Ralf-Dieter Hilgers

• Professor Dr. rer. nat.
• Head of Department at RWTH Aachen University

Background The European Joint Programme on Rare Diseases aims to enhance the rare diseases research ecosystem by bringing together stakeholders such as research funders, institutions and patient organizations. Work Package 20 focuses on the validation, use and development of innovative methodologies for rare disease clinical trials. This paper repo...

Background In clinical research, the most appropriate way to assess the effect of an intervention is to conduct a randomized controlled trial (RCT). In the field of rare diseases, conducting an RCT is challenging, resulting in a low rate of clinical trials, with a high frequency of early termination and unpublished trials. The aim of the EPISTOP tr...

Background Considering multiple endpoints in clinical trials provide a more comprehensive understanding of treatment effects and may lead to increased power or reduced sample size, which may be beneficial in rare diseases. Besides the small sample sizes, allocation bias is an issue that affects the validity of these trials. We investigate the impac...

Purpose In the context of clinical research, there is an increasing need for new study designs that help to incorporate already available data. With the help of historical controls, the existing information can be utilized to support the new study design, but of course, inclusion also carries the risk of bias in the study results. Methods To combi...

Background The conduct of rare disease clinical trials is still hampered by methodological problems. The number of patients suffering from a rare condition is variable, but may be very small and unfortunately statistical problems for small and finite populations have received less consideration. This paper describes the outline of the iSTORE projec...

When data is derived under a single or multiple lower limits of quantification (LLOQ), estimation of distribution parameters as well as precision of these estimates appear to be challenging, as the way to account for unquantifiable observations due to LLOQs needs particular attention. The aim of this investigation is to characterize the precision o...

Background When assessing the efficacy of a treatment in any clinical trial, it is recommended by the International Conference on Harmonisation to select a single meaningful endpoint. However, a single endpoint is often not sufficient to reflect the full clinical benefit of a treatment in multifaceted diseases, which is often the case in rare disea...

Background: A tele-emergency medical service with a remote emergency physician for severe prehospital emergencies may overcome the increasing number of emergency calls and shortage of emergency medical service providers. We analysed whether routine use of a tele-emergency medical service is non-inferior to a conventional physician-based one in the...

Methods: An online survey by the Randomization Working Group in 2022 collecting experiences and perceptions on randomization. Results: Of 145 unique respondents, 137 (94.5%) identified themselves as statisticians. The majority of respondents were from academia and pharmaceutical companies. Permuted block randomization, with or without stratificatio...

Aim: To evaluate general shortcomings and faculty-specific pitfalls as well as to improve antibiotic prescription quality (ABQ) in non-ICU wards, we performed a prospective cluster trial. Methods: An infectious-disease (ID) consulting service performed a prospective investigation consisting of three 12-week phases with point prevalence evaluatio...

Objective: The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcome...

Study design A randomized, controlled, prospective multicenter clinical trial with a parallel group design was initiated in eight surgical centers to compare a large-pore polypropylene mesh (Ultrapro ® ) to a small-pore polypropylene mesh (Premilene ® ) within a standardized retromuscular meshplasty for incisional hernia repair. Methods Between 20...

Objective: The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes...

Background Cardiovascular calcifications are prevented by matrix Gla protein (MGP), a vitamin K-dependent protein. Hemodialysis patients exhibit marked vitamin K deficiency. The randomized, prospective, open-label, multicenter VitaVasK trial analyzed whether vitamin K1 supplementation reduces progression of coronary artery calcifications (CAC) and...

The objective of this prospective randomized controlled single-center clinical trial was to prove the efficacy of adjunctive photobiomodulation in improving selected outcomes following the use of laterally closed tunnel technique for the management of isolated gingival recession. Nineteen participants (with isolated gingival recession) each treated...

OBJECTIVES: The aim of this study was to describe the 30-day mortality rate of patients aged 80 years and older undergoing surgical and nonsurgical procedures under anaesthesia in Europe and to identify risk factors associated with mortality. DESIGN: A prospective cohort study. SETTING: European multicentre study, performed from October 2017 to Dec...

BACKGROUND: Recent guidelines suggest that benzodiazepine premedication should be avoided in elderly patients, though with limited supporting evidence. OBJECTIVE: We conducted a secondary analysis of the POSE data to explore the association of premedication in patients aged 80 years or older with 30-day mortality. DESIGN: We used propensity score m...

Nasopharyngeal carcinoma (NPC) in children and young adults has been treated within two consecutive prospective trials in Germany, the NPC-91 and the NPC-2003 study of the German Society of Pediatric Oncology and Hematology (GPOH). In these studies, multimodal treatment with induction chemotherapy, followed by radio (chemo)therapy and interferon-be...

Background Randomization is the foundation of any clinical trial involving treatment comparison. It helps mitigate selection bias, promotes similarity of treatment groups with respect to important known and unknown confounders, and contributes to the validity of statistical tests. Various restricted randomization procedures with different probabili...

The susceptibility of a clinical trial to allocation bias is related to the randomization procedure used to allocate patients to treatments. Consequently, the choice of a suitable randomization procedure is a crucial part of the trial design. For the unweighted log-rank test with proportional hazards, a trial-specific evaluation model for the selec...

Background and aims: Wilson disease (WD) is an autosomal recessive disorder caused by ATP7B gene mutations leading to pathologic accumulation of copper in the liver and brain. Adoption of initial treatments for WD was based on empiric observations. These therapies are effective, but there are still are unmet needs for which new treatment modalitie...

Objective To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of replication factor complex subunit 1 (RFC1) repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular are-flexia syndrome (CANVAS). Methods Multimodal RFC1 repeat scr...

Background The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's atax...

Objective To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of RFC1-repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Methods Multimodal RFC1 repeat screening (PCR, southern blot, whole-exome...

Background: Randomization is the foundation of any clinical trial involving treatment comparison. It helps mitigate selection bias, promotes similarity of treatment groups with respect to important known and unknown confounders, and contributes to the validity of statistical tests. Various restricted randomization procedures with different probabil...

Purpose The aim of this quantitative study was to compare between a dual-wavelength laser (Er,Cr:YSGG, diode 940 nm) to the XP-Endoshaper/finisher combined with ethylenediaminetetraacetic acid (EDTA) 17% technique in removing secondary smear layer created during endodontic retreatment of curved canals. Methods Twenty-four human curved root canals...

Background Inhibitors of the renin-angiotensin system (RAS) are cornerstones of supportive therapy in patients with IgA nephropathy (IgAN). We analyzed the effects of single versus dual RAS blockaQueryde during our randomized STOP-IgAN trial.MethodsSTOP-IgAN participants with available successive information on their RAS treatment regimen and renal...

[This corrects the article DOI: 10.18632/oncotarget.27303.].

PurposeThe primary aim was to investigate the surface roughness parameters (Rp in μm) in four different implants types after dual-wavelength (2780-nm Er,Cr:YSGG and 940-nm diode) laser irradiation. The secondary aim was to investigate which factors influence the morphological modifications.Methods Twenty-four implants were used in this study; six C...

The randomized, controlled STOP-IgAN trial in patients with IgA nephropathy (IgAN) and substantial proteinuria showed no benefit of immunosuppression added on top of supportive care on renal function over three years. As a follow-up we evaluated renal outcomes in patients over a follow-up of up to ten years in terms of serum creatinine, proteinuria...

Objective: To validate the capability of the dual wavelength laser (Er,Cr:YSGG and diode 940 nm) and the XP-Endoshaper and finisher in removing the smear layer from curved canals. Methods: Forty curved root canals were prepared using the R25 file of the Reciproc® system. The teeth were randomly divided into five groups: G1: negative control irriga...

Introduction Currently, no treatment that delays with the progression of Friedreich ataxia is available. In the majority of patients Friedreich ataxia is caused by homozygous pathological expansion of GAA repeats in the first intron of the FXN gene. Nicotinamide acts as a histone deacetylase inhibitor. Dose escalation studies have shown, that short...

Objective This study aimed to investigate the surface roughness parameters (Rp in μm) of zirconia implants (TAVDental) after erbium YAG (LiteTouchTM) laser irradiation. Material and methods Implants were randomized into two groups according to the laser irradiation parameters (1.5 W/10 Hz and 1.5 W/30 Hz). The surface topography of each implant wa...

Introduction: Mammography is the gold standard for early breast cancer detection, but shows important limitations. Blood-based approaches on basis of cell-free DNA (cfDNA) provide minimally invasive screening tools to characterize epigenetic alterations of tumor suppressor genes and could serve as a liquid biopsy, complementing mammography. Metho...

Objective: This study aimed to investigate the temperature changes and question the safe laser settings and protocols for laser-assisted peri-implantitis treatment in an in vitro environment. Materials and methods: Three types of implants (Neoss, Dentegris, and Camlog) were implanted in an artificial bone model (n = 15). The model was placed into...

The random allocation of patients to treatments is a crucial step in the design and conduct of a randomized controlled trial. For this purpose, a variety of randomization procedures is available. In the case of imperfect blinding, the extent to which a randomization procedure forces balanced group sizes throughout the allocation process affects the...

Background: Among various design aspects, the choice of randomization procedure have to be agreed on, when planning a clinical trial stratified by center. The aim of the paper is to present a methodological approach to evaluate whether a randomization procedure mitigates the impact of bias on the test decision in clinical trial stratified by cente...