NIH Director Francis S. Collins, M.D., Ph.D., publicly announced the launch of the GTR as part of Rare Disease Day on February 29, 2012. Before this, NIH had gathered broad input from stakeholders such as laboratory test developers, manufacturers and heath care providers. This was of prime importance in the development of the GTR, and continued stakeholder interaction is viewed as indispensable to optimizing the utility of the registry. Materials relevant to this process are maintained on the website of the NIH Office of Biotechnology Activities and are accessible through the GTR home page (http://oba.od.nih.gov/GTR/gtr_intro.html
As part of the consultation process, NIH issued several requests for information and public comments, convened a public stakeholder meeting in November 2010 in conjunction with the annual meeting of the ASHG, and fulfilled the requirements by the Paperwork Reduction Act. Additional input was elicited at 19 meetings and teleconferences with stakeholders, 7 meetings of professional societies and from comments submitted through the GTR website.
Stakeholder input, in conjunction with guidance from the two GTR advisory groups, helped shape the GTR in several ways such as defining the scope of the registry, using a phased development approach, specifying the data elements and level of burden for providing these elements and determining the primary audience in the initial phase. Stakeholder input also helped NIH determine which data elements should be excluded from the initial phase of GTR such as test price, turn-around time and patent and licensing information.
During the construction of the GTR, NCBI’s team of usability experts, web developers and content experts conducted usability testing with leaders from ACMG, AMP, ASHG, NSGC, the National Coalition for Health Professional Education in Genetics, genetic counseling training program directors, laboratory associations and laboratory personnel with expertise in biochemical, cytogenetic, molecular and pharmacogenetic testing. The GTR advisory groups provide guidance about display and usability on an ongoing basis.
General features of the website
GTR makes extensive use of hyperlinks to guide users to related information within GTR, other NCBI databases and external sites. Filters are provided on pages listing search results to help users find tests of interest. Tooltips accessed by a ‘?’ icon (D) display the definition of specific fields and identify fields that are provided by submitters.
Test- and condition-specific pages feature a Discovery panel at the right (B) that includes links of interest to the condition. The Reviews section at the top facilitates retrieval of context-specific records from the medical and scientific literature and features PubMed search tools tailored to genetic content. The Practice Guidelines section links to publications by professional organizations and to drug labeling information at the National Library of Medicine’s DailyMed website (http://dailymed.nlm.nih.gov/dailymed/
). Concept-driven links to clinical, molecular and consumer resources are also provided. The juxtaposition of pertinent information enables GTR users to gauge the potential value of registered tests.
Home page and resource links
The GTR home page is the gateway to data, resources and information about GTR. Below the search bar, the left side of the page provides access to information about GTR (how to use the site, how to submit data, policy, structured feedback form, presentations schedule etc.). An extensive set of help documentation is available through the About GTR section, including how to search http://www.ncbi.nlm.nih.gov/gtr/docs/help/
, filter, set preferences using MyNCBI, find services, find all registered laboratories and tests, submit data and access the GTR Fact sheet, presentations archive and YouTube instructional videos.
The right side enables searches of various resources outside GTR. Resources are organized by sections: Clinical Resources (GeneReviews
, OMIM, Orphanet, NHGRI Talking Glossary), Locate a Genetics Professional, Consumer Resources (Genetics Home Reference, Office of Rare Diseases Research) and Molecular Resources (NCBI’s Genetics and Medicine resources). The criteria used to select links to non-government websites are described here: http://www.ncbi.nlm.nih.gov/gtr/docs/linkcriteria/
Interactive data access
Data can be retrieved from the website either by searching all components of the database or focusing on one sector. The home page supports queries specific to Tests, Conditions/Phenotypes, Genes, Labs, GeneReviews and All GTR through tabs. Other pages provide all query types with the exception of GeneReviews through a menu at the right of the query box. Based on analyses of user behavior, the default query on the home page is set to Conditions/Phenotypes.
Queries typed by the user are aided by two tools: autocomplete and spell correction. As a query is typed, a list of terms in the database containing the typed characters is generated (autocomplete). If the desired query is displayed, a click on the term will result in the display of the record. The terms provided are customized to the type of query as summarized in . If a query contains a misspelled word that does not retrieve any record, a suggestion for the correctly spelled word is provided and the query processed for the new term.
Searching for GeneReviews GeneReviews
can be identified using GTR in several ways. In addition to the query tab mentioned above, users can use the link in the Clinical Resources section to go to the GeneReviews
summary page in NCBI’s Bookshelf, where advanced searching is available. GeneReviews
specific to a condition are also reported in the Discovery panel of the test page and condition/phenotype page. Additionally, GeneReviews
are available through hyperlinks and colored chiclets on list result pages for conditions/phenotypes (see below) and the related diseases section of condition pages. GeneReviews
searches are summarized here: http://www.ncbi.nlm.nih.gov/gtr/docs/help/#find_GeneReviews
Query results display in the form of lists or the single result for the sector that was selected. Many paths are possible to retrieve the desired information; users are oriented by use of breadcrumbs summarizing their search path located beneath the search box (A). An All GTR search result references all sectors. A special laboratory comparison page can be produced from a test list page by using the “Compare labs” function. The general layout and special features of these page types are summarized below.
Lists of results
An All GTR search produces a list organized into four sectors: Tests, Conditions/Phenotypes, Genes and Labs. The upper left side of the page provides the total number of data elements, which hyperlink to the analogous list pages; these counts are also listed within each section. Each section displays a maximum of three examples of each item in a standard layout similar to the corresponding list pages.
Ranking of search results is primarily determined by the search term chosen and the filtering strategy. Relevance sorting and the weighting of records that are more complete are described here: http://www.ncbi.nlm.nih.gov/gtr/docs/about/#ranking
. Users may directly influence relevance by setting up preferred laboratories in MyNCBI, as explained in the section Limits, filters and preferences.
Each list produced for a specific sector of information displays the first 20 results of a query and summarizes the total number of results. The Test list also reports the number of tests for the number of conditions in the number of laboratories. All of the displayed data elements are provided by the submitting laboratory: Test name (hyperlinked to the test report page), Methods (chiclet and description), Analytical validity statement, Target population, Laboratory name (hyperlinked to the Laboratory page) and Directors.
The Conditions/Phenotypes list can be viewed as a set of descriptions (the default) or as related diseases. The description view is structured as a condition name (hyperlinked to the page specific to that condition), a brief description and a set of four hyperlinks to Tests, Genes, OMIM condition records and GeneReviews (links are active only when data are available). The related diseases view groups similar diseases together (each hyperlinked to the condition-specific page), provides a hierarchical representation and signals the availability of information by clicking on active colored chiclets for Clinical tests (C), Research tests (R), OMIM records (O) and GeneReviews (G).
Each item in the Gene list page displays the HGNC-approved gene symbol (hyperlinked to the gene item page) and gene name, followed by a gene description, list of alternate gene names, chromosome and location. A set of four hyperlinks (active when data are available) are provided to Tests, Diseases, OMIM gene and condition records, and ‘More about this gene’ links to the NCBI Gene record for the human gene.
Each item in the Laboratory list page is structured as the laboratory name (hyperlinked to the lab item page), institution name, list of directors, list of staff, number of tests, number of services and location. Hyperlinks are provided for the list of tests and the list of services.
Pages for specific tests, conditions, genes and laboratories Test page
The test page () is the focal point of the GTR website. The two main sections of the page reflect the predominant sources of data for the page. The bulk of the page reports information submitted primarily by the test provider, organized under seven tabs. The Discovery panel at the right (B) contains information assembled by NCBI. As is the norm in medicine and science, conflicting views may co-exist. This layout is intended to provide a comprehensive and balanced view of contextually relevant information from reputable sources along with resources for further exploration to facilitate an informed appraisal by the user.
Submitters determine the name of their test. The test fields and corresponding field requirements are enumerated in this table: http://www.ncbi.nlm.nih.gov/gtr/docs/fieldrequirements/#testrequirements
. Data for test fields are distributed among the Overview, How To Order, Indication, Methodology, Performance Characteristics, Interpretation and Laboratory Contact tabs. Key features of the test pages include the unique GTR accession (C), date the record was last updated, purpose of the test, methodologies used, targets of the test and a table summarizing what is tested, analytical validity, clinical validity, target population, clinical utility, proficiency testing, test codes, informed consent and genetic counseling requirements, protocol for interpreting variants of uncertain significance, use of the test sample for research purposes and sample reports. Submitted data are supplemented by NCBI (e.g. clinical features from sources such as OMIM and HPO). Links are provided to conditions and genes pertinent to the test and to the laboratory page.
The Test page content was determined following extensive input by GTR stakeholders and advisory groups, and may evolve as the testing landscape changes and additional feedback is provided. Elements such as turn-around time and cost were determined to be most readily kept up to date by participating laboratories on their own websites, and submitters may provide the direct URLs to this information (a recommended field) in the How to Order tab. Although Current Procedural Terminology (CPT) codes are not included at this time, GTR plans to include the new American Medical Association (AMA) Molecular Pathology (“MOPATH”) CPT codes, which provide more granularity than the stacking codes now in use.
This view orients the user to the specific condition for which tests may be offered by providing a description of disease characteristics. The Available Tests section contains a link to ‘See all available tests’, or the user can choose links to tests grouped by methodologies as a way to narrow the list. The Related Conditions section facilitates exploration of content through disease hierarchies and uses chiclets to signal the availability of content for clinical tests, research tests, OMIM records and GeneReviews. The Associated Genes section lists alternate gene symbols and gene names and links to the GTR gene page. The Clinical Features section provides additional details about the phenotypic features. Conditions for which limited content about disease characteristics is available can be further explored using the Related Conditions section and the Discovery panel.
The gene-specific page is a subset of a report from NCBI Gene, customized for GTR. The complete Gene page is accessed by following the link ‘Go to complete Gene record for…’ at the upper right of the page. The GTR gene page provides a link to ‘See all available tests in GTR for this gene’. Condition-specific links to tests are available within the Associated Conditions section.
This page organizes laboratory-specific information such as laboratory personnel, contact information, services, certifications (e.g. CLIA, CAP) licenses and links to the laboratory’s website.
All tests that the laboratory has registered in the GTR are provided as a scrollable menu in the Conditions and Tests section. A search by condition is provided for long test menus.
The Laboratory services field (http://www.ncbi.nlm.nih.gov/gtr/docs/submit/lab_info/#services
) is a set of general services that may apply to several tests. Services important to everyday clinical operations such as insurance preauthorization, specialized methods such as preimplantation genetic diagnosis, broad analyses such as whole exome sequencing and offerings such as DNA banking may be selected by submitters. These choices display in the Lab page, are accessible through a hyperlink on Lab list pages and may be queried within the Lab or All GTR sectors.
Limits, filters and preferences
Given the breadth of data accessible from GTR, non-specific searches can return a large set of results. To enable a quick reduction of long result lists to specific records of interest, various filters and limits have been constructed for different sectors of information.
The list of conditions and phenotypes in GTR is extensive and the terms vary greatly with respect to the information available. Users may limit search results in a condition list by selecting checkboxes on the upper-left corner for the availability of GTR tests, GeneReviews or OMIM records. These three limits have a Boolean ‘and’ behavior—for example, checking the boxes for GTR Tests and GeneReviews delivers the subset of condition/phenotype results for which both types of records are available.
Searches that return more than one test result can be filtered in a number of ways using the filter section at the left of the page. The user may select one condition of interest and then click the Compare labs button to see laboratories that offer tests for that condition (see below). This function can be performed alone or in combination with additional filters including Test type (clinical or research), Test method (specific methodologies within the general categories Biochemical, Cytogenetic and Molecular), Test services, Lab certification (CLIA Certified, NY CLEP Certified and State Licensed) and Lab location (USA, specific states and other countries).
The Compare labs function supports review of laboratories offering tests for a specific condition. Methodologies offered by each laboratory are displayed horizontally by the use of colored ‘chiclets’ with a letter assigned for each method and a description beneath. Chiclets are vertically aligned for each laboratory on the list, allowing the user to scan the page for combinations of methods to plan their testing strategy. Services (e.g. Carrier testing, Prenatal testing) are also represented by chiclets. Laboratories can be sorted alphabetically or selected through checkboxes. Filters for Test method, Test services, Lab certification and Lab location are available in this view.
Searches that deliver a list of laboratories can be filtered for Lab certification, Test services and Lab location. Additionally, users can select preferred laboratories in GTR with their MyNCBI login, which implements preferential display of tests from selected laboratories at the highest rank in the test result page.