title: Reducing selection bias in case-control studies from rare disease registries.
abstract: BACKGROUND
  In clinical research of rare diseases, where small patient numbers and disease heterogeneity limit study design options, registries are a valuable resource for demographic and outcome information. However, in contrast to prospective, randomized clinical trials, the observational design of registries is prone to introduce selection bias and negatively impact the validity of data analyses. The objective of the study was to demonstrate the utility of case-control matching and the risk-set method in order to control bias in data from a rare disease registry. Data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry were used as an example.
  
  
  METHODS
  A case-control matching analysis using the risk-set method was conducted to identify two groups of patients with type 1 Gaucher disease in the ICGG Gaucher Registry: patients with avascular osteonecrosis (AVN) and those without AVN. The frequency distributions of gender, decade of birth, treatment status, and splenectomy status were presented for cases and controls before and after matching. Odds ratios (and 95% confidence intervals) were calculated for each variable before and after matching.
  
  
  RESULTS
  The application of case-control matching methodology results in cohorts of cases (i.e., patients with AVN) and controls (i.e., patients without AVN) who have comparable distributions for four common parameters used in subject selection: gender, year of birth (age), treatment status, and splenectomy status. Matching resulted in odds ratios of approximately 1.00, indicating no bias.
  
  
  CONCLUSIONS
  We demonstrated bias in case-control selection in subjects from a prototype rare disease registry and used case-control matching to minimize this bias. Therefore, this approach appears useful to study cohorts of heterogeneous patients in rare disease registries.
authors.affiliation: Biomedical Data Sciences and Informatics, Genzyme, a Sanofi Company, 500 Kendall Street, Cambridge, MA 02142, USA.
authors.forename: J Alexander
authors.initials: JA
authors.lastname: Cole
authors.forename: John S
authors.initials: JS
authors.lastname: Taylor
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Hangartner
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Weinreb
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Mistry
authors.forename: Aneal
authors.initials: A
authors.lastname: Khan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003299:Cooperative Behavior; D005260:Female; D005776:Gaucher Disease / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D038622:Internationality; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010020:Osteonecrosis / Q000453:epidemiology* / Q000503:physiopathology; D018579:Patient Selection; D035583:Rare Diseases / Q000453:epidemiology* / Q000503:physiopathology; D012042:Registries; D012107:Research Design; D015983:Selection Bias; D055815:Young Adult