Studies & Statistics for Integrated Research and Projects
Prof. Ruth Ladenstein, MD, MBA, cPM
Head of the Clinical Trials Unit S²IRP
Coordinator of the European Reference Network ERN-PaedCan
Therapy Optimisation Studies (TOS) to guarantee better chances of survival of children and adolescents with cancer.
The Clinical Trial Unit for Studies & Statistics for Integrated Research & Projects (S2IRP) is an important link between the CCRI laboratory research activities and the clinical application of trials at the St. Anna Children’s Hospital. Essentially, S2IRP fosters clinical research in paediatric oncology by coordinating and facilitating international clinical trials.
Within the CCRI, the S2IRP is the centre of excellence for clinical studies and statistics. The S2IRP acts as the study centre for prospective clinical trials aiming to optimise therapies according to EU directives and the Austrian Pharmaceuticals Act (AMG). In addition, by running specific projects various international cooperations are maintained. The skilled multidisciplinary team and personnel resources enable the preparation, coordination and quality-control of TOS. This allows verification of the results and implementation of innovative stratifying diagnostics to optimise risk-adapted treatments.
For more information about our Clinical Trial Unit please visit the S2IRP section.
European Reference Networks (ERNs) represent an ambitious initiative from the European Commission, which is funded under its 3rd Health Programme. ERNs are virtual networks involving healthcare providers across Europe. They aim to facilitate discussion on complex or rare diseases and conditions that require highly specialised treatment, and concentrated knowledge and resources. The ERN initiative is mainly driven by EU countries. The Board of Member States is the formal body in charge of the approval and termination of networks and memberships as provided in the Commission's Implementing Decision. The Board is comprised of representatives of the 28 EU countries and the EEA countries.
To review a patient’s diagnosis and treatment, ERN coordinators will convene a “virtual” advisory board of medical specialists across different disciplines, using a dedicated IT platform and telemedicine tools. This way it is the medical knowledge and expertise that travel rather than the patients, who have the comfort of staying in their supportive home environments.
The first 24 ERNs were launched in 2017, involving more than 900 highly-specialised healthcare units from over 300 hospitals in 26 Member States. Prof Ruth Ladenstein is the coordinator of the European Reference Network on Paediatric Cancer (ERN-PaedCan), which aims at reducing inequalities in childhood cancer survival by providing high-quality, accessible and cost-effective cross-border healthcare to children and adolescents with cancer, regardless of where they live.
Ladenstein R, Pötschger U, Pearson ADJ, Brock P, Luksch R, Castel V, Yaniv I, Papadakis V, Laureys G, Malis J, Balwierz W, Ruud E, Kogner P, Schroeder H, de Lacerda AF, Beck-Popovic M, Bician P, Garami M, Trahair T, Canete A, Ambros PF, Holmes K, Gaze M, Schreier G, Garaventa A, Vassal G, Michon J, Valteau-Couanet D; SIOP Europe Neuroblastoma Group (SIOPEN) (2017).
Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial.
Viprey V, Gregory WM, Corrias MV, Tchirkov A, Swerts K, Vicha A, Dallorso S, Brock P, Luksch R, Valteau-Couanet D, Papadakis V, Laureys G, Schreier G, Pearson AD, Ladenstein R, Burchill S (2014)
Neuroblastoma mRNAs predict outcome in children with stage 4 neuroblastoma: a European HR-NBL1/SIOPEN study.
J Clin Oncol. 2014 Apr 1;32(10):1074-83.
Ladenstein R, Weixler S, Garaventa A, Baykan B, Bleeke M, Kunert R, Katinger D, Pribill I, Glander P, Bauer S , Pistoia V, Michon J, Lode HN (2013)
Ch14.18 Antibody Produced in CHO Cells in Relapsed or Refractory Stage 4 Neuroblastoma Patients: A SIOPEN Phase 1 Study.
Landesbioscience mAbs. 5(5):801-9
Ladenstein R, Pötschger U, Siabalis D, Garaventa A, Bergeron C, Lewis IJ, Stein J, Kohler J, Shaw PJ, Holter W, Pistoia V, Michon J. (2011)
A dose finding study for the effective use of subcutaneous rIL-2 in an outpatient setting for stage 4 neuroblastoma after megatherapy and autologous stem cell reinfusion.
J Clin Oncol. 29(4):441-8.
Ladenstein R, Valteau-Couanet D, Brock P, Yaniv I, Castel V, Laureys G, Malis J, Papadakis V, Lacerda A, Ruud E, Kogner P, Garami M, Balwierz W, Schroeder H, Beck-Popovic M, Schreier G, Machin D, Pötschger U, Pearson A. (2010)
Randomized Trial of Prophylactic Granulocyte Colony-Stimulating Factor During Rapid COJEC Induction in Pediatric Patients With High-Risk Neuroblastoma: The European HR-NBL1/SIOPEN Study.
J Clin Oncol. 28(21):3516-24
Ladenstein R, Pötschger U, Le Deley MC, Whelan J, Paulussen M, Oberlin O, van den Berg H, Dirksen U, Hjorth L, Michon J, Lewis I, Craft A and Jürgens H. (2010)
Primary Disseminated Multifocal Ewing Sarcoma: Results of the Euro-EWING 99 Trial.
J Clin Oncol. 201:28(21):3284-91.
Clinical trial protocols for publication
Amendment 4 HRNBL1 Protocol
Senior Operational Manager: Sonja Schneider-Schwarz, PhD
Scientific Assistant, Scientific Assistant*: Claudia Zeiner, MSc
Statisticians: Evgenia Glogova, MSc, junior statistician l Helga Björk Arnadottir, MSc, data manager and junior statistician (maternal leave) l Andrea Madunic, data manager and junior statistician l Ulrike Pötschger, MSc, senior statistician
Leukaemia and Lymphoma Studies
Corinne Grafl, CRA l Saelde Baumgartner, BSc, CRA l Nora Mühlegger, MSc, CRA l Marek Nykiel, CRA l Assoc. Prof. Georg Mann, MD, CC** (ALL and Lymphoma Studies) l Assoc. Prof. Andishe Attarbashi, MD, CC (ALL and Lymphoma Studies) l Assoc. Prof. Michael Dworzak, MD, CC (AML, MDS, CML Studies)
Studies in Solid Tumours
Markus Mair, PhD, CRA l Eva Sorz, CRA l Ingrid Pribill, PhD, CRA l Dasa Janousek, MSc, CRA l Marion Sebek, CRA, Dagmar Friede, PhD, CRA Assoc. Prof. Ruth Ladenstein, MD, MBA, cPM, CC (Neuroblastoma, Soft Tissue Tumours, Ewing Sarcoma) l Assoc. Prof. Leo Kager, MD, CC (Osteosarcoma, Nephroblastoma)
Elfriede Thiem, MS, CRA l Prof. Milen Minkov, MD, CC
Stem Cell Transplantation Studies
Tijana Frank, MD, CRA l Susanne Karlhuber, PhD, CRA l Barbara Kristufek, CRA l Assoc. Prof. Susanne Matthes-Martin, MD, CC (Allogene Stem Cell Transplantation) l Prof. Christina Peters, MD, CC (Allogene Stem Cell Transplantation) l Assoc. Prof. Ruth Ladenstein, MD, MBA, cPM, CC (Autologous Stem Cell Transplantation)
Phase I/II/III Studies Sponsored by the Pharmaceutical Industry
Assoc. Prof. Michael Dworzak, MD, CC l Assoc. Prof. Ruth Ladenstein, MD, MBA, cPM l Prof. Christina Peters, MD, CC
*CRA: Research and Study Assistant
**CC: Clinical Studies Leader and Collaborator
About the Clinical Trials Unit S²IRP
Collecting and evaluating patient data is of utmost importance for clinical trials.
In total, the S2IRP has registered data from more than 9,000 patients. International studies focus on the fields of Langerhans’ cell histiocytosis (study centre of LCH trials I, II, III), neuroblastoma (study centre of the European High Risk Neuroblastoma Study HR-NBL-1/SIOPEN) and the stem cell transplantation of acute lymphoblastic leukaemia (study centre of the international ALL-SCT Study).
Activities of the S2IRP/Coordinating Centre for paediatric-oncological trials.
The Clinical Trial Unit has been developed and trained towards the necessary expertise and manages the full scope of tasks as required according to GCP and European Directives as well as national legal requirements (AMG [Arzneimittelgesetz] - Austrian Pharmaceuticals Act). For more details, please visit the S2IRP section.
The European Network for Cancer Research in Children and Adolescents (ENCCA)
The Network of Excellence ENCCA is funded by the European Union’s 7th Framework Programme under the Health topic “Structuring clinical research in paediatric and adolescent oncology in Europe”.
Headed by Dr. Ruth Ladenstein, S2IRP plays a key role in the coordination of this consortium that comprises influent European research institutes and organisations recognised for their excellence in paediatric oncology that are dedicated to improve the treatment of children and adolescents suffering from cancer. Ultimately ENCCA aims at facilitating access to therapies and standards of care across Europe to reduce the existing gaps and limitations in paediatric oncology.
O.K.ids A Project on the Political Agenda
An Austrian Network Application to the Austrian Ministry of Health There is a political agenda to raise awareness for the clinical research components for all the respective Paediatric Oncology tasks and research areas in public and there are ongoing efforts to enhance visibility and recognition of these fields in Austria also vis-à-vis universities and Ministries of Health & Science. Close collaborations with the Competent Authorities (AGES) and the Ministry of Health are ongoing.
The primary aim of the O.K.ids project application in 2008 was to fund basic Clinical Trial Unit structures in 5 centres in Austria to cope with requirements of competent authorities and to foster drug development and approval of medicines for children and adolescents. S2IRP was proposed as major Network Coordination Unit. These efforts were driven by the vision to support solutions to overcome off-label and off-licence use in clinical trials for children and adolescents and hence to reduce administrative burden in the future.
A project handbook was written on request of the Austrian Ministry of Health. However, so far the paediatric network has not achieved government support and funding. Political negotiations and working groups ongoing (AGES - Kindergesundheitsdialog). In addition, the commitment in “Politische Kindermedizin” in Austria and problems were summarised in a book chapter for reference in more details.
EHN (EuroHistioNet) Consortium
EuroHistioNet was funded by the Public European Health Agency (PEHA) under the 6th EU Framework Programme (FP6) and coordinated by the Public Assistance - Hospitals of Paris. This reference network for Langerhans Cell Histiocytosis and associated syndromes has been brought up to join efforts in increasing the knowledge of the disease, improving quantity and quality of knowledge exchange, producing guidelines and setting up an international data base. Any newly acquired information will be distributed by a web portal for LCH professionals, doctors and patients at www.eurohistio.net.