Real-world treatment patterns in patients initiating third-line therapy for relapsed or refractory multiple myeloma in Germany, Italy, the United Kingdom, France, and Spain.

OBJECTIVES: To retrospectively analyze real-world treatment patterns in patients with relapsed/refractory multiple myeloma (RRMM) who initiated third-line treatment in Europe. METHODS: German and Italian administrative claims data were sourced from the German AOK PLUS health insurance fund and Italian local health units (2016-2020). Data for the United Kingdom (UK), France, and Spain were sourced from medical chart reviews (MCRs) from 2016 to 2018 (historical) and 2019 to 2021 (new) using electronic case report forms. RESULTS: Across all countries, immunomodulatory imide drug (IMiD)-based regimens were prominent in the third-line setting. From 2016 to 2020, lenalidomide-dexamethasone was most common in Italy (18.0%) and Germany (12.7%). From 2019 to 2021, the most common regimen was ixazomib-lenalidomide-dexamethasone (67.5%) in the UK, pomalidomide-dexamethasone (17.1%) in France, and daratumumab-bortezomib-dexamethasone (15.0%) in Spain. In the historical data (2016-2018), third-line lenalidomide- and pomalidomide-dexamethasone doublet use across the UK (>47%), France (>46%), and Spain (>33%) was high. From historical to new, triplet use increased in Spain (>19% to >60%) as did anti-CD38 agent use in France (15.1% to 51.9%) and Spain (19.7% to 42.1%). CONCLUSIONS: From 2016 to 2021, third-line regimens were mostly IMiD based. The MCR data demonstrated evolving treatment choices from 2016 to 2018 and 2019 to 2021, providing insights into uptake of novel agents and current RRMM European clinical practice.

Claims-based algorithm to estimate the Expanded Disability Status Scale for multiple sclerosis in a German health insurance fund: a validation study using patient medical records.

Background: The Expanded Disability Status Scale (EDSS) quantifies disability and measures disease progression in multiple sclerosis (MS), however is not available in administrative claims databases. Objectives: To develop a claims-based algorithm for deriving EDSS and validate it against a clinical dataset capturing true EDSS values from medical records. Methods: We built a unique linked dataset combining claims data from the German AOK PLUS sickness fund and medical records from the Multiple Sclerosis Management System 3D (MSDS3D). Data were deterministically linked based on insurance numbers. We used 69 MS-related diagnostic indicators recorded with ICD-10-GM codes within 3 months before and after recorded true EDSS measures to estimate a claims-based EDSS proxy (pEDSS). Predictive performance of the pEDSS was assessed as an eight-fold (EDSS 1.0-7.0, ≥8.0), three-fold (EDSS 1.0-3.0, 4.0-5.0, ≥6.0), and binary classifier (EDSS <6.0, ≥6.0). For each classifier, predictive performance measures were determined, and overall performance was summarized using a macro F1-score. Finally, we implemented the algorithm to determine pEDSS among an overall cohort of patients with MS in AOK PLUS, who were alive and insured 12 months prior to and after index diagnosis. Results: We recruited 100 people with MS insured by AOK PLUS who had ≥1 EDSS measure in MSDS3D between 01/10/2015 and 30/06/2019 (620 measurements overall). Patients had a mean rescaled EDSS of 3.2 and pEDSS of 3.0. The pEDSS deviated from the true EDSS by 1.2 points, resulting in a mean squared error of prediction of 2.6. For the eight-fold classifier, the macro F1-score of 0.25 indicated low overall predictive performance. Broader severity groupings were better performing, with the three-fold and binary classifiers for severe disability achieving a F1-score of 0.68 and 0.84, respectively. In the overall AOK PLUS cohort (3,756 patients, 71.9% female, mean 51.9 years), older patients, patients with progressive forms of MS and those with higher comorbidity burden showed higher pEDSS. Conclusion: Generally, EDSS was underestimated by the algorithm as mild-to-moderate symptoms were poorly captured in claims across all functional systems. While the proxy-based approach using claims data may not allow for granular description of MS disability, broader severity groupings show good predictive performance.

Burden of disease among patients with prevalent Crohn's disease: results from a large German sickness fund.

PURPOSE: The aim of this study was to investigate the burden of disease among a real-world cohort of patients with prevalent Crohn's disease (CD) in Germany. METHODS: We conducted a retrospective cohort analysis using administrative claims data from the German AOK PLUS health insurance fund. Continuously insured patients with a CD diagnosis between 01 October 2014 and 31 December 2018 were selected and followed for at least 12 months or longer until death or end of data availability on 31 December 2019. Medication use (biologics, immunosuppressants (IMS), steroids, 5-aminosalicylic acid) was assessed sequentially in the follow-up period. Among patients with no IMS or biologics (advanced therapy), we investigated indicators of active disease and corticosteroid use. RESULTS: Overall, 9284 prevalent CD patients were identified. Within the study period, 14.7% of CD patients were treated with biologics and 11.6% received IMS. Approximately 47% of all prevalent CD patients had mild disease, defined as no advanced therapy and signs of disease activity. Of 6836 (73.6%) patients who did not receive advanced therapy in the follow-up period, 36.3% showed signs of active disease; 40.1% used corticosteroids (including oral budesonide), with 9.9% exhibiting steroid dependency (≥ 1 prescription every 3 months for at least 12 months) in the available follow-up. CONCLUSIONS: This study suggests that there remains a large burden of disease among patients who do not receive IMS or biologics in the real world in Germany. A revision of treatment algorithms of patients in this setting according to the latest guidelines may improve patient outcomes.

Data Resource Profile: The Multiple Sclerosis Documentation System 3D and AOK PLUS Linked Database (MSDS-AOK PLUS).

Real-world evidence in multiple sclerosis (MS) is limited by the availability of data elements in individual real-world datasets. We introduce a novel, growing database which links administrative claims and medical records from an MS patient management system, allowing for the complete capture of patient profiles. Using the AOK PLUS sickness fund and the Multiple Sclerosis Documentation System MSDS3D from the Center of Clinical Neuroscience (ZKN) in Germany, a linked MS-specific database was developed (MSDS-AOK PLUS). Patients treated at ZKN and insured by AOK PLUS were recruited and asked for informed consent. For linkage, insurance IDs were mapped to registry IDs. After the deletion of insurance IDs, an anonymized dataset was provided to a university-affiliate, IPAM e.V., for further research applications. The dataset combines a complete record of patient diagnoses, treatment, healthcare resource use, and costs (AOK PLUS), with detailed clinical parameters including functional performance and patient-reported outcomes (MSDS3D). The dataset currently captures 500 patients; however, is actively expanding. To demonstrate its potential, we present a use case describing characteristics, treatment, resource use, and costs of a patient subsample. By linking administrative claims to clinical information in medical charts, the novel MSDS-AOK PLUS database can increase the quality and scope of real-world studies in MS.

Real-world outcomes associated with switching to anti-TNFs versus other biologics in Crohn's Disease patients: A retrospective analysis using German claims data.

Background: The positioning of new biologic agents for the treatment of Crohn's disease (CD) following failure of initial anti-tumor necrosis factor (anti-TNF) therapy remains a challenge in the real world. Objectives: This study aims to investigate the real-world outcomes associated with the sequential use of biologics in CD patients that newly initiate anti-TNFs, specifically comparing those that switch to another anti-TNF versus biologics with other modes of action. Design: Retrospective cohort study. Methods: We identified CD patients who newly began anti-TNF therapy between 1 October 2014 and 31 December 2018 using two German claims databases. Patients were classified as within-class switchers (WCS) if they switched to another anti-TNF or outside-class switchers (OCS) if they switched to vedolizumab (VDZ) or ustekinumab (UST). To compare WCS and OCS, baseline covariates were adjusted through inverse probability of treatment weighting (IPTW), and time-to-event analyses were performed using Cox Proportional Hazard regressions. Results from both databases were meta-analyzed using an inverse variance model. Results: Overall, 376 prevalent adult CD patients who initiated anti-TNFs and switched to another biologic were identified. After IPTW, there were 152 and 177 patients in the WCS and OCS group, respectively. WCS were more likely to receive prolonged corticosteroid therapy [hazard ratio (HR): 1.63, 95% confidence interval (CI): 1.17-2.27, p = 0.004], switch a second time to a different biologic (HR: 2.44, 95% CI: 1.63-3.66, p < 0.001), and discontinue treatment (HR: 1.71, 95% CI: 1.25-2.34, p = 0.001) than OCS. Conclusion: This study suggests that CD patients exhibit more favorable outcomes when switching outside the anti-TNF class to VDZ or UST after initial anti-TNF failure than switching to a second anti-TNF. With loss of response to anti-TNFs as a concern in the real world, comparative evidence from claims data assessing sequential use of biologics can help optimize treatment algorithms of patients after anti-TNF failure.

Bridging the gap between oncology clinical trials and real-world data: evidence on replicability of efficacy results using German claims data.

Aims: Using German claims, the authors replicated the CHAARTED trial in metastatic hormone-sensitive prostate cancer. Methods: The authors identified metastatic hormone-sensitive prostate cancer patients replicating the inclusion/exclusion criteria of CHAARTED. Patients treated with docetaxel in combination with androgen deprivation therapy (ADT) at first line (docetaxel group) were compared with patients treated with ADT monotherapy (ADT mono group). After propensity score matching, overall survival was compared between the matched cohorts. Results: The authors included 441 patients. After propensity score matching, two equally sized matched cohorts of 74 patients each were compared in terms of overall survival. The hazard ratio (HR) was 0.71 (95% CI: 0.42-1.19), comparable to the HR in CHAARTED (HR: 0.72; 95% CI: 0.59-0.89). Conclusions: Using early comparative evidence from real-world data for regulatory and health technology assessment decisions is useful.

Hospitalized with stroke at the weekend: Higher cost and risk of early death?

OBJECTIVES: Previous studies have shown that weekend hospitalizations are associated with poorer health outcomes and higher mortality ("weekend effect"). However, few of these studies have adjusted for disease severity and little is known about the effect on costs. This work investigates the weekend effect and its costs for patients with cerebral infarction in Germany, adjusting for patient characteristics and proxies of stroke severity. METHODS: Adult patients with a cerebral infarction hospitalization 10th revision of the International statistical classification of diseases and related health problems (ICD-10: I63) between 01 January 2014 and 30 June 2017 were included from German health claims (AOK PLUS dataset). Propensity score matching was used to match patients hospitalized on weekends or on public holidays (weekend group) with patients hospitalized during the working week (workday group), based on baseline characteristics and proxies for disease severity such as concomitant diagnoses of aphasia, ataxia, and coma, or peg tube at index hospitalization. Matched cohorts were compared in terms of in-hospital, 7-day, and 30-day mortality, as well as risk and costs of stroke and rehabilitation stays in the year after first stroke. RESULTS: Of 32,311 patients hospitalized with cerebral infarction between 01 January 2014 and 30 June 2017, 8409 were in the weekend group and 23,902 in the workday group. After propensity score matching, 16,730 patients were included in our study (8365 per group). Matched cohorts did not differ in baseline characteristics or stroke severity. In the weekend group, the risk of in-hospital death (11.2%) and the seven-day mortality rate (6.8%) were 13.1% and 17.2% higher than in the workday group, respectively (both p < 0.01). The hazard ratio for death in the weekend group was 1.1 (p = 0.043). The risks of subsequent stroke hospitalization and rehabilitation stays for a stroke were 8.4% higher and 5.5% higher in the weekend group (both p = 0.02). As a result, the stroke-related hospitalization and rehabilitation costs per patient year were, respectively, 5.6% and 8.0% higher in the weekend group (both p = 0.01). CONCLUSIONS: A significant weekend effect emerged after controlling for observable patient characteristics and proxies of stroke severity. This effect also resulted in higher costs for patients admitted on weekends.

Healthcare resource utilization and associated cost of patients with bone metastases from solid tumors who are naïve to bone-targeting agents: a comparative analysis of patients with and without skeletal-related events.

BACKGROUND: This study analyzes the impact of skeletal-related events (SRE) on healthcare resource utilization (HCRU) and costs incurred by patients with bone metastases (BM) from solid tumors (ST), who are therapy-naïve to bone targeting agents (BTAs). METHODS: German claims data from 01/01/2010 to 30/06/2018 were used to conduct a retrospective comparative cohort analysis of BTA-naive patients with a BM diagnosis and preceding ST diagnosis. HCRU and treatment-related costs were compared in two matched cohorts of patients with and without a history of SREs, defined as pathological fracture, spinal cord compression, surgery to bone and radiation to bone. The first SRE was defined as the patient-individual index date. Conversely, for the non-SRE patients, index dates were assigned randomly. RESULTS: In total, 45.20% of 9,832 patients reported experiencing at least one SRE (n = 4444) while 54.80% experienced none (n = 5388); 2,434 pairs of SRE and non-SRE patients were finally matched (mean age: 70.87/71.07 years; females: 39.07%/38.58%). Between SRE and non-SRE cohorts, significant differences in the average number of hospitalization days per patient-year (35.80/30.80) and associated inpatient-care costs (14,199.27€/10,787.31€) were observed. The total cost ratio was 1.16 (p < 0.001) with an average cost breakdown of 23,689.54€ and 20,403.27€ per patient-year in SRE and non-SRE patients. CONCLUSION: The underutilization of BTAs within a clinical setting poses an ongoing challenge in the real-world treatment of BM patients throughout Germany. Ultimately, the economic burden of treating SREs in patients with BM from ST was found to be considerable, resulting in higher direct healthcare costs and increased utilization of inpatient care facilities.

Recreational Marijuana Legalization and Adolescent Use of Marijuana, Tobacco, and Alcohol.

PURPOSE: Given the rapid expansion of recreational marijuana legalization (RML) polices, it is essential to assess whether such policies are associated with shifts in the use of marijuana and other substances, particularly for adolescents, who are uniquely susceptible to negative repercussions of marijuana use. This analysis seeks to provide greater generalizability, specificity, and methodological rigor than limited prior evidence. METHODS: Youth Risk Behavior Survey data from 47 states from 1999 to 2017 assessed marijuana, alcohol, cigarette, and e-cigarette use among adolescents (14-18+ years; N = 1,077,938). Associations between RML and adolescent past-month substance use were analyzed using quasi-experimental difference-in-differences zero-inflated negative binomial models. RESULTS: Controlling for other state substance policies, year and state fixed effects, and adolescent demographic characteristics, models found that RML was not associated with a significant shift in the likelihood of marijuana use but predicted a small significant decline in the level of marijuana use among users (incidence rate ratio = .844, 95% confidence interval [.720-.989]) and a small increase in the likelihood of any e-cigarette use (odds ratio of zero use = .647, 95% confidence interval [.515-.812]). Patterns did not vary over adolescent age or sex, with minimal differences across racial/ethnic groups. CONCLUSIONS: Results suggest minimal short-term effects of RML on adolescent substance use, with small declines in marijuana use and increase in the likelihood of any e-cigarette use. Given the delayed rollout of commercial marijuana sales in RML states and rapid expansion of RML policies, ongoing assessment of the consequences for adolescent substance use and related health and behavioral repercussions is essential.

Impact of State-Level Changes on Maternal Mortality: A Population-Based, Quasi-Experimental Study.

INTRODUCTION: Recent increases in maternal mortality and persistent disparities have led to speculation about why the U.S. has higher rates than most high-income countries. The aim was to examine the impact of changes in state-level factors plausibly linked to maternal mortality on overall rates and by race/ethnicity. METHODS: This quasi-experimental, population-based, difference-in-differences study used 2007-2015 National Vital Statistics System microdata mortality files from 38 states and DC. The primary exposures were 5 state-level sexual and reproductive health indicators and 6 health and economic conditions. Maternal mortality rate was defined as number of deaths of women while pregnant or within 42 days of termination of pregnancy per 100,000 live births. A difference-in-differences zero-inflated negative binomial regression model was estimated using the race/ethnicity-age-state-year population as the denominator and adjusting for race/ethnicity, age, state, and year. Data were analyzed in 2017-2018. RESULTS: There were 4,767 deaths among women up to age 44 years, resulting in a maternal mortality rate of 17.9. Reducing the proportion of Planned Parenthood clinics by 20% from the state-year mean increased the maternal mortality rate by 8% (incidence rate ratio, 1.08; 95% CI=1.04, 1.12). States that enacted legislation to restrict abortions based on gestational age increased the maternal mortality rate by 38% (incidence rate ratio, 1.38; 95% CI=1.03, 1.84). Planned Parenthood clinic closures negatively impacted all women, increasing mortality by 6%-15% across racial/ethnic groups, whereas gestational limits primarily increased mortality among white women. CONCLUSIONS: Recent fiscal and legislative changes reducing women's access to family planning and reproductive health services have contributed to rising maternal mortality rates.

Associations Between Gun Laws and Suicides.

We examined the impact of a state gun law environment on suicides overall and within demographic subgroups. We linked 211,766 firearm suicides and 204,625 nonfirearm suicides in the 50 states of the United States for 2005-2015 to the population in each state, year, race/ethnicity, sex, and age, as well as to an index of state-level gun control. Difference-in-differences, zero-inflated, negative-binomial models were used to evaluate the impact of strengthening gun control on firearm and nonfirearm suicides. We subsequently stratified by sex and tested for interactions with race/ethnicity and age. We found 25 states strengthened gun control by an average of 6 points. Such an increase may result in a 3.3% (incidence rate ratio = 0.967; 95% confidence interval: 0.938, 0.996) decrease in firearm suicides. Although no impact on nonfirearm suicides was found overall, interaction models showed an increase in nonfirearm suicides among black men, white women, black women, and older individuals. Strengthening gun control may reduce firearm suicides overall but may increase nonfirearm suicides in some populations. The results indicate stricter gun laws should be advocated for and that additional policies are needed for populations who shifted to nonfirearm suicides.

Gun laws and school safety.

BACKGROUND: This paper examines the associations between state-level gun control and adolescent school safety overall and by student sex, age, and race. METHODS: We used data on 926 639 adolescents from 45 states in the 1999-2015 Youth Risk Behavior Surveys. Students self-reported on weapon carrying at school, the number of times they experienced weapon threats or injuries at school, the number of school days missed due to feeling unsafe, and weapon carrying at any location. For each state and year, 133 gun laws were combined into an index of gun control strength. Difference-in-differences logistic regression models were used to evaluate the associations of stricter gun laws with binary measures of students' weapon carrying and perception of school safety, controlling for individual and state characteristics, as well as year and state fixed effects. RESULTS: An IQR increase in the index (ie, a 15-point increase corresponding to a strengthening of gun control) was associated with a 0.8-percentage point decrease in the probability of weapon threats at school (p=0.029), a 1.1-percentage point decrease in the probability of missing school due to feeling unsafe (p=0.002) and a 1.9-percentage point decrease in the probability of carrying weapons at any location (p=0.001). Stricter gun laws had a stronger negative association with weapon carrying among males compared with females. Stricter gun laws were also differentially associated with weapon carrying by race/ethnicity. CONCLUSIONS: The adoption of stricter state gun laws was associated with improvements in school climate and subjective perceptions of safety.

A quasi-experimental evaluation of marijuana policies and youth marijuana use.

BACKGROUND: Marijuana use carries risks for adolescents' well-being, making it essential to evaluate effects of recent marijuana policies. OBJECTIVES: This study sought to delineate associations between state-level shifts in decriminalization and medical marijuana laws (MML) and adolescent marijuana use. METHODS: Using data on 861,082 adolescents (14 to 18+ years; 51% female) drawn from 1999 to 2015 state Youth Risk Behavior Surveys (YRBS), difference-in-differences models assessed how decriminalization and MML policy enactment were associated with adolescent marijuana use, controlling for tobacco and alcohol policy shifts, adolescent characteristics, and state and year trends. RESULTS: MML enactment was associated with small significant reductions (OR = 0.911, 95% CI [0.850, 0.975]) of 1.1 percentage points in current marijuana use, with larger significant declines for male, Black, and Hispanic (2.7-3.9 percentage points) adolescents. Effects of MML increased significantly with each year of exposure (OR = 0.980, 95% CI [0.968, 0.992]). In contrast, decriminalization was not associated with significant shifts in use for the sample as a whole, but predicted significant declines in marijuana use among 14-year olds and those of Hispanic and other ancestry (1.7-4.4 percentage points), and significant increases among white adolescents (1.6 percentage points). Neither policy was significantly associated with heavy marijuana use or the frequency of use, suggesting that heavy users may be impervious to such policy signals. CONCLUSION: As the first study to concurrently assess unique effects of multiple marijuana policies, results assuage concerns over potential detrimental effects of more liberal marijuana policies on youth use.

Associations Between State Tobacco Control Policies and Adolescent ENDS Use.

BACKGROUND: Despite an increase in adolescent use of electronic nicotine delivery systems (ENDS), little is known about the role of tobacco control policies on ENDS use. OBJECTIVE: For aim 1, we examined how trends in adolescent use of cigarettes were affected by the introduction of ENDS; for aim 2, we examined the associations between ENDS age restrictions, cigarette taxes, and smoke-free legislation and adolescent use of ENDS and cigarettes. DESIGN AND SETTING: Repeated cross-sections of the 1999-2015 Youth Risk Behavior Surveys linked to state-level tobacco control policies. PARTICIPANTS: 938 486 adolescents aged 14 to 18 years from 45 states. MAIN OUTCOME MEASURES: For aim 1, we examined adolescent use of cigarettes. For aim 2, we examined adolescent use of ENDS, only ENDS, and cigarettes. RESULTS: We found there was an overall decreasing trend in adolescent use of cigarettes, but the actual decline was greater than the predicted decline for 17- and 18-year-olds. While we found no associations between ENDS use and ENDS age restrictions or cigarette taxes, ENDS use was 3.8 percentage points higher in those states with smoke-free legislation for combustible tobacco products. CONCLUSIONS: Our findings highlight that ENDS age restrictions may not be adequate to curb ENDS use and additional local- and state-level policies governing ENDS are needed.