Real-world data for marginal zone lymphoma patients in the French REALYSA cohort: The REALMA study.

Marginal Zone Lymphoma (MZL) comprises three subtypes: extranodal MZL (EMZL), splenic MZL (SMZL) and nodal MZL (NMZL). Since clinical trials have limited representativeness, there is a need for real-world data (RWD) evidence in MZL. Real-world data in Lymphoma and survival in Adults (REALYSA) is a prospective multicentric French cohort of newly diagnosed lymphoma patients. This study consists of the first abstraction of MZL patients prospectively included in REALYSA between 12/2018 and 01/2021 with at least 1 year of follow-up. It provides a landscape description of clinical characteristics, initial workup, quality of life and first-line therapy performed in routine practice. Among 207 included patients, 122 presented with EMZL, 51 with SMZL and 34 with NMZL. At baseline, median age was 67 years (range 28-96), and patients reported a favorable global health status (75/100 (IQR 58,83)) - which was higher in NMZL and lower in SMZL patients (p = 0.006). 18FDG-PET/CT was frequently performed at initial workup (EMZL 72%, SMZL 73%, NMZL 85%). Active surveillance was the initial management for 58 (28%) patients. The most prescribed therapies were rituximab-chlorambucil in the EMZL population (30%), rituximab monotherapy in the SMZL population (37%) and R-CHOP (24%)/bendamustine-rituximab (15%) in the NMZL population. At end of first line, overall response rate was 93% among treated patients with 75% of complete response. This French nationwide study provided for the first time prospective RWD on clinical characteristics, initial management and treatment response of MZL patients.

Alzheimer's Disease Linkage to Real-World Evidence (AD-LINE) Study: Linking Claims Data to Phase 3 GRADUATE Study of Gantenerumab.

BACKGROUND: Linking data from clinical trials and real-world claims may improve the robustness of trial data and provide information on the health, economic, and societal impacts of a disease. OBJECTIVE: To report on the feasibility of linking trial data to Medicare claims data in early symptomatic Alzheimer's disease (AD) in the US. DESIGN AND SETTING: Alzheimer's Disease Linkage to Real-World Evidence (AD-LINE) was a noninterventional cohort study that included participants recruited from the GRADUATE program whose trial data were linked to their Medicare claims. PARTICIPANTS: AD-LINE participants were 66 years and older with early symptomatic AD (ie, mild cognitive impairment [MCI] due to AD or mild AD dementia) and were enrolled in the GRADUATE program and a Medicare fee-for-service or Medicare Advantage plan. MEASUREMENTS: The Centers for Medicare and Medicaid Services linked participants' clinical trial identifiers to their Medicare beneficiary identifiers using a deterministic, exact matching process. Demographics and clinical characteristics of the AD-LINE cohort at baseline were collected. Outcomes measured in this study included healthcare resource utilization derived from Medicare claims data. RESULTS: In total, 147 participants across 21 US sites were invited to participate and 111 provided informed consent. Of those, 61 patients had linkable data (ie, Medicare beneficiary identifier), Medicare Parts A/B enrollment, and no health maintenance organization (HMO) enrollment in the year before trial entry. Of the 61 participants whose data were analyzed in this study, 30 had MCI due to AD and 31 had mild AD dementia. Participants in the MCI due to AD group had more healthcare resource utilization on average in the baseline period than those in the mild AD dementia group (29.9 [SD, 20.9] vs 24.5 claims [SD, 12.3]). In an ad hoc analysis, a relatively high concordance (85.3%) was seen between the rates of clinically confirmed AD diagnosis and evidence of AD diagnosis in claims data. CONCLUSION: This linkage process may serve as a proof of concept for researchers interested in linking clinical trial and real-world claims data. The lessons learned from AD-LINE and innovation of data linkage approaches may encourage key stakeholders to link data in the future.

Real-world outcomes following ibrutinib dose reduction in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.

This study used real-world data from three separate United States (US) databases to evaluate dosing patterns and time to next treatment (TTNT) following the first-incident adverse event (AE) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treated with first-line ibrutinib with and without dose reduction (DR). Median TTNT or death in patients with and without a DR following an AE in each database was as follows: Optum Clinformatics Data Mart (CDM): 59.5 and 30.6 months; ConcertAI: 27.1 and 18.0 months; and Medicare Fee-for-Service (FFS): 49.8 and 22.0 months, respectively. Median TTNT or death in patients with cardiac AEs, with and without a DR, was: Optum CDM: 44.4 and 22.9 months; ConcertAI: 29.9 and 18.3 months; and Medicare FFS: 49.6 and 14.0 months, respectively. Ibrutinib DR was associated with fewer outpatient visits and lower CLL/SLL-related medical costs. These findings suggest that utilizing ibrutinib DR may effectively manage tolerability without compromising clinical efficacy.

A scalable approach to assess the safety of recently marketed systemic treatments for atopic dermatitis in clinical practice.

Targeted systemic immune-modulating drugs (IMDs) to treat atopic dermatitis (AD) were highly efficacious in randomized trials. Trials with limited number of subjects leave questions about their safety. We describe a data and analytics structure for the production of timely, high-quality evidence on the comparative safety of recently approved IMDs in patients with AD in clinical practice. We established a series of sequential propensity score (PS)-balanced cohorts that grow in size with each annual data refresh. Nine health outcomes of interest plus conjunctivitis as a positive tracer outcome were identified. The initial treatment comparison was dupilumab, an interleukin-4/13 inhibitor, or tralokinumab, an interleukin-13 inhibitor, versus abrocitinib/upadacitinib, both JAK inhibitors. The first analysis cycle (December 2021-February 2023) compared 269 patients initiating JAK inhibitors and 2,650 initiating IL-4/IL-13 inhibitors. Patient characteristics were well balanced after PS-matching. Outpatient infections within 180 days occurred in 18% of JAK-1 inhibitor initiators versus 12% of dupilumab/ tralokinumab initiators (RR=1.50; 0.96 to 2.33) whereas acne risks were 7% vs. 3%, respectively (RR=2.29, 0.96 to 5.46). This sequential monitoring system will produce essential knowledge on the safety of IMDs to treat AD based on its growing study size of patients observed in clinical practice.

Use of transportability methods for real-world evidence generation: a review of current applications.

Aim: To evaluate how transportability methods are currently used for real-world evidence (RWE) generation to inform good practices and support adoption and acceptance of these methods in the RWE context. Methods: We conducted a targeted literature review to identify studies that transported an effect estimate of the clinical effectiveness or safety of a biomedical exposure to a target real-world population. Records were identified from PubMed-indexed articles published any time before 25 July 2023 (inclusive). Two reviewers screened abstracts/titles and reviewed the full text of candidate studies to identify the final set of articles. Data on the therapeutic area, exposure(s), outcome(s), original and target populations and details of the transportability analysis (e.g., analytic method used, estimate transported, stated assumptions) were abstracted from each article. Results: Of 458 unique records identified, six were retained in the final review. Articles were published during 2021-2023, focused on the US/Canada context, and covered a range of therapeutic areas. Four studies transported an RCT effect estimate, while two transported effect estimates derived from real-world data. Almost all articles used weighting methods to transport estimates. Two studies discussed all transportability assumptions, and one evaluated the likelihood of meeting all assumptions and the impact of potential violations. Conclusion: The use of transportability methods for RWE generation is an emerging and promising area of research to address evidence gaps in settings with limited data and infrastructure. More transparent and rigorous reporting of methods, assumptions and limitations may increase the use and acceptability of transportability for producing robust evidence on treatment effectiveness and safety.

The impact of diagnosing provider type on longitudinal care for patients with newly diagnosed Huntington's Disease.

AIMS: This study evaluated the association between provider types for patients with newly diagnosed Huntington's disease (HD) and healthcare resource utilization (HCRU), costs, and treatment patterns. MATERIALS AND METHODS: This retrospective analysis used MarketScan® databases (1/1/2017-12/31/21) to identify provider type who diagnosed and managed US adult patients with HD. Patients with continuous enrollment 6 months pre- and 12 months post-diagnosis were included. Outcomes evaluated over 12 months post-diagnosis included hospitalizations, outpatient visits, antipsychotic or vesicular monoamine transporter 2 (VMAT2) inhibitor use, and total healthcare costs. RESULTS: 340 eligible patients had a mean age at diagnosis of 49 years. 56.5% were female; 71.5% had a Charlson Comorbidity Index of 0. Patients were diagnosed by neurologists (48.5%), primary care providers (PCP) (35.6%), psychiatrists (3.5%), or other providers (12.4%). Patients diagnosed by PCPs or neurologists received significantly more follow-ups by the same diagnosing provider type (P < 0.05).All-cause and HD-related outpatient visits at 12-month follow-up had more patients diagnosed by PCPs (23.9, 5.1) than neurologists (18.0, 2.4), psychiatrists (16.7, 1.67), or others (15.3, 2.4). HD-related mean costs totaled $2,489 ($1,179 inpatient and $1,310 outpatient). Patients diagnosed by neurologists had significantly lower HD-related total non-medication costs vs those diagnosed by PCPs (-$2,256; P < 0.05).Among patients diagnosed by neurologists vs PCPs, similar proportions received antipsychotics within the first year (55% vs 52%, respectively); more patients managed by neurologists received VMAT2 inhibitors (12% vs 7%, respectively). LIMITATIONS: Our study includes limitations inherent to retrospective claims studies. CONCLUSIONS: Patients with HD are most often diagnosed by neurologists or PCPs; the same diagnosing provider type typically manages follow-up. Patients diagnosed by neurologists had significantly fewer HD-related outpatient visits, lower HD-related non-drug costs, and more frequently received VMAT2 inhibitors vs those diagnosed by PCPs. Our findings show an integrated care team may provide evidence-based, personalized care for patients with HD.

Huntington's disease is a rare disease that is caused by changes in genes. Symptoms of Huntington's disease are irritability, depression, loss of memory, and issues with movement. The symptoms are different for each person and can happen at different times during the disease. A team of doctors that can help with all the symptoms is important for treating Huntington's disease. In our study we looked at which type of doctor was diagnosing Huntington's disease and if the patient continued to see the same type of doctor. We also looked at whether the costs of the disease were related to the type of doctor that diagnosed the disease. We found that most patients were diagnosed by a primary care doctor or a neurologist (brain doctor), and they continued to see the same doctor. Patients who saw a neurologist had less doctor visits for their HD and also less costs for their HD. These results show having a team of doctors that can help with all symptoms of HD may make it easier for patients to receive the best care for their symptoms.

Real-world evidence study on the impact of SPECT MPI, PET MPI, cCTA and stress echocardiography on downstream healthcare utilisation in patients with coronary artery disease in the US.

BACKGROUND: Coronary artery disease (CAD) is associated with a large clinical and economic burden. However, consensus on the optimal approach to CAD diagnosis is lacking. This study sought to compare downstream healthcare resource utilisation following different cardiac imaging modalities, to inform test selection for CAD diagnosis. METHODS: Claims and electronic health records data from the Decision Resources Group Real-World Evidence US Data Repository were analysed for 2.5 million US patients who underwent single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI), positron emission tomography myocardial perfusion imaging (PET MPI), coronary computed tomography angiography (cCTA), or stress echocardiography between January 2016 and March 2018. Patients were stratified into nine cohorts based on suspected or existing CAD diagnosis, pre-test risk, and prior events or interventions. Downstream healthcare utilisation, including additional diagnostic imaging, coronary angiography, and cardiac-related health system encounters, was compared by cohort and index imaging modality. RESULTS: Among patients with suspected CAD diagnosed within 3 months of the index test, PET MPI was associated with lower downstream utilisation; 25-37% of patients who underwent PET MPI required additional downstream healthcare resources compared with 40-49% of patients who received SPECT MPI, 35-41% of patients who underwent cCTA, and 44-47% of patients who received stress echocardiography. Patients who underwent PET MPI experienced fewer acute cardiac events (5.3-9.4%) and generally had lower rates of healthcare encounters (0.8-4.1%) and invasive coronary angiography (ICA, 15.4-24.2%) than those who underwent other modalities. SPECT MPI was associated with more downstream ICA (31.3-38.2%) and a higher rate of cardiac events (9.5-13.2%) compared with PET MPI (5.3-9.4%) and cCTA (6.9-9.9%). Across all cohorts, additional diagnostic imaging was 1.6 to 4.7 times more frequent with cCTA compared with PET MPI. CONCLUSION: Choice of imaging modality for CAD diagnosis impacts downstream healthcare utilisation. PET MPI was associated with lower utilisation across multiple metrics compared with other imaging modalities studied.

Real-world effectiveness of first- and second-line anti-angiogenesis therapy in RCC: analysis of a UK-based population.

Aim: Renal cell carcinoma (RCC) is the seventh commonest cancer in the UK, where first-line (1L) sunitinib and second-line (2L) axitinib are treatment options.Methods: Retrospective, non-interventional data from the Christie NHS Foundation Trust (Manchester, UK). The primary end point was median progression-free survival (mPFS).Results: For 1L sunitinib (n = 622) and 2L axitinib (n = 121), mPFS (95% CI) was 8.4 (7.6, 9.9) and 6.2 (4.9, 9.3) months, respectively. In 1L, Karnofsky performance status, lactate dehydrogenase (LDH), neutrophils, hemoglobin, time from diagnosis to treatment and age were predictors (p < 0.05) of PFS. In 2L, LDH and platelets were predictors of PFS (p < 0.05).Conclusion: Sunitinib and axitinib were effective treatments for RCC. PFS predictors varied between 1L and 2L; LDH was a predictor for both.Clinical Trial Registration: NCT04033991 (ClinicalTrials.gov).

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Validation Assessment of Privacy-Preserving Synthetic Electronic Health Record Data: Comparison of Original Versus Synthetic Data on Real-World COVID-19 Vaccine Effectiveness.

PURPOSE: To assess the validity of privacy-preserving synthetic data by comparing results from synthetic versus original EHR data analysis. METHODS: A published retrospective cohort study on real-world effectiveness of COVID-19 vaccines by Maccabi Healthcare Services in Israel was replicated using synthetic data generated from the same source, and the results were compared between synthetic versus original datasets. The endpoints included COVID-19 infection, symptomatic COVID-19 infection and hospitalization due to infection and were also assessed in several demographic and clinical subgroups. In comparing synthetic versus original data estimates, several metrices were utilized: standardized mean differences (SMD), decision agreement, estimate agreement, confidence interval overlap, and Wald test. Synthetic data were generated five times to assess the stability of results. RESULTS: The distribution of demographic and clinical characteristics demonstrated very small difference (< 0.01 SMD). In the comparison of vaccine effectiveness assessed in relative risk reduction between synthetic versus original data, there was a 100% decision agreement, 100% estimate agreement, and a high level of confidence interval overlap (88.7%-99.7%) in all five replicates across all subgroups. Similar findings were achieved in the assessment of vaccine effectiveness against symptomatic COVID-19 Infection. In the comparison of hazard ratios for COVID 19-related hospitalization and odds ratio for symptomatic COVID-19 Infection, the Wald tests suggested no significant difference between respective effect estimates in all five replicates for all patient subgroups but there were disagreements in estimate and decision metrices in some subgroups and replicates. CONCLUSIONS: Overall, comparison of synthetic versus original real-world data demonstrated good validity and reliability. Transparency on the process to generate high fidelity synthetic data and assurances of patient privacy are warranted.

Monitoring Pregnancies Exposed to Galcanezumab for Migraine in a United States Administrative Claims Database.

PURPOSE: Galcanezumab is a calcitonin gene-related peptide monoclonal antibody indicated for migraine prevention in adults. Due to the long half-life of galcanezumab and the prevalence of migraine in women of childbearing age, galcanezumab exposure may occur during pregnancy. However, real-world use and safety of galcanezumab during pregnancy has not been fully described. To help fill this gap, galcanezumab has two ongoing pregnancy safety studies, one of which is an insurance claims database study. METHODS: This database study is actively identifying and following pregnancies exposed to galcanezumab using commercial claims from the Healthcare Integrated Research Database (HIRD). Patient accrual is planned from September 2018 to June 2026, with a final study report planned for December 2027. This study requires 430 galcanezumab-exposed pregnancies with linked infants to reach power for comparative analysis of major congenital malformations. RESULTS: Recent monitoring of patient accrual, including data from 28 September 2018 to 31 January 2023, identified 207 galcanezumab-exposed pregnancies in women with migraine in the HIRD, of which 110 were live births and 73 of which were linked to an infant. This represents an annual accrual rate of approximately 17 pregnancies linked to infants, which is substantially lower than the 55 required annually to reach target size within current regulatory-committed study timelines. CONCLUSIONS: The accrual of a sufficient number of galcanezumab-exposed pregnancies represents a substantial, but not uncommon, barrier to conducting comparative analyses in pregnancy studies. Potential solutions that would allow for timely dissemination of important safety information to patients and providers may be available.

Roxadustat for Treating Anemia in Patients with Advanced Chronic Kidney Disease Not Undergoing Dialysis: A Retrospective Study.

Objective Roxadustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, increases the hemoglobin (Hb) levels in patients with chronic kidney disease (CKD). To date, limited clinical studies have focused on the excessive increase in the Hb levels in the early weeks after switching from erythropoiesis-stimulating agents (ESA) to roxadustat in adult non-dialysis patients. We conducted a retrospective study to examine whether early overshoot frequently occurs after switching to roxadustat. Methods This 8-week retrospective pilot study examined patients with anemic, non-dialyzed CKD who switched from ESA (darbepoetin or epoetin beta pegol) to roxadustat or continued ESA. The Hb levels >12.5 g/dL after starting our observation was defined as Hb overshoot. Patients: Twenty-three patients who switched to roxadustat (roxadustat group) and 63 who continued ESA (ESA group) were included. Results The baseline median estimated glomerular filtration rate and mean Hb levels were 15.7 mL/min/1.73 mShizuokax and 10.77 g/dL in roxadustat group and 15.2 mL/min/1.73 m2 and 10.64 g/dL in ESA group, respectively. Eight patients (34.8%) in the roxadustat group and two patients (3.2%) in the ESA group had Hb overshoot within the 8-week visit (odds ratio: 20.2 [95% confidence interval 3.13-130.0, p<0.01] in the background adjusted model). Among the patients with Hb overshoot in the roxadustat group, the Hb levels were maintained close to baseline 4 weeks after roxadustat discontinuation. A younger age and higher baseline Hb and Hct levels were risk factors for Hb overshoot. Conclusions Hb overshoot was frequently observed in patients switched to roxadustat. Clinicians should be aware of Hb overshoot and emphasize the importance of early Hb level checks.

Drug Review and Approval Policies Based on Real-world Evidence in China and the United States: A Comparative Study.

PURPOSE: The use of real-world evidence (RWE) in regulatory reviews and approvals is currently experiencing significant changes amid increasingly active discussions, primarily reflected in relevant policies, regulations, and guidance documents. However, disparities persist between China and the United States regarding the acceptance and formulation of policies for incorporating real-world data/evidence (RWD/E) in regulatory evaluation and authorization. Furthermore, the current policies lack specific operational details necessary for effective implementation and widespread adoption. METHODS: After conducting a systematic literature review and comparing relevant policies, regulations, and guidelines, as well as the related information published on their official websites, we analyze key aspects of RWE-based drug review and approval policies to highlight similarities and differences in these policies between China and the United States. FINDINGS: This paper reviews the frameworks and existing guidelines in China and the U.S., discussing similarities and differences observed in key policy aspects, including relevant definitions, data sources, data standards, data quality, and connectivity, information requirements, study design, personnel training, and communication, including an example of the application of RWE in drug review and approval processes. IMPLICATIONS: Further develop and refine RWE policies, encourage cooperation, and share best practices and successful examples to enhance the effectiveness of policy implementation and increase its social acceptance.

Generalizing Treatment Effect to a Target Population Without Individual Patient Data in a Real-World Setting.

The innovative use of real-world data (RWD) can answer questions that cannot be addressed using data from randomized clinical trials (RCTs). While the sponsors of RCTs have a central database containing all individual patient data (IPD) collected from trials, analysts of RWD face a challenge: regulations on patient privacy make access to IPD from all regions logistically prohibitive. In this research, we propose a double inverse probability weighting (DIPW) approach for the analysis sponsor to estimate the population average treatment effect (PATE) for a target population without the need to access IPD. One probability weighting is for achieving comparable distributions in confounders across treatment groups; another probability weighting is for generalizing the result from a subpopulation of patients who have data on the endpoint to the whole target population. The likelihood expressions for propensity scores and the DIPW estimator of the PATE can be written to only rely on regional summary statistics that do not require IPD. Our approach hinges upon the positivity and conditional independency assumptions, prerequisites to most RWD analysis approaches. Simulations are conducted to compare the performances of the proposed method against a modified meta-analysis and a regular meta-analysis.

Using a Quality Management System and Risk-based Approach in Observational Studies to Obtain Robust Real-World Evidence.

The results of observational studies using real-world data, known as real-world evidence, have gradually started to be used in drug development and decision-making by policymakers. A good quality management system-a comprehensive system of process, data, and documentation to ensure quality-is important in obtaining real-world evidence. A risk-based approach is a common quality management system used in interventional studies. We used a quality management system and risk-based approach in an observational study on a designated intractable disease. Our multidisciplinary team assessed the risks of the real-world data study comprehensively and systematically. When using real-world data and evidence to support regulatory decisions, both the quality of the database and the validity of the outcome are important. We followed the seven steps of the risk-based approach for both database selection and research planning. We scored the risk of two candidate databases and chose the Japanese National Database of designated intractable diseases for this study. We also conducted a quantitative assessment of risks associated with research planning. After prioritizing the risks, we revised the research plan and outcomes to reflect the risk-based approach. We concluded that implementing a risk-based approach is feasible for an observational study using real-world data. Evaluating both database selection and research planning is important. A risk-based approach can be essential to obtain robust real-world evidence.

Addressing immortal time bias in precision medicine: Practical guidance and methods development.

OBJECTIVE: To compare theoretical strengths and limitations of common immortal time adjustment methods, propose a new approach using multiple imputation (MI), and provide practical guidance for using MI in precision medicine evaluations centered on a real-world case study. STUDY SETTING AND DESIGN: Methods comparison, guidance, and real-world case study based on previous literature. We compared landmark analysis, time-distribution matching, time-dependent analysis, and our proposed MI application. Guidance for MI spanned (1) selecting the imputation method; (2) specifying and applying the imputation model; and (3) conducting comparative analysis and pooling estimates. Our case study used a matched cohort design to evaluate overall survival benefits of whole-genome and transcriptome analysis, a precision medicine technology, compared to usual care for advanced cancers, and applied both time-distribution matching and MI. Bootstrap simulation characterized imputation sensitivity to varying data missingness and sample sizes. DATA SOURCES AND ANALYTIC SAMPLE: Case study used population-based administrative data and single-arm precision medicine program data from British Columbia, Canada for the study period 2012 to 2015. PRINCIPAL FINDINGS: While each method described can reduce immortal time bias, MI offers theoretical advantages. Compared to alternative approaches, MI minimizes information loss and better characterizes statistical uncertainty about the true length of the immortal time period, avoiding false precision. Additionally, MI explicitly considers the impacts of patient characteristics on immortal time distributions, with inclusion criteria and follow-up period definitions that do not inadvertently risk biasing evaluations. In the real-world case study, survival analysis results did not substantively differ across MI and time distribution matching, but standard errors based on MI were higher for all point estimates. Mean imputed immortal time was stable across simulations. CONCLUSIONS: Precision medicine evaluations must employ immortal time adjustment methods for unbiased, decision-grade real-world evidence generation. MI is a promising solution to the challenge of immortal time bias.

Epidemiology of Wilson disease in Germany - real-world insights from a claims data study.

BACKGROUND: Wilson disease (WD) is a rare disorder of copper metabolism, causing copper accumulation mainly in the liver and the brain. The prevalence of WD was previously estimated around 20 to 33.3 patients per million for the United States, Europe, and Asia, but data on the prevalence of WD in Germany are limited. OBJECTIVES: To describe patient characteristics and to assess prevalence of WD in Germany using a representative claims database. METHODS: WD patients were identified in the WIG2 (Wissenschaftliches Institut für Gesundheitsökonomie und Gesundheitssystemforschung; Scientific Institute for Health Economics and Health Systems Research) benchmark database of 4.5 million insured Germans by combining ICD-10-coding with WD-specific lab tests and treatments. The study period ranged from 2013 to 2016 for assessing patient characteristics, and to 2018 for prevalence, respectively. RESULTS: Seventy unique patients were identified. Most patients (86%) were between 18 and 64 years of age and more often male (60%) than female. Two patients (3%) younger than 18 years were included, as well as 8 patients (11%) older than 64 years. Most common WD subtypes were hepatic (57%), psychiatric (49%), and neurologic (44%). Average prevalence was 20.3 patients per million (range: 17.8-24.4), with similar results for two-year prevalence. Generally, prevalence increased steadily over the study period. Observed mortality was low, with only one death during the study period. CONCLUSIONS: This study adds valuable real-world data on the prevalence and patient characteristics of WD in Germany. Generally, our findings align with other reports and contribute to the global understanding of WD epidemiology. Still, regional and temporal trends remain to be investigated more thoroughly to further the understanding of the natural history and epidemiology of this rare disease.

Economic Impact of Postoperative Urinary Retention in the US Hospital Setting.

Background: Postoperative urinary retention (POUR) is a common and distressing surgical complication that may be associated with the pharmacological reversal technique of neuromuscular blockade (NMB). Objective: This study aimed to investigate the impact that POUR has on medical charges. Methods: This was a retrospective observational study of adult patients undergoing select surgeries who were administered neuromuscular blockade agent (NMBA), which was pharmacologically reversed between February 2017 and November 2021 using data from the PINC-AI™ Healthcare Database. Patients were divided into 2 groups: those experiencing POUR (composite of retention of urine, insertion of temporary indwelling bladder catheter, insertion of non-indwelling bladder catheter) during index hospitalization following surgery and those without POUR. Surgeries in inpatient and outpatient settings were analyzed separately. A cross-sectional comparison was performed to report total hospital charges for the 2 groups. Furthermore, patients experiencing subsequent POUR events within three days after discharge from index hospitalization were studied. Results: A total of 330 838 inpatients and 437 063 outpatients were included. POUR developed in 13 020 inpatients and 2756 outpatients. Unadjusted results showed that POUR was associated with greater charges in both inpatient ( 92   529 w i t h P O U R v s 78 556 without POUR, p < .001) and outpatient ( 48   996 w i t h P O U R v s 35 433 without POUR, p < .001) settings. After adjusting for confounders, POUR was found to be associated with greater charges with an overall mean adjusted difference of 10   668 ( 95 95 760- 11   760 , p < .001 ) i n i n p a t i e n t a n d 13 160 (95% CI 11   750 - 14  571, p < .001) in outpatient settings. Charges associated with subsequent POUR events following discharge ranged from 9418 i n p a t i e n t c h a r g e s t o 1694 outpatient charges. Conclusions: Surgical patients who were pharmacologically reversed for NMB and developed a POUR event incurred greater charges than patients without POUR. These findings support the use of NMB reversal agents associated with a lower incidence of POUR.

Critical review of clinical data and expert-based recommendations for the use of bosutinib in the treatment of chronic myeloid leukemia.

Chronic myeloid leukemia (CML), characterized by the presence of the BCR::ABL1 fusion gene, has undergone a transformative shift with the introduction of tyrosine kinase inhibitors (TKIs). The current availability of six different TKIs (imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and asciminib) in clinical practice makes it important to know their efficacy and toxicity profile for treatment optimization. This review examines the latest insights regarding the use of bosutinib in CML treatment. Clinical trials have demonstrated the effectiveness of bosutinib, positioning it as a first-line treatment that can induce sustained molecular responses. Importantly, it can also be effective in patients who have experienced treatment failure or intolerance with prior TKIs, revealing the potential of bosutinib also in second- and later-line settings. Even in the advanced phase of CML, bosutinib has demonstrated its capacity to achieve molecular responses, expanding its usefulness. Real-world evidence studies echo these findings, emphasizing bosutinib's effectiveness in achieving deep molecular responses, maintaining remissions, and serving as an alternative for patients intolerant or resistant to other TKIs as a second-line therapy. Notably, one of the greatest strengths of bosutinib is its favorable safety profile, in particular the low incidence of vascular complications with its use, which is undoubtedly a comparative advantage over other TKIs. In summary, the latest research highlights the versatility of bosutinib in CML treatment and underscores its pivotal role in optimizing patient management in challenging cases. Continuing research and investigation will further establish bosutinib's place in the evolving landscape of CML therapy, offering an alternative for CML patients across different treatment stages.

Emulations of Oncology Trials Using Real-World Data: A Systematic Literature Review.

By evaluating published emulations of oncology RCTs studies in which both the active and comparator groups are sourced from RWD and target trial results are available for benchmarking, this systematic review aims to gain insight into factors related to emulation performance. Thirteen oncology emulation studies using various types of RWD were identified through an online database search of PubMed through 2022. Based on the ROBINS-I tool, most studies (N=8) had a serious risk of overall bias driven by risk of bias from confounding. Approximately half of the studies (N=6) fully proxied the RCT entry criteria. Of 11 RWD studies that provided sufficient detail to quantify emulation performance, the emulation HR estimate fell within the 95% CI of the trial estimate in 9 of the studies. There were no clear trends between risk of bias or degree to which the entry criteria were proxied and emulation performance. Findings may have been influenced by publication bias and researcher degrees of freedom, as only one emulation study pre-registered its protocol. Tools for comprehensively characterizing factors that affect emulation performance, including the real-world clinical context as it relates to the RCT research question, are needed to evaluate the feasibility of a RCT emulation.