Real-world Evidence Studies Research Articles

Clinical Outcomes and Health Care Resource Utilization Associated with Post-Transplant Neutropenia Among Kidney Transplant Recipients: A Real-World Evidence Study

Clinical Outcomes and Health Care Resource Utilization Associated with Post-Transplant Neutropenia Among Kidney Transplant Recipients: A Real-World Evidence Study

Comparative safety and effectiveness of non-vitamin K oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation: A network meta-analysis

The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists (VKAs), has significantly improved the safety profile and treatment adherence of patients with non-valvular atrial fibrillation (AF). However, few studies have compared the effectiveness and safety of NOACs. Therefore, we conducted this systematic review and network meta-analysis to compare the safety and clinical effectiveness of NOACs and VKAs in patients with non-valvular AF. An online bibliographic search was conducted to retrieve real-world evidence studies published between January 2019 and June 2022. Dabigatran was associated with lower risks of major bleeding, ischemic stroke, and intracranial hemorrhage than warfarin. Among the NOACs, only dabigatran had a lower risk of all-cause mortality than warfarin. Dabigatran was also associated with lower risks of major bleeding and intracranial hemorrhage than rivaroxaban. Our meta-analysis confirms that dabigatran's real-world safety and clinical effectiveness align with the results of pivotal clinical trials.

Household food insecurity and child health outcomes: a rapid review of mechanisms and associations

BackgroundHousehold food insecurity (HHFI) has detrimental impact on child health outcomes. The primary aim of this work was to describe the mechanisms, defined as statistically quantified processes or systems, that explain the association between HHFI and poor child health outcomes. The secondary aim was to identify which child health outcomes were significantly associated with HHFI. MethodsIn this rapid review, we included real-world evidence studies in children and adolescents aged 3–24 years, from high-income countries. We searched peer-reviewed literature through the databases Medline, Embase, Web of Science and The Cochrane Library on March 10, 2022, with a 15-year time restriction. Key search terms included “food insecurity”, “food poverty”, “statistics”, “structural equation model*”, “regression”, “conceptual model*”, and “theoretical model*”. We identified additional studies by searching citations and references. Papers were selected using pre-defined criteria and non-English Language studies were excluded. We extracted summary data of published studies using the Cochrane data extraction template as a guide. We included a broad range of health outcomes to identify what aspects of health are affected by HHFI, including metabolic risk factors (eg, BMI), conditions (eg, depression), biological processes (eg, sleep) and parent–child interactions (eg, feeding styles). We performed a narrative synthesis, as heterogeneity precluded statistical synthesis. We used the Quality in Prognosis Studies tool to assess the mechanism studies. FindingsWe included 70 systematic reviews (six mechanism and 64 association reviews) from the UK, Canada, USA, Australia, and Ireland (including 18 887 mechanism studies and 986 759 association studies). Low-to-moderate bias was detected in mechanism studies, and there was variability in HHFI measures. Maternal depression and parenting stress during childhood played a mechanistic role between HHFI and adolescent depression (b=0·008, 95% CI 0·002–0·016) and anxiety (b=0·012, 0·002–0·026). Maternal stress mediated the association between HHFI and child overweight (odds ratio [OR] 1·79, 0·82–3·92, p<0·01), via restrictive feeding styles (OR 1·81, 1·15–2·85, p=0·010) that had negative impact on diet (p<0·01). Ethnicity, income, employment, and education moderated the relationship between HHFI and child health outcomes (p<0·001). InterpretationTwo key mechanistic pathways between HHFI and child health outcomes were diet and mental health of both child and parent, which appeared interrelated. Interventions targeting HHFI in children, should consider these pathways alongside sociodemographic factors. A strength of this review was that it was the first literature summary explaining the mechanisms between HHFI and child health, using evidence from high-income countries. A limitation was that HHFI measures were inconsistent between studies and countries, disallowing study comparisons. FundingUniversity of Sheffield.

The economic value of insulin glargine 300 U/mL (Gla-300) in people ≥18 years of age with type 2 diabetes mellitus: a value-based economic model from a U.S. payer perspective

AimsThis study aimed to evaluate the value and affordability of insulin glargine 300 U/mL (Gla-300) in a budget impact model from a United States (U.S.) payer perspective by leveraging recent real-world evidence (RWE) studies and incorporating the recent insulin price caps where applicable.Materials and methodsAn economic model for a hypothetical one million U.S. health-plan population was developed to assess the budgetary impact of therapeutic interchanges in either direction between the two long- and longer-acting basal insulins (BIs) for patients with type 2 diabetes over a three-year model horizon. The utilization of long-acting BIs, longer-acting BIs, biosimilar BIs, and insulin degludec (IDeg-100) were informed by IQVIA data and internal forecasting at Sanofi. The DELIVER-2 and DELIVER-naïve studies provided healthcare resource utilization (HCRU) parameters. In the model base case, 24% of patients switched from long-acting BIs to insulin glargine biosimilars, IDeg-100, and other longer-acting BIs (Gla-300) by projected year 3.ResultsThe base case total costs were $10,145 per patient per year (PPPY) in year 3 for the cumulative population. When all patients switched to Gla-300, the total costs in year 3 were $8,799, reflecting a net savings of -$660 PPPY compared to the budget increase of $686 PPPY in the base case. However, the longer-acting to long-acting BIs reversal scenario demonstrated a budgetary decrease of $676 PPPY over the model horizon. The reduction in incremental PPPY cost of $93 was observed using net drug costs rather than wholesale acquisition costs (WAC).LimitationsThe market shares for years 1–3 were based on expectations supported by the clinicians’ expert opinions and were not obtained from real-world data.ConclusionsThe economic value of increased utilization of Gla-300 was driven by the reduction in HCRU, costs and market shares assumptions. Budgetary reductions were achieved by switching patients from long-acting BIs to Gla-300.

Association between early-life antibiotics use and the risk of attention-deficit/hyperactivity disorder: A real-world evidence study

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Recently, children using antibiotics showed an increased incidence of neurodevelopmental disorders. AimsThe purpose of this study was to investigate the association between antibiotics use and the risk of ADHD in children. Study designPopulation-based retrospective cohort study. SubjectsThe Taiwan National Health Insurance Research Database was used to collect data of children. Prevalence of antibiotics use was analyzed in the children (age, <2 years) included in this study. There were 1,601,689 children included in this study between 2004 and 2012. Outcome measuresThe risk of developing ADHD was estimated using the Cox proportional hazards model. Results71.25 % of children used at least one antibiotic, and the mean follow-up period was 7.07 years. After controlling for other related influencing factors, children who used antibiotics had a 1.12 times higher risk of ADHD than those who did not. The risk of ADHD increased through the use of penicillin and cephalosporin regardless of the duration of antibiotics use. ConclusionsAntibiotics use in children—especially penicillin and cephalosporin—was associated with a higher risk of ADHD.

Tildrakizumab-induction therapy followed byas-needed dosing in patients with mild-to-moderate psoriasis.

This retrospective real-world evidence study investigates the efficacy of as-needed dosing of tildrakizumab in patients with mild-to-moderate psoriasis. Patients received the first three standard doses of tildrakizumab, and thereafter used as-needed dosing over the course of 2.5 years, rather than the approved interval of every 12 weeks. Adequate disease control was achieved, reaching a mean Psoriasis Area and Severity Index at the end of follow-up of &amp;lt; 1.

Comparative Effectiveness of Transcutaneous Afferent Patterned Stimulation Therapy for Essential Tremor: A Randomized Pragmatic Clinical Trial.

Transcutaneous afferent patterned stimulation (TAPS) is a wrist-worn, non-invasive therapy delivering calibrated stimulation to the median and radial nerves. Previous randomized controlled studies have demonstrated the efficacy and safety of TAPS therapy in some patients with essential tremor (ET), but evidence supporting therapeutic benefits of TAPS versus standard of care (SOC) is lacking. This randomized prospective study evaluated the clinical benefit of adding TAPS treatment to SOC versus SOC alone. This randomized pragmatic trial recruited patients from a large health plan's Commercially Insured and Medicare Advantage population. All 310 patients received a TAPS device and were randomized 1:1 to either one month adding TAPS therapy to usual care (TX arm) or usual care with tremor assessment only (SOC arm). The pre-specified endpoints were changes in tremor power measured by motion sensors on the device (primary) and improvement in Bain & Findley Activities of Daily Living (BF-ADL) upper limb scores (secondary) between TX and SOC in all patients who completed the one-month study. 276 patients completed the one-month study (N = 133 TX, N = 143 SOC). The study met the primary and secondary endpoints, with significantly reduced tremor power in TX compared with SOC (0.017 (0.003) versus 0.08 (0.014) (m/s2)2; geometric mean (SE); p < 0.0001) and greater improvement in the BF-ADL score in TX than SOC (1.6 (0.43) vs 0.2 (0.37) points; mean (SE); p < 0.05). No serious device-related adverse events were reported. This trial demonstrates that adding TAPS treatment to SOC significantly improves tremor power and BF-ADLs in patients with ET compared to SOC alone over one month of home use. This study found that adding TAPS treatment to SOC significantly improves tremor power and BF-ADL scores in patients with ET compared to SOC alone over one month of home use. This real-world evidence study suggests that non-invasive TAPS therapy is a safe and valuable treatment option for patients with ET.

Negation recognition in clinical natural language processing using a combination of the NegEx algorithm and a convolutional neural network

BackgroundImportant clinical information of patients is present in unstructured free-text fields of Electronic Health Records (EHRs). While this information can be extracted using clinical Natural Language Processing (cNLP), the recognition of negation modifiers represents an important challenge. A wide range of cNLP applications have been developed to detect the negation of medical entities in clinical free-text, however, effective solutions for languages other than English are scarce. This study aimed at developing a solution for negation recognition in Spanish EHRs based on a combination of a customized rule-based NegEx layer and a convolutional neural network (CNN).MethodsBased on our previous experience in real world evidence (RWE) studies using information embedded in EHRs, negation recognition was simplified into a binary problem (‘affirmative’ vs. ‘non-affirmative’ class). For the NegEx layer, negation rules were obtained from a publicly available Spanish corpus and enriched with custom ones, whereby the CNN binary classifier was trained on EHRs annotated for clinical named entities (cNEs) and negation markers by medical doctors.ResultsThe proposed negation recognition pipeline obtained precision, recall, and F1-score of 0.93, 0.94, and 0.94 for the ‘affirmative’ class, and 0.86, 0.84, and 0.85 for the ‘non-affirmative’ class, respectively. To validate the generalization capabilities of our methodology, we applied the negation recognition pipeline on EHRs (6,710 cNEs) from a different data source distribution than the training corpus and obtained consistent performance metrics for the ‘affirmative’ and ‘non-affirmative’ class (0.95, 0.97, and 0.96; and 0.90, 0.83, and 0.86 for precision, recall, and F1-score, respectively). Lastly, we evaluated the pipeline against two publicly available Spanish negation corpora, the IULA and NUBes, obtaining state-of-the-art metrics (1.00, 0.99, and 0.99; and 1.00, 0.93, and 0.96 for precision, recall, and F1-score, respectively).ConclusionNegation recognition is a source of low precision in the retrieval of cNEs from EHRs’ free-text. Combining a customized rule-based NegEx layer with a CNN binary classifier outperformed many other current approaches. RWE studies highly benefit from the correct recognition of negation as it reduces false positive detections of cNE which otherwise would undoubtedly reduce the credibility of cNLP systems.

Data collection within patient support programs in Canada and implications for real-world evidence generation: the authors' perspective.

Patient support programs (PSPs) offer a unique opportunity to collect real-world data that can contribute to improving patient care and informing healthcare decision making. In this perspective article, we explore the collection of data through PSPs in Canada, current advances in data collection methods, and the potential for generating acceptable real-world evidence (RWE). With PSP infrastructure already in place for most specialized drugs in Canada, adding and strengthening data collection capacities has been a focus in recent years. However, limitations in PSP data, including challenges related to quality, bias, and trust, need to be acknowledged and addressed. Forward-thinking PSP developers have been taking steps to strengthen the PSP datasphere, such as engaging third parties for data analysis, publishing peer-reviewed studies that utilize PSPs as a data source and incorporating quality controls into data collection processes. This article illustrates the current state of PSP data collection by examining six PSP RWE studies and outlining their data characteristics and the health outcomes collected from the PSP. A framework for collecting real-world data within a PSP and a checklist to address issues of trust and bias in PSP data collection is also provided. Collaboration between drug manufacturers, PSP vendors, and data specialists will be crucial in elevating PSP data to a level acceptable to healthcare decision makers, including health technology assessors and payers, with the ultimate beneficiary being patients.

Efficacy of an extensively hydrolyzed formula with the addition of synbiotics in infants with cow's milk protein allergy: a real-world evidence study.

Cow's milk protein allergy (CMPA) is the most frequent food allergy in early childhood. For those infants requiring breastmilk substitutes, formulas with extensively hydrolyzed proteins (EHF), should be the treatment of choice. As there are limited data showing the progression of initial symptoms in infants newly diagnosed with CMPA who are treated with EHF with added synbiotics, the main objective of this study was to evaluate the resolution of symptoms in said infants after 4 weeks of treatment. As a secondary objective this study aimed to assess the impact of the treatment on the family's quality of life. observational, longitudinal, prospective, and multicentric real-world evidence study. The intervention phase (EHF with synbiotics) lasted 28 days and was completed by 65 patients. Treating physicians registered child´s anthropometry, Infant Gastrointestinal Symptoms Questionnaire (IGSQ-13) and CoMiSS (Cow´s Milk Allergy Symptoms Score) both at baseline and after 28 days of treatment. During treatment, caregivers reported child´s regurgitation and stools, PO-SCORAD (Patient Oriented Scoring of Atopic Dermatitis) and FAQL-PB (Family Quality of Life-Parental Burden). Data were collected using Google Forms and analyzed through the STATA program. 95.4% of the patients showed an improvement or disappearance of the overall initial symptoms after 4 weeks of treatment. Gastrointestinal symptoms improved or disappeared in 92% of patients (p < 0.05) while dermatological symptoms improved or disappeared in 87.5% of patients (p < 0.05). The median CoMiSS at baseline was 9, with 21 patients exceeding the cut-off point of 12. After 4 weeks of treatment, the median dropped to 3, and no patient exceeded the 12-cut-off point (p = 0.000). At baseline, patients had a PO-SCORAD of 11.5 (interquartile range 1-23) that went to 1.0 (interquartile range 1-6) at day 28 (p = 0.000). The treatment diminished stool frequency (p < 0.05), improved stool consistency (p = 0.004) and decreased the frequency of regurgitation in infants with CMPA (p = 0.01). The percentage of patients who no longer had any episode of regurgitation increased from 11% to 31% on day 28 (p = 0.003). At baseline, 13% of patients cried more than 3 h per day, while at day 28 that percentage dropped to 3% (p = 0.03). An improvement in the infants' sleep pattern was also appreciated with the treatment. At study onset, 56% of the families reported feeling very overwhelmed, a percentage that dropped to 17% after 28 days of treatment (p < 0.05). The small percentage of families who did not feel overwhelmed at study onset (17%), grew to 43% on day 28 (p < 0.05). The use of an EHF with synbiotics for the management of infants diagnosed with or suspected to have CMPA suggested a good safety profile, an adequate infant growth, and improvement of overall, gastrointestinal, and dermatological symptoms. It also suggested a lower daily frequency of regurgitations and stools, and an improvement in stool consistency, sleeping pattern, and quality of life of the infant and his family.

Molecular characterization of Clostridium perfringens isolates from a tertiary children’s hospital in Guangzhou, China, establishing an association between bacterial colonization and food allergies in infants

BackgroundCow’s milk protein allergy (CMPA) is one of the most common types of food allergy in infants. Faecal pathogen cultures showed that the positive rate of Clostridium perfringens was more than 30%, which was significantly higher than that for other bacteria. Therefore, it is speculated that Clostridium perfringens colonization may be one of the pathogenetic factors for CMPA in infants. We conducted a real-world evidence study. Infants aged 0–6 months with diarrhoea and mucoid and/or bloody stools were recruited from a large tertiary hospital in China. Faecal pathogen cultures for the detection of Clostridium perfringens were confirmed by flight mass spectrometry, and potential toxin genes were identified using PCR. After 12 months of follow-up, the diagnoses of CMPA and food allergy were recorded. The correlation was assessed by Pearson correlation analysis.ResultsIn this study, 358 infants aged 0–6 months with gastrointestinal symptoms and faecal pathogen cultures were recruited. A total of 270 (44.07% girls; mean age, 2.78 ± 2.84 months) infants were followed up for 12 months. Overall, the rate of positivity for Clostridium perfringens in faecal pathogen cultures was 35.75% (128/358) in infants aged ≤ 6 months. The earliest Clostridium perfringens colonization was detected within 2 days after birth. The majority of Clostridium perfringens isolates were classified as type C in 85 stool samples. In the Clostridium perfringens-positive group, 48.21% (54/112) of infants were clinically diagnosed with food allergies after 12 months, including 37.5% (42/112) with CMPA, which was significantly higher than that of the negative group, with 7.59% (12/158) exhibiting food allergies and 5.06% (8/158) presenting CMPA (P < 0.0001). Faecal Clostridium perfringens positivity was significantly correlated with CMPA, food allergy, faecal occult blood, faecal white blood cells, antibiotic use, increased peripheral blood platelet counts, and decreased haemoglobin levels (P < 0.0001).ConclusionsThis study demonstrates that intestinal colonization by Clostridium perfringens is common in infants. The majority of Clostridium perfringens isolates are classified as type C. Colonization of the intestine by Clostridium perfringens is associated with the development of CMPA and food allergy in infants.

Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib following Immunotherapy: A Real World Evidence Study.

Lenvatinib, a multikinase inhibitor, is an FDA-approved treatment for advanced hepatocellular carcinoma (HCC) in the first-line setting. Recent trial data have established atezolizumab plus bevacizumab as well as tremelimumab plus durvalumab as preferred first-line treatment options for advanced HCC. The role of lenvatinib following progression on immunotherapy in patients with advanced HCC remains unclear. We conducted a multicentric, retrospective analysis of patients with advanced HCC diagnosed between 2010 and 2021 at the Mayo Clinic in Minnesota, Arizona, and Florida who received immunotherapy followed by lenvatinib. Median overall survival and progression-free survival analyses were performed using the Kaplan-Meier method, and responses were determined using RECIST 1.1. Adverse events were determined using CTCAE v 4.0. We identified 53 patients with advanced HCC who received lenvatinib following progression on immunotherapy. Forty five (85%) patients had a Child Pugh class A at diagnosis, while 30 (58%) patients were still Child Pugh A at time of lenvatinib initiation. Lenvatinib was administered as a second-line treatment in 85% of the patients. The median PFS was 3.7 months (95% CI: 3.2-6.6), and the median OS from the time of lenvatinib initiation was 12.8 months (95% CI: 6.7-19.5). In patients with Child Pugh class A, the median OS and PFS was 14 and 5.2 months, respectively. Race, gender, and Child Pugh class was associated with OS on multivariate analysis. Our study, using real-world data, suggests that patients benefit from treatment with lenvatinib following progression on immunotherapy in advanced HCC. The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy remains unknown, and these results need to be validated in a clinical trial.

Budget Impact Analysis of Intensification with iGlarLixi Compared to Alternative Treatment Strategies Among Patients with Type2 Diabetes Mellitus.

The clinical benefits of treating patients with type2 diabetes mellitus (T2DM) with fixed-ratio combination of insulin iGlar (iGlar) plus lixisenatide (iGlarLixi) were demonstrated in clinical trials and real-world evidence studies; however, its cost impact to healthcare payers is unknown. A budget impact model was developed from a United States (US) payer's perspective for a hypothetical healthcare plan of 1million people over a 1-year time horizon. In scenario analysis, patients with uncontrolled glycated hemoglobin (HbA1c) treated with 60units or less of daily insulin (insulin cohort) or oral antidiabetic drugs (OADs) only (OAD cohort) were intensified to iGlarLixi/rapid-acting insulin (RAI)/glucagon-like peptide1 receptor agonists (GLP-1RA) or iGlarLixi/iGlar/GLP-1RA, respectively. Model inputs from real-world data (RWD) included baseline market shares, proportion of patients intensifying to respective treatments, and dosing inputs; unit costs were obtained from published literature. One-way sensitivity analyses assessed the impact of individual parameters. Intensification with iGlarLixi resulted in the lowest incremental per member per month (PMPM) budget impact compared to other intensifying drugs (iGlar, RAI, and GLP-1RA). In the insulin cohort, the incremental PMPM cost for intensification with iGlarLixi ($0.03) was the lowest among intensifying drugs; GLP-1RA ($72.20) and RAI ($4.81). Similarly, the incremental PMPM cost for intensification with iGlarLixi was the lowest ($1.25) in the OAD cohort among intensifying drugs; GLP-1RA ($321.65) and iGlar ($114.82). In scenario analyses, when equal market intensification shares for iGlarLixi and GLP-1RA were explored, the incremental PMPM cost for iGlarLixi ($0.03) remained lower than GLP-1RA ($2.28) and RAI ($10.44) in the insulin cohort. Intensification with iGlarLixi was associated with lower costs compared to other treatment intensifications, as well as overall budget reductions compared to pre-intensification when considering cost savings attributable to reduction in HbA1c; therefore, its inclusion for the treatment of T2DM would represent a budget saving.

A cost comparison of benralizumab, mepolizumab, and dupilumab in patients with severe asthma: A US third-party payer perspective.

BACKGROUND: Clinical trials and real-world evidence (RWE) studies of biologics have demonstrated reduced exacerbations, decreased use of oral corticosteroids (OCS), and improvements in daily symptoms and health-related quality of life in patients with severe eosinophilic asthma (SEA). OBJECTIVE: To compare direct health care costs associated with biologic use for the treatment of SEA from a US third-party payer perspective. METHODS: We developed a cost-minimization model to compare costs and cost offsets associated with 3 biologics-benralizumab, mepolizumab, and dupilumab-for 2- and 4-year periods. The model relied on longitudinal data from clinical trials to inform the primary (base case) analysis cost comparison and RWE study data, in a separate scenario, to compare costs in nonclinical trial settings. Primary model outcomes included exacerbations (including hospitalizations), OCS-dependent years (including associated complications), and total direct health care biologic costs. Results were calculated at the per patient and population level (per 1,000 patients). Sensitivity analyses with key model parameters were performed. RESULTS: Benralizumab had the lowest total biologic costs per patient for both the 2- and 4-year periods. Over 4 years, the marginal cost difference in total biologic costs per patient was $23,061 lower for benralizumab vs mepolizumab and $17,242 lower for benralizumab vs dupilumab. The 4-year population level analysis of benralizumab vs mepolizumab revealed $4.8 million in marginal cost offsets due to 582 fewer exacerbations and 153 fewer OCS-dependent years and a marginal total cost savings of $27.9 million per 1,000 patients for benralizumab. The 4-year population level analysis of benralizumab vs dupilumab revealed $2.3 million in marginal cost offsets due to 291 fewer exacerbations and 64 fewer OCS-dependent years and marginal total cost savings of $19.5 million per 1,000 patients for benralizumab. RWE data were available for a 2-year cost comparison scenario of benralizumab vs mepolizumab, which showed similar results to the base case analysis. Sensitivity analyses varying assumptions on key model parameter estimates confirmed results, with benralizumab having lower total direct health care costs in all scenarios tested, and showed that model results were most sensitive to changes in biologic costs and exacerbation reduction rates. CONCLUSIONS: Patients receiving benralizumab had higher nonbiologic cost offsets because of reductions in exacerbations and OCS-dependent years, leading to greater cost savings for third-party payers compared with patients receiving mepolizumab or dupilumab. Taken together with biologic costs, benralizumab presents greater savings in health care costs for payers than patients with SEA who use mepolizumab or dupilumab. DISCLOSURES: This study was funded by AstraZeneca (Cambridge, UK). Drs Xu, Chung, Genofre, and Katial are or were AstraZeneca employees at the time this research was conducted and may be shareholders of AstraZeneca. Ms Schaefer and Dr Szende are employees of Labcorp Drug Development, which received funding from AstraZeneca to perform this research.

1578P Effect of immune checkpoint inhibitors in metastatic gastric cancer: A real-world evidence study

1578P Effect of immune checkpoint inhibitors in metastatic gastric cancer: A real-world evidence study

268P Evaluating the efficacy of adjuvant capecitabine in triple-negative breast cancer patients with residual disease: A real-world evidence study

268P Evaluating the efficacy of adjuvant capecitabine in triple-negative breast cancer patients with residual disease: A real-world evidence study

VP369 Disease burden, treatment patterns and healthcare resource utilization associated with Pompe disease in Sweden: a real-world evidence study

VP369 Disease burden, treatment patterns and healthcare resource utilization associated with Pompe disease in Sweden: a real-world evidence study

PB0334 Immune-Mediated Thrombotic Thrombocytopenic Purpura Landscaping in Gulf Countries: A Real-World Evidence Study (ATHENA Study)

PB0334 Immune-Mediated Thrombotic Thrombocytopenic Purpura Landscaping in Gulf Countries: A Real-World Evidence Study (ATHENA Study)

1104P Efficacy of immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD1 treatment: A EUMelareg real-world evidence study

1104P Efficacy of immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD1 treatment: A EUMelareg real-world evidence study

Real-world data emulating randomized controlled trials of non-vitamin K antagonist oral anticoagulants in patients with venous thromboembolism

BackgroundEmulating randomized controlled trials (RCTs) by real-world evidence (RWE) studies would benefit future clinical and regulatory decision-making by balancing the limitations of RCT. We aimed to evaluate whether the findings from RWE studies can support regulatory decisions derived from RCTs of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE).MethodsFive landmark trials (AMPLIFY, RE-COVER II, Hokusai-VTE, EINSTEIN-DVT, and EINSTEIN-PE) of NOACs were emulated using the South Korean nationwide claims database (January 2012 to August 2020). We applied an active comparator and new-user design to include patients who initiated oral anticoagulants within 28 days from their VTE diagnoses. The prespecified eligibility criteria, exposure (each NOAC, such as apixaban, rivaroxaban, dabigatran, and edoxaban), comparator (conventional therapy, defined as subcutaneous heparin followed by warfarin), and the definition of outcomes from RCTs were emulated as closely as possible in each separate emulation cohort. The primary outcome was identical to each trial, which was defined as recurrent VTE or VTE-related death. The safety outcome was major bleeding. Propensity score matching was conducted to balance 69 covariates between the exposure groups. Effect estimates for outcomes were estimated using the Mantel–Haenszel method and Cox proportional hazards model and subsequently compared with the corresponding RCT estimates.ResultsCompared to trial populations, real-world study populations were older (range: 63–69 years [RWE] vs. 54–59 years [RCT]), with more females (55–60.5% vs. 39–48.3%) and had a higher prevalence of active cancer (4.2–15.4% vs. 2.5–9.5%). The emulated estimates for effectiveness outcomes showed superior effectiveness of NOAC (AMPLIFY: relative risk 0.81, 95% confidence interval 0.70–0.94; RE-COVER II: hazard ratio [HR] 0.60, 0.37–0.96; Hokusai-VTE: 0.49, 0.31–0.78; EINSTEIN-DVT: 0.54, 0.33–0.89; EINSTEIN-PE: 0.50, 0.34–0.74), when contrasted with trials that showed non-inferiority. For safety outcomes, all emulations except for AMPLIFY and EINSTEIN-DVT yielded results consistent with their corresponding RCTs.ConclusionsThis study revealed the feasibility of complementing RCTs with RWE studies by using claims data in patients with VTE. Future studies to consider the different demographic characteristics between RCT and RWE populations are needed.