none showed a difference in cost of $108,716 (95% CI, $99,193 to $118,239). CONCLUSION: Contemporary CML costs exceeded the cost of treatment of other hematologic malignancies. Cost was primarily driven by TKIs, whose cost continued to increase over time.

Adverse events among chronic myelogenous leukemia patients treated with tyrosine kinase inhibitors: a real-world analysis of health plan enrollees.

With tyrosine kinase inhibitor (TKI) therapy, chronic myelogenous leukemia (CML) is now a chronic disease. CML patients treated with TKIs (n = 1200) were identified from the OptumLabs® Data Warehouse (de-identified claims and electronic health records) between 2000 and 2016 and compared with a non-cancer cohort (n = 7635). The 5-year cumulative incidence of all organ system outcomes was significantly greater for the TKI versus non-cancer group. In the first year, compared with imatinib, later generation TKIs were associated with primary infections (hazard ratios [HR] 1.43, 95% CI 1.02-2.00), circulatory events (HR 1.15, 95% CI 1.01-1.31), and skin issues (HR 1.43, 95% CI 1.13-1.80); musculoskeletal and nervous system/sensory issues were less common (HRs 0.83-0.84, p < 0.05). Increased risk of infections, cardiopulmonary and skin issues associated with later generation TKIs persisted in subsequent years. In this real-world population, TKI therapy was associated with a high burden of adverse events. Later generation TKIs may have greater toxicity than imatinib.

Incidence and costs of cervical intraepithelial neoplasia in a US commercially insured population.

OBJECTIVE: This study aimed to estimate incidence, cost per episode of care, and US population burden of cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: For women continuously enrolled in a US health plan from January 1, 1999 to December 31, 2004, medical claims were used to identify potential CIN diagnosis. Presence and grade of CIN (CIN 1, CIN 2,3, or no CIN) were verified in medical records for a randomly selected subset (n = 254). Incidence, costs, and population burden were calculated. RESULTS: Annual incidence for CIN 1 and CIN 2,3 was 1.6 and 1.2 per 1,000 women, respectively. Incidence was highest among women aged 21 to 30 years (3.3 and 3.6 per 1,000) and women aged 31 to 40 years (2.9 and 2.7 per 1,000). Costs per episode of care were higher for CIN 2,3 ($1,634 vs $1,084). Estimated annual burden per 1,000 US women was $1,059 for CIN 1 and $1,803 for CIN 2,3. CONCLUSIONS: We estimate that 412,000 women in the United States are diagnosed with CIN annually, with an associated cost of approximately $570 million.