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Diagnostic strategies using DNA testing for hereditary haemochromatosis in at-risk populations: a systematic review and economic evaluation

Diagnostic strategies using DNA testing for hereditary haemochromatosis in at-risk populations: a systematic review and economic evaluation
Diagnostic strategies using DNA testing for hereditary haemochromatosis in at-risk populations: a systematic review and economic evaluation
OBJECTIVE: To evaluate DNA testing for detecting hereditary haemochromatosis (HHC) in subgroups of patients suspected of having the disorder and in family members of those diagnosed with HHC. DATA SOURCES: Major electronic databases, searched from inception to April 2007. REVIEW METHODS: A systematic review was undertaken using a priori methods and a de novo model developed to assess costs and consequences of DNA testing. RESULTS: Eleven studies were identified for estimating the clinical validity of genotyping for the C282Y mutation for the diagnosis of HHC. No clinical effectiveness studies meeting the inclusion criteria were identified. Two North American cost-effectiveness studies of reasonable quality were identified but their generalisability to the UK is not clear. Three cohort studies met the inclusion criteria for the review of psychosocial aspects. All had methodological limitations and their generalisability is difficult to determine. The clinical sensitivity of C282Y homozygosity for HHC ranged from 28.4% to 100%, or from 91.3% to 92.4% when considering only the most relevant studies. Clinical specificity ranged from 98.8% to 100%. One study found that gene testing was a cost-effective method of screening relatives of patients with haemochromatosis, whereas the other found that genotyping the spouse of a homozygote was the most cost-efficient strategy. Genetic testing for haemochromatosis appears to be well accepted, is accompanied by few negative psychosocial outcomes and may lead to reduced anxiety. The de novo economic model showed that, in people suspected of having haemochromatosis, the DNA strategy is cost saving compared with the baseline strategy using liver biopsy (cost saved per case detected 123 pounds), largely because of the reduction in liver biopsies. For family testing of siblings the DNA strategy is not cost saving because of the costs of the DNA test (additional cost per case detected 200 pounds). If the cost of the test were to reduce from 100 pounds to 60 pounds, the DNA strategy would be the cheaper one. For family testing of offspring the DNA test strategy is cheaper than the baseline biochemical testing strategy (cost saved per case detected 7982 pounds). Sensitivity analyses showed that the conclusions in each case are robust across all reasonable parameter values. CONCLUSIONS: The preferred strategy in practice is DNA testing in conjunction with testing iron parameters when there is clear clinical indication of risk for haemochromatosis because of biochemical criteria or when there is familial risk for HHC. Access to genetic testing and centralisation of test provision in expert laboratories would lower the cost of testing, improve the cost-effectiveness of the strategy and improve the quality of information provided to clinicians and patients.

dna testing, haemochromatosis, systematic review, economic evaluation, cost-effectiveness, hereditary haemochromatosis
1366-5278
1-126
Bryant, J.
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Cooper, K.
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Picot, J.
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Clegg, A.
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Roderick, P.
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Rosenberg, W.
1a551f54-b4aa-42e0-a5e1-45c6a5232821
Patch, C.
1f70400a-854a-4c51-846d-47148fbb57e0
Bryant, J.
508f497c-8b5a-468f-a37d-be9c26e4e49d
Cooper, K.
ea064f58-d71d-404a-bcf3-49d243b8825b
Picot, J.
324d6f20-a105-49fd-9fb0-88791be84ada
Clegg, A.
838091f5-39df-4dbe-a369-675b26f2301b
Roderick, P.
dbb3cd11-4c51-4844-982b-0eb30ad5085a
Rosenberg, W.
1a551f54-b4aa-42e0-a5e1-45c6a5232821
Patch, C.
1f70400a-854a-4c51-846d-47148fbb57e0

Bryant, J., Cooper, K., Picot, J., Clegg, A., Roderick, P., Rosenberg, W. and Patch, C. (2009) Diagnostic strategies using DNA testing for hereditary haemochromatosis in at-risk populations: a systematic review and economic evaluation. Health Technology Assessment, 13 (23), 1-126. (doi:10.3310/hta13230). (PMID:19406046)

Record type: Article

Abstract

OBJECTIVE: To evaluate DNA testing for detecting hereditary haemochromatosis (HHC) in subgroups of patients suspected of having the disorder and in family members of those diagnosed with HHC. DATA SOURCES: Major electronic databases, searched from inception to April 2007. REVIEW METHODS: A systematic review was undertaken using a priori methods and a de novo model developed to assess costs and consequences of DNA testing. RESULTS: Eleven studies were identified for estimating the clinical validity of genotyping for the C282Y mutation for the diagnosis of HHC. No clinical effectiveness studies meeting the inclusion criteria were identified. Two North American cost-effectiveness studies of reasonable quality were identified but their generalisability to the UK is not clear. Three cohort studies met the inclusion criteria for the review of psychosocial aspects. All had methodological limitations and their generalisability is difficult to determine. The clinical sensitivity of C282Y homozygosity for HHC ranged from 28.4% to 100%, or from 91.3% to 92.4% when considering only the most relevant studies. Clinical specificity ranged from 98.8% to 100%. One study found that gene testing was a cost-effective method of screening relatives of patients with haemochromatosis, whereas the other found that genotyping the spouse of a homozygote was the most cost-efficient strategy. Genetic testing for haemochromatosis appears to be well accepted, is accompanied by few negative psychosocial outcomes and may lead to reduced anxiety. The de novo economic model showed that, in people suspected of having haemochromatosis, the DNA strategy is cost saving compared with the baseline strategy using liver biopsy (cost saved per case detected 123 pounds), largely because of the reduction in liver biopsies. For family testing of siblings the DNA strategy is not cost saving because of the costs of the DNA test (additional cost per case detected 200 pounds). If the cost of the test were to reduce from 100 pounds to 60 pounds, the DNA strategy would be the cheaper one. For family testing of offspring the DNA test strategy is cheaper than the baseline biochemical testing strategy (cost saved per case detected 7982 pounds). Sensitivity analyses showed that the conclusions in each case are robust across all reasonable parameter values. CONCLUSIONS: The preferred strategy in practice is DNA testing in conjunction with testing iron parameters when there is clear clinical indication of risk for haemochromatosis because of biochemical criteria or when there is familial risk for HHC. Access to genetic testing and centralisation of test provision in expert laboratories would lower the cost of testing, improve the cost-effectiveness of the strategy and improve the quality of information provided to clinicians and patients.

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Published date: April 2009
Keywords: dna testing, haemochromatosis, systematic review, economic evaluation, cost-effectiveness, hereditary haemochromatosis
Organisations: Community Clinical Sciences, Medicine

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Local EPrints ID: 72888
URI: http://eprints.soton.ac.uk/id/eprint/72888
ISSN: 1366-5278
PURE UUID: 3bfb5e94-eadf-4da5-8941-be8a4c494e7c
ORCID for K. Cooper: ORCID iD orcid.org/0000-0002-0318-7670
ORCID for J. Picot: ORCID iD orcid.org/0000-0001-5987-996X
ORCID for P. Roderick: ORCID iD orcid.org/0000-0001-9475-6850

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Date deposited: 24 Feb 2010
Last modified: 14 Mar 2024 02:49

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Contributors

Author: J. Bryant
Author: K. Cooper ORCID iD
Author: J. Picot ORCID iD
Author: A. Clegg
Author: P. Roderick ORCID iD
Author: W. Rosenberg
Author: C. Patch

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