ATTACHMENT 1
Genetic Testing Registry Data Fields
Introduction
This document delineates the proposed fields that will be used in the Genetic Testing Registry (GTR) to aggregate relevant data on genetic tests. This registry will provide for:
Collection of data important in the use and evaluation of available genetic tests, including information on analytical validity, clinical validity, and clinical utility
Dissemination of useful information for health care providers, consumers, payers, researchers
Development of a user-friendly genetic testing database for reporting, exchanging, and updating test information
The GTR is designed to collect adequate information on genetic tests while taking into consideration the reporting burden on the laboratories, existing resources, standards and practices, and the practicalities of measuring some test attributes. The information that will be collected is divided into three top-level fields: laboratory, personnel, and test. There are approximately 31 minimal data fields; these fields represent the minimum amount of information that must be submitted in order to register a test in GTR. There are approximately 85 fields that are either recommended or optional; these fields collect relevant information that may not be available for some tests. For the sake of simplicity, elsewhere in the PRA the “recommended” and “optional” fields are grouped together and identified as “optional” fields, as neither set needs to be provided in order to participate in GTR. The difference between recommended and optional fields is in display: recommended fields that are not filled in by the submitter will display on the GTR website with the words “Not Provided,” while optional fields that are not filled in by the submitter will not appear on the website. There are also approximately 24 fields that GTR can automatically complete on behalf of the submitter.
Each data element includes a definition of the element, the planned implementation, and references to outside resources that have suggested the data element or currently request it from laboratories. The following reference short names are listed with the corresponding complete citation:
AMP – Association for Molecular Pathology Survey and Response submitted to the Genetic Testing Registry Request for Information (RFI). Accessible at: http://oba.od.nih.gov/oba/gtr/comments/Association_for_Molecular_Pathology.pdf
McKesson – McKesson Advanced Diagnostics Management: Response submitted to the Genetic Testing Registry RFI and meetings with GTR staff members. Accessible at: http://oba.od.nih.gov/oba/comments/McKesson_Advanced_Diagnostic_Management.pdf
CAP – College of American Pathologists Molecular Checklist. Accessible at http://www.cap.org
MMWR – Centers for Disease Control and Prevention (CDC): Morbidity and Mortality Weekly Report (MMWR): Good Practices for Molecular Genetic Testing for Heritable Diseases and Conditions. (2009). Accessible at: www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.html
eDOS – HL7 Version 2 Implementation Guide: Laboratory Test Compendium Framework, Release 1 (eDOS). 2010 Health Level Seven, International. Accessible at http://www.hl7.org/implement/standards/index.cfm
HL7 LOINC – HL7 Version 2 Implementation Guide: Clinical Genomics; Fully LOINC-Qualified Genetic Variation Model Release 1. 2009 Health Level Seven, International. Accessible at http://www.hl7.org/implement/standards/index.cfm
Visual Hierarchy Used in this Document
Data elements in this document are indicated by the following hierarchy:
Data Fields
It is expected that Laboratory Information will be provided and updated with a different time cycle than Test Information. Laboratory Information may be updated independently of Test Information and vice versa. For a CLIA laboratory, it is expected that some fields will correspond to elements in the CLIA database, as documented below.
References: 77% of AMP respondents are able to provide laboratory information.
In this section, the submitter can provide all information that identifies the submitting entity (in most cases laboratory is used in this document) by populating the fields below.
Complete name of the laboratory performing the test.
References: CLIA [fieldname]
McKesson
Javitt et al
Acronym(s) or short name(s) that identifies the laboratory. Field allows entering multiple acronyms. An auto-complete list of existing institutional acronyms will be included.
Complete name of the institution to which the laboratory belong (e.g., hospital, university). It may be the same as “Name of Laboratory” for independent laboratories. This field may be auto-completed for existing institution names in GTR.
References: Javitt et al
Acronym(s) or short name(s) that identify the institution to which the laboratory belong. Field allows entering multiple acronyms. An auto-complete list of existing institutional acronyms will be included.
This is the name of the department used in the Facility address.
References: Javitt et al
The information collected is shown in the fields below.
Street address of the facility (e.g., building number and street name).
References: Javitt et al
McKesson
This is the subdivision number of the facility address if applicable (e.g., room or suite#).
References: Javitt et al
McKesson
City will be validated along with state against the postal code entered.
State will be validated along with city against postal code entered.
Postal code will be validated against state/city combination entered.
Country used in the Facility address. United States will be set as default.
Submitter can specify any other Facility address as applicable.
References: Javitt et al
McKesson
General phone number for the laboratory. It could be specified as: Country name – Country-specific area code (set parameters) – phone number; field will be validated automatically if possible.
References: Javitt et al
McKesson
Existing general fax number for the laboratory to be made available on GTR website.
References: Javitt et al
McKesson
Existing general email address for the laboratory to be available to on GTR website.
References: Javitt et al
McKesson
URL for the laboratory’s website.
References: Javitt et al
List of all services offered by the laboratory with the ability to multi-select. Services selected in this field represent all services offered by the laboratory and are not test-specific. The laboratory can add any new service not named in the list provided. An initial list is below.
Genetic counseling
Result interpretation
DNA Banking
RNA Banking
Cord Blood Banking
Tissue Banking
Data Storage and Backup
Confirmation of research findings
Preimplantation Genetic Diagnosis (PGD)
Custom Prenatal Testing
Custom Deletion/Duplication Testing
Custom Sequence Analysis
Custom Balanced Chromosome Rearrangement Studies
Marker Chromosome Identification
Uniparental Disomy (UPD) Testing
Identity Testing
X-Chromosome Inactivation Studies
Specimen Source Identification
Other, specify_________________
References: CAP MOL.05075
Javitt et al
Order code that the laboratory uses for the particular service(s) selected in the field above. One order code field per laboratory service selected.
In this field a laboratory can identify if it is linked to a larger health care system and/or clinical unit that cares for individuals with a given disorder. Submitters can identify parent companies of fully owned subsidiaries in this field.
This field allows the submitter to provide its current GeneTests institution ID for identification purposes. NCBI may be able to auto-provide this in some cases. This data field would be shown to submitter only, not publically displayed.
Submitter can specify if the laboratory participates in external programs such as in the fields below. Submitter can select multiple programs. An initial list is below.
ISCA Consortium (International Standards for Cytogenomic Arrays)
Locus-specific Databases
Does the laboratory participate in standardization programs?
Does the laboratory participate in data exchange programs?
In this section, the laboratory will provide information about its staff member(s) and will be able to make choices regarding if and how each person entered will be displayed in the GTR website or only stored in the database. The laboratory can enter multiple Persons.
At least one Person must be identified as the Laboratory Director for each laboratory.
The personnel information is provided only once for the laboratory and can be disseminated to all the tests the laboratory registers in GTR. Furthermore, specific contacts for specific tests can be linked from the test, rather than re-entered.
References: CAP MOL.40000 “Director Qualifications”; CAP MOL.40100 “Personnel – Technical Operations”; CAP MOL.40150 “Technologist Qualifications”
Javitt et al
McKesson
The complete name of a person. This field will be used multiple times – once for each person entered.
Is this person the primary laboratory contact for GTR staff? If checked, this person would receive communication from GTR staff if and when appropriate (e.g., annual update messages, test questions).
Is this person a laboratory director?
Should this person be displayed in the GTR website? A person can be displayed in the GTR website but choose that their contact information be kept private.
Unique key for the Person. It is only for laboratories providing data electronically to ensure that they can link a test uniquely to a person in bulk upload of data.
Person’s professional title in the laboratory as provided by the person. There will be a list of the most common titles to facilitate quick entry and an “Other” field to allow manual entry.
Suggested list:
Lab Director
Lab Associate Director
Medical Director
Genetic Counselor
Nurse
Research Nurse
Administrator
Staff
The academic degree(s) the person holds. Submitter can select multiple academic degrees and whether each degree should be displayed after name on website. An initial list is below.
M.D.
D.O.
D.P.M.
Ph.D.
M.S.
M.A.
B.S.
The certification(s) the person holds from genetic colleges, boards, associations, and any other relevant organization or institution. An initial list is below.
FACMG
CGC
References: 39% of AMP respondents are able to provide this information.
The certification(s) the person holds from all colleges, boards, associations, or any other relevant organization or institution not named in the field above. An initial list is below.
ABP
FAAP
ABIM
FACP
FACOG
List of all credentials named on the prior 3 fields that will be publically displayed. Submitter may select if each credential should be displayed after name on website.
Role of the person in relation to GTR privileges/permissions. Permissions to view submitted information, add, edit or delete information, or all of the above. The suggested list is below.
View Only
Edit Only
Add Only
Delete Only
All
Phone number to be made available for the public to contact the person. If the person is being entered as a test-specific contact, then a public phone number is required; for all other laboratory personnel, a public phone number is optional.
Person’s direct phone number that will not be made public but may be used by GTR staff as needed. GTR requires the contact information of at least one laboratory staff member for communication about submission and maintenance of records. This number can be the same as the public phone number.
Fax number to be made available for the public to contact the person.
Person’s fax number that will not be made public but may be used by GTR staff to contact as needed.
Email address to be made available for the public to contact the person. If the person is being entered as a test-specific contact, then a public email address is required; for all other laboratory personnel, a public phone number is optional.
The email account attached to NCBI login system by default. This field is optional for personnel being listed for the laboratory that are not involved in the submission or maintenance of information in the GTR.
Comment to be displayed with public contact information for this person.
In this section, the submitter can provide information related to the different regulations that govern the laboratory such as Clinical Laboratory Improvement Amendments (CLIA) certifications and state licenses as shown in the fields below.
References: GA
MMWR
Certification number assigned by the Clinical Laboratory Improvement Amendments (CLIA) program to the laboratory. This field is mandatory for laboratories listing “clinical” tests. International laboratories and those registering research tests are not expected to have CLIA certification.
References: Javitt et al
McKesson
eDOS MSH-3 “Sending Application (CLIA ID sending Lab)”
MMWR
Expiration date of the current CLIA certification for the laboratory. Some data will be valid for month and year only. This field is required for U.S. laboratories providing clinical tests that have entered a CLIA certification number.
References: Javitt et al
McKesson
Name of the state under which the laboratory is licensed to practice. Submitter may select multiple.
License number issued by the state to the laboratory. It is mandatory for those with license numbers available.
Expiration date on the state license. Mandatory for those with expiration dates.
Name of all other certifications or licenses that the laboratories holds not named in the fields above. This field can include federal and international certifications/licenses such as ISO. Submitter may select multiple.
References: 69% of AMP respondents are able to provide this information
McKesson
Javitt et al
MMWR
This field is required for those laboratories that have license numbers available.
This field is required for those laboratories that have certification/licenses with expiration dates.
Information stored in the default section can be copied to other fields and to each test offered by the laboratory. The submitter has the option to update all default values at once and override them as appropriate.
The default section is optional and has been designed for the purpose of saving submitters from entering the same information multiple times. The fields below can be provided in the default section if the submitter wants that answer to appear for all of their tests. The same fields appear in their appropriate sections both in this document and in the electronic submitter forms.
Default How to Order: Text + URL – Manual Entry – Optional
Default Specimen Source – Pull Down List – Optional
Default Test Contact Policy – checkbox – Optional
Default Test Orderable By – Pull-Down List – Optional
Default Sample Negative Report – Optional
Default Sample Positive Report – Optional
Default Variants of Unknown Significance (VUS) policy and interpretation
What is the Protocol for Interpreting a Variation as a VUS? – Text Field – Manual Entry – Recommended
What Software is Used to Interpret Novel Variations? – Text Field – Manual Entry – Optional
What Is the Laboratory’s Policy on Reporting Novel Variations? – Text Field – Manual Entry – Recommended
Are Family Members Who Have Defined Clinical Status Recruited to Assess Significance of VUS Without Charge? – Yes/No Checkbox with comments – Recommended
Default VUS Report – Optional
Default Will the Laboratory Re-contact the Ordering Physician if Variant Interpretation Changes? – Yes/No checkbox with comments – Optional
Each Test is a specific, orderable test from a particular laboratory, and receives a unique GTR accession number. The same or similar test performed by different laboratories gets a different accession number. Thus, a laboratory is free to define an orderable test exactly as they represent it in their catalog.
A GTR accession ID has the format GTR00000001.1, a leading prefix “GTR” followed by 8 digits, a period, then 1 or more digits representing the version. When a laboratory updates a test, the accession stays the same, but the version increments. GTR accessions and versions are issued and controlled by NCBI. Any changes to the test information will result in a version change. Changes to laboratory and personnel information will not result in a version change. Access to archived versions of tests will be provided to submitters and users.
References: eDOS OM1-7 “Other Service/Test/Observation/IDs for the Observation”
McKesson
HL7
When a laboratory updates test-specific data fields, the date (format = MM-DD-YYYY) is recorded. This field is associated with the GTR Accession ID, where the accession stays the same but the version increments. The date last touched will update with the test versions. Any changes to the test information will result in a version change and subsequently update the date last touched. Changes to laboratory and personnel information will not result in a version change and will not update the date last touched for the test entry.
Name of test should include one or more of the following subfields.
References: 87% of AMP respondents are able to provide this information.
Test name that will appear as the default title on the GTR test detail page. It should be the test name the laboratory wishes to be commonly associated with the test. By default this name will be displayed as the test name.
References: eDOS OM1- 8 and 51 “Other Names (recognized by the producer for the observation)”
McKesson
MMWR
Submitter’s short name or mnemonic for the test. This is a name that may be used in space limited reports such as lists and tables.
References: e-DOS OM1-10 “Preferred Short name or Mnemonic for the Observation”
MMWR
Common commercial test name (e.g.,. OvaSure, FDA kit name). Manufacturer test could be an FDA approved test, a kit, or some other manufacturer test. A test may point (link) to another test with the ability to override certain values.
The submitter can enter other synonyms and aliases by which the test can be searched. They can classify the type of name: archived, synonym, keyword, and so on.
References: eDOS OM1-11 “Preferred Long Name for the Observation”
Submitter can specify how the test was developed: whether the test is laboratory developed, FDA approved or cleared, an externally manufactured kit, a modified FDA-cleared/approved test, or combination as exemplified in the proposed list below. Please note that reflex testing is not included in this field.
Laboratory Developed Test (no manufacturer test name)
FDA-cleared/approved test (has FDA test name)
Manufactured (research use only; not FDA-reviewed)
Modified FDA (FDA-cleared/approved test, but with laboratory modifications/field changes)
Combination (could include reflex & panels doing multiple tests) (list of tests – LDTs, FDA)
For tests provided in bulk electronically, the Laboratory Unique Code must be provided. This code is unique for the test from that laboratory. NCBI will use this code to determine if the laboratory is providing a new test or an update to an existing test, so it is critical that the same code be submitted for the same test.
References: e-DOS OM1-2 “Producer’s Service/Test/Observation ID”.
Placeholder for other fields under “Test Information” that may become applicable to Services entries.
Description of the test ordering procedure and the laboratory website URL for more details.
References: CAP MOL.32300 and MOL.32350 “Requisition Information”
eDOS OM1-12 “Orderability”
Pull-down list includes only the general specimen type required (e.g., whole blood, frozen tissue, fresh tissue, sputum). Detailed specimen requirements for the ordering physician should be found at the supplied URL. See ‘Default Specimen Source” for a sample list. Multiple entries allowed.
References: 73% of AMP respondents are able to provide this information.
CAP MOL.33050 “Specimen Collection/Handling Requirements”
eDOS OM4-6 “Specimen”
McKesson
Javitt et al
HL7
Submitter can enter one or more default specimen source or type from pre-determined list that will be displayed with all tests. Submitter can select all that apply. An initial list is below.
Peripheral (whole) blood
Buccal swab
Saliva
Amniocytes
Amniotic fluid
Bone marrow
Cell culture
Chorionic villi
Cord blood
Cystic hygroma fluid
Dried blood spot (DBS) card
Fetal blood
Fresh tissue
Fibroblasts
Frozen tissue
Paraffin block
Product of conception (POC)
Serum
Skin
Sputum
Urine
White blood cell prep
Other, specify __________________
In the interactive forms based update, the submitter may select from one of the personnel supplied earlier. For direct electronic submission of data, this field must be supplied as either a unique name matching the personnel list or a personnel ID previously supplied.
If no test-specific contact is given, the laboratory’s general contact information will display by default.
References: eDOS OM1-17 “Telephone Number of Section”
MMWR
The overall policy of the laboratory regarding who (patients vs. health care providers) and when (pre-test/post-test/anytime) can contact the laboratory. The suggested options are:
Pre-test email/phone consultation regarding genetic test results and interpretation is provided to patients/families.
Post-test email/phone consultation regarding genetic test results and interpretation is provided to patients/families.
Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.
This check box can be auto selected by the default laboratory contact policy. Submitters can change the contact policy here and override the default settings.
Submitters can choose to let users know if a test requires informed consent prior to testing. As default, all tests for all laboratories will likely need a disclaimer that informed consent is determined by the ordering physician’s state laws.
Informed consent required: Yes No Informed consent requirements are determined based on applicable state law
References: MMWR
Submitters can choose to let users know if a test requires genetic counseling and if so, whether prior to testing or prior to the release of test results.
References: MMWR
Submitters can describe the suggested sequence of ordering tests, discuss reflex testing, and related issues. This field is for recommendations on how to order the different tests in sequence of relevance to the patient being tested. This field should not include discussion of methodology or test procedural protocols. Laboratories can describe whether a test has a required reflex test or a reflex mechanism. Each test component should be described. If a test is ordered, additional tests may be performed as necessary under certain circumstances based on initial results and that should be described in this field.
References: eDOS OM1-34 “Reflex Tests/Observations”
Laboratory’s order or catalog code for the test (i,e., the order code to put in the requisition to order the test from the laboratory).
References: eDOS OM1-2“Producer’s Service/Test/Observation ID”
MMWR
Submitters can provide a URL for information on codes including LOINC, ICD-9, and ICD-10.
References: eDOS OM1-7 “Other Service/Test/Observation IDs for the Observation”
McKesson
HL7
Submitter-provided link to their website for test-specific information.
References: 26% of AMP respondents are able to provide this information.
Javitt et al
This section identifies the location where different aspects of the test are performed. The intent is to increase transparency of where the test is performed. External means any laboratory/facility that does not belong to the reporting laboratory. For example, a test performed at an outside facility owned by the same company would be considered to be performed “externally.” Submitters can enter details and provide appropriate information for clarification of their entry as needed.
References: McKesson
Identification of where all parts of the test are performed. Suggested option list is below. Submitter can check multiple boxes and provide information in a single text field.
Entire test performed in-house
Entire test performed externally
Specimen preparation performed in-house
Specimen preparation performed externally
Wet lab work performed in-house
Wet lab work performed externally
Interpretation performed in-house
Interpretation performed externally
Report generated in-house
Report generated externally
References: eDOS OM1-27 “Outside Site(s) where Observation may be Performed” - optional
Javitt et al
The following two questions will be required only if the test or any part of the test is performed externally. If submitter chooses that the entire or a portion of the test is performed externally, they may show whether they are authorized to enter the external collaborator’s details of the test and whether the external collaborator had the ability to review the information for accuracy. Submitters will not be required to report the name of external collaborator/lab.
Required if any portion of the test is performed externally.
Required if any portion of the test is performed externally. In the case that more than three facilities are involved in the testing process, if one facility has not reviewed the test and the other has, “No” should be selected. For example, if laboratory A is the reporting laboratory, wet lab work is performed in laboratory B (reviewed entry), interpretation in company C (did not review entry), the answer to this question is “No.”
This section identifies how the test can be ordered as described in the field below.
References: GA
MMWR
Identification of who can order the test from this laboratory (e.g., specify Health Care Providers: Licensed physician, PA, RN, NP, GC). Submitter can select multiple choices. An initial list is below.
Health Care Provider
Public Health Mandate
Out-of-State Patients
In-State Patients
Licensed Physician
Physician Assistant
Registered Nurse
Genetic Counselor
This section contains information on how the laboratory reports test results and clinical interpretation back to the ordering individual and lists the responsibilities the laboratory assumes for reporting results and providing clinical interpretations.
References: CAP MOL.35942 “Result Reporting”
eDOS OM1-32 “Interpretation of Observations”
McKesson
MMWR
HL7-LOINC 51969-4 “Genetic Analysis Summary Report”
Submitter can upload a sample negative report for the corresponding test (auto-populated if information is entered in the default section).
Submitter can upload a sample positive report for the corresponding test (auto-populated if information entered in the default section).
Submitter can enter information on how Variants of Unknown Significance (VUS) are handled in the laboratory by supplying the information in the subfields below.
Description of how the laboratory handles Variants of Unknown Significance.
Examples of software applications for medical molecular genetics interpretation include: Melina II, MEME Suite, VISTACartagenia Bench, Alamut, SIFT, PolyPhen, Align-GVGD, GeneSplicer, laboratory proprietary internal software.
Description of how the laboratory reports novel variations, which could include who gets contacted and how (e.g., person ordering the test will be contacted via telephone as soon as VUS is identified).
Will the laboratory offer the test to family members free of charge?
Submitter can upload a sample VUS report for this test (auto-populated if information entered in the default section).
Description of how the laboratory deals with ongoing interpretation of genetic tests results after the initial report.
The submitter can enter information on the procedures after-processing the sample by supplying the information in the subfields below.
After clinical testing is complete, does the laboratory perform any research testing using the submitted specimen?
This section describes the reasoning for performing the test. Information is provided in the fields below by the submitter and parts are automatically filled with information from NCBI’s ClinVar and/or OMIM databases.
References: CAP MOL.30670 “Clinical Indication/Clinical Utility”
MMWR
Purpose(s) or indication(s) for use of the test. An initial list is are below and submitter can select multiple purposes.
Diagnosis
Screening
Drug Response
Risk Assessment
Pre-symptomatic
Mutation Confirmation (family specific or research results, etc)
Pre-implantation genetic diagnosis
References: 61% of AMP respondents are able to provide this information.
McKesson
Javitt et al
MMWR
Submitters can indicate whether the test is for clinical purposes or is a research test. Definitions/Rules for what qualifies as a clinical test must be determined. Clinical tests can only be provided by CLIA certified laboratories.
Name of the disease/syndrome/drug response/etc. for which the test can be ordered.
References: Javitt et al
HL7 LOINC 51963-7 “Medication Assessed”
HL7-LOINC 51967-8 “Genetic Disease Assessed”
HL7-LOINC 53577-3 “Reason for Study, Additional Note”
The submitter can provide the disease name they want associated with the test if the disease name is different from the one automatically provided by GTR.
NCBI will provide the SNOMED CT name and identifier as available.
References: McKesson
The submitter can provide the disease synonym they want associated with the test if the disease synonym is different from the one automatically provided by GTR.
The submitter can provide the disease acronym they want associated with the test if the disease acronym is different from the one automatically provided by GTR.
This field names the type or category of the disease. An initial example list is below.
Dysmorphology Syndrome
Cancer Syndrome
Neurology
For pharmacogenetic tests, additional information can be provided by NCBI in substitution for disease clinical summary and clinical features provided for other conditions.
Identification of the disease mechanism (e.g., haploinsufficiency, imprinting, etc).
This field contains the differential or a list of disorders similar to the one for which the test is used.
The most current estimated number of cases of the disease in the population.
References: 34% of AMP respondents are able to provide this information.
Explanation of which segment(s) of the population should be tested for this disease and why.
References: MMWR (recommended patient population)
This section contains technical information about the test as submitted by the laboratory.
Name of the general category the test belongs to. A list of examples is provided below.
Method to detect nucleotide changes ≤5bp
Method to detect deletions/duplications >5 and <250bp
Method to detect deletions/duplications ≥250bp
Method to detect enzyme/metabolite levels
References: 73% of AMP respondents are able to provide this information.
eDOS OM1-14 “Coded Representation of Method”
MMWR
Name of the test method used in the assay. A list of examples is provided below.
Examples:
PCR-RFLP with Southern hybridization
RT-PCR with gel analysis
Trinucleotide repeat by PCR or Southern Blot
Protein truncation
Enzymatic levels
Metabolite levels
Gene expression profiling
Comparative genomic hybridization
GeneID
Chromatin Immunoprecipitation on ChIP
DamID
SNP Detection
Alternative splicing detection
Fusion genes microarrays
Tiling Arrays
Other, specify______________________
References: CAP MOL.30680 “Manufacturer Instructions”
CAP MOL.31705 “LDT Reporting”
CAP MOL.31935 “Modified FDA-Approved Assay”
HL7-LOINC 55233-1 “Genetic Analysis Master Panel”
HL7-LOINC 55232-3 “Genetic Analysis Summary Panel”
McKesson
Information provided by the submitter, such as chips and arrays used in the test. Submitter will be able to select multiple items. Laboratories will be able to bulk upload platform information (e.g.,. their own array) and point to it.
Examples:
Affymetrix GeneChip
Agilent microarrays
CodeLink Bioarray
NimbleGen microarray
Febit microarray
Xeotron microarray
Expression Array (Applied Biosystems)
Spotted cDNA Array
References: CAP MOL.29290 “Reagent Data”
Javitt et al
HL7
Submitters can name the instruments used and point to them electronically. Submitter will be able to select multiple items.
Examples:
Qiagen AutoPure LS
Qiagen QIAcube
Tecan Genesis Robotic Workstation 150
PerkinElmer Victor3 1420 Multilabel Plate Reader
Agilent 2100 Bioanalyzer
Applied Biosystems 7900HT Sequence Detection System
Applied Biosystems SOLiD v4 System Sequencer
Applied Biosystems 9700 Thermal Cycler
Covaris S2 Sonicator
Roche LightCycler 480
BioRad CFX96
References: eDOS OM1-13 “Identity of Instrument used to Perform this Study”
Javitt et al
Summary of the methodology, which may include the description of the specific steps for each method used in the assay.
References: CAP MOL.34921 “Sequencing Assay Optimization”
eDOS OM1-41 “Description of Test Methods”
Submitters can provide further information about whether they confirm results, and how. Example: “Positive results are confirmed on a new DNA preparation using repeat sequence analysis”.
Category of the analyte being tested. A list of examples is provided below.
Nucleotide Mutations
Haplotypes
Chromosome Rearrangements
Full genome
Enzymes
Metabolites
References: HL7-LOINC 48006-1 “Amino Acid Change Type”
HL7-LOINC 48019-4 “DNA Sequence Variation Type”
Javitt et al
MMWR
Name of the gene that the test targets. When the gene name is identified, the gene symbol, synonym, location, family, and OMIM # will be provided automatically if available.
References: 87% of AMP respondents are able to provide this information.
CAP MOL.34914 “Gene Information”
Javitt et al
HL7-LOINC 48018-6 “HGNC Gene Identifier”
MMWR
References: CAP MOL.36842 “Standard Nomenclature”
HL7-LOINC 48018-6 “HGNC Gene Identifier”
References: HL7-LOINC 48008-7 “Allele Name”
References: HL7-LOINC 47999-8 “DNA Region Name”
Currently, this information is likely not available on most genes.
Submitters must provide a gene name, analyte or chromosomal location. If a gene name is provided, the chromosomal location will be automatically provided if available. Submitters can provide the precise location being or just the chromosome band number.
References: HL7-LOINC 47999-8 “DNA Region Name”
Submitter can specify which exons are being tested and their location.
Submitter can specify which mutations are tested, their location or provide an identifier such as a dbSNP rs number. For biochemical tests, the submitter can specify which analyte is being tested.
References: 79% of AMP respondents are able to provide this information.
CAP MOL.34907 “Restriction Endonuclease Digestion Confirmation”
CAP MOL.34914 “Gene Information”
CAP MOL.34931 “Sense/Antisense Sequence”
HL7-LOINC 48003-8 “DNA Sequence Variation Identifier (dbSNP rs#)”
HL7-LOINC 48004-6 “DNA Sequence Variation (HGVS)”
HL7-LOINC 48005-3 “Amino Acid Change”
dbSNP (rs#) and dbVar (nsv#) associated with provided variants, if applicable.
References: HL7-LOINC 48003-8 “DNA Sequence Variation Identifier (dbSNP rs#)”
Location of the chromosome, gene, or variant (tested regions) on the various genome assemblies. Needs to include the location and the assembly. Example: NG# on GRCh37.
Submitters can provide as specific a location being tested as possible. If specific and detailed information is provided, it would be possible to map it to RefSeqGene and validate against NCBI resources. It would also make it possible to auto-populate the information on most gene and protein fields.
References: HL7-LOINC 48013-7 “Genomic RefSeq Identifier”
HL7-LOINC 51958-7 “Transcript RefSeq Identifier”
HL7-LOINC 47998-0 “DNA Sequence Variation Display Name”
Submitters can identify the probes used in the test.
References: CAP MOL.34188 “Probe Characteristics”
This field will name the protein type or function. An initial list is below.
Receptor
Enzyme
Structural
Proposed pick list:
Pathogenic
Presumed pathogenic
Benign
Presumed benign
Unknown significance
Drug response
Other
Not assessed
This field will allow submitters to provide additional details on the targets for the test. For example, they may add details such as, “Bi-directional sequencing of exons 1-5 with concurrent analysis of Glu234Gly”.
This section contains information such as analytical validity and assay limitations, as provided by the laboratory. The suggested fields below will capture the test’s performance characteristics.
References: GA
Laboratories can provide an explanation of test accuracy and reliability by describing the available information on the fields below that represent the information available from a typical validation study (e.g., as required for CAP).
References: CAP MOL.30785 “Validation Studies – LDT’s”
CAP MOL.31475 “Validation Study”
MMWR
In this field, the submitter can describe the analytical detection rate.
References: 55% of AMP respondents are able to provide this information.
CAP MOL.31475 “Validation Study”
McKesson
Javitt et al
References: CAP MOL.30900 “Validation Studies – Specimen Selection”
In this field, the submitter can describe the analytical false positive rate.
References: 55% of AMP respondents are able to provide this information.
CAP MOL.31475 “Validation Study”
McKesson
Javitt et al
In this field, the submitter can describe how close the results match those from independent sources (known to be the true results).
References: 37% of AMP respondents are able to provide this information.
CAP MOL.31475 “Validation Study”
eDOS OM2-3 “Range of Decimal Precision”
McKesson
In this field, the submitter can describe how close repeated results match each other.
References: 42% of AMP respondents are able to provide this information.
CAP MOL.31475 “Validation Study”
McKesson
In this field, the submitter can describe any factors that affect the value of the test for its intended use by providing information on test limitations and restrictions.
References: 58% of AMP respondents are able to provide this information.
CAP MOL.31245 “Reference/Reportable Range”
MMWR
References: 45% of AMP respondents are able to provide this information.
This section contains information on the test quality control (QC) and quality assurance (QA) methods, such as proficiency testing and validation procedures, as provided by the laboratory.
References: 37% of AMP respondents are able to provide this information.
CAP MOL.20000 “Documented QM/QC Plan”
References: MMWR
Submitter can specify which proficiency testing is performed for the laboratory; for example, whether the laboratory participates in a formal proficiency testing (PT) program or alternative assessment such as intra-laboratory sample exchanges. This field is mandatory if PT is performed on this test. An initial list is below.
Formal PT program
Alternative Assessment (e.g., Intra-Laboratory)
References: CAP MOL.10150 “PT Participation”
CAP MOL.10160 “Alternative Performance Assessment”
Submitter can identify the institution or agency that provides PT for the test.
This field only appears if CAP is chosen as PT provider for the test. Submitter can select multiple items.
Submitter can explain how PT is performed for the test and include information on PT results, reportable range, testing interval and number of specimens tested.
References: CAP MOL.10170 “PT Integration Routine Workload”
References: CAP MOL.10200 “PT Evaluation”
References: CAP MOL.31245 “Reference/Reportable Range”
Submitter can explain how the laboratory validates the test (initially or when test is changed).
References: CAP MOL.30785 “Validation Studies – LDTs”
CAP MOL.30900 “Validation Studies – Specimen Selection”
CAP MOL.30957 “Verification Studies- FDA cleared”
CAP MOL.31015 “Validation studies – Specimen Types”
CAP MOL.31130 “Validation Study Comparison”
CAP MOL.31475 “Validation Study”
Javitt et al
References: CAP MOL.31245 “Reference/Reportable Range”
CAP MOL.31360 “Reference/Reportable Range Quantitative”
In this section, the submitter can provide available information on clinical specificity and sensitivity, describe the population and identify the number of specimens used in the validation procedure, and list calculated predictive positive and negative values as exemplified in the fields below.
References: 39% of AMP respondents are able to provide this information.
CAP MOL.31590 “Clinical Performance Characteristics”
McKesson
Javitt et al
GA
MMWR
Submitter can provide the proportion of negative test results obtained from patients who do not have the defined clinical presentation.
References: 29% of AMP respondents are able to provide this information.
CAP MOL.31590 “Clinical Performance Characteristics”
Javitt et al
Submitter can provide the proportion of positive test results obtained from patients with the defined clinical presentation.
References: 27% of AMP respondents are able to provide this information.
CAP MOL.31590 “Clinical Performance Characteristics”
Javitt et al
Submitter can describe the population used for clinical validity studies.
References: CAP MOL.31590 “Clinical Performance Characteristics”
The submitter can provide the lifetime risk to develop the disease if the test is positive.
References: CAP MOL.31590 “Clinical Performance Characteristics”
The submitter can provide the probability not to develop the disease if the test is negative.
References: CAP MOL.31590 “Clinical Performance Characteristics”
In this section, the submitter can provide available information related to clinical utility such as: describe whether diagnosis can be made without the test; what the burdens are for the patient; cost effectiveness; impact of the test result to the patient (i.e., disease management, lifestyle, prevention); describe impact of test result to family members. Suggested fields to capture this information are shown below.
References: 40% of AMP respondents are able to provide this information.
CAP MOL.30670 “Clinical Indication/Clinical Utility”
McKesson
Javitt et al
GA
MMWR
Submitter can explain the impact the test may have to the general population.
References: Javitt et al
Submitter can describe the utility of the different outcomes of the test, for instance, in relation to clinical progression and treatment options, lifestyle, prevention, decision making, and whether there is evidence that the genetic test is useful for the patient or his/her relatives in the absence of immediate medical consequences.
Submitter can describe the medical, clinical, personal and familial benefits of performing the test.
Submitter can discuss the potential harms of performing the test.
Submitter can describe how performing the test influences the patient and their health when compared to not having the test done (e.g., enabling predictive test in the family or prenatal diagnosis).
Submitter can discuss the clinical treatment(s) available to patients that test positive for the variation.
This section delineates information for the test-specific FDA regulations, applicable certifications and licenses as described in the fields below.
References: Javitt et al
GA
HL-7
MMWR
Submitter can provide information related to the test’s FDA approval or clearance by providing the applicable information in the fields below.
Default is Laboratory Developed Test (LDT) and submitter can choose from the proposed list below.
IVD – In Vitro Device
RUO – Research Use Only
IUO – Informational/Investigational Use Only
LDT – Laboratory Developed Test
Not Applicable
References: CAP MOL.29290 “Reagent Data”
Submitter can name item(s) for which they are providing FDA approval/clearance information. An initial list is below.
Test kit(s)
Assay(s)
Reagent(s)
Instrument(s)
Not Applicable
Submitter can specify the status of the application for FDA approval/clearance of choice from above (e.g., test kit, assay, reagents, instruments). An initial list of options is below.
Approved
510(k) Cleared
PMA Approved
HDE approved
Pending
Not Submitted
References: 50% of AMP respondents are able to provide this information.
Javitt et al
GA
HL7
MMWR
Mandatory if FDA reviewed is chosen.
Submitter can provide links to the FDA website with information on approval or clearance of the genetic test or upload the documents.
Submitters can select state-specific licenses and other test-specific certifications from the pull-down list. An example is NYSCLEP. “None” will be an option.
Certification/License number is mandatory if certification/license selected above.
Expiration date is mandatory if certification/license selected above.
Data fields that are specifically associated with research tests, not clinical tests.
Description of how the laboratory releases the test results: person to whom results are delivered, who delivers the results, delivery method, etc.
| File Type | application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| File Title | Appendix 1 |
| Author | colemaja |
| File Modified | 0000-00-00 |
| File Created | 2021-01-25 |