Two assumptions of the prior event rate ratio approach for controlling confounding can be evaluated by self-controlled case series and dynamic random intercept modeling.

OBJECTIVES: The prior event rate ratio (PERR) is a recently developed approach for controlling confounding by measured and unmeasured covariates in real-world evidence research and observational studies. Despite its rising popularity in studies of safety and effectiveness of biopharmaceutical products, there is no guidance on how to empirically evaluate its model assumptions. We propose two methods to evaluate two of the assumptions required by the PERR, specifically, the assumptions that occurrence of outcome events does not alter the likelihood of receiving treatment, and that earlier event rate does not affect later event rate. STUDY DESIGN AND SETTING: We propose using self-controlled case series (SCCS) and dynamic random intercept modeling (DRIM), respectively, to evaluate the two aforementioned assumptions. A nonmathematical introduction of the methods and their application to evaluate the assumptions are provided. We illustrate the evaluation with secondary analysis of deidentified data on pneumococcal vaccination and clinical pneumonia in The Gambia, West Africa. RESULTS: SCCS analysis of data on 12,901 vaccinated Gambian infants did not reject the assumption of clinical pneumonia episodes had no influence on the likelihood of pneumococcal vaccination. DRIM analysis of 14,325 infants with a total of 1719 episodes of clinical pneumonia did not reject the assumption of earlier episodes of clinical pneumonia had no influence on later incidence of the disease. CONCLUSION: The SCCS and DRIM methods can facilitate appropriate use of the PERR approach to control confounding. PLAIN LANGUAGE SUMMARY: The prior event rate ratio is a promising approach for analysis of real-world data and observational studies. We propose two statistical methods to evaluate the validity of two assumptions it is based on. They can facilitate appropriate use of the prior even rate ratio.

Real-world data to support post-market safety and performance of embolization coils: evidence generation from a medical device manufacturer and data institute partnership.

BACKGROUND: Recognizing the limitations of pre-market clinical data, regulatory authorities have embraced total product lifecycle management with post-market surveillance (PMS) data to assess medical device safety and performance. One method of proactive PMS involves the analysis of real-world data (RWD) through retrospective review of electronic health records (EHR). Because EHRs are patient-centered and focused on providing tools that clinicians use to determine care rather than collecting information on individual medical products, the process of transforming RWD into real-world evidence (RWE) can be laborious, particularly for medical devices with broad clinical use and extended clinical follow-up. This study describes a method to extract RWD from EHR to generate RWE on the safety and performance of embolization coils. METHODS: Through a partnership between a non-profit data institute and a medical device manufacturer, information on implantable embolization coils' use was extracted, linked, and analyzed from clinical data housed in an electronic data warehouse from the state of Indiana's largest health system. To evaluate the performance and safety of the embolization coils, technical success and safety were defined as per the Society of Interventional Radiology guidelines. A multi-prong strategy including electronic and manual review of unstructured (clinical chart notes) and structured data (International Classification of Disease codes), was developed to identify patients with relevant devices and extract data related to the endpoints. RESULTS: A total of 323 patients were identified as treated using Cook Medical Tornado, Nester, or MReye embolization coils between 1 January 2014 and 31 December 2018. Available clinical follow-up for these patients was 1127 ± 719 days. Indications for use, adverse events, and procedural success rates were identified via automated extraction of structured data along with review of available unstructured data. The overall technical success rate was 96.7%, and the safety events rate was 5.3% with 18 major adverse events in 17 patients. The calculated technical success and safety rates met pre-established performance goals (≥ 85% for technical success and ≤ 12% for safety), highlighting the relevance of this surveillance method. CONCLUSIONS: Generating RWE from RWD requires careful planning and execution. The process described herein provided valuable longitudinal data for PMS of real-world device safety and performance. This cost-effective approach can be translated to other medical devices and similar RWD database systems.

Risk of antimuscarinic initiation with cholinesterase inhibitor use in Alzheimer's disease.

BACKGROUND: The use of cholinesterase inhibitors (CHEIs) is commonly associated with urinary incontinence in patients with Alzheimer's disease (AD). This study evaluated the risk of antimuscarinic initiation drugs with the use of CHEIs in AD patients. METHODS: The study used a nested case-control study design involving 2013-2015 Medicare data of AD patients 65 years and older without antimuscarinic use in 2013. Cases were defined as those who initiated antimuscarinic treatment in 2014-2015. Controls with no antimuscarinic use were selected through incidence density sampling and matched to cases on age using a variable-ratio method. The CHEI utilization pattern was classified as current (event-30 days), recent (event-31 to event-90 days), and past (event-91 to event-180 days). Conditional logistic regression was used to assess the association between CHEI use and the risk of antimuscarinic initiation. RESULTS: This study included 1,909 cases and 9,064 controls. The adjusted model found that overall CHEI (Adjusted Odds Ratio [aOR] = 1.90, 95 % Confidence Interval [CI]: 1.58-2.28) and current CHEI use (aOR = 1.62, 95 % CI: 1.18-2.21) were associated with an increase in the risk of antimuscarinic initiation compared to non-CHEI use. In addition, the current use of donepezil and rivastigmine significantly increased the risk of antimuscarinic initiation by 48 % (95 % CI: 1.03-2.12) and 171 % (95 % CI: 1.46-5.03), respectively. CONCLUSION: The study found an increased risk of antimuscarinic initiation with the current use of CHEIs, particularly with donepezil and rivastigmine. These findings underscore the need for careful medication management to minimize prescribing cascades and associated consequences in AD.

A real-world analysis of adherence, biochemical outcomes, and healthcare costs in patients treated with rosuvastatin/ezetimibe as single-pill combination vs. free combination in Italy.

Aims: To compare medication adherence, lipid goal attainment, and healthcare costs between patients receiving a single-pill combination (SPC) vs. a free combination treatment (FCT) of rosuvastatin/ezetimibe (ROS/EZE) in Italy. Methods and results: Administrative databases of healthcare entities covering ∼7 million individuals were used to identify adults prescribed with ROS/EZE as SPC or FCT between January 2018 and June 2020. Adherence was calculated as the proportion of days covered (PDC) after cohort balancing by propensity score matching. Patients with available LDL cholesterol testing were assessed for the proportion of those who at baseline were above lipid targets recommended by ESC/EAS Guidelines for their cardiovascular risk category and reached the target during follow-up. Among 25 886 patients on SPC and 7309 on FCT, adherent patients were more represented in SPC than FCT cohort (56.8 vs. 44.5%, P < 0.001), and this difference remained significant (P < 0.001) after stratification by cardiovascular risk (very high, high, and other). The proportion of patients reaching LDL cholesterol target at 1 year follow-up was significantly (P < 0.001) higher in SPC vs. FCT cohort: 35.4 vs. 23.8% for very high cardiovascular risk, 46.9 vs. 23.1% for high risk and 71.6 vs. 49.5% for other risk. Total healthcare costs per patient at 1 year follow-up were lower in SPC vs. FCT users (2337€ vs. 1890€, P < 0.001). In both cohorts, costs were mainly driven by drug expenses and hospitalizations. Conclusion: This real-world analysis in dyslipidaemic patients found that treatment with ROS/EZE as SPC resulted in better adherence, higher chances of reaching lipid goals, and cost savings over FCT, in all cardiovascular risk categories.

PIONEER REAL UK: A Multi-Centre, Prospective, Real-World Study of Once-Daily Oral Semaglutide Use in Adults with Type 2 Diabetes.

INTRODUCTION: Oral semaglutide provides an alternative to injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) for treatment of type 2 diabetes (T2D). The PIONEER REAL studies evaluate clinical outcomes of oral semaglutide treatment of T2D in a real-world setting. PIONEER REAL UK focused on adults living with T2D in the UK. METHODS: The multi-centre, prospective and non-interventional single-arm study enrolled 333 participants and followed them for 34-44 weeks. Participants were treated as part of routine clinical practice and had not been previously treated with injectable glucose-lowering medication. The primary endpoint was change in glycated haemoglobin (HbA1C) from baseline to end of study (EOS). Secondary endpoints included change in body weight, proportion of participants with HbA1C < 7% (53 mmol/mol) at EOS and proportion of participants with ≥ 1%-point HbA1C reduction and body weight reduction of ≥ 3% or ≥ 5% at EOS. Treatment satisfaction was assessed by Diabetes Treatment Satisfaction Questionnaire (DTSQ) status and change. RESULTS: Of 333 participants, 299 completed the study and 227 were on treatment at EOS. People treated with oral semaglutide experienced significantly reduced HbA1C by an estimated change of - 1.1%-points (95% CI - 1.27 to - 0.96; P < 0.0001) or - 12.2 mmol/mol (CI - 13.87 to - 10.47; P < 0.0001). Estimated change in body weight was - 4.8 kg (CI - 5.47 to - 4.12; P < 0.0001). At EOS, an HbA1C level < 7% (53 mmol/mol) was recorded in 46.3% of participants. A ≥ 1%-point reduction in HbA1C combined with a ≥ 3% reduction in body weight was observed in 36.4% of participants, and 27.1% had a ≥ 1%-point reduction in HbA1C and a ≥ 5% body weight reduction. Treatment satisfaction improved significantly during the study. No new safety concerns or cases of severe hypoglycaemia were reported. CONCLUSION: People living with T2D in the UK experienced a meaningful decrease in HbA1C and body weight after initiation of oral semaglutide treatment. No new safety issues were observed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04862923. Graphical plain language summary available for this article.

PIONEER REAL UK investigated the use of a tablet form of the medicine semaglutide in people living with type 2 diabetes in the UK. The purpose was to determine how well the tablet works for blood sugar control and weight loss in everyday clinical practice. The study followed 333 participants whose doctors had given them semaglutide tablets. Their blood sugar levels and body weight were measured before and after taking the semaglutide tablet for 34­44 weeks. The participants were also asked to fill out questionnaires about their treatment satisfaction and how it changed when taking the semaglutide tablet. The participants' blood sugar levels dropped a lot, and body weight was lowered by an average of 4.8 kg during the 34­44 weeks of the study. The participants were also more satisfied with their treatment at the end of the study than before taking the semaglutide tablet. Doctors treating the participants found the treatment to be a success in more than two-thirds of participants. The study also found that the semaglutide tablet was not associated with cases of too low blood sugar and was generally well tolerated. In summary, the semaglutide tablet is a good option for people living with type 2 diabetes who need better blood sugar control and would benefit from weight loss. The treatment is generally well tolerated, and people are very satisfied with it.

Comprehensive Codified Algorithms to Identify the Underestimated Burden of Hidradenitis Suppurativa in the United States.

INTRODUCTION: Hidradenitis suppurativa (HS) is a painful, inflammatory skin disease associated with a high disease burden and long diagnostic delay. Prevalence estimates of HS vary widely in the literature owing to differing estimation methodologies. This study aimed to apply stepwise algorithms to estimate the prevalence of possible/diagnosed cases of HS in the US. METHODS: This was a retrospective cohort study in adult and pediatric patients with HS which utilized data from four US databases (MarketScan [Medicare and Medicaid] and Optum [electronic health record (EHR) and Clinformatics Data Mart (CDM)]). Patients with possible/diagnosed HS were identified using two algorithms (termed Algorithm 1 and Algorithm 2), which assessed symptoms such as multiple skin boils in site-specific areas based on international classification of disease (ICD) codes. Patients with diagnosed HS were defined as having ≥ 2 outpatient or ≥ 1 inpatient diagnosis codes of HS. In each database, patients with continuous medical and pharmacy benefits in the 365 days pre-index and 0-365 days post-index periods were eligible for inclusion. RESULTS: Across all databases, Algorithm 2 (MarketScan Medicare [N = 309,916]; MarketScan Medicaid [N = 188,783]; Optum EHR [N = 366,158]; Optum CDM [N = 173,812]) identified more patients with possible/diagnosed HS than Algorithm 1 (MarketScan Medicare [N = 194,353]; MarketScan Medicaid [N = 99,276]; Optum EHR [N = 177,957]; Optum CDM [N = 112,244]). Based on ICD-9/10 codes, the 5-year period prevalence of HS ranged from 0.06% to 0.12% across all databases, while for Algorithm 1 and Algorithm 2, this ranged from 0.27% to 0.41% and 0.49% to 0.78%, respectively. Adults and females generally had a higher 5-year period prevalence versus pediatric patients and males, respectively. CONCLUSION: This real-world study highlights that HS diagnosis codes alone may be insufficient to estimate the prevalence of HS, demonstrating the value of employing algorithms in practice which assess for parameters such as multiple skin boils in site-specific areas. Integrating robust methods to identify the prevalence of HS may improve the diagnostic delay observed in HS and improve treatment outcomes.

Real-World Analysis of Survival and Treatment Efficacy in Stage IIIA-N2 Non-Small Cell Lung Cancer.

BACKGROUND: Stage IIIA-N2 non-small cell lung cancer (NSCLC) poses a significant clinical challenge, with low survival rates despite advances in therapy. The lack of a standardised treatment approach complicates patient management. This study utilises real-world data from Guy's Thoracic Cancer Database to analyse patient outcomes, identify key predictors of overall survival (OS) and disease-free survival (DFS), and address the limitations of randomised controlled trials. METHODS: This observational, single-centre, non-randomised study analysed 142 patients diagnosed with clinical and pathological T1/2 N2 NSCLC who received curative treatment from 2015 to 2021. Patients were categorised into three groups: Group A (30 patients) underwent surgery for clinical N2 disease, Group B (54 patients) had unsuspected N2 disease discovered during surgery, and Group C (58 patients) received radical chemoradiation or radiotherapy alone (CRT/RT) for clinical N2 disease. Data on demographics, treatment types, recurrence, and survival rates were analysed. RESULTS: The median OS for the cohort was 31 months, with 2-year and 5-year OS rates of 60% and 30%, respectively. Group A had a median OS of 32 months, Group B 36 months, and Group C 25 months. The median DFS was 18 months overall, with Group A at 16 months, Group B at 22 months, and Group C at 17 months. Significant predictors of OS included ECOG performance status, lymphovascular invasion, and histology. No significant differences in OS were found between treatment groups (p = 0.99). CONCLUSIONS: This study highlights the complexity and diversity of Stage IIIA-N2 NSCLC, with no single superior treatment strategy identified. The findings underscore the necessity for personalised treatment approaches and multidisciplinary decision-making. Future research should focus on integrating newer therapeutic modalities and conducting multi-centre trials to refine treatment strategies. Collaboration and ongoing data collection are crucial for improving personalised treatment plans and survival outcomes for Stage IIIA-N2 NSCLC patients.

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.

Corrigendum: Real-world experience with secukinumab in the entire axial spondyloarthritis spectrum.

[This corrects the article DOI: 10.3389/fmed.2023.1156557.].

Real-world impact of acupuncture on analgesics and healthcare resource utilization in breast cancer survivors with pain.

BACKGROUND: This study evaluated the real-world impact of acupuncture on analgesics and healthcare resource utilization among breast cancer survivors. METHODS: From a United States (US) commercial claims database (25% random sample of IQVIA PharMetrics® Plus for Academics), we selected 18-63 years old malignant breast cancer survivors experiencing pain and ≥ 1 year removed from cancer diagnosis. Using the difference-in-difference technique, annualized changes in analgesics [prevalence, rates of short-term (< 30-day supply) and long-term (≥ 30-day supply) prescription fills] and healthcare resource utilization (healthcare costs, hospitalizations, and emergency department visits) were compared between acupuncture-treated and non-treated patients. RESULTS: Among 495 (3%) acupuncture-treated patients (median age: 55 years, stage 4: 12%, average 2.5 years post cancer diagnosis), most had commercial health insurance (92%) and experiencing musculoskeletal pain (98%). Twenty-seven percent were receiving antidepressants and 3% completed ≥ 2 long-term prescription fills of opioids. Prevalence of opioid usage reduced from 29 to 19% (P < 0.001) and NSAID usage reduced from 21 to 14% (P = 0.001) post-acupuncture. The relative prevalence of opioid and NSAID use decreased by 20% (P < 0.05) and 19% (P = 0.07), respectively, in the acupuncture-treated group compared to non-treated patients (n = 16,129). However, the reductions were not statistically significant after adjustment for confounding. Patients receiving acupuncture for pain (n = 264, 53%) were found with a relative decrease by 47% and 49% (both P < 0.05) in short-term opioid and NSAID fills compared to those treated for other conditions. High-utilization patients (≥ 10 acupuncture sessions, n = 178, 36%) were observed with a significant reduction in total healthcare costs (P < 0.001) unlike low-utilization patients. CONCLUSIONS: Although adjusted results did not show that patients receiving acupuncture had better outcomes than non-treated patients, exploratory analyses revealed that patients treated specifically for pain used fewer analgesics and those with high acupuncture utilization incurred lower healthcare costs. Further studies are required to examine acupuncture effectiveness in real-world settings.

Prevalence of obesity and cardiovascular disease in adults with type 2 diabetes and use of diabetes medication in Germany: A claims data study.

AIMS: To identify the prevalence of cardiovascular disease (CVD) and obesity in patients with type 2 diabetes (T2D) in Germany and to evaluate if antidiabetic treatment patterns varied by comorbidity status. MATERIALS AND METHODS: Patients with T2D (aged ≥18 years) were identified during the study period (2014-2020) from medical claims of 4.5 million publicly insured German residents and divided into different cohorts based on CVD and/or obesity diagnosis. Annual prevalence and incidence were estimated for each study year, while characteristics and treatments were assessed in 2020. Data were extrapolated to the German population by age and sex. RESULTS: The prevalence of T2D in 2020 was 11.4%. Among patients with T2D, 53.0% had CVD, 39.3% had obesity, and 20.9% had CVD and obesity. Since 2014, CVD increased by 1.4%, obesity by 4.5%, and CVD with obesity by 2.7% in patients with T2D. The incidence of T2D in 2020 was 1.0% (42.9% had CVD, 37.9% had obesity, and 15.8% had CVD and obesity). Among the prevalent T2D population in 2020, 4.9% received glucagon-like peptide-1 receptor agonists (GLP-1RAs), 9.7% received sodium-glucose cotransporter-2 (SGLT2) inhibitors, and 13.0% received GLP-1 RAs and/or SGLT2 inhibitors. Of those with CVD, 12.9% received GLP-1 RAs and/or SGLT2 inhibitors (without CVD, 13.2%). Of those with obesity, 19.4% received GLP-1RAs and/or SGLT2 inhibitors (without obesity, 9.0%). CONCLUSIONS: In this retrospective claims database study, more than two thirds of patients with T2D also had CVD, obesity, or both CVD and obesity. GLP-1 RA and SGLT2 inhibitor use remained low.

Diabetes mellitus and adverse clinical events in patients with atrial fibrillation: A report from the GLORIA-AF registry phase III.

AIMS: Atrial fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations have not been fully elucidated, particularly with concomitant insulin use. This study aimed to analyse the associations between adverse events and DM, as well as adverse events and sole insulin use. MATERIALS AND METHODS: Our analysis included individuals with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-year follow-up. Outcomes included all-cause death, major bleeding, cardiovascular (CV) death, myocardial infarction (MI), stroke, thromboembolism and major adverse cardiovascular events (MACE). RESULTS: A total of 15 861 AF individuals were included (age 70.0 ± 10.2 years; 55% male, 20% Asian), of whom, 3666 had DM (age 70.0 ± 9.5 years ; 59% male, 21% Asian). After adjustment, those with DM had higher risks of all-cause death (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 1.28-1.66), CV death (HR: 1.53 95% CI: 1.27-1.86), major bleeding (HR: 1.23, 95% CI: 1.01-1.48), MI (HR: 1.50, 95% CI: 1.17-1.94) and MACE (HR: 1.42, 95% CI: 1.23-1.63). Compared to individuals with DM receiving oral hypoglycaemic agents, those receiving insulin alone were associated with increased risks of all-cause death (HR: 2.16, 95% CI: 1.61-2.91), CV death (HR: 2.24, 95% CI: 1.45-3.47), major bleeding (HR: 1.89, 95% CI: 1. 21-2.95), MI (HR: 2.24, 95% CI: 1.31-3.82) and MACE (HR: 2.11, 95% CI: 1.54-2.88). CONCLUSIONS: DM was independently associated with higher risks of all-cause death, CV death, MI, major bleeding and MACE in AF individuals. Individuals receiving insulin alone were associated with higher risks of all-cause death, CV death, MI, major bleeding and MACE.

Techniques for Implementing Continuous Glucose Monitoring in Primary Care: Key CGM Updates and Highlights from the ADA 2024 Conference [Podcast].

This podcast discusses innovations, advancements, and discoveries in continuous glucose monitoring that were presented at the American Diabetes Association 84th Scientific Sessions held in Orlando, Florida, June 2024. Specifically, the author will discuss sessions focused on (1) Equity and access to new technologies; (2) The role of the interdisciplinary team in technology onboarding in primary care; (3) New technologies for glucose monitoring and sensing; (4) New technologies for continuous glucose monitoring (CGM); and (5) CGM implementation in primary care.

Pharmacovigilance study of the association between peripheral neuropathy and antibody-drug conjugates using the FDA adverse event reporting system.

Antibody-drug conjugates (ADCs) are among the fastest-growing classes of anticancer drugs, making it crucial to evaluate their potential for causing peripheral neuropathy. We analyzed data from the FAERS database (January 1, 2014, to June 30, 2023) using disproportionality and Bayesian methods. We identified 3076 cases of ADC-associated peripheral neuropathy. Our study revealed significant signals for all ADCs (ROR 1.82, 95% CI 1.76-1.89). ADCs with tubulin-binding payloads showed significant peripheral neuropathy signals (ROR 2.31, 95% CI 2.23-2.40), whereas those with DNA-targeting (ROR 0.48, 95% CI 0.39-0.59) and topoisomerase 1 inhibitor (ROR 0.56, 95% CI 0.48-0.66) payloads exhibited non-significant signals. Signals for peripheral sensory neuropathy were 4.83, 2.44, 2.74, and 2.21 (calculated based on IC025) for brentuximab vedotin, trastuzumab emtansine, enfortumab vedotin, and polatuzumab vedotin, while signals for peripheral motor neuropathy were 5.31, 0.34, 2.27, and 0.03, respectively. The median time to onset for all ADCs was 127 days (interquartile range 40-457). Tisotumab vedotin had the highest hospitalization rate at 26.67%, followed by brentuximab vedotin at 25.5%. Trastuzumab emtansine had the highest mortality rate ,with 80 deaths (11.96%) among 669 cases. Based on FAERS database, only ADCs with tubulin-binding payloads exhibited significant peripheral neuropathy signals. Brentuximab vedotin and enfortumab vedotin showed similar profiles for peripheral sensory neuropathy and motor neuropathy. Given the delayed time to onset and potentially poor outcomes, ADC-related peripheral neuropathy warrants significant attention.

The impact of different censoring methods for analyzing survival using real-world data with linked mortality information: a simulation study.

BACKGROUND: Evaluating outcome reliability is critical in real-world evidence studies. Overall survival is a common outcome in these studies; however, its capture in real-world data (RWD) sources is often incomplete and supplemented with linked mortality information from external sources. Conflicting recommendations exist for censoring overall survival in real-world evidence studies. This simulation study aimed to understand the impact of different censoring methods on estimating median survival and log hazard ratios when external mortality information is partially captured. METHODS: We used Monte Carlo simulation to emulate a non-randomized comparative effectiveness study of two treatments with RWD from electronic health records and linked external mortality data. We simulated the time to death, the time to last database activity, and the time to data cutoff. Death events after the last database activity were attributed to linked external mortality data and randomly set to missing to reflect the sensitivity of contemporary real-world data sources. Two censoring schemes were evaluated: (1) censoring at the last activity date and (2) censoring at the end of data availability (data cutoff) without an observed death. We assessed the performance of each method in estimating median survival and log hazard ratios using bias, coverage, variance, and rejection rate under varying amounts of incomplete mortality information and varying treatment effects, length of follow-up, and sample size. RESULTS: When mortality information was fully captured, median survival estimates were unbiased when censoring at data cutoff and underestimated when censoring at the last activity. When linked mortality information was missing, censoring at the last activity date underestimated the median survival, while censoring at the data cutoff overestimated it. As missing linked mortality information increased, bias decreased when censoring at the last activity date and increased when censoring at data cutoff. CONCLUSIONS: Researchers should consider the completeness of linked external mortality information when choosing how to censor the analysis of overall survival using RWD. Substantial bias in median survival estimates can occur if an inappropriate censoring scheme is selected. We advocate for RWD providers to perform validation studies of their mortality data and publish their findings to inform methodological decisions better.

Low prevalence of testing for apolipoprotein B and lipoprotein (a) in the real world.

Objective: Apolipoprotein B (ApoB) and lipoprotein (a) (Lp[a]) are predictors of cardiovascular disease (CVD) risk; therefore, current recommendations for CVD risk assessment and management advocate that patients receive testing for ApoB and Lp(a) in addition to the standard lipid panel. However, US guidelines around ApoB and Lp(a) testing have evolved over time and vary slightly by expert committee. The objective of this analysis was to estimate the number of insured individuals in the USA who received any component of a lipid test, or ApoB and/or Lp(a) testing, during 2019. Methods: We conducted a cross-sectional analysis to estimate the prevalence of any component of a lipid test, ApoB, and/or Lp(a) in the USA using four different claim data sources (including Medicaid, Medicare, and commercially insured enrollees). Prevalence estimates were age-, sex-, payor-, and region-standardized to the 2019 US Annual Social and Economic Supplement of the Current Population Survey. We also described the clinical profile of patients who received lipid testing between 2019 and 2021 (cohort analysis) in Optum claims database. Enrollees were grouped into four non-mutually exclusive cohorts based on their completion of any component of the lipid panel, ApoB, Lp(a), or ApoB and Lp(a). Results: In the prevalence cohort, over a third (38 %) of insured adults in the USA underwent testing for any component of a lipid panel in 2019. This proportion was higher for individuals aged ≥65 years compared to younger adults (62% vs 31 %). The proportion of ApoB and Lp(a) testing represented only <1 % of testing for any component of a lipid panel. In the cohort analysis, we found that lipid testing increased with age and comorbidities. Conclusion: These data should be considered by guideline-issuing agencies and organizations to develop education campaigns encouraging more frequent use of tests beyond the standard lipid panel.

Development of a Canadian Guidance for Reporting Real-world Evidence for Regulatory and Health-Technology Assessment (HTA) Decision Making.

Real-world evidence (RWE) can complement and fill knowledge gaps from randomized controlled trials to assist in health-technology assessment (HTA) for regulatory decision-making. However, the generation of RWE is an intricate process with many sequential decision points, and different methods and approaches may impact the quality and reliability of evidence. Standardization and transparency in reporting these decisions is imperative to appraise RWE and incorporate it into HTA decision-making. A partnership between Canadian health system stakeholders, namely Health Canada and Canada's Drug Agency (formerly the Canadian Agency for Drugs and Technologies in Health (CADTH)), was established to develop a guidance for standardization of reporting of RWE for regulatory and HTA decision-making in Canada. In this article, we describe the methods to develop the Guidance for Reporting Real-World Evidence document and checklist for reporting RWE for regulatory and HTA decision-making in Canada. This guidance can be adapted for other jurisdictions and will have future extensions to incorporate emerging issues with RWE and HTA decision-making.

The interdependence of targets for continuous glucose monitoring outcomes in type 1 diabetes with automated insulin delivery.

AIM: The aim was to determine the interdependence of targets for glucose management indicator (GMI), time within the ranges of 70-180 mg/dL (TIR) and 70-140 mg/dL (time in tight glucose range [TITR]), time above 180 mg/dL (TA180) and 250 mg/dL (TA250) and time below 70 mg/dL (TB70) and 54 mg/dL (TB54) and its implications for setting targets in automated insulin delivery (AID). MATERIALS AND METHODS: Real-world data from individuals with type 1 diabetes using the 780G system were used to calculate the receiver operating characteristic curves and establish interdependent targets for time in ranges based on several GMI benchmarks. Correlation, regression and principal component analysis were used to determine their association and dimensionality. RESULTS: In individuals aged >15 years (n = 41 692), a GMI <6.5% required targets of >81%, >58%, <15% and <1.9% for TIR, TITR, TA180 and TA250, respectively, with high sensitivity, specificity and accuracy (>90%), whereas these values were poor for time in hypoglycaemia and GMI, which had a modest correlation (-0.21 to -0.43). Two dimensions emerged: (1) GMI, TIR, TITR, TA180 and TA250, and (2) TB70 and TB54, explaining 95% of total variability. GMI (or TIR) and TB70 explained >81% of the variability in the remaining continuous glucose monitoring (CGM) metrics, providing accurate predictions. Individuals aged ≤15 years (n = 14 459) showed similar results. CONCLUSION: We developed a methodology to establish interdependent CGM targets for therapies with CGM data outputs. In AID with the 780G system, a GMI <7% requires time in ranges close to consensus targets. Targets for GMI, TIR, TITR, TA180 and TA250 could be reduced to targets for GMI or TIR, whereas targets for time in hypoglycaemia are not inherently tied to GMI/TIR targets.

Sex inequalities in cardiovascular risk factors and their management in primary prevention in adults living with type 1 diabetes in Germany and France: findings from DPV and SFDT1.

INTRODUCTION & OBJECTIVES: To evaluate whether cardiovascular risk factors and their management differ in primary prevention between adult males and females with type 1 diabetes (T1D) in two European countries in 2020-2022 and sex inequalities in achievement of standards of care in diabetes. METHODS: We used 2020-2022 data of patients without a cardiovascular history in the Prospective Diabetes Follow-up registry (DPV) centres, in Germany, and the Société Francophone du Diabète- Cohorte Diabète de Type 1 cohort (SFDT1), in France. RESULTS: We included 2,657 participants from the DPV registry and 1,172 from the SFDT1 study. Body mass indexes were similar in females and males with similar proportions of HbA1c < 7% (DPV: 36.6 vs 33.0%, p = 0.06, respectively; SFDT1: 23.4 vs 25.7%, p = 0.41). Females were less overweight compared to men in DPV (55.4 vs 61.0%, p < 0.01) but not in SFDT1 (48.0 vs 44.9%, p = 0.33) and were less prone to smoke (DPV: 19.7 vs 25.8%, p < 0.01; SFDT1: 21.0 vs 26.0%, p = 0.07). Systolic blood pressure was lower in females than males with a higher rate of antihypertensive therapy in case of hypertension in females in DPV (70.5 vs 63.7%, p = 0.02) but not in SFDT1 (73.3 vs 68.6%, p = 0.64). In the case of microalbuminuria, ACEi-ARB were less often prescribed in women than men in DPV (21.4 vs 37.6%, p < 0.01) but not SFDT1 (73.3 vs 67.5.0%, p = 0.43). In females compared to males, HDL-cholesterol levels were higher; triglycerides were lower in both countries. In those with LDL-cholesterol > 3.4 mmol/L (DPV: 19.9 (females) vs 23.9% (males), p = 0.01; SFDT1 17.0 vs 19.2%, p = 0.43), statin therapy was less often prescribed in females than males in DPV (7.9 vs 17.0%, p < 0.01), SFDT1 (18.2 vs 21.0%, p = 0.42). CONCLUSION: In both studies, females in primary prevention have a better cardiovascular risk profile than males. We observed a high rate of therapeutic inertia, which might be higher in females for statin treatment and nephroprotection with ACEi-ARB, especially in Germany. Diabetologists should be aware of sex-specific differences in the management of cardiorenal risk factors to develop more personalized prevention strategies.