Collaborative Real-World Evidence Among Regulators: Lessons and Perspectives.

The International Coalition of Medicines Regulatory Authorities (ICMRA), comprising 38 global medicines regulatory authorities, collaborates on shared challenges, notably during the COVID-19 pandemic. This article focuses on the ICMRA COVID-19 Real-World Evidence (RWE) and Observational Studies Working Group. The Working Group aimed to address challenges related to RWE and observational studies during the pandemic, resulting in impactful studies and ICMRA statements on international collaboration for RWE and COVID-19 vaccine safety.

Trends in the Completeness and Validity of Sources of Death Data Against the National Death Index From 2010 to 2018.

Purpose: We investigated time trends in validation performance characteristics for six sources of death data available within the Healthcare Integrated Research Database (HIRD) over 8 years.

Methods: We conducted a secondary analysis of a cohort of advanced cancer patients with linked National Death Index (NDI) data identified in the HIRD between 2010 and 2018. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for six sources of death status data and an algorithm combining data from available sources using NDI data as the reference standard.

Factors associated with receipt of systemic anticancer treatment for locally advanced or metastatic urothelial carcinoma in England: a population-based study.

Introduction: Systemic anticancer therapy for locally advanced or metastatic urothelial carcinoma (la/mUC) is associated with efficacy benefits, including longer overall survival (OS), but many patients remain untreated. This observational, real-world, national study aimed to investigate factors associated with receiving systemic anticancer therapy for la/mUC in England.

Patients And Methods: Adults diagnosed with la/mUC between 2013 and 2019 were identified in the National Cancer Registration Dataset and followed until March 2021.

Real-World Evidence to Support EU Regulatory Decision Making-Results From a Pilot of Regulatory Use Cases.

Studies using real-world data (RWD) can complement evidence from clinical trials and fill evidence gaps during different stages of a medicine's lifecycle. This review presents the experience resulting from the European Medicines Agency (EMA) pilot to generate RWE to support evaluations by EU regulators and down-stream decision makers from September 2021 to February 2023. A total of 61 research topics were identified for RWE generation during this period, covering a wide range of research questions, primarily generating evidence on medicines safety (22, 36%), followed by questions on the design and feasibility of clinical trials (11, 18%), drug utilization (10, 16%), clinical management (10, 16%), and disease epidemiology.

Leveraging patient experience data to guide medicines development, regulation, access decisions and clinical care in the EU.

Patient experience data (PED), provided by patients/their carers without interpretation by clinicians, directly capture what matters more to patients on their medical condition, treatment and impact of healthcare. PED can be collected through different methodologies and these need to be robust and validated for its intended use. Medicine regulators are increasingly encouraging stakeholders to generate, collect and submit PED to support both scientific advice in development programs and regulatory decisions on the approval and use of these medicines.

Effectiveness of recombinant human FSH: recombinant human LH combination treatment versus recombinant human FSH alone for assisted reproductive technology in women aged 35-40 years.

Research Question: According to real-world data, is recombinant human FSH (r-hFSH) combined with recombinant human LH (r-hLH) or r-hFSH alone more effective for women of advanced maternal age (AMA) in terms of live birth?

Design: Non-interventional study comparing the effectiveness of r-hFSH and recombinant r-hLH (2:1 ratio) versus r-hFSH alone for ovarian stimulation during ART treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register.

Results: Overall clinical pregnancy (29.8%, 95% CI 28.

Principles for Good Practice in the Conduct of Non-interventional Studies: The View of Industry Researchers.

This reflection paper presents a consolidated view of EFPIA on the need for principles for good practice in the generation and use of non-interventional studies (NIS), including overarching principles such as the registration of hypothesis evaluating treatment effect (HETE) studies. We first define NIS and the important adjacencies to clinical trials and relationship with real-world evidence (RWE). We then outline the principles for good practice with respect to appropriate research design, study protocol, fit-for-purpose variables and data quality, analytical methods, bias reduction, transparency in conduct and use, privacy management and ethics review.

Dosing Characteristics of Recombinant Human Luteinizing Hormone or Human Menopausal Gonadotrophin-Derived LH Activity in Patients Undergoing Ovarian Stimulation: A German Fertility Database Study.

Objectives: The aim of the study was to evaluate dosing of recombinant human luteinizing hormone (r-hLH) or human menopausal gonadotrophin (hMG)-derived medications with LH activity in ovarian stimulation (OS) cycles for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).

Design: A non-interventional study was performed to analyse data from the German RecDate database (January 2007-December 2011).

Participants/materials, Setting, Methods: Starting/total r-hLH/hMG dose, OS duration/cycle number, r-hLH/hMG initiation day (first day of administration), and population/cycle characteristics were assessed in women (≥18 years) undergoing OS for IVF/ICSI using r-hLH or hMG-derived medications (excluding corifollitropin alfa, clomiphene citrate, letrozole, mini/micro-dose human chorionic gonadotrophin, and urofollitropin alone).

Effectiveness of recombinant human follicle-stimulating hormone (r-hFSH): recombinant human luteinizing hormone versus r-hFSH alone in assisted reproductive technology treatment cycles among women aged 35-40 years: A German database study.

This non-interventional study compared the effectiveness of recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) (2:1 ratio) versus r-hFSH alone for ovarian stimulation (OS) during assisted reproductive technology treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register (D·I·R). Numerically higher clinical pregnancy (29.8% [95% CI 28.

Fetal Lung Volume Appears to Predict Respiratory Morbidity in Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia and respiratory morbidity. To assess whether respiratory morbidity during the first 2 years of life in infants with left-sided CDH is associated with fetal lung volume (FLV) evaluated by the observed-to-expected FLV ratio (o/e FLV) on antenatal magnetic resonance imaging (MRI). In this retrospective study, o/e FLV measures were collected.

Comparative effectiveness of gonadotropins used for ovarian stimulation during assisted reproductive technologies (ART) in France: A real-world observational study from the French nationwide claims database (SNDS).

This comparative non-interventional study using data from the French National Health Database (Système National des Données de Santé) investigated real-world (cumulative) live birth outcomes following ovarian stimulation, leading to oocyte pickup with either originator recombinant human follicle-stimulating hormone (r-hFSH) products (alfa or beta), r-hFSH alfa biosimilars, or urinaries including mainly HP-hMG (menotropins), and marginally u-hFSH-HP (urofollitropin). Using data from 245,534 stimulations (153,600 women), biosimilars resulted in a 19% lower live birth (adjusted odds ratio (OR) 0.81, 95% confidence interval (CI) 0.

Rare metabolic disease mimicking COL4A1/COL4A2 fetal brain phenotype.

Pathogenic variants of collagen type IV alpha 1 and 2 (COL4A1/COL4A2) genes cause various phenotypic anomalies, including intracerebral hemorrhage and a wide spectrum of developmental anomalies. Only 20% of fetuses referred for COL4A1/COL4A2 molecular screening (fetuses with a suspected intracerebral hemorrhage) carry a pathogenic variant in these genes, raising questions regarding the causative anomaly in the remaining 80% of these fetuses. We examined, following termination of pregnancy or in-utero fetal death, a series of 113 unrelated fetuses referred for COL4A1/COL4A2 molecular screening, in which targeted sequencing was negative.

Incidence of safety events after immune checkpoint inhibitor initiation for advanced-stage non-small-cell lung cancer: a real-world study.

To describe the incidence of safety events after immune checkpoint inhibitor (ICI) initiation for advanced-stage non-small-cell lung cancer. Retrospective cohort study using the HealthCore Integrated Research Database in the USA to examine the incidence of prespecified safety events of interest after ICI initiation (n = 5278). The most common safety events after ICI initiation included malaise/fatigue (incidence rate [IR]: 70.

Treatment effectiveness in a rare oncology indication: Lessons from an external control cohort study.

Real-world data (RWD) reflecting patient treatment in routine clinical practice can be used to develop external control groups for single-arm trials. External controls can provide valuable benchmark results on potential comparator drug effectiveness, particularly in rare indications when randomized controlled trials are either infeasible or unethical. This paper describes lessons learned from a descriptive real-world external control cohort study conducted to provide benchmark data for a single-arm clinical trial in a rare oncology biomarker driven disease.

Identifying Valid Algorithms for Number of Lines of Anti-Neoplastic Therapy in the Danish National Patient Registry Among Patients with Advanced Ovarian, Gastric, Renal Cell, Urothelial, and Non-Small Cell Lung Cancer Attending a Danish University Hospital.

Purpose: To develop algorithms to identify number of lines of anti-neoplastic therapy per patient based on the Danish National Patient Registry (DNPR) and identify which algorithm has the highest percentage agreement with a reference standard of documentation in medical records.

Patients And Methods: We included 179 patients diagnosed between January 1, 2012, and December 31, 2016, with stage II, III, or IV urothelial cell carcinoma or stage III or IV epithelial ovarian cancer, gastric adenocarcinoma, renal cell carcinoma, or non-small cell lung cancer (NSCLC). We developed two algorithms for number of lines of anti-neoplastic therapy based on dates and treatment codes (eg, "treatment with cisplatin" or "cytostatic treatment") in the DNPR.

Cystic adenomyoma surgery.

Objective: Cystic adenomyoma is a lesion located within the myometrium. It is lined with endometrium and has hemorrhagic content. This rare entity has been described as a focal form of adenomyosis.

Treatment and Survival in Advanced Non-Small Cell Lung Cancer, Urothelial, Ovarian, Gastric and Kidney Cancer: A Nationwide Comprehensive Evaluation.

Purpose: Few studies have described real-world treatment patterns and survival before the widespread use of immune checkpoint inhibitors (ICIs). We aimed to describe anti-cancer treatment including the use of programmed cell death-1 and ligand-1 (PD-1/PD-L1) ICIs and overall survival (OS) in advanced cancer patients as a benchmarking real-world standard before widespread use of ICIs.

Patients And Methods: Using nationwide Danish medical registries, we assembled cohorts of Danish patients with advanced non-small cell lung cancer (NSCLC) (n=12,283), urothelial carcinoma (n=2504), epithelial ovarian cancer (n=1466), gastric adenocarcinoma (n=1457), and renal cell carcinoma (RCC) (n=1261) diagnosed between 1/1/2013 and 31/12/2017.

Comparative effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG HP) in assisted reproductive technology (ART) treatments: a non-interventional study in Germany.

Background: This study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f) with urinary highly purified human menopausal gonadotropin (hMG HP; Menogon HP), during assisted reproductive technology (ART) treatments in Germany.

Methods: Data were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012, for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC).

High-dose corticosteroid use and risk of hospitalization for infection in patients treated with immune checkpoint inhibitors--A nationwide register-based cohort study.

High-dose corticosteroids have been associated with increased risk of serious infection in patients with metastatic melanoma treated with immune checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen 4. This potential association needs to be examined further among patients with other cancer types and for other immune checkpoint inhibitors. We examined whether receipt of high-dose corticosteroids was associated with increased rates of hospitalization for infection among 981 Danish renal, urothelial, and lung cancer patients followed from first administration of programmed death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint inhibitors.

[Contribution of the pre-operative Mri-coloscan couple in the surgical planning of deep digestive pelvic endometriosis].

Introduction: The digestive involvement of endometriosis accounts for up to 20-25% of deep localisations. Precise mapping of digestive lesions is essential in order to plan surgery and specialized teams. The aim of this study is to assess the contribution of the MRI-coloscan couple in the preoperative assessment of digestive endometriosis.

A real-world study on characteristics, treatments and outcomes in US patients with advanced stage ovarian cancer.

Background: Detailed epidemiologic descriptions of large populations of advanced stage ovarian cancer patients have been lacking to date. This study aimed to describe the patient characteristics, treatment patterns, survival, and incidence rates of health outcomes of interest (HOI) in a large cohort of advanced stage ovarian cancer patients in the United States (US).

Methods: This cohort study identified incident advanced stage (III/IV) ovarian cancer patients in the US diagnosed from 2010 to 2018 in the HealthCore Integrated Research Database (HIRD) using a validated predictive model algorithm.

Prenatal prediction of postnatal survival in fetuses with congenital diaphragmatic hernia using MRI: lung volume measurement, signal intensity ratio, and effect of experience.

Objective: To evaluate various signal intensity ratios in isolated congenital diaphragmatic hernia (CDH) and to compare their potential in predicting survival with that of the observed-to-expected (O/E) ratio of total fetal lung volume (TFLV) using magnetic resonance imaging (MRI) measurements. Our second objective was to evaluate the impact of operator's experience in comparing the prediction of postnatal survival by O/E-TFLV.

Methods: In 75 conservatively managed CDH fetuses and in 50 who underwent fetoscopic endoluminal tracheal occlusion (FETO), the fetal lung-to-amniotic fluid, lung-to-liver, lung-to-muscle, lung-to-spinal fluid signal intensity ratios, respectively LAFSIR, LLSIR, LMSIR, and LSFSIR, were measured, as was O/E-TFLV.

How reproducible are classical and new CT-pelvimetry measurements?

Purpose: The objective of this study was to assess the reliability and reproducibility of existing and new computed tomography (CT)-pelvimetry measurements.

Material And Methods: A retrospective cohort study of 63 women with a mean age of 33.9±5.

Development of predictive models to identify advanced-stage cancer patients in a US healthcare claims database.

Background: Although healthcare databases are a valuable source for real-world oncology data, cancer stage is often lacking. We developed predictive models using claims data to identify metastatic/advanced-stage patients with ovarian cancer, urothelial carcinoma, gastric adenocarcinoma, Merkel cell carcinoma (MCC), and non-small cell lung cancer (NSCLC).

Methods: Patients with ≥1 diagnosis of a cancer of interest were identified in the HealthCore Integrated Research Database (HIRD), a United States (US) healthcare database (2010-2016).