Overview of the Registry

Introduction
Patient Eligibility
Design
Institutional Review Board/Ethics Committee Review
Patient Authorization
Patient Discontinuation
Data Collection and Submission
Quality Assurance of Data
Statistical Methods and Data Reporting

Introduction
The Fabry Registry is an ongoing, observational database that tracks the natural history and outcomes of patients with Fabry disease. All Fabry patients are eligible for enrollment irrespective of their enzyme replacement therapy (ERT) status, and all physicians managing patients with Fabry disease are encouraged to participate in the Fabry Registry.

The Fabry Registry is a global outcomes assessment and disease management program that compiles patient outcomes data from routine clinical practice to provide the medical community with resources to help optimize patient care.

Physicians are encouraged to collaborate, share observations, and generate hypotheses for evaluation, as well as assist in the collection of clinical data in an effort to guide and assess future therapeutic interventions.

The primary objectives of the Fabry Registry are:

• To enhance the understanding of the variability, progression, and natural history of Fabry disease, including heterozygous females with the disease;
• To assist the Fabry medical community with the development of recommendations for monitoring patients and reports on patient outcomes to help optimize patient care;
• To characterize and describe the Fabry population as a whole; and
• To evaluate the long-term safety and effectiveness of Fabrazyme® (agalsidase beta)

Patient Eligibility

Inclusion Criteria
All patients with a confirmed diagnosis of Fabry disease are eligible for inclusion in the Fabry Registry. Confirmed diagnosis is defined as:

• a documented plasma or leukocyte α-galactosidase A (α-gal A) deficiency OR
• a documented α-gal A deficiency and/or mutation in the α-gal A gene in heterozygous females.

For all patients, appropriate patient authorization will be obtained.

Exclusion Criteria
There are no exclusion criteria for participation in the Fabry Registry. Participation does not exclude participation in other clinical studies.

Design
The Fabry Registry is an international multi-center, strictly observational program for patients with Fabry disease; no experimental intervention is involved. Thus, a patient will undergo clinical assessments and receive the standard of care as determined by the patient’s physician. The long-term program will proceed for a minimum of 15 years.

Institutional Review Board / Ethics Committee Review
The Fabry Registry protocol, sample patient authorization and relevant supporting information may be submitted to an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) for review and approval by the participating physician, in accordance with the physician’s institution’s policies. Since no experimental procedures are included in the protocol, approval of the Patient Authorization may be all that is required for expedited review by the committee chairperson.

Patient Authorization
For every patient, appropriate patient authorization will be obtained according to applicable national privacy regulations and other state and local laws relating to medical information before data are submitted to the Fabry Registry.

Patient Discontinuation
Patient participation is voluntary. A patient may decline to participate or withdraw consent at any time and without affecting their medical treatment.

Data Collection and Submission
The purpose of the Fabry Registry is to collect uniform and meaningful clinical data on patients with Fabry disease. Since, at the time of enrollment, patients will be at various stages in their disease course and medical care, the Fabry Registry is focused on collecting all assessments and clinical outcomes associated with the management of their disease. Thus, to promote data uniformity among all Fabry Registry patients, both retrospective and prospective data collection are encouraged and a standard set of case report forms (CRFs) will be utilized by participating physicians. View sample CRF. Data collection will focus on cardiac, renal, and cerebrovascular manifestations, as well as neurological (i.e. pain), quality of life, pregnancy outcomes and other clinical assessments that are routinely evaluated for patients with Fabry disease. The data collected by physicians or their designees are submitted to the Fabry Registry for central processing by Genzyme. Secure Internet technology and other electronic advancements will be utilized to enhance data collection, education, and reporting capabilities. Where secure Internet technology is not available, data are collected on paper CRFs. The data collected are maintained by Genzyme Corporation in an electronic database.

A primary Fabry Registry contact person located at the participating institution should be designated, and is responsible for completing and submitting the standard (or electronic) Fabry Registry CRFs. Refer to the Submit Data section for guidance on the data collection and submission process.

Quality Assurance of Data
Data collected through the Fabry Registry will be entered into a database and analyzed. Staff of the Genzyme Global Registry Programs will review the data for missing data points, incomplete information, and discrepancies with previously submitted data. If necessary, issues will be resolved with the site electronically, by telephone, FAX, or site visit. All data management and analysis will occur in a validated computing environment. However, Registry data are not verified against source documents, in contrast with clinical trials, where source verification is performed in accordance with Good Clinical Practice (GCP) guidelines.

Statistical Methods and Data Reporting
Data will be analyzed and reported periodically and upon individual requests from participating physicians. In addition, annual reports summarizing data from patients receiving Fabrazyme will be provided to appropriate regulatory authorities. Analyses will be performed using the SAS statistical software system. Data are summarized using descriptive statistics for patients enrolled in the Fabry Registry.

Refer to Data Reporting for a more detailed explanation of possible data reports and the process for requesting a report.