A Comparison of Statistical Methods for Time-To-Event Analyses in Randomized Controlled Trials Under Non-Proportional Hazards.

While well-established methods for time-to-event data are available when the proportional hazards assumption holds, there is no consensus on the best inferential approach under non-proportional hazards (NPH). However, a wide range of parametric and non-parametric methods for testing and estimation in this scenario have been proposed. To provide recommendations on the statistical analysis of clinical trials where non-proportional hazards are expected, we conducted a simulation study under different scenarios of non-proportional hazards, including delayed onset of treatment effect, crossing hazard curves, subgroups with different treatment effects, and changing hazards after disease progression.

Study protocol of the METAPANC trial - intensified treatment in patients with local operable but oligometastatic pancreatic cancer - multimodal surgical treatment versus chemotherapy alone: a randomized controlled trial.

Background: Based on current guidelines, surgical treatment of hepatic oligometastases in patients with pancreatic ductal adenocarcinoma (PDAC) is not primarily recommended. Systematic chemotherapy is the therapy of choice for these patients. The relevance of subsequent surgical resection after chemotherapy remains unclear.

Real world federated learning with a knowledge distilled transformer for cardiac CT imaging.

Federated learning is a renowned technique for utilizing decentralized data while preserving privacy. However, real-world applications often face challenges like partially labeled datasets, where only a few locations have certain expert annotations, leaving large portions of unlabeled data unused. Leveraging these could enhance transformer architectures' ability in regimes with small and diversely annotated sets.

Multi-modal dataset creation for federated learning with DICOM-structured reports.

Purpose Federated training is often challenging on heterogeneous datasets due to divergent data storage options, inconsistent naming schemes, varied annotation procedures, and disparities in label quality. This is particularly evident in the emerging multi-modal learning paradigms, where dataset harmonization including a uniform data representation and filtering options are of paramount importance.Methods DICOM-structured reports enable the standardized linkage of arbitrary information beyond the imaging domain and can be used within Python deep learning pipelines with highdicom.

Rationale and design of the FAIR-HF2-DZHK05 trial: Ferric carboxymaltose assessment of morbidity and mortality in patients with iron deficiency and chronic heart failure.

Aims: While it is widely accepted that intravenous (IV) iron improves functional capacity, symptoms, and cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction (HFrEF) diagnosed with iron deficiency (ID), three recently published cardiovascular outcome trials (AFFIRM-AHF, IRONMAN and HEART-FID) of IV iron supplementation in HF failed to demonstrate a significant benefit on their respective primary endpoints. Dosing of IV iron after the initial correction of baseline ID - by design or as a result of trial circumstances - was relatively low (i.e.

Rationale and design of the HERZCHECK trial: Detection of early heart failure using telemedicine and cardiovascular magnetic resonance in structurally weak regions (NCT05122793).

Background And Aims: Heart failure (HF) is an imminent global health problem. Yet established screening algorithms for asymptomatic pre-HF, allowing for early and effective preventive interventions, are largely lacking. The HERZCHECK trial, conducted in structurally underserved rural regions of North-Eastern Germany, aims to close this gap by evaluating the feasibility, diagnostic efficacy, and cost-effectiveness of a fully mobile, telemedically-supervised screening approach, combining cardiovascular magnetic resonance (CMR) imaging and laboratory testing as central elements.

Real-world multicentre cohort study on choices and effectiveness of immunotherapies in NMOSD and MOGAD.

Background: Recurrent attacks in neuromyelitis optica spectrum disorders (NMOSDs) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can lead to severe disability. We aimed to analyse the real-world use of immunotherapies in patients with NMOSD and MOGAD, focusing on changes in treatment strategies, effects on attack rates (ARR) and risk factors for attacks.

Methods: This longitudinal registry-based cohort study included 493 patients (320 with aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (65%), 44 with AQP4-IgG seronegative NMOSD (9%) and 129 MOGAD (26%)) with 1247 treatments from 19 German and one Austrian centre from the registry of the neuromyelitis optica study group (NEMOS).

Effects of timely case conferencing between general practitioners and specialist palliative care services on symptom burden in patients with advanced chronic disease: results of the cluster-randomised controlled KOPAL trial.

Background: Patients with advanced chronic non-malignant conditions often experience significant symptom burden. Therefore, overcoming barriers to interprofessional collaboration between general practitioners (GPs) and specialist palliative home care (SPHC) teams is essential to facilitate the timely integration of palliative care elements. The KOPAL trial aimed to examine the impact of case conferences between GPs and SPHC teams on symptom burden and pain in patients with advanced chronic heart failure, chronic obstructive pulmonary disease, and dementia.

SGLT2-Inhibition in Patients With Alport Syndrome.

Introduction: Large-scale trials showed positive outcomes of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in adults with chronic kidney disease (CKD). Whether the use of SGLT2i is safe and effective in patients with the common hereditary CKD Alport syndrome (AS) has not yet been investigated specifically in larger cohorts.

Methods: This observational, multicenter, international study (NCT02378805) assessed 112 patients with AS after start of SGLT2i.

[Structured triage in the emergency department via intelligent assistant service OPTINOFA : Results of a multicenter, cluster-randomized and controlled interventional study in Germany].

In Germany, a substantial reform of emergency care is strictly recommended. Regulation of patient flows into the ambulatory and stationary sectors remains a major issue.In the OPTINOFA project funded by Innovationsfunds, a new triage system was developed for a structured primary evaluation of both urgency and care level of emergency cases.

Treatment effect modifiers of immunotherapies for relapsing-remitting multiple sclerosis-A systematic review and meta-analysis.

Background: This meta-analysis aimed to assess the treatment effects of immunotherapies in subgroups of adults with clinically isolated syndrome or relapsing forms of multiple sclerosis (MS) and the effect of potential treatment effect modifiers (TEMs).

Methods: Phase 2 and 3 RCTs with a placebo comparator were analyzed. Risk of bias was assessed.

Statistical methods for clinical trials interrupted by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic: A review.

Cancellation or delay of non-essential medical interventions, limitation of face-to-face assessments or outpatient attendance due to lockdown restrictions, illness or fear of hospital or healthcare centre visits, and halting of research to allow diversion of healthcare resources to focus on the pandemic led to the interruption of many clinical trials during the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic. Appropriate analysis approaches are now required for these interrupted trials. In trials with long follow-up and longitudinal outcomes, data may be available on early outcomes for many patients for whom final, primary outcome data were not observed.

Safety, tolerability, and efficacy of fasudil in amyotrophic lateral sclerosis (ROCK-ALS): a phase 2, randomised, double-blind, placebo-controlled trial.

Background: Fasudil is a small molecule inhibitor of Rho-associated kinase (ROCK) and is approved for the treatment of subarachnoid haemorrhage. In preclinical studies, fasudil has been shown to attenuate neurodegeneration, modulate neuroinflammation, and foster axonal regeneration. We aimed to investigate the safety, tolerability, and efficacy of fasudil in patients with amyotrophic lateral sclerosis.

Stakeholders' Perspectives on Current Issues in Data Monitoring Committees.

Data Monitoring Committees (DMCs) are groups of experts that review accumulating data from one or more ongoing clinical studies and advise the Sponsor regarding the continuing safety of study subjects along with the continuing validity and scientific merit of the study. Although DMCs are widely used, considerable variability exists in their conduct. This paper offers recommendations, derived from sessions given at the 2023 Central European Network International Biometric and Statisticians in the Pharmaceutical Industry Conferences' and the authors' experiences.

Adherence-enhancing interventions for pharmacological and oxygen therapy in patients with COPD: a systematic review and component network meta-analyses.

Introduction: Adherence to COPD management strategies is complex, and it is unclear which intervention may enhance it.

Objectives: We aim to evaluate the effectiveness of adherence-enhancing interventions, alone or compared to interventions, for patients with COPD.

Methods: This review comprises a component network meta-analysis with a structured narrative synthesis.

Investigating the Heterogeneity of "Study Twins".

Meta-analyses are commonly performed based on random-effects models, while in certain cases one might also argue in favor of a common-effect model. One such case may be given by the example of two "study twins" that are performed according to a common (or at least very similar) protocol. Here we investigate the particular case of meta-analysis of a pair of studies, for example, summarizing the results of two confirmatory clinical trials in phase III of a clinical development program.