DNA cascade testing for heart disease
Evaluating the value of alternative approaches for FH cascade testing using data from services in three regions
Funder: National Institute for Health Research – Health Technology Assessment Programme
The project:Familial hypercholesterolaemia (FH) is the commonest autosomal dominant disorder, which if left untreated will cause around 50% of men to develop coronary heart disease by the age of 50 years and women approximately 10 years later. Around 50% of first-degree relatives in people with FH will also have the condition. Cascade testing of relatives is the most efficient and cost-effective approach to identifying additional people with FH. However, the most effective approach of how to contact relatives is unknown. This project aims to evaluate the cost-effectiveness of alternative approaches for FH cascade testing using data from services in three regions, the literature using systematic review techniques, and linkage of national clinical databases.
A systematic review of cascade strategies that included 24 non-comparative studies found the combined approach of direct and indirect contacting of relatives led to a higher yield of relatives tested than either of the two approaches alone.
From routinely collected data identified 21-29% of index cases have genetically-confirmed FH, and women, first-degree relatives and those contacted directly by health professionals were more likely to complete cascade testing. 26% of patients with FH remain untreated after 2 years of diagnosis, and another 70% did not achieve target treatment levels. A cost-effectiveness cohort Markov model found the net health gain from diagnosis ranged between -0.27 to 2.51 QALYs at the £15,000/QALY threshold, being greater in males and people with higher baseline cholesterol.
Decision modelling found protocols on the cost-effectiveness frontier generally involved starting cascade testing from genetically-confirmed index cases and contacting first and second degree relatives simultaneously and directly by the service.
Interviews found a service-led direct contact approach was more reliable, but combining direct and indirect approaches (using either or both), guided by index patients and differing relationships within families, was most acceptable.
Although the most cost-effective approach to cascade screening of relatives is by services directly contacting relatives; adopting a more flexible approach of combining direct and/or indirect methods of contacting, according to individual family relationships, may be more acceptable in practice.
For more information contact: nadeem.qureshi@nottingham.ac.uk
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