Abstract
Objectives: Whole exome sequencing (WES) is commonly used for diagnosing familial hypercholesterolemia
(FH). The emergence of long-read sequencing (LRS) promises to improve the characterization of genetic FH. By
pilot-testing our newly developed economic evaluation reference case for precision medicine, we conducted
cost-effectiveness analysis (CEA) on FH cascade testing in Thailand, including conventional CEA to estimate the
value for money of WES at market-access stage, and early CEA to identify target product profiles (TPPs) of LRS.
Methods: We formed an expert panel consisting of health economists, clinicians and developers. Following
expert consultation, we developed hybrid decision tree and Markov models to reflect Thailand clinical practice.
The comparator was standard-of-care (SoC). Input parameters were sourced from the Thai FH registry, local
hospitals, published literature and expert elicitation. The willingness-to-pay threshold was 160,000 THB.
Sensitivity analyses were performed. TPPs were developed using reversed CEA approach to determine a range
of desirable cost packages for LRS at minimally acceptable target, acceptable target and Ideal target values.
Uncertainty in TPPs were assessed stepwise, including probabilistic analysis for LRS accuracy and scenario
analysis for uptake.
Results: The estimated incremental cost-effectiveness ratio (ICER) of cascade testing versus SoC was
89,619/QALY for WES. WES was 77.05% likely to be cost-effective versus SoC at Thai WTP threshold. Parameters
with the greatest impact were number of relatives contacted and the uptake of relatives. LRS requires a
maximum cost package of THB 173,134 for LRS to be cost-effective versus SoC under the minimally acceptable
target, THB 46,197 to be cost-effective versus WES under the acceptable target, and THB 39,491 to be the best
product at the ideal target.
Conclusion: FH cascade testing is generally cost-effective in Thailand. WES is advantageous over SoC of THB
39,491 to THB 173,134, and higher cost ceilings can be accepted as accuracy and uptake increase. In addition,
this study follows aligns with PM-RC recommendations, addressing crucial aspects such as defining the target
population, evaluating all comparator options including accuracy and uptake, integrating disutility
considerations, and encompassing comprehensive costs like patient recruitment, sample collection, result
communication, and genetic testing. Expert elicitation was employed where applicable, contributing to robust
study outcomes. Notably, this study represents a pioneering effort in providing health economic evaluations for
both conventional and early FH cascade testing methodologies.
