scholarly journals Clinical and Cost Effectiveness of Two “New” Lynch Syndrome Case Finding Protocols in Endometrial Cancer Population Contrasted with the IHC-based Protocol

2019 ◽  
Author(s):  
James M. Gudgeon ◽  
Michael W. Varner ◽  
Mia Hashibe ◽  
Marc S. Williams
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Screening Program ◽  
Cost Effective ◽  
Case Finding ◽  
Local Data ◽  
Screening Programs ◽  
Family History Questionnaire ◽  
Program Costs ◽  
Index Cases

AbstractPurposeTo investigate the effectiveness and costs of two Lynch syndrome screening protocols among endometrial cancer (EC) patients and compare to an immunohistochemistry (IHC)–based protocol.MethodsAnalytic models were developed to represent the two protocols: a brief cancer family history questionnaire (bFHQ) and direct-to-sequencing of the germline. Data from reviews of published literature, augmented by local data and expert opinion were used to populate the model representing the number of women diagnosed in the U.S. in 2018. Multiple analyses employing simulation modeling were performed to estimate a variety of clinical and economic outcomes.ResultsUnder conditions considered here to be plausible, the bFHQ is expected to miss 58% (min./max. = 24 to 80%) of LS index cases, a direct-to-sequencing protocol to miss 30% (min./max. = 6% to 53%), and the IHC-based protocol based on previous analysis 58% (min./max. = 33 to 80%). When direct costs of testing and genetic counseling are added to the models, the total screening program costs for the bFHQ protocol are substantially lower at all sequencing price points than the other protocols. For example, at the low end of the sequencing price point (ie, $250), the total cost of screening programs for IHC, bFHQ, and sequencing are $22.9 million, $5.3 million, and $13.8 million, respectively. The best estimate of the break-even price of sequencing, when the cost of the program is equivalent between the IHC and sequencing protocols, is about $635.ConclusionThe bFHQ and direct-to-sequencing LS screening protocols are more effective and cost effective at identifying LS index cases than the standard IHC-based protocol under the conditions represented in our models. These estimates of various outcome metrics of the three LS index case finding protocols may help stakeholders make decisions of the use of limited healthcare dollars.

Model-Based Re-Examination of the Effectiveness of Tumor/Immunohistochemistry and Direct-to-Sequencing Protocols for Lynch Syndrome Case Finding in Endometrial Cancer

2021 ◽  
pp. OP.20.00988
Author(s):  
James M. Gudgeon ◽  
Michael W. Varner ◽  
Jing Hao ◽  
Marc S. Williams
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Simulation Models ◽  
Clinical Effectiveness ◽  
Case Finding ◽  
Current Evidence ◽  
Screening Programs ◽  
Direct Testing ◽  
Variable Success ◽  
Potential Impact

PURPOSE: Despite widespread provision of Lynch syndrome (LS) screening programs, questions remain about the most effective and efficient protocol for LS case finding. The purpose of this study was to explore the performance of the two protocols widely shown to be the most efficient and effective, respectively: immunohistochemical (IHC) staining of tumor and direct-to-sequencing (DtS) in endometrial cancer populations. METHODS: Simulation models were developed to explore performance of the IHC and DtS protocols, updated to reflect current evidence. Analyses explicitly account for protocol complexity and failure points, as well as decreased sequencing costs. Key outcomes are percent of LS cases identified, total protocol costs and efficiency, and break-even analyses of sequencing costs. All costs are in 2020 US dollars (USD). RESULTS: Under plausible conditions, the IHC protocol is expected to identify 40%-78% of LS cases and DtS protocol from 49% to 97%. When the key variable success in proceeding to sequencing is fixed for both protocols at 50%, 75%, and 100%, the DtS protocol is 9%, 12%, and 16% better at case finding, respectively, than the IHC protocol. The break-even cost of sequencing is about $488 USD when the outcome is total direct testing protocol costs; it is about $670 USD when the outcome is cost per LS case detected. CONCLUSION: This study quantifies the plausible differences in the clinical effectiveness and cost-effectiveness of the two LS case-finding protocols. We demonstrate the large influence of success in proceeding to sequencing and potential impact of decreasing sequencing prices.

scholarly journals Cost-Effectiveness of the Manchester Approach to Identifying Lynch Syndrome in Women with Endometrial Cancer

2020 ◽  
Vol 9 (6) ◽  
pp. 1664 ◽  
Author(s):  
Tristan M. Snowsill ◽  
Neil A. J. Ryan ◽  
Emma J. Crosbie
Keyword(s):  
Endometrial Cancer ◽  
Cost Effectiveness ◽  
Lynch Syndrome ◽  
Cancer Patients ◽  
Cost Effective ◽  
Hereditary Cancer Syndrome ◽  
Cancer Syndrome ◽  
Universal Testing ◽  
Life Years

Lynch syndrome (LS) is a hereditary cancer syndrome responsible for 3% of all endometrial cancer and 5% in those aged under 70 years. It is unclear whether universal testing for LS in endometrial cancer patients would be cost-effective. The Manchester approach to identifying LS in endometrial cancer patients uses immunohistochemistry (IHC) to detect mismatch repair (MMR) deficiency, incorporates testing for MLH1 promoter hypermethylation, and incorporates genetic testing for pathogenic MMR variants. We aimed to assess the cost-effectiveness of the Manchester approach on the basis of primary research data from clinical practice in Manchester. The Proportion of Endometrial Tumours Associated with Lynch Syndrome (PETALS) study informed estimates of diagnostic performances for a number of different strategies. A recent microcosting study was adapted and was used to estimate diagnostic costs. A Markov model was used to predict long-term costs and health outcomes (measured in quality-adjusted life years, QALYs) for individuals and their relatives. Bootstrapping and probabilistic sensitivity analysis were used to estimate the uncertainty in cost-effectiveness. The Manchester approach dominated other reflex testing strategies when considering diagnostic costs and Lynch syndrome cases identified. When considering long-term costs and QALYs the Manchester approach was the optimal strategy, costing £5459 per QALY gained (compared to thresholds of £20,000 to £30,000 per QALY commonly used in the National Health Service (NHS)). Cost-effectiveness is not an argument for restricting testing to younger patients or those with a strong family history. Universal testing for Lynch syndrome in endometrial cancer patients is expected to be cost-effective in the U.K. (NHS), and the Manchester approach is expected to be the optimal testing strategy.

HIV Screening of Surgeons and Dentists: A Cost-Effectiveness Analysis

1994 ◽  
Vol 15 (10) ◽  
pp. 635-645 ◽  
Author(s):  
Randall L. Sell ◽  
Albert J. Jovell ◽  
Joanna E. Siegel
Keyword(s):  
Cost Effectiveness ◽  
Hiv Transmission ◽  
Program Effectiveness ◽  
Screening Program ◽  
Cost Effective ◽  
Hiv Positive ◽  
Hiv Screening ◽  
Case Scenario ◽  
Screening Programs ◽  
Voluntary Program

AbstractObjective:To assess the cost-effectiveness of human immunodeficiency virus (HIV) screening strategies of surgeons and dentists.Design:We constructed a model to project costs and HIV transmissions prevented over 15 years for four screening scenarios: 1) one-time voluntary screening, 2) one-time mandatory screening, 3) annual voluntary screening, and 4) annual mandatory screening. One-time screening occurs only in the first year of the program; annual screening occurs once each year. Under mandatory screening, all practitioners are tested and risks of practitioner-to-patient transmission are eliminated for all practitioners testing positive. Voluntary screening assumes 90% of HIV-positive and 50% of HIV-negative practitioners are tested, and risks of transmission in the clinical setting are eliminated for 90% of HIV-positive surgeons and dentists. All costs and benefits are discounted at 5% per annum over 15 years.Results:Using “best-case” scenario assumptions, we find for surgeons that a one-time voluntary screening program would be most cost-effective, at $899,336 for every HIV transmission prevented. For dentists, the one-time voluntary program also is the most cost-effective, at $139,571 per transmission prevented. Annual mandatory programs were least cost-effective for both surgeons and dentists, at $63.3 million and $2.2 million per transmission prevented, respectively.Conclusions:HIV screening of surgeons and dentists ranks among the more expensive medical lifesaving programs, even using liberal assumptions about program effectiveness. Frequency of screening and whether testing is mandatory or voluntary dramatically affect cost per transmission prevented; these features should be considered carefully in designing specific HIV screening programs.

Implementing Lynch syndrome screening utilizing a community partnership.

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 203-203
Author(s):  
Jennifer N. Eichmeyer ◽  
Matthew Burtelow ◽  
Michael Carey ◽  
Paul Montgomery ◽  
Cynthia Graham ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Screening Program ◽  
Community Organization ◽  
Financial Burden ◽  
Molecular Genetic ◽  
Community Outreach ◽  
Sufficient Evidence ◽  
Genetic Test Results

203 Background: Lynch syndrome (LS) is an autosomal dominant condition associated with an 80% risk of colorectal cancer, a 60% risk of endometrial cancer, and additional risks for extra-colonic cancers. Amsterdam and Bethesda criteria can be used to identify patients who may be at risk. However, 25% of colon cancer and 65% of endometrial cancer patients with LS will be missed by using family history criteria alone. LS is caused by mutations in mismatch repair genes (MMR): MLH1, MSH2, MSH6, PMS2, and EPCAM. Tumor screening by immunohistochemistry (IHC) is available, and abnormal results can be flagged for more definitive genetic counseling and testing. Recommendations from the 2009 EGAPP (Evaluation of Genomic Applications in Practice and Prevention) Working Group concluded there is sufficient evidence to use this tumor testing for LS, and the screening would provide moderate population benefits. Cost effectiveness studies have shown universal screening detects nearly twice as many cases of LS and is < $25,000 per life year saved. Methods: St. Luke’s Mountain States Tumor Institute (MSTI) implemented these recommendations in 2012 using a unique strategy: collaborating with a community organization. The Brian Olson Foundation (BOF) strives to “prevent(ing) colon cancer through community outreach and education and saving lives by detecting colon cancer as early as possible.”These objectives were aligned with the MSTI screening program for LS in Idaho by using BOF funding to eliminate a financial burden to the patient for 12 months. Results: 204 specimens were screened for LS using IHC with the following results: 73% normal, 21% abnormal staining for MLH1/PMS2, and 6% abnormal staining for a single protein. Three families were confirmed to have LS after molecular genetic testing, and 6 families have genetic test results pending. Conclusions: Our system had IHC numbers consistent with national data, if not slightly higher. MSTI has elected to continue the program long-term. This kind of collaboration eased the change in practice such that LS screening could become a standard of care in Idaho.

Performance characteristics of a brief Family History Questionnaire to screen for Lynch syndrome in women with newly diagnosed endometrial cancer

2015 ◽  
Vol 136 (2) ◽  
pp. 311-316 ◽  
Author(s):  
Lua Eiriksson ◽  
Melyssa Aronson ◽  
Blaise Clarke ◽  
Golnessa Mojtahedi ◽  
Christine Massey ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Family History ◽  
Lynch Syndrome ◽  
Performance Characteristics ◽  
Newly Diagnosed ◽  
Family History Questionnaire

scholarly journals Lynch Syndrome Presenting as Endometrial Cancer

2014 ◽  
Vol 60 (1) ◽  
pp. 111-121 ◽  
Author(s):  
Laura J Tafe ◽  
Eleanor R Riggs ◽  
Gregory J Tsongalis
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Screening Program ◽  
Gene Mutations ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Hereditary Colon Cancer ◽  
High Prevalence ◽  
Cost Efficient ◽  
Tumor Types

Abstract BACKGROUND Lynch syndrome (LS) is the most common form of the hereditary colon cancer syndromes. Because of its high prevalence, a nationwide campaign has begun to screen all colorectal cancers for the genetic abnormalities associated with LS. CONTENT Next to colorectal cancer, endometrial cancer is the most common form of malignancy found in women with LS. Identifying individuals who harbor the well-characterized mismatch-repair gene mutations via immunohistochemistry, microsatellite instability analysis, or direct gene sequencing is critical to managing the LS patient and to surveillance for the development of other associated tumor types. SUMMARY Although many institutions have begun screening all colorectal tumors for LS, the evidence is sufficient to warrant the testing of all endometrial cancers for LS as well. Various testing algorithms, along with genetic-counseling efforts, can lead to a cost-efficient and beneficial screening program.

QUALITY-ADJUSTED LIFE-YEARS FOR THE ESTIMATION OF EFFECTIVENESS OF SCREENING PROGRAMS: A SYSTEMATIC LITERATURE REVIEW

2012 ◽  
Vol 28 (2) ◽  
pp. 145-151 ◽  
Author(s):  
Suvi Mäklin ◽  
Pirjo Räsänen ◽  
Riikka Laitinen ◽  
Niina Kovanen ◽  
Ilona Autti-Rämö ◽  
...  
Keyword(s):  
Full Text ◽  
Screening Program ◽  
Cost Effective ◽  
Quality Adjusted Life Years ◽  
Screening Programs ◽  
Hrqol Data ◽  
Life Years ◽  
Related Quality ◽  
Health Related ◽  
Quality Adjusted Life

Objectives: The aim of this study was to identify and characterize studies that have used quality-adjusted life-years (QALYs) based on measurements of patients’ health-related quality of life (HRQoL) as an indicator of effectiveness of screening programs.Methods: Systematic search of the literature until March 2010, using several electronic databases. Initial screening of articles based on abstracts, and evaluation of full-text articles were done by at least two of the authors.Results: The search identified 1,610 articles. Based on review of abstracts, 431 full-text articles were obtained for closer inspection and, of these, 81 reported QALYs based on patient-derived data using a valid HRQoL assessment. The most frequently used method to assess HRQoL was Time Trade-Off (55 percent) followed by EQ-5D (26 percent). The most frequently studied medical conditions were malignant diseases (23 percent) followed by cardiovascular diseases (19 percent). All studies employed some kind of modeling with the Markov model being the most prevalent type (65 percent). Majority of the articles (59 percent) concluded that the screening program studied was cost-effective.Conclusions: The use of QALYs in the evaluation of screening programs has expanded during the last few years. However, only a minority of studies have used HRQoL data derived from patients, using direct or indirect valuation. Further investigation and harmonization of the methodology in evaluation of screening programs is needed to ensure better comparability across different screening programs.

scholarly journals How to Choose Diseases for Newborn Screening by Tandem Mass Spectrometry Under the Nationally Recommended Program in Shenzhen, China Evidence From a Cost-Effectiveness Analysis

2021 ◽  
Author(s):  
Mingren Yu ◽  
Juan Xu ◽  
Xiaohong Song ◽  
Jiayue Du
Keyword(s):  
Mass Spectrometry ◽  
Cost Effectiveness ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Screening Program ◽  
Cost Effective ◽  
Tandem Mass ◽  
National Program ◽  
Screening Programs ◽  
The Cost

Abstract Background: Newborn screening (NBS) can prevent inborn errors of metabolism (IEMs), which may cause long-term disability and even death in newborns. However, in China, tandem mass spectrometry (MS/MS) screening has just started. This study is to determine the cost-effectiveness of NBS using MS/MS in Shenzhen under the nationally recommended program, and determine IEMs for detection.Methods: A Markov model was built to estimate the cost and quality-adjusted life-years (QALYs) of different screening programs. The current screening program and nationally recommended program were compared and we also compared the programs detecting different numbers of IEMs, which are chosen from the national program. A sensitivity analysis and budget impact analysis (BIA) were performed.Results: The incremental cost-effectiveness ratio (ICER) of detecting all 12 IEMs in the national program is 277,823 RMB per QALY, below three times per capita GDP in Shenzhen. MS/MS screening in Shenzhen can be cost-effective only if at least three diseases (PKU, PCD and MMA) are covered and when the screening program covers five diseases (PKU, PCD, MMA, MSUD, IVA), the ICER closely approaches its critical value. The BIA indicated the implementation cost of the national program to be around 580 million RMB over 10 years and showed no difference in budget between programs detecting different numbers of IEMs. Conclusions: We conclude that the newborn screening using MS/MS in Shenzhen is cost-effective, and the budget affordable for the Shenzhen government. Two concepts for selecting the IEMs to be detected, which we label the “ICER maximization idea” and the “ICER validation idea” are also presented.

Screening for Lynch syndrome in unselected women with endometrial cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5508-5508
Author(s):  
Sarah E. Ferguson ◽  
Melyssa Aronson ◽  
Lua R Eiriksson ◽  
Golnessa Mojtahedi ◽  
Aaron Pollett ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Family History ◽  
High Risk ◽  
Lynch Syndrome ◽  
Germline Mutation ◽  
Mutation Testing ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Mutation Status ◽  
Family History Questionnaire

5508 Background: Endometrial cancer (EC) is often the sentinel cancer in women with Lynch Syndrome (LS) however it is often not recognized in this population. A prospective cohort study comparing family history, immunohistochemistry (IHC) for mismatch repair (MMR) proteins, and tumour morphology to germline mutation status in MMR genes was performed in unselected women with EC to determine which screening strategy was superior in identifying women with LS. Methods: All women with newly diagnosed EC between July 2010 and June 2011 were asked to participate in the prospective screening protocol for LS which included completing an extended family history questionnaire (eFHQ), tumor assessment for LS-associated morphologic features and IHC as well as germline mutation testing. Results: 119 (n = 182, 65%) consented to the study. The median age was 61 (26-91), 96 (81%) stage I, and 42 (35%) had high risk histology. There were 6 (7.4%, n = 81) women that were germline mutation positive (MLH1 N=3; MSH6 n = 2; MSH2 n =1), representing a mutation positive rate of at least 5% in this cohort (6/119). All 3 MLH1 mutation positive women had low grade histology while mutations in MSH2/6 were exclusively found in women with high risk histology. Two of the six mutation positive women were not identified by family history. Mutation positivity was higher in women under age 50 (23%; 5/22) compared to women > age 50 (1%; 1/97)( (p = 0.0008). LS-morphologic features were found in 58 (59%, n = 98) women. The sensitivity, specificity, PPV and NPV of the LS-associated features in predicting LS mutation status was 100%, 42.6%, 7.9% and 100% compared to IHC which was 100%, 76%, 18% and 100% and eFHQ which was 67%, 84%, 27%, 97%. Conclusions: In this unselected population of women with newly diagnosed EC the germline mutation rate for LS was 2-3 times that has previously been reported. Previously described LS-associated morphologic features were not specific to germline mutation status and family history missed one third of women with LS. IHC was the best strategy to identify women with EC who should undergo germline mutation testing.

Comparing two Modalities of Management of Women with Cytologic Evidence of Squamous Or Glandular Atypia: Early Repeat Cytology or Colposcopy

1997 ◽  
Vol 83 (4) ◽  
pp. 732-734 ◽  
Author(s):  
Silvia Cecchini ◽  
Anna lossa ◽  
Rita Bonardi ◽  
Stefano Ciatto ◽  
Paola Cariaggi
Keyword(s):  
Screening Program ◽  
Cost Effective ◽  
Punch Biopsy ◽  
Easy Access ◽  
Squamous Cells ◽  
Screening Programs ◽  
Large Loop ◽  
Intraepithelial Lesion ◽  
A Prospective Study ◽  
The Cost

Early repeat cytology is recommended in most screening programs for cervical cancer in subjects with squamous or glandular abnormalities not amounting to neoplasia (atypical squamous cells of undetermined significance, ASCUS), but immediate colposcopy is also recommended in some countries, especially those where there is easy access to colposcopic facilities. We evaluated the cost-effectiveness of the two procedures in a prospective study of women with cytologic ASCUS, invited to cytocolposcopic assessment after 6 months. Colposcopy-directed biopsy was assumed as the gold standard, and the accuracy of colposcopy at 6 months was assumed to be equal to that of immediate colposcopy. Out of 874 compilers, punch biopsy was performed in 303 cases (34.7%), and 19 CIN2+ lesions were detected (CIN2 = 12, CIN3 = 6, microinvasive carcinoma = 1). Detecting 13 CIN2+ lesions at colposcopy required 874 colposcopies and 303 directed biopsies: the cost per CIN2+ lesion detected with the procedure was 2,749 US$. Detecting 15 CIN2+ lesions at repeat cytology required 874 cytologic examinations, 137 colposcopies, 64 directed biopsies, and 6 diagnostic large-loop resections, the latter being performed in subjects with high-grade squamous intraepithelial lesion and less severe lesions at punch biopsy: the cost per CIN2+ lesion detected with the procedure was 1,961 US$. The policy of repeat smear was more cost-effective than immediate colposcopy. According to such results, the protocol of the Florence screening program has been modified since October 1996.

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