| アブストラクト | BACKGROUND: Cascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective. OBJECTIVES: The objectives were to determine the yield of cases from different cascade-testing protocols, treatment patterns, and short- and long-term outcomes for people with familial hypercholesterolaemia; to evaluate the cost-effectiveness of alternative protocols for familial hypercholesterolaemia cascade testing; and to qualitatively assess the acceptability of different cascade-testing protocols to individuals and families with familial hypercholesterolaemia, and to health-care providers. DESIGN AND METHODS: This study comprised systematic reviews and analysis of three data sets: PASS (PASS Software, Rijswijk, the Netherlands) hospital familial hypercholesterolaemia databases, the Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked primary-secondary care data set, and a specialist familial hypercholesterolaemia register. Cost-effectiveness modelling, incorporating preceding analyses, was undertaken. Acceptability was examined in interviews with patients, relatives and health-care professionals. RESULT: Systematic review of protocols: based on data from 4 of the 24 studies, the combined approach led to a slightly higher yield of relatives tested [40%, 95% confidence interval (CI) 37% to 42%] than the direct (33%, 95% CI 28% to 39%) or indirect approaches alone (34%, 95% CI 30% to 37%). The PASS databases identified that those contacted directly were more likely to complete cascade testing (p < 0.01); the CPRD-HES data set indicated that 70% did not achieve target treatment levels, and demonstrated increased cardiovascular disease risk among these individuals, compared with controls (hazard ratio 9.14, 95% CI 8.55 to 9.76). The specialist familial hypercholesterolaemia register confirmed excessive cardiovascular morbidity (standardised morbidity ratio 7.17, 95% CI 6.79 to 7.56). Cost-effectiveness modelling found a net health gain from diagnosis of -0.27 to 2.51 quality-adjusted life-years at the willingness-to-pay threshold of pound15,000 per quality-adjusted life-year gained. The cost-effective protocols cascaded from genetically confirmed index cases by contacting first- and second-degree relatives simultaneously and directly. Interviews found a service-led direct-contact approach was more reliable, but combining direct and indirect approaches, guided by index patients and family relationships, may be more acceptable. LIMITATIONS: Systematic reviews were not used in the economic analysis, as relevant studies were lacking or of poor quality. As only a proportion of those with primary care-coded familial hypercholesterolaemia are likely to actually have familial hypercholesterolaemia, CPRD analyses are likely to underestimate the true effect. The cost-effectiveness analysis required assumptions related to the long-term cardiovascular disease risk, the effect of treatment on cholesterol and the generalisability of estimates from the data sets. Interview recruitment was limited to white English-speaking participants. CONCLUSIONS: Based on limited evidence, most cost-effective cascade-testing protocols, diagnosing most relatives, select index cases by genetic testing, with services directly contacting relatives, and contacting second-degree relatives even if first-degree relatives have not been tested. Combined approaches to contact relatives may be more suitable for some families. FUTURE WORK: Establish a long-term familial hypercholesterolaemia cohort, measuring cholesterol levels, treatment and cardiovascular outcomes. Conduct a randomised study comparing different approaches to contact relatives. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018117445 and CRD42019125775. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 16. See the NIHR Journals Library website for further project information. |
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| ジャーナル名 | Health technology assessment (Winchester, England) |
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| 投稿日 | 2023/11/4 |
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| 投稿者 | Qureshi, Nadeem; Woods, Bethan; Neves de Faria, Rita; Saramago Goncalves, Pedro; Cox, Edward; Leonardi Bee, Jo; Condon, Laura; Weng, Stephen; Akyea, Ralph K; Iyen, Barbara; Roderick, Paul; Humphries, Steve E; Rowlands, William; Watson, Melanie; Haralambos, Kate; Kenny, Ryan; Datta, Dev; Miedzybrodzka, Zosia; Byrne, Christopher; Kai, Joe |
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| 組織名 | PRISM Research Group, Centre for Academic Primary Care, School of Medicine,;University of Nottingham, Nottingham, UK.;Centre for Health Economics, University of York, York, UK.;Cardiovascular and Metabolism, Janssen Research and Development, High Wycombe,;UK.;Primary Care, Population Sciences and Medical Education, University of;Southampton, Southampton, UK.;Centre for Cardiovascular Genetics, Institute for Cardiovascular Science,;University College London, London, UK.;Patient representative.;Wessex Clinical Genetics Service, University Hospital Southampton NHS Foundation;Trust, Southampton, UK.;Familial Hypercholesterolaemia Service, University Hospital of Wales, Cardiff,;Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne,;Lipid Unit, University Hospital Llandough, Penarth, UK.;Division of Applied Medicine, University of Aberdeen, Aberdeen, UK.;Southampton National Institute for Health and Care Research Biomedical Research;Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/37924278/ |
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