TY - JOUR
T1 - Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways
T2 - A scoping review and recommended methods
AU - Ferket, Bart S.
AU - Baldwin, Zach
AU - Murali, Priyanka
AU - Pai, Akila
AU - Mittendorf, Kathleen F.
AU - Russell, Heidi V.
AU - Chen, Flavia
AU - Lynch, Frances L.
AU - Lich, Kristen Hassmiller
AU - Hindorff, Lucia A.
AU - Savich, Renate
AU - Slavotinek, Anne
AU - Smith, Hadley Stevens
AU - Gelb, Bruce D.
AU - Veenstra, David L.
N1 - Publisher Copyright:
© 2022 American College of Medical Genetics and Genomics
PY - 2022/10
Y1 - 2022/10
N2 - Purpose: Methodological challenges have limited economic evaluations of genome sequencing (GS) and exome sequencing (ES). Our objective was to develop conceptual frameworks for model-based cost-effectiveness analyses (CEAs) of diagnostic GS/ES. Methods: We conducted a scoping review of economic analyses to develop and iterate with experts a set of conceptual CEA frameworks for GS/ES for prenatal testing, early diagnosis in pediatrics, diagnosis of delayed-onset disorders in pediatrics, genetic testing in cancer, screening of newborns, and general population screening. Results: Reflecting on 57 studies meeting inclusion criteria, we recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses of costs of ES strategies and postpartum care, as well as genetic diagnoses and pregnancy outcomes. For early diagnosis in pediatrics, modeling quality-adjusted life years (QALYs) and costs over ≥20 years for rapid turnaround GS/ES. For hereditary cancer syndrome testing, modeling cumulative costs and QALYs for the individual tested and first/second/third-degree relatives. For tumor profiling, not restricting to treatment uptake or response and including QALYs and costs of downstream outcomes. For screening, modeling lifetime costs and QALYs and considering consequences of low penetrance and GS/ES reanalysis. Conclusion: Our frameworks can guide the design of model-based CEAs and ultimately foster robust evidence for the economic value of GS/ES.
AB - Purpose: Methodological challenges have limited economic evaluations of genome sequencing (GS) and exome sequencing (ES). Our objective was to develop conceptual frameworks for model-based cost-effectiveness analyses (CEAs) of diagnostic GS/ES. Methods: We conducted a scoping review of economic analyses to develop and iterate with experts a set of conceptual CEA frameworks for GS/ES for prenatal testing, early diagnosis in pediatrics, diagnosis of delayed-onset disorders in pediatrics, genetic testing in cancer, screening of newborns, and general population screening. Results: Reflecting on 57 studies meeting inclusion criteria, we recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses of costs of ES strategies and postpartum care, as well as genetic diagnoses and pregnancy outcomes. For early diagnosis in pediatrics, modeling quality-adjusted life years (QALYs) and costs over ≥20 years for rapid turnaround GS/ES. For hereditary cancer syndrome testing, modeling cumulative costs and QALYs for the individual tested and first/second/third-degree relatives. For tumor profiling, not restricting to treatment uptake or response and including QALYs and costs of downstream outcomes. For screening, modeling lifetime costs and QALYs and considering consequences of low penetrance and GS/ES reanalysis. Conclusion: Our frameworks can guide the design of model-based CEAs and ultimately foster robust evidence for the economic value of GS/ES.
KW - Cost-effectiveness analysis
KW - Decision modeling
KW - Economic evaluation
KW - Exome sequencing
KW - Genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85134755262&partnerID=8YFLogxK
U2 - 10.1016/j.gim.2022.06.004
DO - 10.1016/j.gim.2022.06.004
M3 - Article
C2 - 35833928
AN - SCOPUS:85134755262
SN - 1098-3600
VL - 24
SP - 2014
EP - 2027
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 10
ER -