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.

Contemporary trends and barriers to oral anticoagulation therapy in Non-valvular atrial fibrillation during DOAC predominant era.

There is a need to reassess contemporary oral anticoagulation (OAC) trends and barriers against guideline directed therapy in the United States. Most previous studies were performed before major guideline changes recommended direct oral anticoagulant (DOAC) use over warfarin or have otherwise lacked patient level data. Data on overuse of OAC in low-risk group is also limited. To address these knowledge gaps, we performed a nationwide analysis to analyze current trends. This is a retrospective cohort study assessing non-valvular AF identified using a large United States de-identified administrative claims database, including commercial and Medicare Advantage enrollees. Prescription fills were assessed within a 90-day follow-up from the patient's index AF encounter between January 1, 2016, and December 31, 2020. Among the 339,197 AF patients, 4.4%, 8.0%, and 87.6% were in the low-, moderate-, and high-risk groups (according to CHA2DS2-VASc score). An over (29.6%) and under (52.2%) utilization of OAC was reported in low- and high-risk AF patients. A considerably high frequency for warfarin use was also noted among high-risk group patients taking OAC (33.1%). The results suggest that anticoagulation use for stroke prevention in the United States is still comparable to the pre-DOAC era studies. About half of newly diagnosed high-risk non-valvular AF patients remain unprotected against stroke risk. Several predictors of OAC and DOAC use were also identified. Our findings may identify a population at risk of complications due to under- or over-treatment and highlight the need for future quality improvement efforts.

Maternal comorbidity and adverse perinatal outcomes in survivors of adolescent and young adult cancer: A cohort study.

OBJECTIVE: To evaluate risks of preterm birth (PTB) and severe maternal morbidity (SMM) in female survivors of adolescent and young adult cancer and assess maternal comorbidity as a potential mechanism. To determine whether associations differ by use of assisted reproductive technology (ART). DESIGN: Retrospective cohort. SETTING: Commercially insured females in the USA. SAMPLE: Females with live births from 2000-2019 within a de-identified US administrative health claims data set. METHODS: Log-binomial regression models estimated relative risks of PTB and SMM by cancer status and tested for effect modification. Causal mediation analysis evaluated the proportions explained by maternal comorbidity. MAIN OUTCOME MEASURES: PTB and SMM. RESULTS: Among 46 064 cancer survivors, 2440 singleton births, 214 multiple births and 2590 linked newborns occurred after cancer diagnosis. In singleton births, the incidence of PTB was 14.8% in cancer survivors versus 12.4% in females without cancer (aRR 1.19, 95% CI 1.06-1.34); the incidence of SMM was 3.9% in cancer survivors versus 2.4% in females without cancer (aRR 1.44, 95% CI 1.13-1.83). Cancer survivors had more maternal comorbidities before and during pregnancy; 26% of the association between cancer and PTB and 30% of the association between cancer and SMM was mediated by maternal comorbidities. Tests for effect modification of cancer status on perinatal outcomes by ART were non-significant. CONCLUSIONS: Preterm birth and SMM risks were modestly increased after cancer. Significant proportions of elevated risks may result from increased comorbidities. ART did not significantly modify the association between adolescent and young adult cancer and adverse perinatal outcomes. The prevention and treatment of comorbidities provides an opportunity to improve perinatal outcomes among cancer survivors.

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.

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.

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.

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.

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.

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.

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.

A Population-based Study of Immunotherapy-related Toxicities in Lung Cancer.

BACKGROUND: Population-level data regarding incidences of immune-related adverse events (irAEs) are lacking. This study evaluated the frequencies of irAEs among patients with non-small-cell lung cancer (NSCLC) who received immune checkpoint inhibitors. PATIENTS AND METHODS: Administrative claims data from a large United States commercial insurance database (OptumLabs Data Warehouse) were used to retrospectively identify patients with NSCLC between January 1, 2015 and December 31, 2017 who received a programmed death-ligand 1/programmed cell death protein-1 (PD(L)-1) inhibitor. Cumulative risks for irAEs were estimated at 1, 3, 6, 9, and 12 months after initiation of a PD-(L)1 inhibitor. Additionally, associations between patient characteristics and frequency of irAEs were investigated utilizing multivariate logistic modeling. RESULTS: The risk of developing any irAE was 52.5% (95% confidence interval, 49.9%-55.2%) after 12 months in 3164 patients with NSCLC who initiated a PD-(L)1 inhibitor (median age, 69.0 years; 1763 [55.7%] males; 1401 [44.3%] females). Cumulative risks of irAEs increased over time: pneumonitis was recorded in 2.5% of patients 1 month after initiation of treatment, and increased to 14.3% after 9 months. Risks of hypophysitis and pericarditis were 3.6% and 1.7% at 9 months, respectively. Patients who received PD-(L)1 inhibitors in the first line had lower frequencies of irAEs (hazard ratio, 0.77; 95% confidence interval, 0.67-0.87). CONCLUSION: Our findings suggest that the frequencies of some irAEs may be higher than the rates reported in the pivotal trials that led to United States Food and Drug Administration approvals for PD-(L)1 inhibitors. These real-world data refine provider and patient expectations for outcomes in a broader population beyond what is observed in clinical trials.

Severe Hypoglycemia Attributable to Intensive Glucose-Lowering Therapy Among US Adults With Diabetes: Population-Based Modeling Study, 2011-2014.

OBJECTIVE: To estimate the contemporary prevalence of intensive glucose-lowering therapy among US adults with diabetes and model the number of hypoglycemia-related emergency department (ED) visits and hospitalizations that are attributable to such intensive treatment. PATIENTS AND METHODS: US adults with diabetes and glycated hemoglobin (HbA1c) levels less than 7.0% who were included in the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014. Participants were categorized as clinically complex if 75 years or older or with 2 or more activities of daily living limitations, end-stage renal disease, or 3 or more chronic conditions. Intensive treatment was defined as any glucose-lowering medications with HbA1c levels of 5.6% or less or 2 or more with HbA1c levels of 5.7% to 6.4%. First, we quantified the proportion of clinically complex and intensively treated individuals in the NHANES population. Then, we modeled the attributable hypoglycemia-related ED visits/hospitalizations over a 2-year period based on published data for event risk. RESULTS: Almost half (48.8% [10,719,057 of 21,980,034]) of US adults with diabetes (representing 10.7 million US adults) had HbA1c levels less than 7.0%. Among them, 32.3% (3,466,713 of 10,719,057) were clinically complex, and 21.6% (2,309,556 of 10,719,057) were intensively treated, with no difference by clinical complexity. Over a 2-year period, we estimated 31,511 hospitalizations and 30,954 ED visits for hypoglycemia in this population; of these, 4774 (95% CI, 954-9714) hospitalizations and 4804 (95% CI, 862-9851) ED visits were attributable to intensive treatment. CONCLUSION: Intensive glucose-lowering therapy, particularly among vulnerable clinically complex adults, is strongly discouraged because it may lead to hypoglycemia. However, intensive treatment was equally prevalent among US adults, irrespective of clinical complexity. Over a 2-year period, an estimated 9578 hospitalizations and ED visits for hypoglycemia could be attributed to intensive diabetes treatment, particularly among clinically complex patients. Patients at risk for hypoglycemia may benefit from treatment deintensification to reduce hypoglycemia risk and treatment burden.

An Exploratory Analysis of Real-World End Points for Assessing Outcomes Among Immunotherapy-Treated Patients With Advanced Non-Small-Cell Lung Cancer.

PURPOSE: This pilot study examined the ability to operationalize the collection of real-world data to explore the potential use of real-world end points extracted from data from diverse health care data organizations and to assess how these relate to similar end points in clinical trials for immunotherapy-treated advanced non-small-cell lung cancer. PATIENTS AND METHODS: Researchers from six organizations followed a common protocol using data from administrative claims and electronic health records to assess real-world end points, including overall survival (rwOS), time to next treatment, time to treatment discontinuation (rwTTD), time to progression, and progression-free survival, among patients with advanced non-small-cell lung cancer treated with programmed death 1/programmed death-ligand 1 inhibitors in real-world settings. Data sets included from 269 to 6,924 patients who were treated between January 2011 and October 2017. Results from contributors were anonymized. RESULTS: Correlations between real-world intermediate end points (rwTTD and time to next treatment) and rwOS were moderate to high (range, 0.6 to 0.9). rwTTD was the most consistent end points as treatment detail was available in all data sets. rwOS at 1 year post-programmed death-ligand 1 initiation ranged from 40% to 57%. In addition, rwOS as assessed via electronic health records and claims data fell within the range of median OS values observed in relevant clinical trials. Data sources had been used extensively for research with ongoing data curation to assure accuracy and practical completeness before the initiation of this research. CONCLUSION: These findings demonstrate that real-world end points are generally consistent with each other and with outcomes observed in randomized clinical trials, which substantiates the potential validity of real-world data to support regulatory and payer decision making. Differences observed likely reflect true differences between real-world and protocol-driven practices.

Trends in opioid use in commercially insured and Medicare Advantage populations in 2007-16: retrospective cohort study.

OBJECTIVE: To describe trends in the rate and daily dose of opioids used among commercial and Medicare Advantage beneficiaries from 2007 to 2016. DESIGN: Retrospective cohort study of administrative claims data. SETTING: National database of medical and pharmacy claims for commercially insured and Medicare Advantage beneficiaries in the United States. PARTICIPANTS: 48 million individuals with any period of insurance coverage between 1 January 2007 and 31 December 2016, including commercial beneficiaries, Medicare Advantage beneficiaries aged 65 years and over, and Medicare Advantage beneficiaries under age 65 years (eligible owing to permanent disability). MAIN ENDPOINTS: Proportion of beneficiaries with any opioid prescription per quarter, average daily dose in milligram morphine equivalents (MME), and proportion of opioid use episodes that represented long term use. RESULTS: Across all years of the study, annual opioid use prevalence was 14% for commercial beneficiaries, 26% for aged Medicare beneficiaries, and 52% for disabled Medicare beneficiaries. In the commercial beneficiary group, quarterly prevalence of opioid use changed little, starting and ending the study period at 6%; the average daily dose of 17 MME remained unchanged since 2011. For aged Medicare beneficiaries, quarterly use prevalence was also relatively stable, ranging from 11% at the beginning of the study period to 14% at the end. Disabled Medicare beneficiaries had the highest rates of opioid use, the highest rate of long term use, and the largest average daily doses. In this group, both quarterly use rates (39%) and average daily dose (56 MME) were higher at the end of 2016 than the low points observed in 2007 for each endpoint (26% prevalence and 53 MME). CONCLUSIONS: Opioid use rates were high during the study period of 2007-16, with the highest rates in disabled Medicare beneficiaries versus aged Medicare beneficiaries and commercial beneficiaries. Opioid use and average daily dose have not substantially declined from their peaks, despite increased attention to opioid abuse and awareness of their risks.

Novel Type 2 Diabetes Medication Access and Effect of Patient Cost Sharing.

BACKGROUND: Although drug formulary restrictions may reduce use of prescription medication and pharmacy costs, the effect of patient cost sharing on medication adherence and health care utilization and cost is unclear. OBJECTIVE: To evaluate the relationship between patient cost sharing for novel type 2 diabetes mellitus (T2DM) medications and medication adherence, persistence, and health care utilization and cost. METHODS: This retrospective study used medical and pharmacy claims linked to pharmacy benefit plan design data. Patients with T2DM were identified via ICD-9-CM codes (medical claims), outpatient prescription fills (pharmacy claims), and pharmacy benefit design information. Patients with T2DM treated with novel T2DM medications (DPP4 or GLP-1) were enrolled in plans with fixed or coinsurance medication copayment structures and followed for 12-48 months. Endpoints included medication persistence and adherence and total all-cause health care cost. Multivariable regression analysis estimated the effect of benefit design parameters, adjusting for baseline patient characteristics. RESULTS: The integrated database included 36,475 patients with T2DM. The majority (83.1%) had fixed copayment plans, and 3-tier plans were common (93.1%). Higher third-tier copayment was associated with poorer medication adherence and persistence but not total health care cost during follow-up. A $10 higher third-tier copayment was associated with 11% greater risk of novel T2DM medication discontinuation and 3% lower adherence. A comparison of patients with fixed versus coinsurance plans found that fixed plans were associated with higher adjusted persistence and total all-cause health care costs. CONCLUSIONS: Higher medication copayment amounts were associated with lower patient medication adherence and persistence in T2DM but not total health care costs, as health plan costs decreased while patient out-of-pocket costs increased. We observed higher total all-cause health care costs among T2DM patients with a fixed copay (vs. coinsurance) pharmacy benefit. Additional research incorporating plan design information is needed to further examine this finding. DISCLOSURES: This study was funded by Janssen Scientific Affairs, which was involved in study design, interpretation of data, editing manuscript content, and had final approval of the manuscript before submission. Lopez and Bookhart are employed by Janssen Scientific Affairs. At the time of this study, Henk was employed by Optum HEOR, which was contracted by Janssen to conduct this study. Portions of this study were presented at the 21st Annual International Meeting, ISPOR; May 21-25, 2016; in Washington, DC.

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.