Familial hypercholesterolemia: A systematic review of modeling studies on screening interventions

Beate Jahn; Júlia Santamaria; Hans Dieplinger; Christoph J Binder; Christoph Ebenbichler; Sabine Scholl-Bürgi; Annette Conrads-Frank; Ursula Rochau; Felicitas Kühne; Igor Stojkov; Jovan Todorovic; Lyndon James; Uwe Siebert

doi:10.1016/j.atherosclerosis.2022.06.1011

Familial hypercholesterolemia: A systematic review of modeling studies on screening interventions

Atherosclerosis. 2022 Aug:355:15-29. doi: 10.1016/j.atherosclerosis.2022.06.1011. Epub 2022 Jun 21.

Affiliations

¹ Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria; Division of Health Technology Assessment, ONCOTYROL - Center for Personalized Cancer Medicine, Innsbruck, Austria.
² Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria.
³ Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
⁴ Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
⁵ Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria.
⁶ University Clinic for Pediatrics I, Tirol Kliniken GmbH, Innsbruck, Austria.
⁷ Institute for Technology Assessment and Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria; Division of Health Technology Assessment, ONCOTYROL - Center for Personalized Cancer Medicine, Innsbruck, Austria; Institute for Technology Assessment and Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Health Decision Science and Departments of Epidemiology and Health Policy & Management, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: uwe.siebert@umit-tirol.at.

PMID: 35870306
DOI: 10.1016/j.atherosclerosis.2022.06.1011

Abstract

Background and aims: FH is still underdiagnosed. Cost-effectiveness results of preventive screening strategies vary. We aimed at systematically assessing the benefits, harms and cost effectiveness of screening for familial hypercholesterolemia (FH) and at providing an overview of the main characteristics and methodological approaches of applied decision-analytic models.

Methods: A systematic literature search was conducted in MEDLINE, EconLit, CRD-databases and the CEA-registry for FH screening starting 2012. Earlier studies were included from a published systematic review. Results were reported in standardized semi-quantitative evidence tables. Costs were converted to current euros. Incremental cost-effectiveness ratios (ICERs) were recalculated according to economic guidelines.

Results: Out of our 211 retrieved studies, eight were included in the review in addition to six studies from an earlier review. Studies were conducted in Europe (UK, The Netherlands, Spain, Poland), USA and Australia evaluating cascade (CS), opportunistic (OS), universal screening (UniS), or combinations using genetic testing, clinical criteria or combinations. Studies evaluating only CS identified strategies with an ICER of up to 37,100 EUR/quality-adjusted life-year (QALY) but some strategies were dominated depending on test combinations. UniS of newborns in combination with CS had an ICER≤15,000 EUR/QALY for sequential cholesterol-genetic screening. In other studies, UniS was dominated by OS/CS.

Conclusions: Our systematic review demonstrates the values of FH screening and provides an overview of potentially relevant screening strategies to be tested using a decision-analytic model for the respective country or region. Future research is needed on the transferability of results to other countries and modeling spillover effects to newborns.

Keywords: Cost effectiveness; Cost-utility analysis; Familial hypercholesterolemia; Familial hyperlipidemia; Genetic disorders; Screening.

Publication types

Review
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Cost-Benefit Analysis
Genetic Testing / methods
Humans
Hyperlipoproteinemia Type II* / diagnosis
Hyperlipoproteinemia Type II* / genetics
Infant, Newborn
Mass Screening / methods
Quality-Adjusted Life Years