Reducing selection bias in case-control studies from rare disease registries

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.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.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.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.Rare diseases, exemplified by Gaucher disease, are defined as having a prevalence of fewer than 200,000 patients [1]. A major impediment to the study of these diseases is the scarcity of patients in any one city or country. Nevertheless, the global burden of patients affected by rare diseases is substantial: at least 30 million patients are estimated to suffer from one of the 7,000 rare diseases currently identified [2]. On average, each rare disease is estimated to afflict 4,200 patients [2]. Our search of the word 'registry' on clinicaltrials.gov as of 4 May 2011 identified