Customized "Clinical Interpretive Reports"of Genomic Sequencing Results for Non-Genetics Providers in Safety-Net Neonatal Intensive Care Units: Development and Implementation
Health Services and Implementation
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Primary Categories:
- Health services and Implementation
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Secondary Categories:
- Health services and Implementation
Introduction:
Rapid genomic sequencing (rGS) has high diagnostic and clinical utility in Neonatal Intensive Care Units (NICUs). However, safety-net NICUs that disproportionately serve marginalized populations face barriers that limit access to rGS, including limited genetics expertise, high cost, and complicated logistics. The Virtual Genome Center (VIGOR) study is an implementation study that aims to address these barriers by providing rGS in safety-net NICUs using an innovative virtual delivery model. In the VIGOR study, neonatal providers with often limited genetics expertise who work in safety-net NICUs disclose rGS results to families. We investigated the feasibility and utility of using customized “Clinical Interpretive Reports” (CIRs) to assist non-genetics neonatal providers with interpreting, disclosing, and managing care based on rGS results.
Methods:
In the VIGOR study, non-genetics neonatal providers at participating safety-net NICUs identify eligible infants, the central study team consents families, and enrolled infants receive rGS through a clinically accredited vendor. We developed five types of CIRs to provide additional customized interpretation of rGS results based on reported phenotypes, literature review, expert opinion, and vendor reports. The CIRs link the rGS results to clinical management considerations (for workup and treatment), research opportunities (including clinical trials and assessment of pathogenic variant amenability to antisense oligonucleotide therapy approaches), and patient and family resources. We developed workflows for the multidisciplinary central study team with expertise in neonatology and genetics/genomics to rapidly triage rGS results, create CIRs, and deliver CIRs to participating sites. Neonatal providers receive the vendor report and the customized CIR, disclose rGS results to families of enrolled infants, and complete a post-disclosure survey. We analyzed summary statistics for the vendor reports, CIRs, and post-disclosure surveys for the first 100 enrolled infants who received rGS.
Results:
The vendor issued 23 (23%) Positive, 45 (45%) Negative, and 32 (32%) Possibly Associated with Reported Phenotype rGS reports for the clinical indication. In comparison, the CIRs were triaged to 22 (22%) Diagnostic, 10 (10%) Likely of Clinical Relevance, 10 (10%) Indeterminate Clinical Relevance, 5 (5%) Less Likely of Clinical Relevance, and 53 (53%) Non-Diagnostic. We delivered 97/100 CIRs (97%) within our goal timeframe of 3 business days from the vendor report (average 1.3). We made clinical management recommendations in 40/100 CIRs (40%), including consideration of treatment changes in 4 cases (4%), referral to one or more specialists in 35 (35%), additional laboratory tests in 11 (11%), additional imaging in 13 (13%), monitoring for associated clinical features in 7 (7%), and family member genetic testing in 4 (4%). For the 86 disclosures in which the neonatal provider filled out the post-disclosure survey, most neonatal providers reported using the CIR prior to disclosing results to families (80, 93%). For the 6 (7%) who did not view the CIR prior to disclosure, 5 disclosed rGS results based off of the preliminary verbal results prior to the final vendor report and CIR, and 1 reported insufficient time to view the CIR prior to disclosure. Of the 80 providers who viewed the CIR prior to disclosure, 59 (74%) found it very helpful, 20 (25%) found it somewhat helpful, and 1 found it not helpful (1%).
Conclusion:
It is feasible to rapidly develop customized genomic sequencing reports to assist non-genetics neonatal providers with returning rGS results. Neonatal providers in safety-net NICUs report using these reports and finding them helpful. Our findings suggest that virtual delivery models including guidance like CIRs may hold promise for equitably advancing genomic care.
Rapid genomic sequencing (rGS) has high diagnostic and clinical utility in Neonatal Intensive Care Units (NICUs). However, safety-net NICUs that disproportionately serve marginalized populations face barriers that limit access to rGS, including limited genetics expertise, high cost, and complicated logistics. The Virtual Genome Center (VIGOR) study is an implementation study that aims to address these barriers by providing rGS in safety-net NICUs using an innovative virtual delivery model. In the VIGOR study, neonatal providers with often limited genetics expertise who work in safety-net NICUs disclose rGS results to families. We investigated the feasibility and utility of using customized “Clinical Interpretive Reports” (CIRs) to assist non-genetics neonatal providers with interpreting, disclosing, and managing care based on rGS results.
Methods:
In the VIGOR study, non-genetics neonatal providers at participating safety-net NICUs identify eligible infants, the central study team consents families, and enrolled infants receive rGS through a clinically accredited vendor. We developed five types of CIRs to provide additional customized interpretation of rGS results based on reported phenotypes, literature review, expert opinion, and vendor reports. The CIRs link the rGS results to clinical management considerations (for workup and treatment), research opportunities (including clinical trials and assessment of pathogenic variant amenability to antisense oligonucleotide therapy approaches), and patient and family resources. We developed workflows for the multidisciplinary central study team with expertise in neonatology and genetics/genomics to rapidly triage rGS results, create CIRs, and deliver CIRs to participating sites. Neonatal providers receive the vendor report and the customized CIR, disclose rGS results to families of enrolled infants, and complete a post-disclosure survey. We analyzed summary statistics for the vendor reports, CIRs, and post-disclosure surveys for the first 100 enrolled infants who received rGS.
Results:
The vendor issued 23 (23%) Positive, 45 (45%) Negative, and 32 (32%) Possibly Associated with Reported Phenotype rGS reports for the clinical indication. In comparison, the CIRs were triaged to 22 (22%) Diagnostic, 10 (10%) Likely of Clinical Relevance, 10 (10%) Indeterminate Clinical Relevance, 5 (5%) Less Likely of Clinical Relevance, and 53 (53%) Non-Diagnostic. We delivered 97/100 CIRs (97%) within our goal timeframe of 3 business days from the vendor report (average 1.3). We made clinical management recommendations in 40/100 CIRs (40%), including consideration of treatment changes in 4 cases (4%), referral to one or more specialists in 35 (35%), additional laboratory tests in 11 (11%), additional imaging in 13 (13%), monitoring for associated clinical features in 7 (7%), and family member genetic testing in 4 (4%). For the 86 disclosures in which the neonatal provider filled out the post-disclosure survey, most neonatal providers reported using the CIR prior to disclosing results to families (80, 93%). For the 6 (7%) who did not view the CIR prior to disclosure, 5 disclosed rGS results based off of the preliminary verbal results prior to the final vendor report and CIR, and 1 reported insufficient time to view the CIR prior to disclosure. Of the 80 providers who viewed the CIR prior to disclosure, 59 (74%) found it very helpful, 20 (25%) found it somewhat helpful, and 1 found it not helpful (1%).
Conclusion:
It is feasible to rapidly develop customized genomic sequencing reports to assist non-genetics neonatal providers with returning rGS results. Neonatal providers in safety-net NICUs report using these reports and finding them helpful. Our findings suggest that virtual delivery models including guidance like CIRs may hold promise for equitably advancing genomic care.