scholarly journals Creation of an Expert Curated Variant List for Clinical Genomic Test Development and Validation: A ClinGen and GeT-RM Collaborative Project

2021 ◽  
Author(s):  
Emma Wilcox ◽  
Steven M Harrison ◽  
Edward Lockhart ◽  
Karl Voelkerding ◽  
Ira M Lubin ◽  
...  
Keyword(s):  
Reference Materials ◽  
Validation Studies ◽  
Expert Knowledge ◽  
Test Development ◽  
Genomic Test ◽  
Large Numbers ◽  
Disease Associated Genes ◽  
Modern Genomic ◽  
Development And Validation ◽  
Clinical Genomic

Modern genomic sequencing tests often interrogate large numbers of genes. Identification of appropriate reference materials for development, validation studies, and quality assurance of these tests poses a significant challenge for laboratories. It is difficult to develop and maintain expert knowledge to identify all variants that must be validated to assure analytic and clinical validity. Additionally, it is usually not possible to procure appropriate and characterized genomic DNA reference materials containing the number and scope of variants required. To address these challenges, the Centers for Disease Control and Prevention's Genetic Testing Reference Material Program (GeT-RM) has partnered with the Clinical Genome Resource (ClinGen) to develop a publicly available list of expert curated, clinically important variants. ClinGen Variant Curation Expert Panels nominated 546 variants found in 84 disease associated genes, including common pathogenic and difficult to detect variants. Variant types nominated included 346 SNVs, 104 deletions, 37 CNVs, 25 duplications, 18 deletion-insertions, 5 inversions, 4 insertions, 2 complex rearrangements, 3 in difficult to sequence regions, and 2 fusions. This expert-curated variant list is a resource that provides a foundation for designing comprehensive validation studies and for creating in silico reference materials for clinical genomic test development and validation.

The Team Role Test: Development and validation of a team role knowledge situational judgment test.

2008 ◽  
Vol 93 (2) ◽  
pp. 250-267 ◽  
Author(s):  
Troy V. Mumford ◽  
Chad H. Van Iddekinge ◽  
Frederick P. Morgeson ◽  
Michael A. Campion
Keyword(s):  
Test Development ◽  
Situational Judgment Test ◽  
Situational Judgment ◽  
Development And Validation

Evaluation of cohort diversity in development and validation studies of hereditary cancer genetic risk assessment models.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10600-10600
Author(s):  
Amanda Gammon ◽  
Ambreen Khan ◽  
Joanne M. Jeter
Keyword(s):  
Risk Assessment ◽  
Validation Studies ◽  
Genetic Risk ◽  
External Validation ◽  
Ashkenazi Jewish ◽  
Genetic Risk Assessment ◽  
Internal Validation ◽  
Risk Assessment Models ◽  
Race Ethnicity ◽  
Development And Validation

10600 Background: Multiple models estimate a person’s chance of harboring a pathogenic variant increasing cancer risk. Some pathogenic variants are more common in individuals from specific ancestries, such as the BRCA1 and BRCA2 founder variants in Ashkenazi Jews. Yet data remains limited on the larger variant spectrum seen among people of different ancestral backgrounds and whether or not the pathogenic variant frequency differs in many populations. Due to this, it is important that genetic risk assessment models be validated in a diverse cohort including Black, Indigenous, People of Color (BIPOC). Methods: A literature search was conducted to identify published development and validation studies for the following genetic risk assessment models: BRCAPRO, MMRPRO, CanRisk/BOADICEA, Tyrer-Cuzick, and PREMM. Validation studies that only evaluated the cancer risk prediction capabilities of the models (and not the genetic variant risk prediction) were excluded. The following participant information was abstracted from each study: total number of participants, gender, race, and ethnicity. Authors were contacted to obtain missing information (if available). Results: 12 development and 12 validation studies of the genetic risk assessment models BRCAPRO, MMRPRO, CanRisk/BOADICEA, Tyrer-Cuzick, and PREMM were abstracted. Of the validation studies, five were internal validation studies conducted by the model developers, and seven were external validation studies. Four external validation studies compared multiple models. 75% (18/24) of papers did not include reporting of participant race or ethnicity information in their published reports. External validation studies (4/7, 57%) more often reported participant race/ethnicity than development (0/12, 0%) or internal validation (2/5, 40%) studies. The external validation studies for BRCAPRO reporting race/ethnicity information involved cohorts that ranged from 50-51% non-Ashkenazi Jewish white, 28% African American, 1% Asian, 2-49% Hispanic, and 19-42% Ashkenazi Jewish. The external validation studies for MMRPRO and PREMM reporting race/ethnicity information involved cohort that ranged from 0-82% white, 4-100% Asian, 7% Black, and 7% Hispanic. Conclusions: Increased reporting of participant ancestry and ethnicity is needed in the development and validation studies of genetic risk assessment models. BRCAPRO’s validation cohorts have included a higher percentage of Hispanic and Black/African American participants, while MMRPRO and PREMM have been validated in a higher percentage of Asian participants. As debate continues about the utility of currently used racial categories in genetics research, it will be important to determine how best to report on participant diversity. These findings highlight the continued need for genetics researchers to engage BIPOC and identify ways to diversify their participant cohorts.

scholarly journals Understanding the Return of Genomic Sequencing Results Process: Content Review of Participant Summary Letters in the eMERGE Research Network

2020 ◽  
Vol 10 (2) ◽  
pp. 38 ◽  
Author(s):  
John Lynch ◽  
Richard Sharp ◽  
Sharon Aufox ◽  
Sarah Bland ◽  
Carrie Blout ◽  
...  
Keyword(s):  
Medical Records ◽  
Reading Level ◽  
Research Network ◽  
Significant Heterogeneity ◽  
Test Results ◽  
Negative Results ◽  
Genomic Test ◽  
Large Numbers ◽  
Content Review ◽  
Suggested Reading

A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine the features of genetic results letters produced at each Electronic Medical Records and Genomics (eMERGE3) Network site to assess their readability and content. Letters were collected from each site, and a qualitative analysis of letter content and a quantitative analysis of readability statistics were performed. Because letters were produced independently at each eMERGE site, significant heterogeneity in readability and content was found. The content of letters varied widely from a baseline of notifying participants that results existed to more detailed information about positive or negative results, as well as materials for sharing with family members. Most letters were significantly above the Centers for Disease Control-suggested reading level for health communication. While continued effort should be applied to make letters easier to understand, the ongoing challenge of explaining complex genomic information, the implications of negative test results, and the uncertainty that comes with some types of test and result makes simplifying letter text challenging.

ECVAM's Role in the Implementation of the Three Rs Concept in the Field of Biologicals

2002 ◽  
Vol 30 (2_suppl) ◽  
pp. 41-46 ◽  
Author(s):  
Coenraad Hendriksen ◽  
Klaus Cussler ◽  
Marlies Halder
Keyword(s):  
Quality Control ◽  
Animal Models ◽  
Validation Studies ◽  
Polyclonal Antibodies ◽  
Blood Products ◽  
Regulatory Authorities ◽  
Large Numbers ◽  
Related Quality ◽  
Living Organisms ◽  
The Three Rs

Biologicals can be defined as products that are derived from living organisms or are produced by them. They include vaccines, hormones, monoclonal and polyclonal antibodies, blood products and rDNA products. The production of conventionally produced biologicals requires an extensive batch-related quality control, to ensure that these products are both safe and potent. As several of the control tests rely on animal models, it is inevitable that large numbers of animals are used. Many initiatives have been undertaken in the last few decades to reduce, refine and replace the use of animals in this area. ECVAM has been involved in many activities to support the development, validation and implementation of these Three Rs methods. The role that ECVAM has played in a number of validation studies is summarised. It is concluded that ECVAM should continue to support the activities that have been shown to be successful, preferably in collaboration with the regulatory authorities.

A Methodology for Multilingual Automatic Item Generation

2016 ◽  
Vol 37 (3) ◽  
pp. 39-61 ◽  
Author(s):  
Mark J. Gierl ◽  
Hollis Lai
Keyword(s):  
Computer Technology ◽  
Test Development ◽  
Cost Effective ◽  
Computer Algorithms ◽  
Timely Manner ◽  
Item Generation ◽  
Assessment Task ◽  
Test Items ◽  
Large Numbers ◽  
Automatic Item Generation

Testing agencies require large numbers of high-quality items that are produced in a cost-effective and timely manner. Increasingly, these agencies also require items in different languages. In this paper we present a methodology for multilingual automatic item generation (AIG). AIG is the process of using item models to generate test items with the aid of computer technology. We describe a three-step AIG approach where, first, test development specialists identify the content that will be used for item generation. Next, the specialists create item models to specify the content in the assessment task that must be manipulated to produce new items. Finally, elements in the item model are manipulated with computer algorithms to produce new items. Language is added in the item model step to permit multilingual AIG. We illustrate our method by generating 360 English and 360 French medical education items. The importance of item banking in multilingual test development is also discussed.

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