Down syndrome (DS) is the most common genetic cause of intellectual and developmental disabilities (IDD) and results in most individuals from triplication of the smallest human autosome, chromosome 21 (Trisomy 21). DS affects individuals of all ethnic and ancestral groups, and its birth prevalence in the U.S. population is about 1:691 live births (http://www.cdc.gov/ncbddd/birthdefects/data.html
]. Although many people have discussed the creation of contact registries, research databases, and biobanks to speed the pace of discovery in DS research, the great expansion of technology and private investment in research in the past ten years has renewed considerable interest in these resources among families, clinicians, advocates, and researchers who study DS. The purpose of this conference was to bring together all four communities to discuss the best strategies to enhance an increasing transition from basic and clinical research to clinical trials and rational translational therapeutic approaches to ameliorate the effects of DS in individuals of all ages, ancestry, and socioeconomic status. In part, the mechanism chosen was to provide the DS community with examples of existing successful models of registries, databases, and biobanks, as these do not exist at a national level for people with DS. This need for research resources was made apparent by the objectives of the NIH Research Plan on Down Syndrome published in 2007 (http://www.nichd.nih.gov/publications/pubs_details.cfm?from=&pubs_id=5695
This 2-day conference was sponsored jointly by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health (NIH), and the Global Down Syndrome Foundation (GDSF)/Linda Crnic Institute for Down Syndrome and held in Bethesda, MD. The focus of this conference was to discuss three types of organized support for research: contact registries, research databases, and biobanks. Contact registries often are formed and maintained by organizations and researchers to facilitate participation by individuals in research projects or clinical trials. Often one significant outcome of a contact registry is to facilitate communication among families and self-advocates who share information about their condition with one another. Research databases are created by researchers and clinicians as outcomes of specific projects that have a defined question or to gather standardized longitudinal information about the natural history of a given condition. Biobanks consist of repositories of samples of tissues, organs, or fluids collected from individual donors during life or by donation after death.
The birth prevalence of DS has demonstrated some increase in the past several decades in Western countries, most likely related to the increase in maternal age [2
]. In addition, the number of newborns with DS who survive infancy and childhood with DS has also increased greatly. Overall, people with DS live longer, enjoy better quality of life, and integrate as productive members of the workforce of many societies around the world [3
The meeting began with welcoming remarks from Dr. Yvonne Maddox (NICHD) and Dr. Edward McCabe (Linda Crnic Institute for Down Syndrome). The question presented to the group at large was not whether, but how best, to create a contact registry, a research database, and a biobank to facilitate DS research and treatment. Attendees were encouraged to plan for a future that would advance DS research and improve the lives of individuals with DS and their families.
Two speakers then presented their experiences with issues relevant to the creation of registries that encourage participant involvement in research activities. Dr. Sonja Rasmussen (Centers for Disease Control and Prevention (CDC)) provided the CDC perspective on the use of surveillance data to inform public health action [6
]. Surveillance is crucial to CDC's activities because it defines the magnitude of specific health problems and their risk factors and creates a source of participants for future studies, but there can be challenges in establishing a surveillance system for individuals with disabilities [7
], including those with DS. Health surveillance systems use a number of different study designs that must be balanced (e.g., few people with considerable individual data or more people with fewer data entries per person). These designs are most useful when they are population-based (that is, they consist of a representative sample of individuals selected from a defined population).
Surveillance registries may be population-based with active ascertainment and multiple data sources within the same geographic area for a single condition, like DS, or multiple conditions; or they may use hospital data from a multi-state area to monitor the health care received for a specific condition to lessen the incidence of premature death and disability resulting from that condition. Data from surveillance systems have allowed us to recognize that people with DS now live longer than in the 1980s, but racial disparities persist with regard to longevity [8
]. In addition, surveillance data have demonstrated that children with DS are more likely to receive a diagnosis of an autism spectrum disorder than children in the general population [10
Four key issues to consider when setting up a surveillance system for DS are: (1) the system of data collection, (2) the amount and type of data to collect, (3) how to manage and maintain the data, and (4) how to ensure patient confidentiality. Decisions on these key issues depend on the goals and objectives of the surveillance system.
Dr. Roger Reeves (Johns Hopkins University School of Medicine) and later in the day, Dr. Stephanie Sherman (Emory University), provided overviews of their participation in a September 2010 meeting on DS Registries sponsored by the National Down Syndrome Society (NDSS) in Washington, D.C. Dr. Reeves reported on two of the four breakout groups: Design and Governance & Ethics, with the other two being Stakeholder Engagement and Resources. Dr. Sherman provided additional details from the discussion of the Design group.
The Design workgroup's overall design philosophy was tripartite: to build trust, to be transparent, and to begin small and build with time. It recommended two goals to achieve by September 2012. The first was to implement a simple version of a national DS contact registry and begin its pilot-testing. Implementing the registry would involve developing content, data control guidelines, governance, and marketing, as well as potential strategies for achieving these. The registry could contain information such as contact information, availability for clinical research projects and basic demographics to determine eligibility. Of three possible methods of data entry, curation, and storage discussed, all require data verification but vary based on the process of data entry. For effective marketing of the registry to prospective registrants, people with DS and their families must understand the importance and potential risks of the registry. Successful marketing to scientists and clinicians requires that the registry have scientific credibility. Governance is necessary to ensure the equitable use of data for approved projects and to maintain transparency. A steering or executive committee would manage overarching concerns, such as finances, administration, marketing, and data access, and a project review committee would review project applications and allow access to the registry.
The Design workgroup recommended a second goal for the upcoming year: to initiate a Down Syndrome Centers of Excellence Clinical Consortium that would incorporate clinicians and researchers. Activities for the first year should focus on specifying the consortium's goals, infrastructure, membership, and other basic characteristics.
One needs to confirm parents' and self-advocates' interest in a registry before moving forward. Since a registry has the potential to be misused or administered incorrectly, care must be taken in its creation. A “graduated functions” model for the registry, which would allow for baseline functionality and the addition of more complexity as needed, might be useful for building consensus while creating a registry of sufficient functionality. The platform chosen for a registry should serve the multiple needs of clinicians and investigators as well as those of all users.
The Governance & Ethics workgroup highlighted some of the topics that must be considered when creating a registry. These include informed consent procedures, especially for individuals who will be brought into the national registry from another registry; rules for access; and data/information ownership. This committee also emphasized that every interaction connected to the registry will require some level of governance. This group agreed to continue to work on developing basic demographic elements that should be collected in such a DS registry.