A discrete event simulation to evaluate the cost effectiveness of germline<i>BRCA1</i>and<i>BRCA2</i>testing in UK women with ovarian cancer

Eccleston, Anthony; Bentley, Anthony; Dyer, Matthew; Strydom, Ann; Vereecken, Wim; George, Angela; Rahman, Nazneen

doi:10.1101/060418

Cited by 2 publications

(4 citation statements)

References 42 publications

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“…However, the Mainstreaming Cancer Genetics programme has operated successfully including only one post-test counselling session for index individuals found to have a pathogenic BRCA mutation, one pretest counselling session for relatives and one post-test counselling session for relatives with the mutation. 190,191 Such a regime would reduce costs further, as generally half or fewer of those tested for LS mutations are found to have a pathogenic MMR mutation.…”

Section: Areas Of Uncertaintymentioning

confidence: 99%

Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation

Snowsill

Coelho

Huxley

et al. 2017

Health Technol Assess

112

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BackgroundInherited mutations in deoxyribonucleic acid (DNA) mismatch repair (MMR) genes lead to an increased risk of colorectal cancer (CRC), gynaecological cancers and other cancers, known as Lynch syndrome (LS). Risk-reducing interventions can be offered to individuals with known LS-causing mutations. The mutations can be identified by comprehensive testing of the MMR genes, but this would be prohibitively expensive in the general population. Tumour-based tests – microsatellite instability (MSI) and MMR immunohistochemistry (IHC) – are used in CRC patients to identify individuals at high risk of LS for genetic testing.MLH1(MutL homologue 1) promoter methylation andBRAFV600E testing can be conducted on tumour material to rule out certain sporadic cancers.ObjectivesTo investigate whether testing for LS in CRC patients using MSI or IHC (with or withoutMLH1promoter methylation testing andBRAFV600E testing) is clinically effective (in terms of identifying Lynch syndrome and improving outcomes for patients) and represents a cost-effective use of NHS resources.Review methodsSystematic reviews were conducted of the published literature on diagnostic test accuracy studies of MSI and/or IHC testing for LS, end-to-end studies of screening for LS in CRC patients and economic evaluations of screening for LS in CRC patients. A model-based economic evaluation was conducted to extrapolate long-term outcomes from the results of the diagnostic test accuracy review. The model was extended from a model previously developed by the authors.ResultsTen studies were identified that evaluated the diagnostic test accuracy of MSI and/or IHC testing for identifying LS in CRC patients. For MSI testing, sensitivity ranged from 66.7% to 100.0% and specificity ranged from 61.1% to 92.5%. For IHC, sensitivity ranged from 80.8% to 100.0% and specificity ranged from 80.5% to 91.9%. When tumours showing low levels of MSI were treated as a positive result, the sensitivity of MSI testing increased but specificity fell. No end-to-end studies of screening for LS in CRC patients were identified. Nine economic evaluations of screening for LS in CRC were identified. None of the included studies fully matched the decision problem and hence a new economic evaluation was required. The base-case results in the economic evaluation suggest that screening for LS in CRC patients using IHC,BRAFV600E andMLH1promoter methylation testing would be cost-effective at a threshold of £20,000 per quality-adjusted life-year (QALY). The incremental cost-effectiveness ratio for this strategy was £11,008 per QALY compared with no screening. Screening without tumour tests is not predicted to be cost-effective.LimitationsMost of the diagnostic test accuracy studies identified were rated as having a risk of bias or were conducted in unrepresentative samples. There was no direct evidence that screening improves long-term outcomes. No probabilistic sensitivity analysis was conducted.ConclusionsSystematic review evidence suggests that MSI- and IHC-based testing can be used to identify LS in CRC patients, although there was heterogeneity in the methods used in the studies identified and the results of the studies. There was no high-quality empirical evidence that screening improves long-term outcomes and so an evidence linkage approach using modelling was necessary. Key determinants of whether or not screening is cost-effective are the accuracy of tumour-based tests, CRC risk without surveillance, the number of relatives identified for cascade testing, colonoscopic surveillance effectiveness and the acceptance of genetic testing. Future work should investigate screening for more causes of hereditary CRC and screening for LS in endometrial cancer patients.Study registrationThis study is registered as PROSPERO CRD42016033879.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Section: Areas Of Uncertaintymentioning

confidence: 99%

Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation

Snowsill

Coelho

Huxley

et al. 2017

Health Technol Assess

112

View full text Add to dashboard Cite

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“…The incremental cost‐effectiveness ratio (ICER) was £4339 per quality‐adjusted life‐year gained, which was well below the UK willingness‐to‐pay threshold of £20,000. The results were predominantly driven by reductions in the number of cases of ovarian and breast cancers and the resulting reduced mortality . In the other report, US costs were used.…”

Section: The Differential Effectiveness Of Screening and Preventionmentioning

confidence: 99%

“…The results were predominantly driven by reductions in the number of cases of ovarian and breast cancers and the resulting reduced mortality. 2 In the other report, US costs were used. The cost of 3 different BRCA testing strategies, based on different criteria for testing the index case, followed by testing of family members with risk-reducing mastectomy/salpingo-oophorectomy in carriers, was compared with treating the cancers surgically (no chemotherapy) once they developed.…”

Section: Cost Of Surgical Prevention Compared With Treating Ovarian Cmentioning

confidence: 99%

“…1 Knowledge of the index patient's BRCA status has 3 important downstream benefits: 1) therapeutic, because of the recent introduction of poly ADPribose polymerase (PARP) inhibitors; 2) prevention, because risk-reduction strategies can be offered previously unaffected family members who have the mutation; and 3) financial, because cost savings for the patient/family and the health care system from the prevention of EOC are more cost effective than treatment. 2,3 Despite these potential benefits, less than 20% of women with EOC (on a population basis) in Ontario, Canada, are referred for counseling and BRCA mutation testing. 4,5 Novelty does not explain the low rates-the ability to test for mutated BRCA is about 20 years old.…”

Section: Introductionmentioning

confidence: 99%

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Missed therapeutic and prevention opportunities in women with BRCA‐mutated epithelial ovarian cancer and their families due to low referral rates for genetic counseling and BRCA testing: A review of the literature

Hoskins

Gotlieb

2017

CA A Cancer J Clinicians

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Answer questions and earn CME/CNE Fifteen percent of women with epithelial ovarian cancer have inherited mutations in the BRCA breast cancer susceptibility genes. Knowledge of her BRCA status has value both for the woman and for her family. A therapeutic benefit exists for the woman with cancer, because a new family of oral drugs, the poly ADP-ribose polymerase (PARP) inhibitors, has recently been approved, and these drugs have the greatest efficacy in women who carry the mutation. For her family, there is the potential to prevent ovarian cancer in those carrying the mutation by using risk-reducing surgery. Such surgery significantly reduces the chance of developing this, for the most part, incurable cancer. Despite these potential benefits, referral rates for genetic counseling and subsequent BRCA testing are low, ranging from 10% to 30%, indicating that these therapeutic and prevention opportunities are being missed. The authors have reviewed the relevant available literature. Topics discussed are BRCA and its relation to ovarian cancer, the rates of referral for genetic counseling/BRCA testing, reasons for these low rates, potential strategies to improve on those rates, lack of effectiveness of current screening strategies, the pros and cons of risk-reducing surgery, other prevention options, and the role and value of PARP inhibitors. CA Cancer J Clin 2017;67:493-506. © 2017 American Cancer Society.

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A discrete event simulation to evaluate the cost effectiveness of germlineBRCA1andBRCA2testing in UK women with ovarian cancer

Abstract: Abbreviations: CI = confidence interval; HR = hazard ratio; RRBSO = risk-reducing bilateral salpingo-oophorectomy; RRM = risk-reducing mastectomy; RRS = risk-reducing surgery.

Cited by 2 publications

References 42 publications

Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation

Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation

Missed therapeutic and prevention opportunities in women with BRCA‐mutated epithelial ovarian cancer and their families due to low referral rates for genetic counseling and BRCA testing: A review of the literature

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