Challenges for academic investigator-initiated pediatric trials for rare diseases

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.

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.

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.

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).

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.