The Clinician-reported Genetic Testing Utility Index (C-GUIDE) for Prenatal Care: Initial evidence of content and construct validity

Robin Z Hayeems; Stephanie Luca; Bowen Xiao; Christie Boswell-Patterson; Carolina Lavin Venegas; Clarissa R Abi Semaan; Tessa Kolar; Diane Myles-Reid; Lauren Chad; David Dyment; Kym M Boycott; Joanna Lazier; Wendy J Ungar; Christine M Armour

doi:10.1016/j.gim.2024.101306

The Clinician-reported Genetic Testing Utility Index (C-GUIDE) for Prenatal Care: Initial evidence of content and construct validity

Genet Med. 2024 Oct 24;27(1):101306. doi: 10.1016/j.gim.2024.101306. Online ahead of print.

Affiliations

¹ Program in Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada. Electronic address: [email protected].
² Program in Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada.
³ Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
⁴ Division of Medical Genetics, British Columbia Children's Hospital, Vancouver, BC, Canada.
⁵ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Markham Fertility Centre, Toronto, ON, Canada.
⁶ Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, Canada; Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada; Department of Bioethics, The Hospital for Sick Children, Toronto, ON, Canada.
⁷ Program in Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada.

PMID: 39489893
DOI: 10.1016/j.gim.2024.101306

Abstract

Purpose: To develop and assess the face and construct validity of the Clinician-reported Genetic Testing Utility Index (C-GUIDE) for genetic testing in prenatal care.

Methods: After a literature review and consultation with clinical experts, a preliminary draft of C-GUIDE Prenatal was developed. Its face and content validity were then assessed by 19 prenatal genetics' providers using interviews and surveys. Feedback informed further revisions. To test construct validity, 4 geneticist raters completed C-GUIDE on a retrospective sample of cases that received prenatal genetic testing and completed a concurrent global assessment of utility of these cases using an anchor item. A generalized estimating equations model was used to adjust for rater correlation and measure the association between C-GUIDE scores, global item scores, and potential clinical variables.

Results: To develop C-GUIDE Prenatal, 7 items were removed, 10 items were modified, and 4 items were added. For 101 cases rated for validation, on average, a 1-point increase in the global item score was associated with an increase of 1.1 in the C-GUIDE score (P = .04). Compared with uninformative results, informative positive and informative negative results were associated with a mean increase of 10.7 (SE = 1.05) (P < .001) and 5.6 (SE = 1.85) (P < .001), respectively. As indications for testing, known/familial variants were associated with a mean increase in the C-GUIDE score of 4.7 (SE = 2.21) (P < .001) compared with ultrasound findings. C-GUIDE scores increased by a mean of 3.0 (SE = 0.23) among cases for whom pregnancies were ongoing compared with those for whom they were not (P < .01).

Conclusion: The significant positive associations between C-GUIDE total and the global item score and between C-GUIDE total, result type, indication for testing, and pregnancy status in the expected directions provide evidence of construct validity.

Keywords: Clinical utility; Measurement index; Outcomes research; Prenatal diagnostics; Validation.