Case Example 29Data Collection Challenges in Rare Disease Registries

DescriptionFabry disease is a rare lysosomal storage disorder caused by deficiency of the enzyme α-galactosidase A. The Fabry Outcome Survey (FOS) was established in 2001 to increase understanding of the natural history of Fabry disease and assess patients’ response to enzyme replacement therapy with agalsidase alfa (Replagal®). Development and analysis of FOS data are driven by the participating physicians. An Executive Committee and International Board oversee the types of data collected and any changes required. In addition, a number of working groups (e.g., pediatric, renal, cardiac) are responsible for analyzing and improving data collection for their specialties.
SponsorShire HGT
Year Started2001
Year EndedOngoing
No. of Sites140 centers in 21 countries
No. of Patients1,795 patients


Rare disease registries such as the Fabry Outcome Survey face unique challenges in data collection and quality assurance. Because there are very few patients with the disease of interest, most participating physicians have only one to two patients in the registry. The registry is not part of their daily, or even weekly, practice, and many of the physicians have difficulty remembering what to collect for the registry and how to capture the data when they do see an eligible patient. The FOS registry is also a global project, and the standards of care for patients with a rare disease often differ among physicians and among countries. As a result, a laboratory value or other data element that is routinely captured at one site may not be readily available at another site, leading to missing data. Finally, FOS is a long-term registry, with no defined end date. As physicians learn more about the disease and new treatments become available, the registry must adapt and update its data collection tools. This creates a need for continual training with participating physicians.

Despite these challenges, it is essential that the registry collect high-quality data to fulfill its goal of increasing knowledge about Fabry disease. A recent major objective of the registry staff has been to improve collection and quality of the data, so as to provide a more robust dataset for analysis.

Proposed Solution

Beginning in 2006, three measures were implemented to improve the collection and quality of data: development of a core dataset to ensure evaluation of variables relevant to disease progression and the effect of treatment; increased concentration on centers that have enrolled 20 or more patients in FOS; and use of clinical projects associates to monitor data capture and quality.

The clinical projects associates are employees of the registry sponsor who generally have experience with clinical trial monitoring. For FOS, a clinical projects associate is typically assigned to a specific geographical area to serve as the contact person for the centers, examine centers’ data for inconsistencies, and help with training center staff. The registry staff developed guidelines for the clinical projects associates to use when examining the data for inconsistencies, with particular focus on core variables. The clinical projects associates visit the sites in person to examine the data and provide targeted training based on any inconsistencies that they may find. The data examination is not monitoring, as in a clinical trial, as there is no source validation. Instead, it is a review for logical inconsistencies and missing data.


A random sample (25 percent) of all enrolled patients was taken before and after the introduction of the above measures to assess their effectiveness. This sample consisted of 197 out of 815 patients enrolled in 2005, and 404 out of 1,616 patients enrolled in 2008.

Increases in data capture were found for 9 of the 10 core variables, the only exception being patient weight, which remained unchanged at 90 percent for both time points. Data capture increased from 66 percent to 83 percent for signs and symptoms, from 89 percent to 91 percent for serum creatinine, from 48 percent to 55 percent for left ventricular mass, and from 84 percent to 87 percent for NYHA (New York Heart Association) score. The proportion of females enrolled increased from 48 percent to 54 percent, which is more representative of the true Fabry population.

During 2008, results from three important patient subgroups were also analyzed: patients who had received agalsidase alfa treatment for at least 5 years, females who had received agalsidase alfa for at least 3 years, and children who had received agalsidase alfa for at least 2 years. Data capture from the core variables increased in all three subgroups during 2008; for example, data capture increased by 20 percent for proteinuria and by 19 percent for left ventricular mass in the 153 females who were available for evaluation.

Key Point

Periodic review of a random sample of data can provide important information on the quality of data in a registry. Due to the unique challenges facing rare disease registries, additional efforts may be necessary to improve data collection and data quality. These efforts may include site visits, ongoing training programs, and regular audits of the data for completeness. Because these efforts may require significant resources, it is important to conduct assessments of the effectiveness of the efforts and to alter the strategies as needed.

For More Information

  1. Mehta A, Beck M, Elliott P, et al. Enzyme replacement therapy with agalsidase alfa in patients with Fabry’s disease: an analysis of registry data. Lancet 2009;Dec 12;374(9706):1986-96. [PubMed: 19959221]
  2. Mehta A, Clarke JTR, Giugliani R. et al. Natural course of Fabry disease: changing pattern of causes of death in FOS - Fabry Outcome Survey. J Med Genet. 2009;46:548–52. [PubMed: 19473999]
  3. Feriozzi S, Schwarting A, Sunder-Plassmann G. et al. Agalsidase alfa slows the decline in renal function in patients with Fabry disease. Am J Nephrol. 2009;29:353–61. [PubMed: 18974635]
  4. Deegan PB, Baehner AF, Barba Romero M-Á. et al. Natural history of Fabry disease in females in the Fabry Outcome Survey. J Med Genet. 2006;43:347–52. [PMC free article: PMC2563231] [PubMed: 16227523]

From: Chapter 10, Data Collection and Quality Assurance

Cover of Registries for Evaluating Patient Outcomes: A User's Guide
Registries for Evaluating Patient Outcomes: A User's Guide. 2nd edition.
Gliklich RE, Dreyer NA, editors.

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