Incorporating Cascade Effects of Genetic Testing in Economic Evaluation: A Scoping Review of Methodological Challenges

Abstract

Cascade genetic testing is indicated for family members of individuals testing positive on a genetic test, and is particularly relevant for child health because of their vulnerability and the long-term health and economic implications. Cascade testing has patient- and health system-level implications; however cascade costs and health effects are not routinely considered in economic evaluation. The methodological challenges associated with incorporating cascade effects in economic evaluation require examination. The purpose of this scoping review was to identify published economic evaluations that considered cascade genetic testing. Citation databases were searched for English-language economic evaluations reporting on cascade genetic testing. Nineteen publications were included. In four, genetic testing was used to identify new index patients—cascade effects were also considered; thirteen assessed cascade genetic testing strategies for the identification of at-risk relatives; and two calculated the costs of cascade genetic testing as a secondary objective. Methodological challenges associated with incorporating cascade effects in economic evaluation are related to study design, costing, measurement and valuation of health outcomes, and modeling. As health economic studies may currently be underestimating both the cost and health benefits attributable to genetic technologies through omission of cascade effects, development of methods to address these difficulties is required.

Recommendations for Emerging Good Practice and Future Research in Relation to Family and Caregiver Health Spillovers in Health Economic Evaluations: A Report of the SHEER Task Force

“…Furthermore, restriction of the perspective to that of the healthcare system/health payer limits full examination of the interaction of more broadly incurred costs, and the characteristics and extent of spillovers. For example, limited consideration has been given to spillover effects associated with the sharing of genetic information, also termed “cascade effects” [ 89 ], which may inform disease risks not only for the patient but for other members of the family. The task force also forwent differentiation between ‘first-order’ and ‘second-order’ spillovers.…”

Swiss cost-effectiveness analysis of universal screening for Lynch syndrome of patients with colorectal cancer followed by cascade genetic testing of relatives

“…Our cost-effectiveness analysis incorporated costs of carrier testing of relatives, an aspect that is often omitted from cost-effectiveness analyses of genetic testing technologies. 30 Universal LS screening with cascade testing of relatives is cost-effective in around 80% of scenarios. The alternative strategy prevents 17 deaths at the cost of CHF785 645 per death avoided, with ICER of CHF65 058 per QALY saved and below the acceptable Swiss cost-effectiveness threshold of CHF100 000.…”

Access to novel drugs and therapeutics for children and youth: Eliciting citizens' values to inform public funding decisions

“…In the context of precision health interventions, evaluations must weigh uncertainties related to limited data on safety and efficacy. When applied to child health technologies, these frameworks face the additional challenge of incorporating the unique evidentiary, physiological, health‐system and societal considerations attached to children 27–31 . The absence of a standardized framework for the evaluation and reimbursement of precision health technologies for children thus has significant consequences for children and youth.…”