The history and accomplishments of the ICGG G aucher registry

The International Collaborative Gaucher Group (ICGG) Gaucher Registry (clinicaltrials.govNCT00358943) is the largest ongoing, longitudinal, international database in the world that tracks the clinical, demographic, genetic, biochemical, and therapeutic characteristics of patients with Gaucher disease globally, irrespective of disease severity, treatment status, or treatment choice.Launched in 1991, the governance and scientific direction of the Registry is provided by an international group of physician experts in Gaucher disease with operational support from Genzyme, a Sanofi company (Cambridge, MA).Here we describe the history and some representative accomplishments of the ICGG Gaucher Registry.Gaucher disease, a rare (approximately 1:70,000 live births), autosomal recessive lysosomal storage disorder (LSD) is caused by deficient acid bglucosidase (glucocerebrosidase) with accumulation of glucosylceramide (glucocerebroside) in tissue macrophages.Gaucher disease type 1, found in 90% of all patients with Gaucher disease worldwide, is differentiated from Gaucher disease type 2 and type 3 by the absence of early-onset neurological signs and symptoms.The clinical manifestations of the disease are variable and somewhat unpredictable.Patients may have a lengthy asymptomatic course with few signs of disease, or present at any age from childhood to late adulthood with combinations of thrombocytopenia, anemia, leukopenia, splenic and hepatic enlargement, skeletal disease (chronic bone pain, acute bone crises, defective bone mineralization, infarction, osteonecrosis, osteolysis, and pathological fractures), growth retardation, and decreased health-related quality of life [1].Until about 25 years ago, only non-specific palliative treatment (blood transfusion, splenectomy, orthopedic surgery) was available.The sole Gaucher disease registry was a 530-patient paper database compiled by Robert Lee [2].Despite a problem with selection bias favoring overtly symptomatic patients, the Lee Registry contributed important observations about risks of splenectomy and about concurrent malignancy in Gaucher disease type 1 patients and continues as a resource for follow-up of long-term outcomes and mortality analysis [3].In 1990, recognizing the rarity of Gaucher disease and the unmet needs of symptomatic patients, the U.S. Food and Drug Administration (FDA) approved mannose-terminated, human placental acid b-glucosidase intravenous infusion treatment for Gaucher disease (alglucerase, CeredaseV R , Genzyme, a Sanofi company) based on a 12-patient, non-randomized, open-label clinical trial, but contingent on the manufacturer's commitment to comprehensive post-marketing reporting of response outcomes and adverse events.Going beyond minimal compliance standards, Genzyme subsequently initiated the ICGG Gaucher Registry, which has since grown from an initial enrollment of 16 U.S. patients in 1991 to more than 6,000 Gaucher disease type 1, type 2, and type 3 patients, regardless of treatment status, from 62 countries (54,000 patient-years of data) [4].For a rare disease such as Gaucher disease, a disease registry format was very suitable for meeting the objectives of the founding committee of Genzyme team members and independent Gaucher disease experts: to enhance the understanding of the variability, progression, and natural history of Gaucher disease; to help optimize care by providing recommendations for monitoring patients and reports on patient outcomes; and to evaluate the short-, intermediate-and long-term effectiveness of treatment.Unlike clinical trials or treatment registries that have restricted eligibility requirements, disease registries can collect clinical information in larger, more heterogeneous populations [5,6].They are intended to collect observational longitudinal data from a "real world" setting, annotate phenotypes that define the natural history of chronic diseases in untreated patients, and provide context for evaluating therapeutic responses.Registries are useful for diseases affecting very small patient populations such as those with Gaucher disease (approximately 10,000 identified patients worldwide) and for analyzing sub-populations (e.g., children, pregnant women, patients with neuronopathic disease, or from a single country or region or with a specific genotype).With careful design and modern technology, registries can assure patient anonymity and confidentiality yet remain accessible for individual patient reports as well as queries and research projects.For more than 20 years, the ICGG Gaucher Registry has functioned as depicted above to increase scientific knowledge of Gaucher disease, to provide practical management guidance, and to positively impact patient care.With informed consent, all patients with Gaucher disease, regardless of treatment status or type of treatment, are eligible for inclusion.Registry benefits include generation of individual patient case reports (PCRs) that depict changes in the patient's condition and their current position relative to individualized treatment goals, assistance with data requests, queries and clinical questions, and inclusion at regional and national meetings.Participating physicians have full access to all their patient data and are encouraged to check and verify its accuracy.