Why and how should we simulate platform trials? Learnings from EU-PEARL.

Background: Platform trials are innovative clinical trials governed by a master protocol that allows for the evaluation of multiple investigational treatments that enter and leave the trial over time. Interest in platform trials has been steadily increasing over the last decade. Due to their highly adaptive nature, platform trials provide sufficient flexibility to customize important trial design aspects to the requirements of both the specific disease under investigation and the different stakeholders.

Epidural analgesia and neonatal short-term outcomes during routine childbirth: a 10-year retrospective analysis from the national birth registry of Austria.

Background: Epidural analgesia (EA) is well-accepted for pain relief during labor. Still, the impact on neonatal short-term outcome is under continuous debate. This study assessed the outcome of neonates in deliveries with and without EA in a nationwide cohort.

Regulatory Issues of Platform Trials: Learnings from EU-PEARL.

Although platform trials have many benefits, the complexity of these designs may result not only in increased methodological but also regulatory and ethical challenges. These aspects were addressed as part of the IMI project EU Patient-Centric Clinical Trial Platforms (EU-PEARL). We reviewed the available guidelines on platform trials in the European Union and the United States.

A meta-analysis and real-world cohort study on the sex-related differences in efficacy and safety of immunotherapy for hepatocellular carcinoma.

Background & Aims: Sex-related differences in the immune pathogenesis of hepatocellular carcinoma (HCC), particularly related to oestrogen-dependent secretion of pro-tumourigenic cytokines, are well-known. Whether sex influences the efficacy and safety of immunotherapy is not known.

Methods: We performed a restricted maximum likelihood random effects meta-analysis of five phase III trials that evaluated immune checkpoint inhibitors (ICIs) in advanced HCC and reported overall survival (OS) hazard ratios (HRs) stratified by sex to evaluate sex-related differences in OS.

Influence of a Capsular Tension Ring on Capsular Bag Behavior of a Plate Haptic Intraocular Lens: An Intraindividual Randomized Trial.

Purpose: To evaluate the influence of a capsular tension ring (CTR) on rotational stability, decentration, tilt, and axial stability of an 11.0-mm plate haptic intraocular lens (IOL).

Design: Intraindividual, randomized, double-masked, controlled clinical trial.

Predicting survival in patients with 'non-high-risk' acute variceal bleeding receiving β-blockers+ligation to prevent re-bleeding.

Background & Aims: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13).

Disturbances in sodium and chloride homeostasis predict outcome in stable and critically ill patients with cirrhosis.

Background: Hyponatremia has prognostic implications in patients with cirrhosis, and thus, has been incorporated in the 2016 MELD-UNOS update. Changes in serum chloride are commonly perceived as 'just' parallel to changes in serum sodium. However, these are less well studied in the context of cirrhosis.

Designing an exploratory phase 2b platform trial in NASH with correlated, co-primary binary endpoints.

Non-alcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD) and a disease with high unmet medical need. Platform trials provide great benefits for sponsors and trial participants in terms of accelerating drug development programs. In this article, we describe some of the activities of the EU-PEARL consortium (EU Patient-cEntric clinicAl tRial pLatforms) regarding the use of platform trials in NASH, in particular the proposed trial design, decision rules and simulation results.

Non-invasive tests for clinically significant portal hypertension after HCV cure.

Background & Aims: Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH; hepatic venous pressure gradient [HVPG] ≥10 mmHg) have predominantly been studied in patients with active HCV infection. Investigations after HCV cure are limited and have yielded conflicting results. We conducted a pooled analysis to determine the diagnostic/prognostic utility of liver stiffness measurement (LSM)/platelet count (PLT) in this setting.

Evaluation of a Bariatric Monitoring Pass for Primary Care Physicians.

Introduction: There are a growing number of patients undergoing bariatric surgery requiring lifelong follow-up. Therefore, follow-up care can no longer be covered by specialized outpatient clinics alone due to the sharp rise in the number of bariatric patients. Bariatric Patients in Primary Care: Postoperative Nutrition and Lifestyle Management (BagEL) is a survey to evaluate a newly developed structured disease management program including nutrition and lifestyle management in primary care.

Decision rules for identifying combination therapies in open-entry, randomized controlled platform trials.

Platform trials have become increasingly popular for drug development programs, attracting interest from statisticians, clinicians and regulatory agencies. Many statistical questions related to designing platform trials-such as the impact of decision rules, sharing of information across cohorts, and allocation ratios on operating characteristics and error rates-remain unanswered. In many platform trials, the definition of error rates is not straightforward as classical error rate concepts are not applicable.

HCC risk stratification after cure of hepatitis C in patients with compensated advanced chronic liver disease.

Background & Aims: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in patients with advanced chronic liver disease (ACLD) caused by chronic hepatitis C who have achieved sustained virologic response (SVR). We developed risk stratification algorithms for de novo HCC development after SVR and validated them in an independent cohort.

Methods: We evaluated the occurrence of de novo HCC in a derivation cohort of 527 patients with pre-treatment ACLD and SVR to interferon-free therapy, in whom alpha-fetoprotein (AFP) and non-invasive surrogates of portal hypertension including liver stiffness measurement (LSM) were assessed pre-/post-treatment.

A novel electrosurgical divider: performance in a self-controlled tonsillectomy study.

Purpose: Tonsillectomies are among the most common surgeries in otorhinolaryngology. A novel electrosurgical temperature-controlled instrument (device) promises rapid tonsillectomies and might reduce postoperative pain, but comparative studies to assess performance are warranted.

Methods: This randomized self-controlled clinical trial was conducted from October 2019 to October 2020 at the Department of Otorhinolaryngology, Head and Neck Surgery of the Medical University of Vienna.

Adjunctive treatment with high-titre convalescent plasma in severely and critically ill COVID-19 patients - a safe but futile intervention. A comparative cohort study.

Background: Convalescent plasma (CP) containing antibodies derived from coronavirus disease 2019 (COVID-19) survivors has been proposed as a promising therapeutic option for severe COVID-19.

Methods: In our intensive care unit (ICU), 55 patients (46 male, median age 61 years) with PCR-confirmed COVID-19 (35 = 63.6% on mechanical ventilation, 7 = 14.

Systematic review of available software for multi-arm multi-stage and platform clinical trial design.

Background: In recent years, the popularity of multi-arm multi-stage, seamless adaptive, and platform trials has increased. However, many design-related questions and questions regarding which operating characteristics should be evaluated to determine the potential performance of a specific trial design remain and are often further complicated by the complexity of such trial designs.

Methods: A systematic search was conducted to review existing software for the design of platform trials, whereby multi-arm multi-stage trials were also included.

Reliability of coronary computed tomography angiography in acute coronary syndrome in an emergency setting.

Background: Cardiovascular computed tomography (cardiovascular CT) is currently used as a fast non-invasive method for the visualization of coronary plaques and walls and the assessment of lumen stenosis severity. Previous studies demonstrated the high negative predictive value of CT for the exclusion of coronary lumen stenoses. In this study we hypothesize that coronary CT angiography (CTA) represents a reliable method as diagnostic procedure in acute coronary syndrome (ACS) even in emergency settings.

Impact of Timely Public Health Measures on Kidney Transplantation in Austria during the SARS-CoV-2 Outbreak-A Nationwide Analysis.

SARS-CoV-2 led to considerable morbidity/mortality worldwide and tremendously impacted on daily life. Strict lockdown measures were implemented early to contain the viral outbreak in Austria. Massive changes in organizational structures of healthcare facilities followed with unclear implications on the care of non-COVID-19-affected patients.

Comparison of Long-Term Rotational Stability of Three Commonly Implanted Intraocular Lenses.

Purpose: To compare rotational stability and its influencing factors in 3 different widely used hydrophobic acrylic intraocular lenses (IOLs) from the end of surgery (EoS) to 4-7 months (6 months) in over 380 eyes.

Design: Prospective interventional comparative clinical study.

Methods: Setting: Department of Ophthalmology, Medical University of Vienna.

The Evolution of Master Protocol Clinical Trial Designs: A Systematic Literature Review.

Purpose: Recent years have seen a change in the way that clinical trials are being conducted. There has been a rise of designs more flexible than traditional adaptive and group sequential trials which allow the investigation of multiple substudies with possibly different objectives, interventions, and subgroups conducted within an overall trial structure, summarized by the term master protocol. This review aims to identify existing master protocol studies and summarize their characteristics.

POSTOPERATIVE MOVEMENT OF THE FOVEA AFTER SUCCESSFUL SURGERY IN PATIENTS WITH IDIOPATHIC EPIRETINAL MEMBRANES.

Purpose: To evaluate the change in the fovea's postoperative location after successful pars plana vitrectomy with combined epiretinal and internal limiting membrane peeling in patients with idiopathic epiretinal membranes (iERMs).

Methods: In this prospective study 32 eyes of 32 patients with iERMs were followed from baseline before until 3 months after surgery. Study measures included 4-m Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, enhanced-depth imaging-optical coherence tomography, and intraoperative fundus photographs.

The fetal fibronectin test is superior to cervical length measurement in predicting preterm birth in twin pregnancies: a retrospective observational study.

Objectives: Twin pregnancies have a higher likelihood to experience spontaneous preterm birth (PTB). Those with imminent PTB need to be determined in order to undergo fetal lung maturation with glucocorticoids and therewith improve neonatal outcomes. The aim of this study was to assess the predictive value of the fetal fibronectin (fFN) test and the measurement of cervical length in twin pregnancies with symptoms of imminent PTB.

Retinal and Choroidal Perfusion Status in the Area of Laser Scars Assessed With Swept-Source Optical Coherence Tomography Angiography.

Purpose: To evaluate the perfusion status of the retina and choriocapillaris in the area of laser scars on swept-source optical coherence tomography angiography (OCTA) images of eyes previously treated with panretinal photocoagulation (PRP).

Methods: Cross-sectional exploratory analysis of swept-source OCTA images, which were retrospectively reviewed for laser scars. The appearance of the capillary networks in the area of previous laser were evaluated following a three-step grading system (normal/sparse/missing capillary network).