eprintid: 10041887
rev_number: 31
eprint_status: archive
userid: 608
dir: disk0/10/04/18/87
datestamp: 2018-01-29 11:55:07
lastmod: 2021-12-13 01:37:31
status_changed: 2018-01-29 11:55:07
type: article
metadata_visibility: show
creators_name: Manchanda, R
creators_name: Patel, S
creators_name: Gordeev, VS
creators_name: Antoniou, AC
creators_name: Smith, S
creators_name: Lee, A
creators_name: Hopper, JL
creators_name: MacInnis, RJ
creators_name: Turnbull, C
creators_name: Ramus, SJ
creators_name: Gayther, SA
creators_name: Pharoah, PDP
creators_name: Menon, U
creators_name: Jacobs, I
creators_name: Legood, R
title: Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population Women
ispublished: pub
divisions: UCL
divisions: B02
divisions: D65
divisions: J38
keywords: mutation, cancer, cost effectiveness, brca1 protein, brca2 protein, brca1 gene, brca2 gene, life expectancy, quality-adjusted life years, mastectomy, breast cancer, brca2 mutation testing, sensitivity analysis, palb2 gene
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: Background: The cost-effectiveness of population-based panel testing for high- and moderate-penetrance ovarian cancer (OC)/breast cancer (BC) gene mutations is unknown. We evaluate the cost-effectiveness of population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutation testing compared with clinical criteria/family history (FH) testing in unselected general population women. Methods: A decision-analytic model comparing lifetime costs and effects of criteria/FH-based BRCA1/BRCA2 testing is compared with BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing in those fulfilling clinical criteria/strong FH of cancer (≥10% BRCA1/BRCA2 probability) and all women age 30 years or older. Analyses are presented for UK and US populations. Identified carriers undergo risk-reducing salpingo-oophorectomy. BRCA1/BRCA2/PALB2 carriers can opt for magnetic resonance imaging/mammography, chemoprevention, or risk-reducing mastectomy. One-way and probabilistic sensitivity analysis (PSA) enabled model uncertainty evaluation. Outcomes include OC, BC, and additional heart disease deaths. Quality-adjusted life-years (QALYs), OC incidence, BC incidence, and incremental cost-effectiveness ratio (ICER) were calculated. The time horizon is lifetime and perspective is payer. Results: Compared with clinical criteria/FH-based BRCA1/BRCA2 testing, clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is cost-effective (ICER = £7629.65/QALY or $49 282.19/QALY; 0.04 days' life-expectancy gained). Population-based testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutations is the most cost-effective strategy compared with current policy: ICER = £21 599.96/QALY or $54 769.78/QALY (9.34 or 7.57 days' life-expectancy gained). At £30 000/QALY and $100 000/QALY willingness-to-pay thresholds, population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 panel testing is the preferred strategy in 83.7% and 92.7% of PSA simulations; criteria/FH-based panel testing is preferred in 16.2% and 5.8% of simulations, respectively. Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing can prevent 1.86%/1.91% of BC and 3.2%/4.88% of OC in UK/US women: 657/655 OC cases and 2420/2386 BC cases prevented per million. Conclusions: Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than any clinical criteria/FH-based strategy. Clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than BRCA1/BRCA2 testing alone.
date: 2018-07
date_type: published
official_url: https://doi.org/10.1093/jnci/djx265
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1527616
doi: 10.1093/jnci/djx265
pii: 4816906
lyricists_name: Manchanda, Ranjit
lyricists_name: Menon, Usha
lyricists_id: RMANC30
lyricists_id: UMENO29
actors_name: Manchanda, Ranjit
actors_id: RMANC30
actors_role: owner
full_text_status: public
publication: Journal of the National Cancer Institute
volume: 110
number: 7
pagerange: 714-725
event_location: United States
issn: 1460-2105
citation:        Manchanda, R;    Patel, S;    Gordeev, VS;    Antoniou, AC;    Smith, S;    Lee, A;    Hopper, JL;                                 ... Legood, R; + view all <#>        Manchanda, R;  Patel, S;  Gordeev, VS;  Antoniou, AC;  Smith, S;  Lee, A;  Hopper, JL;  MacInnis, RJ;  Turnbull, C;  Ramus, SJ;  Gayther, SA;  Pharoah, PDP;  Menon, U;  Jacobs, I;  Legood, R;   - view fewer <#>    (2018)    Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population Women.                   Journal of the National Cancer Institute , 110  (7)   pp. 714-725.    10.1093/jnci/djx265 <https://doi.org/10.1093/jnci%2Fdjx265>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10041887/1/17-0764R2%20Manchanda_AB_RM-v1_FINALaccepted.pdf