title: Methodology of clinical research in rare diseases: development of a research program in juvenile neuronal ceroid lipofuscinosis (JNCL) via creation of a patient registry and collaboration with patient advocates.
abstract: BACKGROUND
  Juvenile neuronal ceroid lipofuscinosis (JNCL; Batten disease) is a rare, inherited, fatal lysosomal storage childhood disorder. True for many rare diseases, there are no treatments that impact the course of JNCL. The University of Rochester Batten Center's (URBC) mission is to find treatments to slow, halt, or prevent JNCL.
  
  
  OBJECTIVE
  Our initial objective was to develop clinical research infrastructure preparatory to clinical trials, establish a JNCL research cohort, construct a disease-specific clinical outcome measure, and validate a non-invasive diagnostic sampling method. The long-term objective is to design and implement JNCL clinical trials.
  
  
  METHODS
  The Unified Batten Disease Rating Scale (UBDRS) was developed. The Batten Disease Support and Research Association (BDSRA) referred participants; annual BDSRA meetings provided a mobile research setting for registry enrollment and UBDRS piloting. Neuropsychological examinations were performed, enabling external validation of the UBDRS. Buccal epithelial cell collection for genotyping was introduced. Telemedicine for remote UBDRS assessment was piloted.
  
  
  RESULTS
  The registry enrolled 198 families representing 237 children with NCL. The UBDRS was piloted, was validated and has been used to collect natural history data from 120 subjects. Funding and regulatory approval were obtained for a recently launched phase II clinical trial. Several additional lines of inquiry were reported.
  
  
  CONCLUSIONS
  The registry and BDSRA collaboration have enabled development of a clinical rating scale, natural history and neuropsychological studies, and genetic studies for disease confirmation. This work highlights an approach for preparatory natural history research and infrastructure development needed to facilitate efficient implementation of clinical trials in rare diseases.
authors.affiliation: University of Rochester, Rochester, NY 14642, USA. lisa.deblieck@chet.rochester.edu
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: de Blieck
authors.forename: Erika F
authors.initials: EF
authors.lastname: Augustine
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Marshall
authors.forename: Heather
authors.initials: H
authors.lastname: Adams
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cialone
authors.forename: Leon
authors.initials: L
authors.lastname: Dure
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Kwon
authors.forename: Nicole
authors.initials: N
authors.lastname: Newhouse
authors.forename: Katherine
authors.initials: K
authors.lastname: Rose
authors.forename: Paul G
authors.initials: PG
authors.lastname: Rothberg
authors.forename: Amy
authors.initials: A
authors.lastname: Vierhile
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Mink
mesh_terms: D035843:Biomedical Research / Q000379:methods*; D002986:Clinical Trials as Topic / Q000379:methods*; D003299:Cooperative Behavior; D005190:Family; D005838:Genotype; D006801:Humans; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000628:therapy*; D010344:Patient Advocacy; D018579:Patient Selection; D035583:Rare Diseases / Q000235:genetics / Q000628:therapy*; D012042:Registries; D017216:Telemedicine
keywords: BDSRA; Batten Disease Support and Research Association; Clinical trials; JNCL; Juvenile neuronal ceroid lipofuscinosis; NCL; NIH; National Institutes of Health; Patient advocacy; Patient registry; Rare disease; Subject recruitment; UBDRS; URBC; Unified Batten Disease Rating Scale; University of Rochester Batten Center; juvenile neuronal ceroid lipofuscinosis; neuronal ceroid lipofuscinosis