Cost-effectiveness of population-wide genomic screening for Lynch syndrome in the United States

PurposeGenomic screening for Lynch syndrome (LS) could prevent colorectal cancer (CRC) by identifying high-risk patients and instituting intensive CRC screening. We estimated the cost-effectiveness of a population-wide LS genomic screening vs family history–based screening alone in an unselected US population.MethodsWe developed a decision-analytic Markov model including health states for precancer, stage-specific CRC, and death and assumed an inexpensive test cost of $200. We conducted sensitivity and threshold analyses to evaluate model uncertainty.ResultsScreening unselected 30-year-olds for LS variants resulted in 48 (95% credible range [CR] = 35-63) fewer overall CRC cases per 100,000 screened individuals, leading to 187 quality-adjusted life-years (QALYs; 95% CR = 123-260) gained at an incremental cost of $24.6 million (95% CR = $20.3 million-$29.1 million). The incremental cost-effectiveness ratio was $132,200, with an 8% and 71% probability of being cost-effective at $100,000 and $150,000 per QALY willingness-to-pay thresholds, respectively.ConclusionPopulation LS screening may be cost-effective in younger patient populations under a $150,000 willingness-to-pay per QALY threshold and with a relatively inexpensive test cost. Further reductions in testing costs and/or the inclusion of LS testing within a broader multiplex screening panel are needed for screening to become highly cost-effective.     

Economic evaluation of genetic screening for Lynch syndrome in Germany

PurposeLynch syndrome (LS) screening among patients with newly diagnosed colorectal cancer can decrease mortality in their affected first-degree relatives. In Germany, it is not yet clinical practice and the cost-effectiveness of different testing strategies is unknown.MethodsWe developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the German Statutory Health Insurance system. A total of 22 testing strategies considering family-history assessment, analysis of tumor samples (i.e., immunohistochemistry (IHC), microsatellite instability, and BRAF mutation testing) and genetic sequencing were analyzed. Life-years gained in relatives by closed-meshed colonoscopy and aspirin prophylaxis were estimated by Markov models. Uncertainty was assessed deterministically and probabilistically.ResultsOn average, detected mutation carriers gained 0.52 life-years (undiscounted: 1.34) by increased prevention. Most strategies were dominated, with three exceptions: family assessment by the Bethesda criteria followed by IHC and BRAF testing and genetic sequencing; IHC and BRAF testing and genetic sequencing; and direct sequencing of all index patients. Their incremental cost-effectiveness was €77,268, €253,258, and €4,188,036 per life-year gained, respectively.ConclusionThe results were less favorable than those of previous models. Chemoprevention appears to provide comparably low additional benefit and improves cost-effectiveness only slightly.     

Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives

Summary of RecommendationsThe Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found sufficient evidence to recommend offering genetic testing for Lynch syndrome to individuals with newly diagnosed colorectal cancer to reduce morbidity and mortality in relatives. We found insufficient evidence to recommend a specific genetic testing strategy among the several examined.RationaleGenetic testing to detect Lynch syndrome in individuals with newly diagnosed colorectal cancer (CRC) is proposed as a strategy to reduce CRC morbidity and mortality in their relatives (see Clinical Considerations section for definition of Lynch syndrome). The EGAPP Working Group (EWG) constructed a chain of evidence that linked genetic testing for Lynch syndrome in patients with newly diagnosed CRC with improved health outcomes in their relatives. We found that assessing patients who have newly diagnosed CRC with a series of genetic tests could lead to the identification of Lynch syndrome. Relatives of patients with Lynch syndrome could then be offered genetic testing, and, where indicated, colorectal, and possibly endometrial, cancer surveillance, with the expectation of improved health outcome. The EWG concluded that there is moderate certainty that such a testing strategy would provide moderate population benefit.Analytic ValidityThe EWG found adequate evidence to conclude that the analytic sensitivity and specificity for preliminary and diagnostic tests were high.Clinical ValidityAfter accounting for the specific technologies and numbers of markers used, the EWG found at least adequate evidence to describe the clinical sensitivity and specificity for three preliminary tests, and for four selected testing strategies. These measures of clinical validity varied with each test and each strategy (see Clinical Considerations section).Clinical UtilityThe EWG found adequate evidence for testing uptake rates, adherence to recommended surveillance activities, number of relatives approachable, harms associated with additional follow-up, and effectiveness of routine colonoscopy. This chain of evidence supported the use of genetic testing strategies to reduce morbidity/mortality in relatives with Lynch syndrome. Several genetic testing strategies were potentially effective, but none was clearly superior. The evidence for or against effectiveness of identifying mismatch repair (MMR) gene mutations in reducing endometrial cancer morbidity or mortality was inadequate.Contextual IssuesCRC is a common disease responsible for an estimated 52,000 deaths in the United States in 2007. In about 3% of newly diagnosed CRC, the underlying cause is a mutation in a MMR gene (Lynch syndrome) that can be reliably identified with existing laboratory tests. Relatives inheriting the mutation have a high (about 45% by age 70) risk of developing CRC. Evidence suggests these relatives will often accept testing and increased surveillance.     

The predicted effect and cost-effectiveness of tailoring colonoscopic surveillance according to mismatch repair gene in patients with Lynch syndrome

PurposeLynch syndrome-related colorectal cancer (CRC) risk substantially varies by mismatch repair (MMR) gene. We evaluated the health impact and cost-effectiveness of MMR gene-tailored colonoscopic surveillance.MethodsWe first estimated sex- and MMR gene-specific cumulative lifetime risk of first CRC without colonoscopic surveillance using an optimization algorithm. Next, we harnessed these risk estimates in a microsimulation model, “Policy1-Lynch,” and compared 126 colonoscopic surveillance strategies against no surveillance.ResultsThe most cost-effective strategy was 3-yearly surveillance from age 25 to 70 years (pathogenic variants [path_] in MLH1 [path_MLH1], path_MSH2) with delayed surveillance for path_MSH6 (age 30-70 years) and path_PMS2 (age 35-70 years) heterozygotes (incremental cost-effectiveness ratio = Australian dollars (A) $8,833/life-year saved). This strategy averted 60 CRC deaths (153 colonoscopies per death averted) over the lifetime of 1000 confirmed patients with Lynch syndrome (vs no surveillance). This also reduced colonoscopies by 5% without substantial change in health outcomes (vs nontailored 3-yearly surveillance from 25-70 years). Generally, starting surveillance at age 25 (vs 20) years was more cost-effective with minimal effect on life-years saved and starting 5 to 10 years later for path_MSH6 and path_PMS2 heterozygotes (vs path_MLH1 and path_MSH2) further improved cost-effectiveness. Surveillance end age (70/75/80 years) had a minor effect. Three-yearly surveillance strategies were more cost-effective (vs 1 or 2-yearly) but prevented 3 fewer CRC deaths.ConclusionMMR gene-specific colonoscopic surveillance would be effective and cost-effective.     

The cost-effectiveness of returning incidental findings from next-generation genomic sequencing

PurposeThe American College of Medical Genetics and Genomics (ACMG) recommended that clinical laboratories performing next-generation sequencing analyze and return pathogenic variants for 56 specific genes it considered medically actionable. Our objective was to evaluate the clinical and economic impact of returning these results.MethodsWe developed a decision-analytic policy model to project the quality-adjusted life-years and lifetime costs associated with returning ACMG-recommended incidental findings in three hypothetical cohorts of 10,000 patients.ResultsReturning incidental findings to cardiomyopathy patients, colorectal cancer patients, or healthy individuals would increase costs by $896,000, $2.9 million, and $3.9 million, respectively, and would increase quality-adjusted life-years by 20, 25.4, and 67 years, respectively, for incremental cost-effectiveness ratios of $44,800, $115,020, and $58,600, respectively. In probabilistic analyses, returning incidental findings cost less than $100,000/quality-adjusted life-year gained in 85, 28, and 91%, respectively, of simulations. Assuming next-generation sequencing costs $500, the incremental cost-effectiveness ratio for primary screening of healthy individuals was $133,400 (<$100,000/quality-adjusted life-year gained in 10% of simulations). Results were sensitive to the cohort age and assumptions about gene penetrance.ConclusionReturning incidental findings is likely cost-effective for certain patient populations. Screening of generally healthy individuals is likely not cost-effective based on current data, unless next-generation sequencing costs less than $500.Genet Med 17 7, 587–595.     

Genomic testing for suspected monogenic kidney disease in children and adults: A health economic evaluation

PurposeTo assess the relative cost-effectiveness of genomic testing compared with standard non-genomic diagnostic investigations in patients with suspected monogenic kidney disease from an Australian health care system perspective.MethodsDiagnostic and clinical information was used from a national cohort of 349 participants. Simulation modelling captured diagnostic, health, and economic outcomes during a time horizon from clinical presentation until 3 months post-test results based on the outcome of cost per additional diagnosis and lifetime horizon based on cost per quality-adjusted life-year (QALY) gained.ResultsGenomic testing was Australian dollars (AU$) 1600 more costly per patient and led to an additional 27 diagnoses out of a 100 individuals tested, resulting in an incremental cost-effectiveness ratio of AU$5991 per additional diagnosis. Using a lifetime horizon, genomic testing resulted in an additional cost of AU$438 and 0.04 QALYs gained per individual compared with standard diagnostic investigations, corresponding to an incremental cost-effectiveness ratio of AU$10,823 per QALY gained. Sub-group analyses identified that the results were largely driven by the cost-effectiveness in glomerular diseases.ConclusionBased on established or expected thresholds of cost-effectiveness, our evidence suggests that genomic testing is very likely to be cost saving for individuals with suspected glomerular diseases, whereas no evidence of cost-effectiveness was found for non-glomerular diseases.     

Cost-effectiveness of routine screening for Lynch syndrome in colorectal cancer patients up to 70 years of age

PurposeTo assess the cost-effectiveness of routine Lynch syndrome (LS) screening among colorectal cancer (CRC) patients ≤70 years of age.MethodsA population-based series of CRC patients ≤ 70 years of age was routinely screened for LS. We calculated life years gained (LYG) and incremental cost-effectiveness ratios (ICERs) for different age cutoffs and comparing age-targeted screening with the revised Bethesda guidelines.ResultsScreening 1,117 CRC patients identified 23 LS patients, of whom 7 were ≤50 years of age, 7 were 51–60, and 9 were 61–70. Additionally, 70 LS carriers were identified among relatives (14, 42, and 14 per age category). Screening amounted to 205.9 LYG or 43.6, 118.0, and 44.3 LYG per age category. ICERs were €4.226/LYG for screening CRC patients ≤60 years of age compared with those ≤50 years and €7.051/LYG for screening CRC patients ≤70 years compared with those ≤60 years. The revised Bethesda guidelines identified 70 of 93 (75%) LS carriers. The ICER for LS screening in CRC patients ≤70 years of age compared with the revised Bethesda guidelines was €7.341/LYG. All ICERs remained less than €13.000/LYG in one-way sensitivity analyses.ConclusionRoutine LS screening by analysis of microsatellite instability, immunohistochemistry, and MLH1 hypermethylation in CRC patients ≤70 years of age is a cost-effective strategy with important clinical benefits for CRC patients and their relatives.Genet Med18 10, 966–973.     

Immunohistochemistry staining for the mismatch repair proteins in the clinical care of patients with colorectal cancer

PurposeThe Ohio State University was one of the first medical centers to begin routinely performing immunohistochemical staining for the four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) on all newly diagnosed patients with colorectal cancer. The results of implementing this testing on a clinical basis are critically assessed.MethodsFrom March 1, 2006, to March 31, 2008, 270 newly diagnosed colorectal cancer tumors received immunohistochemical staining for MLH1, MSH2, MSH6, and PMS2. If any stain was absent, the cancer genetic counselors were alerted, so that they could contact the patient. A follow-up genetic consultation was recommended for all patients with any stain absent other than MLH1 and to patients with absence of MLH1 ± PMS2 who were diagnosed younger than 60 years had a multiple Lynch syndrome-associated cancers or had a first-degree relative with colorectal cancer or endometrial cancer. Those attending the genetic consultation were offered appropriate follow-up testing.ResultsThere were 57 (21.1%) cases with abnormal immunohistochemical results. Genetics was able to contact 54 (94.7%) of these patients. It was determined that 34 (62.9%) of these 54 patients should be referred for a cancer genetics consultation, however, only nine (26.5%) made an appointment. Seven of the nine underwent additional testing, which was informative in five of the patients. Two (0.7%) new cases of Lynch syndrome were diagnosed and three patients were found to have proven/probable MLH1 promoter methylation.ConclusionsRoutine immunohistochemical of the mismatch repair proteins on all newly diagnosed patients with colorectal cancer can be implemented clinically, however, patient uptake of follow-up genetic consultation is lower than expected.     

The Cost-Effectiveness of Triple Nucleoside Analogue Therapy Antiretroviral Regimens in the Treatment of HIV in the United Kingdom

Abstract

Purpose: Treatment of HIV infection has improved markedly in recent years due to the use of combination antiretroviral therapies. However, the cost of these treatments remains a concern for those who fund health services. This article reports the results of an economic evaluation to determine the incremental cost-effectiveness of triple combination nucleoside analogue (NA) therapy compared with dual NA therapy. Method: A Markov model was developed to assess the incremental cost effectiveness of triple therapy treatment versus dual therapy treatment. Clinical data was derived from published clinical trials and large observational cohorts whilst cost data was derived from a prospective database that monitors health care resource use in the UK HIV population. Results: The model predicted that triple NA combination treatment extended life expectancy by an additional 1.2 years compared with dual therapy NA treatment with an incremental cost-effectiveness ratio of £8,419 per life-year saved. The incremental cost per quality-adjusted life-year (QALY) was estimated to be between £10,072–£16,168 per QALY gained depending on the assumptions. Conclusion: The results show triple nucleoside analogue therapy to be a cost effective means of delaying HIV progression and extending life expectancy. However, further research into this issue is warranted.     

Cost-effectiveness analysis of germ-line BRCA testing in women with breast cancer and cascade testing in family members of mutation carriers

PurposeTo evaluate the cost-effectiveness of BRCA testing in women with breast cancer, and cascade testing in family members of BRCA mutation carriers.MethodsA cost-effectiveness analysis was conducted using a cohort Markov model from a health-payer perspective. The model estimated the long-term benefits and costs of testing women with breast cancer who had at least a 10% pretest BRCA mutation probability, and the cascade testing of first- and second-degree relatives of women who test positive.ResultsCompared with no testing, BRCA testing of affected women resulted in an incremental cost per quality-adjusted life-year (QALY) gained of AU$18,900 (incremental cost AU$1,880; incremental QALY gain 0.10) with reductions of 0.04 breast and 0.01 ovarian cancer events. Testing affected women and cascade testing of family members resulted in an incremental cost per QALY gained of AU$9,500 compared with testing affected women only (incremental cost AU$665; incremental QALY gain 0.07) with additional reductions of 0.06 breast and 0.01 ovarian cancer events.ConclusionBRCA testing in women with breast cancer is cost-effective and is associated with reduced risk of cancer and improved survival. Extending testing to cover family members of affected women who test positive improves cost-effectiveness beyond restricting testing to affected women only.     

Cost-effectiveness of varenicline and three different behavioral treatment formats for smoking cessation

There is a lack of evidence of the relative cost-effectiveness of proactive telephone counseling (PTC) and Web-based delivery of smoking cessation services in conjunction with pharmacotherapy. We calculated the differential cost-effectiveness of three behavioral smoking cessation modalities with varenicline treatment in a randomized trial of current smokers from a large health system. Eligible participants were randomized to one of three smoking cessation interventions: Web-based counseling (n=401), PTC (n=402), or combined PTC-Web counseling (n=399). All participants received a standard 12-week course of varenicline. The primary outcome was a 7-day point prevalent nonsmoking at the 6month follow-up. The Web intervention was the least expensive followed by the PTC and PTC-Web groups. Costs per additional 6-month nonsmoker and per additional lifetime quitter were $1,278 and $2,601 for Web, $1,472 and $2,995 for PTC, and $1,617 and $3,291 for PTC-Web. Cost per life-year (LY) and quality-adjusted life-year (QALY) saved were $1,148 and $1,136 for Web, $1,320 and $1,308 for PTC, and $1,450 and $1,437 for PTC-Web. Based on the cost per LY and QALY saved, these interventions are among the most cost-effective life-saving medical treatments. Web, PTC, and combined PTC-Web treatments were all highly cost-effective, with the Web treatment being marginally more cost-effective than the PTC or combined PTC-Web treatments.     

A cost-effectiveness model of genetic testing and periodical clinical screening for the evaluation of families with dilated cardiomyopathy

PurposeTo assess the relative cost-effectiveness of cascade genetic testing in asymptomatic relatives of patients with dilated cardiomyopathy (DCM) compared with periodical clinical surveillance.MethodsA decision-analytic model, combining a decision tree and a Markov model, was used to determine the lifetime costs and quality-adjusted life years (QALYs) for the two strategies. Deterministic and probabilistic sensitivity analyses were undertaken to assess the robustness of findings and to explore decision uncertainty.ResultsThe incremental cost per additional QALY of cascade genetic testing prior to periodical clinical surveillance of first-degree relatives compared with periodical clinical surveillance alone was estimated at approximately AUD $6100. At established thresholds of cost-effectiveness, there is a 90% probability that cascade genetic testing is cost-effective. Extensive sensitivity analyses, including the addition of second-degree relatives, did not alter the conclusions drawn from the main analysis.ConclusionUsing cascade genetic testing to guide clinical surveillance of asymptomatic relatives of patients with DCM is very likely to be cost-effective. As the DCM pathogenic variant detection rate rises and new evidence for personalized treatment of at-risk individuals becomes available, the cost-effectiveness of cascade testing will further increase.     

Cost-effectiveness of the 21-gene recurrence score assay in the context of multifactorial decision making to guide chemotherapy for early-stage breast cancer

PurposeNew evidence is available regarding the utility of the 21-gene recurrence score assay in guiding chemotherapy use for node-negative, estrogen receptor–positive breast cancer. We applied this evidence in a decision-analytic model to re-evaluate the cost-effectiveness of the assay.MethodsWe cross-classified patients by clinicopathologic characteristics from the Adjuvant! risk index and by recurrence score risk group. For non-recurrence score-guided treatment, we assumed patients receiving hormonal therapy alone had low-risk characteristics and patients receiving chemotherapy and hormonal therapy had higher-risk characteristics. For recurrence score-guided treatment, we assigned chemotherapy probabilities conditional on recurrence score risk group and clinicopathologic characteristics.ResultsAn estimated 40.4% of patients in the recurrence score-guided strategy and 47.3% in the non-recurrence score-guided strategy were expected to receive chemotherapy. The incremental gain in quality-adjusted life-years was 0.16 (95% confidence interval, 0.08–0.28) with the recurrence score-guided strategy. Lifetime medical costs to the health system were $2,692 ($1,546–$3,821) higher with the recurrence score-guided strategy, for an incremental cost-effectiveness ratio of $16,677/quality-adjusted life-year ($7,613–$37,219). From a societal perspective, the incremental cost-effectiveness was $10,788/quality-adjusted life-year ($6,840–$30,265).ConclusionThe findings provide supportive evidence for the economic value of the 21-gene recurrence score assay in node-negative, estrogen receptor–positive breast cancer.Genet Med 2013:15(3):203–211     

Early Antiretroviral Therapy for Patients With Acute AIDS-Related Opportunistic Infections: A Cost-Effectiveness Analysis of ACTG A5164

Abstract

Purpose: ACTG A5164 demonstrated that early antiretroviral therapy (ART) in HIV-infected patients with acute opportunistic infections (OIs) reduced death and AIDS progression compared to ART initiation 1 month later. We project the life expectancies, costs, and incremental cost-effectiveness ratios (ICERs) of these strategies. Method: Using an HIV simulation model, we compared 2 strategies for patients with acute OIs: (1) an intervention to deliver early ART, and (2) deferred ART. Parameters from ACTG A5164 included initial mean CD4 count (47/μL), linkage to outpatient care (87%), and immune reconstitution inflammatory syndrome 1 month after ART initiation (7%). The estimated intervention cost was $1,650/patient. Results: Early ART lowered projected 1-year mortality from 10.4% to 8.2% and increased life expectancy from 10.07 to 10.39 quality-adjusted life-years (QALYs). Lifetime costs increased from $385,220 with deferred ART to $397,500 with early ART, primarily because life expectancy increased, producing an ICER of $38,600/QALY. Results were most sensitive to increased intervention cost and decreased virologic efficacy in the early ART strategy. Conclusions: An intervention to initiate ART early in patients with acute OIs improves survival and meets US cost-effectiveness thresholds. Programs should be developed to implement this strategy at sites where HIV-infected patients present with OIs.     

Cost-effectiveness of exome and genome sequencing for children with rare and undiagnosed conditions

PurposeThis study aimed to estimate the cost-effectiveness of exome sequencing (ES) and genome sequencing (GS) for children.MethodsWe modeled costs, diagnoses, and quality-adjusted life years (QALYs) for diagnostic strategies for critically ill infants (aged <1 year) and children (aged <18 years) with suspected genetic conditions: (1) standard of care (SOC) testing, (2) ES, (3) GS, (4) SOC followed by ES, (5) SOC followed by GS, (6) ES followed by GS, and (7) SOC followed by ES followed by GS. We calculated the 10-year incremental cost per additional diagnosis, and lifetime incremental cost per QALY gained, from a health care perspective.ResultsFirst-line GS costs $15,048 per diagnosis vs SOC for infants and $27,349 per diagnosis for children. If GS is unavailable, ES represents the next most efficient option compared with SOC ($15,543 per diagnosis for infants and $28,822 per diagnosis for children). Other strategies provided the same or fewer diagnoses at a higher incremental cost per diagnosis. Lifetime results depend on the patient’s assumed long-term prognosis after diagnosis. For infants, GS ranged from cost-saving (vs all alternatives) to $18,877 per QALY (vs SOC). For children, GS (vs SOC) ranged from $119,705 to $490,047 per QALY.ConclusionFirst-line GS may be the most cost-effective strategy for diagnosing infants with suspected genetic conditions. For all children, GS may be cost-effective under certain assumptions. ES is nearly as efficient as GS and hence is a viable option when GS is unavailable.     

Underutilization of Lynch syndrome screening in a multisite study of patients with colorectal cancer

PurposeThe aim of this study was to examine Lynch syndrome screening of patients with metastatic colorectal cancer in integrated health-care-delivery organizations.MethodsWe determined the availability of Lynch syndrome screening criteria and actual Lynch syndrome screening in the medical records of 1,188 patients diagnosed with metastatic colorectal cancer between 2004 and 2009 at seven institutions in the Cancer Research Network.ResultsWe found infrequent use of Lynch syndrome screening (41/1,188). Family history was available for 937 of the 1,188 patients (79%). There was sufficient information to assess Lynch syndrome risk using family history–based criteria in 719 of the 937 patients (77%) with family history documentation. In 391 individuals with a family history of a Lynch syndrome–associated cancer, 107 (27%) could not be evaluated due to missing information such as age of cancer onset. Eleven percent of patients who met the Bethesda criteria and 25% of individuals who met the Amsterdam II criteria were screened for Lynch syndrome. Recommended guidelines were adhered to during screening, but no testing method was preferred.ConclusionThe information required for Lynch syndrome screening decisions is routinely collected but seldom used. There is a critical gap between collection of family history and its use to guide Lynch syndrome screening, which may support a case for implementation of universal screening guidelines.Genet Med15 12, 933–940.     

Cost-effectiveness analysis of COVID-19 vaccination in Poland

IntroductionThe aim of our study was to assess the potential value of the Comirnaty vaccine (BNT162b2) in Poland. A model was used to estimate patient events, direct medical costs, utilities, and cost-effectiveness for 1 year with and without implementation of the vaccine.Material and methodsThe Markov model with 1-week cycles was used to estimate patient events, direct medical costs, utilities, and cost-effectiveness for 1 year with and without implementing the Comirnaty vaccine in Poland. The incremental cost per quality-adjusted life-year (QALY) gained vs. no vaccine was calculated for the general population and selected age-groups. All costs are reported in PLN (average exchange rate in 2020: 1 EUR = 4.44 PLN).ResultsIn the base case analysis the incremental cost per QALY gained associated with vaccinating the whole population is 6249 PLN. For individuals aged 60–69 years and > 80 years vaccination is less costly and more effective than no vaccination. The incremental cost per QALY gained when vaccinating individuals aged 40–49 and 30–39 years is 28,135 PLN and 67,823 PLN, respectively. In the general population and in younger subpopulations the incremental cost-effectiveness ratio is most sensitive to the vaccine effectiveness, vaccine price, and SARS-CoV-2 infection rates.ConclusionsWhen prioritization is required due to supply constraints, vaccination of the elderly is justified because it gives the highest number of QALY gained and generates savings for the health care system. Continual updates of the model concerning vaccine real-life effectiveness and epidemic course are required to refine the prioritisation scheme in the future.     

Economic evidence on identifying clinically actionable findings with whole-genome sequencing: a scoping review

The American College of Medical Genetics and Genomics (ACMG) recommends that mutations in 56 genes for 24 conditions are clinically actionable and should be reported as secondary findings after whole-genome sequencing (WGS). Our aim was to identify published economic evaluations of detecting mutations in these genes among the general population or among targeted/high-risk populations and conditions and identify gaps in knowledge. A targeted PubMed search from 1994 through November 2014 was performed, and we included original, English-language articles reporting cost-effectiveness or a cost-to-utility ratio or net benefits/benefit–cost focused on screening (not treatment) for conditions and genes listed by the ACMG. Articles were screened, classified as targeting a high-risk or general population, and abstracted by two reviewers. General population studies were evaluated for actual cost-effectiveness measures (e.g., incremental cost-effectiveness ratios (ICER)), whereas studies of targeted populations were evaluated for whether at least one scenario proposed was cost-effective (e.g., ICER of ≤$100,000 per life-year or quality-adjusted life-year gained). A total of 607 studies were identified, and 32 relevant studies were included. Identified studies addressed fewer than one-third (7 of 24; 29%) of the ACMG conditions. The cost-effectiveness of screening in the general population was examined for only 2 of 24 conditions (8%). The cost-effectiveness of most genetic findings that the ACMG recommends for return has not been evaluated in economic studies or in the context of screening in the general population. The individual studies do not directly address the cost-effectiveness of WGS.     

Implementation of routine screening for Lynch syndrome in university and safety-net health system settings: successes and challenges

PurposeRoutine screening for evidence of DNA mismatch repair abnormalities can identify colorectal cancer patients with Lynch syndrome, but impact in usual care settings requires study. After implementing routine screening at our university and safety-net health systems as usual practice, our aims were to determine outcomes, including screening process quality.MethodsWe conducted a retrospective cohort study from 1 May 2010 to 1 May 2011. Screening included reflexive immunohistochemistry to evaluate DNA mismatch repair protein expression for patients with colorectal cancer aged ≤70 years, with a cancer genetics team following up results. Screening outcomes, as well as challenges to a high-quality screening process were evaluated.ResultsWe included 129 patients (mean age 56 years, 36% female); 100 had immunohistochemistry screening completed. Twelve patients had abnormal immunohistochemistry: four with definite Lynch syndrome, four with probable Lynch syndrome, and three without Lynch syndrome; one patient had an incomplete work-up. Lynch syndrome was confirmed for 6/13 asymptomatic relatives tested. Screening process quality was optimal for 77.5% of patients. Barriers to optimal quality screening included ensuring reflexive immunohistochemistry completion, complete follow-up of abnormal immunohistochemistry, and timely incorporation of results into clinical decision making.ConclusionUsual care implementation of routine screening for Lynch syndrome can result in significant rates of detection, even in a largely safety-net setting. To optimize implementation, challenges to high-quality Lynch syndrome screening, such as ensuring reflexive screening completion and clinically indicated genetic testing and follow-up for abnormal screens, must be identified and addressed.Genet Med15 12, 925–932.     

Implementing screening for Lynch syndrome among patients with newly diagnosed colorectal cancer: summary of a public health/clinical collaborative meeting

Lynch syndrome is the most common cause of inherited colorectal cancer, accounting for approximately 3% of all colorectal cancer cases in the United States. In 2009, an evidence-based review process conducted by the independent Evaluation of Genomic Applications in Practice and Prevention Working Group resulted in a recommendation to offer genetic testing for Lynch syndrome to all individuals with newly diagnosed colorectal cancer, with the intent of reducing morbidity and mortality in family members. To explore issues surrounding implementation of this recommendation, the Centers for Disease Control and Prevention convened a multidisciplinary working group meeting in September 2010. This article reviews background information regarding screening for Lynch syndrome and summarizes existing clinical paradigms, potential implementation strategies, and conclusions which emerged from the meeting. It was recognized that widespread implementation will present substantial challenges, and additional data from pilot studies will be needed. However, evidence of feasibility and population health benefits and the advantages of considering a public health approach were acknowledged. Lynch syndrome can potentially serve as a model to facilitate the development and implementation of population-level programs for evidence-based genomic medicine applications involving follow-up testing of at-risk relatives. Such endeavors will require multilevel and multidisciplinary approaches building on collaborative public health and clinical partnerships.