title: Challenges for academic investigator-initiated pediatric trials for rare diseases.
abstract: BACKGROUND
  Clinical trials require great effort, time, expertise, and money. For clinicians at university hospitals with their full work load of teaching and medical care, the planning of an investigator-initiated clinical trial seems almost unthinkable. Despite their expertise in distinct diseases, university clinicians lack the time necessary to organize the funding and to initiate and conduct Phase III clinical trials in adults or in children.
  
  
  OBJECTIVE
  We sought to determine whether the difficulties faced by a clinician conducting a pediatric clinical trial can be overcome by passionate motivation and external support.
  
  
  METHODS
  Critical aspects of the application process of the world's first clinical trial in children with the rare hereditary kidney disease Alport syndrome treated with an angiotensin-converting enzyme inhibitor (Early Prospective Therapy Trial to Delay Renal Failure in Children With Alport Syndrome [EARLY PRO-TECT Alport]; http://www.clinicaltrials.gov NCT01485978; EudraCT 2010-024300-10) are described.
  
  
  RESULTS
  The following crucial factors enabled the investigator to complete this trial: (1) support through clinical trial, biometrician, and regulatory experts (Institute for Applied Research and Clinical Studies [IFS], Göttingen, Germany); (2) advice from the university's ethics committee (University Medicine Göttingen, Göttingen, Germany); (3) public funding (€1 million from the German Federal Ministry of Education and Research); (4) support from the respective medical society, aiming at the resolution of an important clinical problem (German Society of Pediatric Nephrology); and (5) support from the investigator's university as the official sponsor of the trial, providing long-term commitment and covering financial risks (University Medical Center Göttingen, Göttingen, Germany).
  
  
  CONCLUSIONS
  The study could pave the way for approval of ramipril as a drug to treat children with Alport syndrome. Even though the study might not result in label changes, the EARLY PRO-TECT Alport trial provides the basis of an educational campaign to sensitize physicians, especially pediatricians, general practitioners, and nephrologists, to pay special attention to the early detection of kidney diseases in children, which could improve medical care for all children with kidney diseases.
authors: Institute for Applied Research and Clinical Trials GmbH, Georg August University Göttingen, Göttingen, Germany; Institute for Applied Research and Clinical Trials GmbH, Georg August University Göttingen, Göttingen, Germany.
authors: Raees
authors: R
authors: Ahmed
authors: Institute for Applied Research and Clinical Trials GmbH, Georg August University Göttingen, Göttingen, Germany; Institute for Applied Research and Clinical Trials GmbH, Georg August University Göttingen, Göttingen, Germany.
authors: Ulrike
authors: U
authors: Duerr
authors: Institute for Applied Research and Clinical Trials GmbH, Georg August University Göttingen, Göttingen, Germany.
authors: Karsten
authors: K
authors: Gavenis
authors: University Medical Center Göttingen, Institute of Medical Statistics, Göttingen, Germany.
authors: Reinhard
authors: R
authors: Hilgers
authors: University Medical Center Göttingen, Clinic for Nephrology and Rheumatology, Göttingen, Germany. Electronic address: gross.oliver@med.uni-goettingen.de.
authors: Oliver
authors: O
authors: Gross
mesh_terms: D000046:Academic Medical Centers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002648:Child; D017326:Clinical Trials, Phase III as Topic / Q000191:economics / Q000331:legislation & jurisprudence / Q000379:methods; D006801:Humans; D009394:Nephritis, Hereditary / Q000188:drug therapy*; D010820:Physicians; D017257:Ramipril / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril
keywords: COL4A5; European Alport Registry; hematuria; microalbuminuria; pediatric glomerulopathy; pediatric investigation; proteinuria; ramipril; renal failure