Cost effectiveness of cascade testing for familial hypercholesterolaemia, based on data from familial hypercholesterolaemia services in the UK

Abstract

AimsFamilial hypercholesterolaemia (FH) is a vastly under-diagnosed genetic disorder, associated with early development of coronary heart disease and premature mortality which can be substantially reduced by effective treatment. Patents have recently expired on high-intensity statins, reducing FH treatment costs. We build a model using UK data to estimate the cost effectiveness of DNA testing of relatives of those with monogenic FH.Methods and ResultsA Markov model was used to estimate the cost effectiveness of cascade testing, using data from UK cascade services. The estimated incremental cost effectiveness ratio (ICER) was £5806 and the net marginal lifetime cost per relative tested was £2781. More than 80% of lifetime costs were diagnosis-related and incurred in the 1st year. In UK services, 23% of 6396 index cases were mutation-positive. For each mutation-positive index case, 1.33 relatives were tested, resulting overall in a rate of 0.31 tested relatives per tested index case. If the number of relatives tested per tested index case rose to 3.2 (projected by National Institute for Health and Care Excellence in 2008) the ICER would reduce to £2280 and lifetime costs to £1092.ConclusionCascade testing of relatives of those with suspected FH is highly cost effective. The current Europe-wide high levels of undiagnosed FH, and associated morbidity and mortality, mean adoption of cascade services should yield substantial quality of life and survival gains.

Reverse cascade screening for familial hypercholesterolemia in high‐risk Chinese families

“…from index children with heterozygous FH, emphasizing the greater yield of reverse cascade screening in the present setting.Several international studies have emphasized that cascade screening in adults is highly cost-effective. [22][23][24] However, owing to China's one-child policy (and, recently, two-child policy), few children have siblings, so the yield of cascade screening may be restricted.Adjusting for pedigree size, yield of detection of FH in the strategy presented was approximately 3-fold higher than that found in cascade screening programs in heterozygous FH adults. [25][26][27][28][29][30] The yield of any cascade testing program, and hence its potential to identify a greater proportion of affected individuals in the community, is dependent on an effective detection of index cases.…”

Cost-effectiveness of universal screening for familial hypercholesterolaemia (fh) at age 1-2 years

“…Markov models estimated lifetime costs and health outcomes for the cohorts screened under each alternative, in view of the number of diagnoses made Data for parameter estimation were obtained from a systematic review (published 2000), 26 updated with a systematic literature search (detailed in Supplementary File 1) and data from a recent economic evaluation and the Welsh FH CT programme. 17,28 As relevant data were sparse, no formal syntheses were undertaken and model parameters were estimated conservatively.…”

“…That is, where RCT was part of the screening alternative it was assumed two mutation-positive individuals would be identified via RCT for every mutation-positive individual identified in US. It was assumed the age-distribution of those identified by RCT would be as observed in the Welsh CT programme, 17,28 and that 70% of RCT-identified mutation-positive relatives would meet the base case FH definition. [30][31][32] For purposes of costing RCT (see below), probability of mutation detection among relatives was assumed to be Mendelian.…”

“…9,16 Since 2008, the UK National Institute for Health and Care Excellence (NICE) has recommended cascade testing (CT, of first-, second-and third-degree relatives) for FH, 16 and this has been shown to be feasible, acceptable and cost-effective. 17,18 There has been limited roll-out of CT in England, as local teams have not commissioned the relevant services, but it has been relatively successful in other parts of the UK. 19 As CT depends on index case supply, there is interest in screening to identify index cases.…”

Widening the spectrum of genetic testing in familial hypercholesterolaemia: Will it translate into better patient and population outcomes?

“…In contrast with homozygous FH, cascade screening would not be of value in this recessive condition.2.5 | Cost-effectiveness of genetic analysis in FHNo prospective, randomised studies designed to assess the economic consequences of genetic testing for FH have been conducted. However, various health economic analyses from Australia, Spain, Poland and the United Kingdom have generally found genetic testing of suspected index cases and cascade testing of family members, to be cost-effective relative to accepted thresholds for public health insurer expenditure per quality-adjusted life year gained [37][38][39][40]. A United States analysis did not find genetic screening to be cost-effective.…”