The Impact of Biomarker Screening and Cascade Genetic Testing on the Cost-Effectiveness of MODY Genetic Testing

Abstract

In the US, genetic testing for MODY is frequently delayed due to difficulty with insurance coverage. Understanding the economic implications of clinical genetic testing is imperative to advance precision medicine for diabetes. The objective of this paper is to assess the cost-effectiveness of genetic testing, preceded by biomarker screening and followed by cascade genetic testing of first-degree relatives, for subtypes of MODY in US pediatric patients with diabetes. Research Design and Methods: We used simulation models of distinct forms of diabetes to forecast the clinical and economic consequences of a systematic genetic testing strategy compared to usual care over a 30-year time horizon. In the genetic testing arm, patients with MODY received treatment changes (sulfonylureas for HNF1A-/HNF4A-MODY associated with a 1.0% reduction in HbA1c; no treatment for GCK-MODY). Study outcomes included costs, life expectancy (LE), and quality-adjusted life years (QALY). Results: The strategy of biomarker screening and genetic testing was cost-saving as it increased average quality of life (+0.0052 QALY) and decreased costs (-$191) per simulated patient relative to the control arm. Adding cascade genetic testing increased quality of life benefits (+0.0081 QALY) and lowered costs further (-$735). Conclusions: A combined strategy of biomarker screening and genetic testing for MODY in the US pediatric diabetes population is cost-saving compared to usual care, and the addition of cascade genetic testing accentuates the strategy's benefits. Widespread implementation of this strategy could improve the lives of patients with MODY while saving the health system money, illustrating the potential population health benefits of personalized medicine.

Clinical Genetic Screening in Adult Patients with Kidney Disease

“…More research is also needed to investigate the long-term effect of establishing a molecular diagnosis on health care utilization and outcomes, to facilitate third-party payer coverage for diagnostic testing. In this regard, there are emerging data on the cost benefit of genetic testing in fields such as diabetes or cancer (118)(119)(120), and similar research would benefit the nephrology field. With the rapid pace of discovery, we also anticipate that the nephrology field will increasingly deploy clinical trials stratified on specific molecular defects rather than the clinical category of disease, increasing the power and safety profile of studies.…”

Localized increases in CEPT1 and ATGL elevate plasmalogen phosphatidylcholines in HDLs contributing to atheroprotective lipid profiles in hyperglycemic GCK-MODY

“…In China, clinical misdiagnosis for GCK-MODY was reported at 85.4%, with 58.2% of these patients receiving incorrect treatment [ 4 ]. While genetic testing remains a gold standard for diagnosis of GCK-MODY, technical and financial constraints preclude its clinical implementation on a large scale [ 5 ]. Developing a good biomarker screening that precedes genetic testing, therefore, is expected to increase the cost-effectiveness of genetic testing for GCK-MODY [ 5 ].…”

Pathogenic variants in actionable MODY genes are associated with type 2 diabetes

“…Actionable genes linked with monogenic diabetes also include HNF1B, GATA4 and GATA6 as they are associated with necessary additional clinical investigations focused on the heart or kidney function [14][15][16] . In this context, the genetic diagnosis of young patients with a suspicion of monogenic diabetes has proven cost-effective and improved the quality of life of patients 17,18 . Recent large-scale association studies have started to bridge the gap between monogenic diabetes and common T2D, as a way to develop precision medicine in diabetes.…”