Istore: a project on innovative statistical methodologies to improve rare diseases clinical trials in limited populations

Orphanet Journal of Rare Diseases, vol. 19, pp. 96

Abstract

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 project, its ambitions, and its methodological approaches. METHODS: In very small populations, methodological challenges exacerbate. iSTORE's ambition is to develop a comprehensive perspective on natural history course modelling through multiple endpoint methodologies, subgroup similarity identification, and improving level of evidence. RESULTS: The methodological approaches cover methods for sound scientific modeling of natural history course data, showing similarity between subgroups, defining, and analyzing multiple endpoints and quantifying the level of evidence in multiple endpoint trials that are often hampered by bias. CONCLUSION: Through its expected results, iSTORE will contribute to the rare diseases research field by providing an approach to better inform about and thus being able to plan a clinical trial. The methodological derivations can be synchronized and transferability will be outlined.

Authors 11

1. Stefanie Schoenen Aachen Institute of Medical Statistics

   RWTH Aachen University

   Affiliation as printed

   Institute of Medical Statistics, RWTH Aachen University, Pauwelsstrasse 19, 52074, Aachen, Germany

2. Johan Verbeeck

   Hasselt University

   Affiliation as printed

   I-BioStat, Data Science Institute, Hasselt University, Martelarenlaan 42, 3500, Hasselt, Belgium

3. Lukas Koletzko

   Ruhr University Bochum

   Affiliation as printed

   Institute of Statistics, Ruhr-University Bochum, Universitätsstraße 150, 44801, Bochum, Germany

4. Isabella Brambilla

   University of Verona

   Affiliation as printed

   Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Research Center for Pediatric Epilepsies, University of Verona, Via S. Francesco, 22, 37129, Verona, Italy

   Dravet Italia Onlus - European Patient Advocacy Group (ePAG) EpiCARE, 37100, Verona, Italy

   Dravet Italia Onlus – European Patient Advocacy Group (ePAG) EpiCARE, 37100, Verona, Italy

5. Mathieu Kuchenbuch

   Hôpital Necker-Enfants Malades · Institut Necker Enfants Malades · Institut des Maladies Génétiques Imagine

   Affiliation as printed

   Institut des Maladies Gènètiques Imagine-Necker Enfants malades Hospital, 24 Boulevard du Montparnasse, 75015, Paris, France

   Necker Enfants malades Hospital, 149 Rue de Sèvre, 75015, Paris, France

6. Maya Dirani

   Hôpital Necker-Enfants Malades · Institut Necker Enfants Malades · Institut des Maladies Génétiques Imagine

   Affiliation as printed

   Institut des Maladies Gènètiques Imagine-Necker Enfants malades Hospital, 24 Boulevard du Montparnasse, 75015, Paris, France

   Necker Enfants malades Hospital, 149 Rue de Sèvre, 75015, Paris, France

7. Georg Zimmermann

   Paracelsus Medical University

   Affiliation as printed

   Team Biostatistics and Big Medical Data, IDA Lab Salzburg, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria

8. Holger Dette

   Ruhr University Bochum

   Affiliation as printed

   Institute of Statistics, Ruhr-University Bochum, Universitätsstraße 150, 44801, Bochum, Germany

9. R.-D Hilgers corresponding Aachen Institute of Medical Statistics

   RWTH Aachen University

   Affiliation as printed

   Institute of Medical Statistics, RWTH Aachen University, Pauwelsstrasse 19, 52074, Aachen, Germany. rhilgers@ukaachen.de

   Institute of Medical Statistics, RWTH Aachen University, Pauwelsstrasse 19, 52074, Aachen, Germany

10. Geert Molenberghs

    Hasselt University · KU Leuven

    Affiliation as printed

    I-BioStat, Data Science Institute, Hasselt University, Martelarenlaan 42, 3500, Hasselt, Belgium

    I-BioStat, KU Leuven, Kapucijnenvoer 35, 3000, Leuven, Belgium

11. Rima Nabbout

    Hôpital Necker-Enfants Malades · Institut Necker Enfants Malades · Institut des Maladies Génétiques Imagine

    Affiliation as printed

    Institut des Maladies Gènètiques Imagine-Necker Enfants malades Hospital, 24 Boulevard du Montparnasse, 75015, Paris, France

    Necker Enfants malades Hospital, 149 Rue de Sèvre, 75015, Paris, France