Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia : systematic reviews, qualitative study and cost-effectiveness analysis
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 £15,000 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Health technology assessment (Winchester, England) - 27(2023), 16 vom: 01. Okt., Seite 1-140 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Qureshi, Nadeem [VerfasserIn] |
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| Links: |
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| Themen: |
97C5T2UQ7J |
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| Anmerkungen: |
Date Completed 17.01.2024 Date Revised 17.01.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.3310/CTMD0148 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364161310 |
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| 100 | 1 | |a Qureshi, Nadeem |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia |b systematic reviews, qualitative study and cost-effectiveness analysis |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 £15,000 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a Study registration: This study is registered as PROSPERO CRD42018117445 and CRD42019125775 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CARDIOVASCULAR DISEASES | |
| 650 | 4 | |a CHOLESTEROL | |
| 650 | 4 | |a GENETIC TESTING | |
| 650 | 4 | |a HEART DISEASE RISK FACTORS | |
| 650 | 4 | |a HYPERCHOLESTEROLAEMIA | |
| 650 | 4 | |a HYPERLIPOPROTEINEMIA TYPE II | |
| 650 | 4 | |a PEDIGREE | |
| 650 | 7 | |a Cholesterol |2 NLM | |
| 650 | 7 | |a 97C5T2UQ7J |2 NLM | |
| 700 | 1 | |a Woods, Bethan |e verfasserin |4 aut | |
| 700 | 1 | |a Neves de Faria, Rita |e verfasserin |4 aut | |
| 700 | 1 | |a Saramago Goncalves, Pedro |e verfasserin |4 aut | |
| 700 | 1 | |a Cox, Edward |e verfasserin |4 aut | |
| 700 | 1 | |a Leonardi Bee, Jo |e verfasserin |4 aut | |
| 700 | 1 | |a Condon, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Weng, Stephen |e verfasserin |4 aut | |
| 700 | 1 | |a Akyea, Ralph K |e verfasserin |4 aut | |
| 700 | 1 | |a Iyen, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Roderick, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Humphries, Steve E |e verfasserin |4 aut | |
| 700 | 1 | |a Rowlands, William |e verfasserin |4 aut | |
| 700 | 1 | |a Watson, Melanie |e verfasserin |4 aut | |
| 700 | 1 | |a Haralambos, Kate |e verfasserin |4 aut | |
| 700 | 1 | |a Kenny, Ryan |e verfasserin |4 aut | |
| 700 | 1 | |a Datta, Dev |e verfasserin |4 aut | |
| 700 | 1 | |a Miedzybrodzka, Zosia |e verfasserin |4 aut | |
| 700 | 1 | |a Byrne, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Kai, Joe |e verfasserin |4 aut | |
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