Skip directly to search Skip directly to A to Z list Skip directly to navigation Skip directly to page options Skip directly to site content

Hot Topics of the Day|PHGKB
Search PHGKB:

Archive

Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

Search Archive:
163 hot topic(s) found with the query "Cost-effectiveness"

Wilson and Jungner Revisited: Are Screening Criteria Fit for the 21st Century?
(Posted: Sep 23, 2024 8AM)

From the abstract: "This systematic review revealed a set of general limitations of the WJ criteria, such as imprecise terminology, lack of measurability and objectivity, missing pediatric focus, and absent guidance on program management. Furthermore, it unraveled specific aspects of criticism on clinical, diagnostic, therapeutic, and economical aspects. A major obstacle was found to be the incompletely understood natural history and phenotypic diversity of rare diseases prior to NBS implementation, resulting in uncertainty about case definition, risk stratification, and indications for treatment. This gap could be closed through the systematic collection and evaluation of real-world evidence on the quality, safety, and (cost-)effectiveness of NBS, as well as the long-term benefits experienced by screened individuals. "


Health Care Costs After Genome-Wide Sequencing for Children With Rare Diseases in England and Canada
(Posted: Jul 15, 2024 9AM)

From the abstract: "Is diagnosis from genome-wide sequencing associated with reduced health care costs for children with suspected rare diseases? Findings: In this cohort study of 3 groups of children who underwent genome-wide sequencing in England (7775 children in a research study) or Canada (118 children who received publicly funded sequencing and 77 children in a research study), diagnosis from genome-wide sequencing was not associated with changes in health care or diagnostic costs. Meaning: These findings suggest that sustainable clinical implementation of genome-wide sequencing must be motivated by evidence of patient and family benefit and cost-effectiveness rather than promises of cost savings from earlier diagnosis. "


Systematic reanalysis of genomic data by diagnostic laboratories: a scoping review of ethical, economic, legal and (psycho)social implications.
Marije A van der Geest et al. Eur J Hum Genet 2024 3 (Posted: Mar 18, 2024 9AM)

From the abstract: "In total, we identified nine ELSI aspects, such as (perceived) professional responsibilities, implications for consent and cost-effectiveness. The identified ELSI aspects brought forward necessary trade-offs for GHPs to consciously take into account when considering responsible implementation of systematic reanalysis of NGS data in routine diagnostics, balancing the various strains on their laboratories and personnel while creating optimal results for new and former patients. "


Improving Noninvasive Colorectal Cancer Screening.
John M Carethers et al. N Engl J Med 2024 3 (11) 1045-1046 (Posted: Mar 14, 2024 10AM)

From the article: "Screening for colorectal cancer saves lives. Screening tests have evolved to include stool-based, endoscopic and image-based, and blood-based methods, with minimal thresholds for sensitivity and specificity for colorectal cancer set by the baseline characteristics of FIT. Although multiple tests have been developed over time and vary in cost-effectiveness for colorectal cancer screening, the best screening test is the one that gets completed by the patient. Most of the recommended tests, including the two newer tests assessed in the studies now published in the Journal, improve on the sensitivity and approach the specificity of FIT. "


Cost-Effectiveness of Population-Based Multigene Testing for Breast and Ovarian Cancer Prevention.
Fangjian Guo et al. JAMA Netw Open 2024 2 (2) e2356078 (Posted: Feb 15, 2024 9AM)

From the abstract: "Is a population-wide genetic testing strategy more cost-effective than the current family history–based testing strategy for breast and ovarian cancer prevention? This economic evaluation found that population-based BRCA1, BRCA2, and PALB2 testing among unselected women was cost-effective for the prevention of breast and ovarian cancer and remained cost-effective in extensive 1-way sensitivity analyses. Population-wide genetic testing was 100% cost-effective for all the simulations in probabilistic sensitivity analyses; it became cost-inefficient only when the cost of the test exceeded a certain threshold ($825). The findings support the need for a shift toward more comprehensive genetic testing strategies to identify pathogenic variant carriers and enable informed decision-making for personalized risk management. "


Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer.
Xia Wei et al. JAMA Netw Open 2024 2 (2) e2355324 (Posted: Feb 11, 2024 10AM)

From the abstract: This economic evaluation using a decision-analytic Markov model with a simulated cohort of women aged 30 years found that undergoing both risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) was most cost-effective, maximizing cancers prevented for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) pathogenic variants, while RRSO was cost-effective at age 45 years for women with RAD51C, RAD51D, and BRIP1 pathogenic variants." "


Cost-Effectiveness of Screening Strategies for Familial Hypercholesterolaemia: An Updated Systematic Review.
Clara Marquina et al. Pharmacoeconomics 2024 1 (Posted: Jan 30, 2024 10AM)

From the abstract: "A total of 21 studies evaluating 62 strategies were included in this review, most of the studies (95%) adopted a healthcare perspective in the base case, and majority were set in high-income countries. Strategies analysed included cascade screening (23 strategies), opportunistic screening (13 strategies), systematic screening (11 strategies) and population-wide screening (15 strategies). Most of the strategies relied on genetic diagnosis for case ascertainment. Based on reported willingness to pay thresholds for each setting, most CEA studies concluded that screening for FH compared with no screening was cost-effective, regardless of the screening strategy. Cascade screening resulted in the largest health benefits per person tested. "


Cost-Effectiveness of Whole-Genome vs Whole-Exome Sequencing Among Children With Suspected Genetic Disorders.
Mario Cesare Nurchis et al. JAMA Netw Open 2024 1 (1) e2353514 (Posted: Jan 30, 2024 8AM)

From the abstract: "Is whole-genome sequencing (WGS) more cost-effective than whole-exome sequencing for children with suspected genetic disorders? The results of this economic evaluation of a cohort of 870 pediatric patients suggest that adopting WGS as a first-tier strategy would be cost-effective at a willingness-to-pay threshold of €30 000 to €50 000 (US $32?625-$54?375), specifically for the diagnosis of severely ill infants with suspected genetic disorders. ng These findings suggest that wider use of WGS may minimize diagnostic delays and facilitate timely implementation of appropriate treatments. "


Cost Effectiveness of Genomic Population Health Screening in Adults: A Review of Modeling Studies and Future Directions.
Robert S Wildin et al. J Appl Lab Med 2024 1 (1) 92-103 (Posted: Jan 09, 2024 9AM)

From the abstract: " Eight recent cost-effectiveness modeling studies for high penetrance monogenic dominant diseases that used input parameters from 3 different countries are reviewed. Results and their uses in refining implementations are analyzed and the roles for laboratory medicine in facilitating success are discussed. The reviewed studies generally found evidence for cost-effectiveness of genomic population health screening in at least a subset of their base case screening scenario. Sensitivity analyses identified opportunities for improving the likelihood of cost-effectiveness. On the whole, the modeling results suggest genomic population health screening is likely to be cost-effective for high penetrance disorders in younger adults."


Real-world diagnostic outcomes and cost-effectiveness of genome-wide sequencing for developmental and seizure disorders: evidence from Canada
DA Regier et al, Genetics in Medicine, January 8, 2024 (Posted: Jan 08, 2024 8AM)

From the abstract: "Based on medical records review, we estimated real-world costs and outcomes for 491 patients who underwent standard of care (SOC) diagnostic testing at BC Children’s Hospital. Results informed a state-transition Markov model examining cost-effectiveness of three competing diagnostic strategies: (1) SOC with last-tier access to ES; (2) streamlined ES access; (3) first-tier GS. We found earlier access to ES may yield more rapid genetic diagnosis of childhood developmental and seizure disorders and cost savings compared to current practice. "


Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia: systematic reviews, qualitative study and cost-effectiveness analysis.
Nadeem Qureshi et al. Health Technol Assess 2023 11 (16) 1-140 (Posted: Nov 07, 2023 0PM)

From the abstract: "Cascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective. "


Long-term cost-effectiveness of a melanoma prevention program using genomic risk information compared with standard prevention advice in Australia
CK Law et al, Genetics in Medicine, August 30, 2023 (Posted: Aug 31, 2023 7AM)

From the abstract: "Evidence indicates a melanoma prevention program using personalized genomic risk provision and genetic counselling, can impact prevention behaviors, including reducing sunburns in adults with no melanoma history. This analysis evaluated its longer-term cost-effectiveness from an Australian health system perspective. We found that genomic risk provision targeted to high-traditional melanoma risk individuals is likely a cost-effective strategy for reducing sunburns and will likely prevent future melanomas and keratinocyte carcinomas."


Cost effectiveness review of text messaging, smartphone application, and website interventions targeting T2DM or hypertension.
Ruben Willems et al. NPJ Digit Med 2023 8 (1) 150 (Posted: Aug 21, 2023 8AM)

Digital health interventions have been shown to be clinically-effective for type 2 diabetes mellitus (T2DM) and hypertension prevention and treatment. This study synthesizes and compares the cost-effectiveness of text-messaging, smartphone application, and websites. We found that digital interventions are cost-effective without substantial differences between the different delivery modes. Future health economic studies should increase transparency, conduct sufficient sensitivity analyses, and appraise the ICUR more critically in light of a reasoned willingness-to-pay threshold.


AI-based skin cancer detection: the balance between access and overutilization
KP Venkatesh et al, NPJ Digital Medicine, August 15, 2023 (Posted: Aug 15, 2023 0PM)

A recent study evaluated the healthcare implications and costs of an AI-enabled mobile health app for skin cancer detection, involving 18,960 beneficiaries of a Netherlands insurer. They report a 32% increase in claims for premalignant and malignant skin lesions among app users, largely attributed to benign skin lesions and leading to higher annual costs for app users (€64.97) compared to controls (€43.09). Cost-effectiveness analysis showed a comparable cost to dermatologist-based diagnosis alone. This editorial emphasizes the balance in AI-based dermatology between increased access and increased false positives resulting in overutilization.


Implementing preconception expanded carrier screening in a universal healthcare system: a model-based cost-effectiveness analysis
A Busnelli et al, Genet Med, July 2023 (Posted: Jul 24, 2023 11AM)


The English National Lynch Syndrome Transformation Project
Brit Soc Gastro, July 14, 2023 (Posted: Jul 16, 2023 9AM)

Lynch syndrome (LS) affects approximately 1 in 400 individuals and predisposes to multiple cancers including colorectal, endometrial, gastric, small bowel, cholangiocarinoma and other tumors. Although a common condition, it is estimated that only 5% of patients with LS are known in the UK. There is consistent evidence of the cost-effectiveness and clinical benefit of a structured diagnostic pathway in patients with LS following a diagnosis of cancer linked to cascade testing in families. NICE DG27 and DG42 guidelines recommend universal testing of newly diagnosed colorectal and endometrial cancer for Lynch syndrome (LS), however there is strong evidence of variation in delivery of these guidelines by clinical services.


The Promise of Population-based Genomic Screening for Selected Hereditary Conditions: Contributions of Cost-Effectiveness Analysis
ND Rao et al, CDC Blog Post, July 14, 2023 Brand (Posted: Jul 14, 2023 1PM)

Initial cost-effectiveness research suggests that simultaneous population genomic screening for three CDC Tier 1 genomic applications (hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia) can be cost effective and reduce morbidity and mortality if implemented in adults younger than 40 years old, costs of screening tests are low, and those found carrying a pathogenic variant have access to preventive care.


Cost-Effectiveness Analysis of Personalized Hypertension Prevention
ST Wang, J Per Med, June 15, 2023 (Posted: Jun 16, 2023 1PM)

While a population-wide strategy involving lifestyle changes and a high-risk strategy involving pharmacological interventions have been described, the recently proposed personalized medicine approach combining both strategies for the prevention of hypertension has increasingly gained attention. However, a cost-effectiveness analysis has been hardly addressed. The personalized preventive treatment appeared more cost-effective than population-based conventional care. These findings are extremely valuable for making hypertension-based health decisions based on precise preventive medication.


Cost-Effectiveness Analysis in Public Health Genomics and Precision Health: Recent Findings, Methodologic Issues, and the Path Forward
CDC Public Health Genomics Webinar, October 26, 2023 Brand (Posted: Jun 09, 2023 8AM)

Dr David Veenstra from the University of Washington in Seattle will review the field as a whole and his research projects including evaluation of the cost-effectiveness of population-level genomic screening, pharmacogenomics in diverse populations, decision modeling techniques to assess evidence thresholds, and stakeholder preferences for precision medicine. He will address recent findings, methodologic issues and the path forward.


Population Genomic Screening for Three Common Hereditary Conditions : A Cost-Effectiveness Analysis.
Gregory F Guzauskas et al. Ann Intern Med 2023 5 (Posted: May 09, 2023 5AM)

The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown. We estimated the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH). We found that population genomic screening with a restricted panel of high-evidence genes is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions.


Cost-effectiveness of Pharmacogenomic Testing: How to Measure the Value of Having the Right Dose of the Right Drug for the Right Patient
L Shi et al, CDC Blog Post, May 8, 2023 Brand (Posted: May 08, 2023 4PM)

A recent systematic review that assessed the cost-effectiveness of pharmacogenetic testing for drugs with existing guidelines concluded that most studies favored pharmacogenomic testing. The significance of this conclusion must be interpreted with caution and in the context of study factors, such as funding sources, geography, cohort, and the cost-effectiveness comparisons being made.


Cost-effectiveness and Return on Investment of a Nationwide Case-Finding Program for Familial Hypercholesterolemia in Children in the Netherlands.
Zanfina Ademi et al. JAMA Pediatr 2023 5 (Posted: May 02, 2023 8AM)

In this economic evaluation of a hypothetical population of 1000 FH children aged 10 years, nationwide case finding was associated with saved lives and improved quality of life over a lifetime. The incremental cost-effectiveness ratio for cascade screening and initiation of treatment with statins in children vs later detection and treatment was €9220 ($10?050) per quality-adjusted life-year gained, that from a health care perspective and a societal perspective was cost saving and the return on investment for the detection and treatment program for FH in children was €8.37 ($9.12).


A systematic review of economic evaluations of whole-genome sequencing for the surveillance of bacterial pathogens.
Vivien Price et al. Microbial genomics 2023 2 (2) (Posted: Feb 17, 2023 9AM)

Six hundred and eighty-one articles were identified, of which 49 proceeded to full-text screening, with 9 selected for inclusion. All had been published since 2019. Heterogeneity was high. Five studies assessed WGS for hospital surveillance and four analyzed foodborne pathogens. Four were cost-benefit analyses, one was a cost-utility analysis, one was a cost-effectiveness analysis, one was a combined cost-effectiveness and cost-utility analysis, one combined cost-effectiveness and cost-benefit analyses and one was a partial analysis. All studies supported the use of WGS as a surveillance tool on economic grounds.


Prioritizing the detection of rare pathogenic variants in population screening.
Lacaze Paul et al. Nature reviews. Genetics 2023 1 (Posted: Jan 15, 2023 3PM)

Population genomic screening to detect carriers of rare monogenic variants for medically actionable conditions is supported by substantial evidence of clinical utility and cost effectiveness. Much less evidence supports screening by polygenic risk scores, which do not detect rare variants. Using only polygenic scores in population screening initiatives, while ignoring the detection of higher-risk rare monogenic variants, is ill-advised.


Editorial: Digitalization for precision healthcare
F Cascini et al, Front Public Health, December 2022 (Posted: Dec 21, 2022 8AM)

The creation of digital infrastructure and technologies to collect, analyse and connect electronic health and life-science data supports—now more than ever—the growth of precision healthcare. However, the current adoption of digital health tools and infrastructures is geographically variable and often missing an assessment, as shown in a systematic review of the cost-effectiveness of digital interventions. This lacking approach to the digitalisation of the health sector has the effect of wasting resources with no improvement in care.


Cost-effectiveness of a gene sequencing test for Alzheimer's disease in Ontario.
Iragorri Nicolas et al. Journal of community genetics 2022 11 (Posted: Nov 28, 2022 11AM)

ONDRISeq saved $54 per patient relative to OOC testing and led to a small QALY gain in the base case (0.0014 per patient). Results were most sensitive to testing costs, uptake rates, and treatment efficacy. ONDRISeq represented better value for money relative to OOC testing throughout 75% of 10,000 probabilistic iterations. Using ONDRISeq is expected to provide health system cost savings. Switching to ONDRISeq for AD genetic testing would be dependent on the ability to accommodate the expected testing volumes.


Integrating genome-wide polygenic risk scores and non-genetic risk to predict colorectal cancer diagnosis using UK Biobank data: population based cohort study
SEW Briggs et al, BMJ, November 2022 (Posted: Nov 14, 2022 7AM)

Integrating polygenic risk scores with QCancer-10 modestly improves risk prediction over use of QCancer-10 alone. Given that QCancer-10 data can be obtained relatively easily from health records, use of polygenic risk score in risk stratified population screening for colorectal cancer currently has no clear justification. The added benefit, cost effectiveness, and acceptability of polygenic risk scores should be carefully evaluated in a real life screening setting before implementation in the general population.


Artificial intelligence for strengthening healthcare systems in low- and middle-income countries: a systematic scoping review.
Ciecierski-Holmes Tadeusz et al. NPJ digital medicine 2022 10 (1) 162 (Posted: Oct 29, 2022 11AM)

Only half of the papers reported which algorithms and datasets were used in order to train the AI. A number of challenges of using AI tools were reported, including issues with reliability, mixed impacts on workflows, poor user friendliness and lack of adeptness with local contexts. Many barriers exists that prevent the successful development and adoption of well-performing, context-specific AI tools, such as limited data availability, trust and evidence of cost-effectiveness in LMICs.


Resource allocation in genetic and genomic medicine
J Buchanan et al, J Community Genetics, September 24, 2022 (Posted: Sep 26, 2022 7AM)

Integrating genomic medicine within national health services has so far not been straightforward . Amongst other considerations, effective translation requires that careful attention is paid to issues surrounding priority setting and resource allocation. Commissioning genomic medicine services in a fair, equitable, and appropriate manner necessitates rigorous exploration of the ethical, policy, and practical implications, including factors such as cost, opportunity cost, clinical effectiveness, cost-effectiveness, need, ability to benefit, and procedural fairness.


Correspondence on “Cost-effectiveness of exome and genome sequencing for children with rare and undiagnosed conditions”
SD Grosse et al, Genetics in Medicine, September 21, 2022 (Posted: Sep 22, 2022 6AM)

The relative cost-effectiveness of rES and rGS should be informed by up-to-date evidence on costs and diagnostic performance and reflect specific clinical settings, meeting the needs of decision-makers in those settings. Published economic evaluations of GS should distinguish between the price and cost (value of resources used) of sequencing and suggested that the use of microcosting data could improve the accuracy of cost-effectiveness analyses from either the societal or health care perspectives.


The cost-effectiveness of digital health interventions: A systematic review of the literature
A Gentili et al, Front Public Health, August 2022 (Posted: Aug 11, 2022 7AM)

The studies were heterogeneous by country (mostly conducted in upper and upper-middle income countries), type of eHealth intervention, method of implementation, and reporting perspectives. The qualitative analysis identified the economic and effectiveness evaluation of six different types of interventions: (1) seventeen studies on new video-monitoring service systems; (2) five studies on text messaging interventions; (3) five studies on web platforms and digital health portals; (4) two studies on telephone support; (5) three studies on new mobile phone-based systems and applications; and (6) three studies on digital technologies and innovations.


Modelling the Cost-Effectiveness and Budget Impact of a Newborn Screening Program for Spinal Muscular Atrophy and Severe Combined Immunodeficiency
STF Shih et al, IJNS, July 20, 2022 (Posted: Jul 21, 2022 7AM)

Over a 60-year time horizon, screening every newborn in the population and treating diagnosed SCID by early hematopoietic stem cell transplantation and SMA by gene therapy, would result in 95 QALYs gained per 100,000 newborns, and result in cost savings of USD 8.6 million. Sensitivity analysis indicates 97% of simulated results are considered cost-effective against commonly used willingness-to-pay thresholds. The introduction of combined NBS for SCID and SMA is good value for money from the long-term clinical and economic perspectives, representing a cost saving to governments in the long-term, as well as improving and saving lives


Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways: A scoping review and recommended methods.
Ferket Bart S et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 7 (Posted: Jul 15, 2022 5AM)

We recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses of costs of ES strategies and postpartum care, as well as genetic diagnoses and pregnancy outcomes. For early diagnosis in pediatrics, modeling quality-adjusted life years (QALYs) and costs over =20 years for rapid turnaround GS/ES. For hereditary cancer syndrome testing, modeling cumulative costs and QALYs for the individual tested and first/second/third-degree relatives. For tumor profiling, not restricting to treatment uptake or response and including QALYs and costs of downstream outcomes. For screening, modeling lifetime costs and QALYs and considering consequences of low penetrance and GS/ES reanalysis.


‘Diagnostic shock’: the impact of results from ultrarapid genomic sequencing of critically unwell children on aspects of family functioning
HB Smart et al, EJHG, July 13, 2022 (Posted: Jul 13, 2022 7AM)

Rapid genomic sequencing (rGS) is being increasingly used in neonatal and paediatric intensive care units. While there is emerging evidence of clinical utility and cost-effectiveness, concerns have been raised regarding the impact of delivering genomic results in an acute care setting. To help investigate these concerns, we analysed survey data collected from caregivers whose children had received rGS through a national rapid genomic diagnosis program.


Exome/Genome-Wide Testing in Newborn Screening: A Proportionate Path Forward
V Rahimzadeh et al, Frontiers in Genetics, May 2022 (Posted: May 31, 2022 8AM)

In this paper we consider recommendations from professional genetic societies in Europe and North America in light of scientific advances in ES/GS and our current understanding of the limitations of ES/GS approaches in the NBS context. We invoke the principle of proportionality—that benefits clearly outweigh associated risks—and the human right to benefit from science to argue that rigorous evidence is still needed for ES/GS that demonstrates clinical utility, accurate genomic variant interpretation, cost effectiveness and universal accessibility of testing and necessary follow-up care and treatment.


Paying for artificial intelligence in medicine
RB Parikh et al, NPJ Digital Medicine, May 20, 2022 (Posted: May 20, 2022 8AM)

We review current models of paying for AI in medicine and describe five alternative and complementary reimbursement approaches, including incentivizing outcomes instead of volume, utilizing advance market commitments and time-limited reimbursements for new AI applications, and rewarding interoperability and bias mitigation. As AI rapidly integrates into routine healthcare, careful design of payment for AI is essential for improving patient outcomes while maximizing cost-effectiveness and equity.


Assessing the impacts of timing on the health benefits, cost-effectiveness and relative affordability of COVID-19 vaccination programmes in 27 African Countries
Y Liu et al, MEDRXIV, May 10, 2022 (Posted: May 11, 2022 7AM)


Sustainability of surveillance systems for SARS-CoV-2
C Adhlhoch et al, Lancet Infectious Diseases, April 22, 2022 (Posted: Apr 24, 2022 7AM)

How can we ensure that we will be able to identify, track, and assess the epidemiological situation for SARS-CoV-2, including new variants, with less comprehensive systems? Surveillance systems, testing, and sequencing efforts need to be representative and targeted, interlinked, robust, and detailed enough to establish rapid evidence for a situation overview. The balance between specific or marker PCRs accompanied by the right level of full genomic data needs to be found for the best cost-effectiveness and system sustainability. Expanding such a system to include diseases other than COVID-19 could benefit public health as a whole.


Real-world economic evaluation of prospective rapid whole-genome sequencing compared to a matched retrospective cohort of critically ill pediatric patients in the United States
V Diaby et al, The PGX Journal, April 18, 2022 (Posted: Apr 18, 2022 9AM)

We aimed to assess the cost-effectiveness of rWGS in critically ill pediatric patients with diseases of unknown cause. Data were collected prospectively of patients admitted to the Nicklaus Children’s Hospital’s intensive care units from March 2018 to September 2020, with rWGS (N?=?65). Comparative data were collected in a matched retrospective cohort with standard diagnostic genetic testing. We determined total costs, diagnostic yield (DY), and incremental cost-effectiveness ratio (ICER) adjusted for selection bias and right censoring. Sensitivity analyses explored the robustness of ICER through bootstrapping. rWGS resulted in a diagnosis in 39.8% while standard testing in 13.5% (p?=?0.026). rWGS resulted in a mean saving per person of $100,440 (SE?=?26,497, p?<?0.001) and a total of $6.53?M for 65 patients. rWGS in critically ill pediatric patients is cost-effective, cost-saving, shortens diagnostic odyssey, and triples the DY of traditional approaches.


Implementation of pharmacogenomic clinical decision support for health systems: a cost-utility analysis
S Jiang et al, The PGX journal, April 1, 2022 (Posted: Apr 02, 2022 8AM)

We constructed a cost-effectiveness model to assess the clinical and economic value of a CDS alert program that provides pharmacogenomic (PGx) testing results, compared to no alert program in acute coronary syndrome (ACS) and atrial fibrillation (AF), from a health system perspective. We defaulted that 20% of 500,000 health-system members between the ages of 55 and 65 received PGx testing for CYP2C19 (ACS-clopidogrel) and CYP2C9, CYP4F2 and VKORC1 (AF-warfarin) annually. Clinical events, costs, and quality-adjusted life years (QALYs) were calculated over 20 years with an annual discount rate of 3%. In total, 3169 alerts would be fired. The CDS alert program would help avoid 16 major clinical events and 6 deaths for ACS; and 2 clinical events and 0.9 deaths for AF.


A systematic review on the cost effectiveness of pharmacogenomics in developing countries: implementation challenges
A Sukri et al, The PGX Journal, March 22, 2022 (Posted: Mar 25, 2022 7AM)


Cost-effectiveness of population-wide genomic screening for Lynch syndrome in the United States.
Guzauskas Gregory F et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 (Posted: Mar 05, 2022 7AM)

We 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. Population 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.


Modeling comparative cost-effectiveness of SARS-CoV-2 vaccine dose fractionation in India
Z Du et al, Nature Medicine, February 24, 2022 (Posted: Feb 24, 2022 8AM)

We developed a multi-scale model incorporating population-level transmission and individual-level vaccination to estimate the costs of hospitalization and vaccination and the economic benefits of reducing COVID-19 deaths due to dose-fractionation strategies in India. We used large-scale survey data of the willingness to pay together with data of vaccine and hospital admission costs to build the model. We found that fractional doses of vaccines could be an economically viable vaccination strategy compared to alternatives of either full-dose vaccination or no vaccination. Dose-sparing strategies could save a large number of lives, even with the emergence of new variants with higher transmissibility.


Index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes
M Abedalthagafi, EJHG, January 22, 2022 (Posted: Jan 24, 2022 2PM)

Identification of a cancer pathogenic variant variant in an index-case facilitates management strategies such as decisions around the extent of surgical management or targeted therapeutic strategies. It also defines the cancer prevention and early detection strategies in at-risk family members. Cascade screening also reassures non-carrier relatives, excluding them from intensive surveillance and at the same time, contributing to the cost-effectiveness of genetic testing for a wider population.


Cost-effectiveness analysis of BNT162b2 COVID-19 booster vaccination in the United States
R Li et al, MEDRXIV, November 14, 2021 (Posted: Nov 15, 2021 6AM)


Rapid genomic testing for critically ill children: time to become standard of care?
Z Stark et al, EJHG, November 8, 2021 (Posted: Nov 08, 2021 7AM)

We review the reported diagnostic and clinical outcomes, as well as broader evaluations of family and professional experiences, cost effectiveness, implementation challenges and bioethical issues arising from rapid testing. As rapid genomic testing transitions from the research to the healthcare setting to become a ‘standard of care’ test, there is a need to develop effective service delivery models to support scalability at both the laboratory and clinical level and promote equity of access, prompt test initiation, integrated multidisciplinary input and holistic family support.


Beyond performance metrics: modeling outcomes and cost for clinical machine learning
JA Diao et al, NPJ Digital Medicine, August 10, 2021 (Posted: Aug 10, 2021 3PM)

Advances in medical machine learning are expected to help personalize care, improve outcomes, and reduce wasteful spending. In quantifying potential benefits, it is important to account for constraints arising from clinical workflows. Practice variation is known to influence the accuracy and generalizability of predictive models, but its effects on cost-effectiveness and utilization are less well-described.


Polygenic Risk Scores for Breast Cancer—Can They Deliver on the Promise of Precision Medicine?
PD Shah, JAMA Network Open, August 4, 2021 (Posted: Aug 04, 2021 0PM)

Currently, guidelines advise against the clinical use of PRSs due to limitations in interpretation and encourage further research. Essential objectives of this research must be to examine if, when, and in whom PRSs are useful. Studies will need to not only consider discriminatory capacity, equity, and clinical utility, but also psychosocial impact and cost-effectiveness, each in context. Polygenic risk scores may well personalize cancer risk management and improve patient outcomes, but we will need to further investigate these critical issues before determining whether they can fully deliver.


Genetic-guided pharmacotherapy for venous thromboembolism: a systematic and critical review of economic evaluations
KK Lim et al, Pharmacogenomics Journal, June 15, 2021 (Posted: Jun 16, 2021 8AM)

The ten eligible studies, all model-based, examined heterogeneous interventions and comparators. Findings varied widely; testing was cost-saving in two base-cases, cost-effective in four, not cost-effective in three, dominated in one. Of 22 model variables that changed decisions about cost-effectiveness, effectiveness/relative effectiveness of the intervention was the most frequent, albeit of poor quality.


New publications in health economics and genomics 8th June 2021
J Buchanan, Health Economics and Genomics, June 2021 (Posted: Jun 09, 2021 7AM)

Five publications from the past week: Genomic sequencing for the diagnosis of childhood mitochondrial disorders; A Systematic Review of Discrete Choice Experiments and Conjoint Analysis on Genetic Testing; Rapid precision care incorporating rWGS in 5 California children’s hospitals; Understanding decisions to participate in genomic medicine in children’s cancer care; Diagnostic Yield and Cost-Effectiveness of “Dynamic” Exome Analysis in Epilepsy with Neurodevelopmental Disorders.


Health information technology interventions and engagement in HIV care and achievement of viral suppression in publicly funded settings in the US: A cost-effectiveness analysis.
Shade Starley B et al. PLoS medicine 2021 4 (4) e1003389 (Posted: Apr 12, 2021 8AM)


Pharmacogenetic-guided glimepiride therapy in type-2 diabetes mellitus: a cost-effectiveness study
C Fokoun et al, PGX Journal, March 17, 2021 (Posted: Mar 19, 2021 8AM)

With pharmacogenetic-guided therapy, the cost to avoid an episode of severe hypoglycemia event per 100 000 patients treated was €421 834. Genotyping cost was the most influential factor on the incremental cost-effectiveness ratio. In conclusion, the potential cost of CYP2C9 genotype-guided dosing for glimepiride therapy is relatively high, and associated with modest improvements with respect to the number of hypoglycemia avoided, as compared with standard dosing.


Newborn screening for severe combined immunodeficiency: clinical and cost-effectiveness approaches.
Boyarchuk Oksana et al. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego 2021 49(289) 80-83 (Posted: Mar 16, 2021 10AM)

Newborn screening for SCID with T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) assay for the identification of T- and B-lymphopenia has been implemented in a number of highly developed countries of the world. A number of studies proved the clinical and cost-effectiveness of screening for SCID by using TREC assay. However, both clinical benefits and economic costs for screening may vary depending on country and continent.


Comparative cost-effectiveness of SARS-CoV-2 testing strategies in the USA: a modelling study
Z Du et al, Lancet Public Health, February 4, 2021 (Posted: Feb 06, 2021 7AM)

Our modelling showed that daily testing combined with a 2-week isolation period was the most costly strategy considered, reflecting increased costs with greater test frequency and length of isolation period. Assuming a societal willingness to pay of US$100?000 per YLL averted and a price of $5 per test, the strategy most likely to be cost-effective under a rapid transmission scenario is weekly testing followed by a 2-week isolation period subsequent to a positive test result.


A New State-Space Epidemiological Model for Cost-Effectiveness Analysis of Non-Medical Interventions- A Study on COVID-19 in California and Florida
V Deo et al, MEDRXIV, December 26, 2020 (Posted: Dec 27, 2020 11AM)


Cost-effectiveness of Population-Wide Genomic Screening for Hereditary Breast and Ovarian Cancer in the United States
GF Gusauskas et al, JAMA Network Open, October 29, 2020 (Posted: Oct 29, 2020 11AM)

his decision analytical model study found that genomic screening for HBOC among unselected women may be cost-effective depending on the age distribution of the women screened. Cascade testing of first-degree relatives added a modest improvement in clinical and economic value.


Cost-effectiveness of genome-wide sequencing for unexplained developmental disabilities and multiple congenital anomalies.
Li Chunmei et al. Genetics in medicine : official journal of the American College of Medical Genetics 2020 Oct (Posted: Oct 29, 2020 11AM)

A cost-effectiveness analysis was conducted using a simulation from a public payer perspective. Six strategies involving ES or GS were compared. Outcomes reported were direct medical costs, number of molecular diagnoses, number of positive findings, and number of active treatment changes. ES would likely be cost-saving if used earlier in the diagnostic pathway.


A model-based cost-effectiveness analysis of pharmacogenomic panel testing in cardiovascular disease management: preemptive, reactive, or none?
Y Zhu et al, Genetics in Medicine, October 12, 2020 (Posted: Oct 12, 2020 0PM)

This study compared the cost-effectiveness between preemptive PGx panel testing, reactive PGx panel testing and usual care in cardiovascular disease management. Preemptive testing was found to be cost-effective compared with usual care (ICER $86,227/QALY) at the willingness-to-pay threshold of $100,000/QALY while reactive testing was not (ICER $148,726/QALY).


Cost-effectiveness Analysis of Genetic Testing and Tailored First-Line Therapy for Patients With Metastatic Gastrointestinal Stromal Tumors
S Banerjee et al, JAMA Network Open, September 28, 2020 (Posted: Sep 28, 2020 1PM)

This economic evaluation examined the cost-effectiveness of targeted gene testing with tailored imatinib dosing for patients with gastrointestinal stromal tumor based on KIT exon variation status. The model found that targeted gene testing was cost-effective, with an incremental cost-effectiveness ratio of $92?100, compared with empirical treatment with imatinib.


A cost-effectiveness analysis of genomic sequencing in a prospective versus historical cohort of complex pediatric patients
A Yeung et al, Genetics in Medicine, August 10, 2020 (Posted: Aug 10, 2020 9AM)

Cost-effectiveness evaluations of first-line genomic sequencing (GS) in the diagnosis of children with genetic conditions are limited by the lack of well-defined comparative cohorts. We sought to evaluate the cost-effectiveness of early GS in pediatric patients with complex monogenic conditions compared with a matched historical cohort.


Economic value of exome sequencing for suspected monogenic disorders
BS Ferket et al, Genetics in Medicine, June 30, 2020 (Posted: Jul 01, 2020 8AM)

Assessment of the cost-effectiveness of ES and other next-generation sequencing interventions in the diagnostic work-up of infants with suspected inherited disorders will be increasingly important to support their large scale use, insurance coverage, and equitable access.


A pragmatic randomized waitlist-controlled effectiveness and cost-effectiveness trial of digital interventions for depression and anxiety
D Richards et al, NPJ Digital Medicine, June 15, 2020 (Posted: Jun 16, 2020 9AM)

Utilization of internet-delivered cognitive behavioral therapy (iCBT) for treating depression and anxiety disorders in stepped-care models, such as the UK’s Improving Access to Psychological Therapies (IAPT), is a potential solution for addressing the treatment gap in mental health.


Digital Health Equity as a Necessity in the 21st Century Cures Act Era
JA Rodriguez et al, JAMA, May 28, 2020 (Posted: May 28, 2020 0PM)

Improvements in patient self-management, care coordination, quality, and cost-effectiveness may be stymied by persisting digital divides. Given the recognition of the higher morbidity and mortality for underserved patients with COVID-19, including African Americans, understanding and eliminating these digital divides are critical.


Cost-effectiveness Evaluation of Targeted Surgical and Endoscopic Therapies for Early Colorectal Adenocarcinoma Based on Biomarker Profiles
SR Jang et al. JAMA Network Open, March 9, 2020 (Posted: Mar 10, 2020 8AM)


Assessment of Treatment Cost-effectiveness Using a Colorectal Cancer Mutation Profile
TJ Yeatman et al, JAMA Netwotk Open, March 9, 2020 (Posted: Mar 10, 2020 8AM)

The addition of genetic testing to clinicopathologic features (ie, the current standard of care) may provide a new means of determining the most cost-effective, highest-quality approach for this early stage of disease. A prospective comparison of genetic vs pathologic staging in predicting surgical pathologic staging will be necessary.


Selecting the optimal risk threshold of diabetes risk scores to identify high-risk individuals for diabetes prevention: a cost-effectiveness analysis.
Mühlenbruch Kristin et al. Acta diabetologica 2019 Nov (Posted: Feb 26, 2020 9AM)


Testing for Breast Cancer Susceptibility Genes
JAMA Learning Podcast, February 2020 (Posted: Feb 12, 2020 8AM)

Breast cancer is a leading cause of death in women. Some women have a cancer susceptibility gene known as BRCA, and women should be tested for BRCA under some circumstances. This podcast discusses when testing is appropriate and the cost-effectiveness of BRCA screening for women who have had breast cancer.


APOL1 Genotyping in Potential African American Living Kidney Donors: Utility and Cost-Effectiveness.
Gudsoorkar Prakash et al. American journal of nephrology 2020 Jan 1-3 (Posted: Jan 22, 2020 9AM)


Cost-effectiveness of targeted screening for the identification of patients with atrial fibrillation: Evaluation of a machine learning risk prediction algorithm.
Hill Nathan R et al. Journal of medical economics 2019 Dec 1 (Posted: Jan 02, 2020 9AM)

As many cases of atrial fibrillation (AF) are asymptomatic, patients often remain undiagnosed until complications manifest. Risk-prediction algorithms may help to efficiently identify people with undiagnosed AF. This study aimed to assess the cost-effectiveness of targeted screening, informed by a machine learning risk prediction algorithm, to identify patients with AF.


Polygenic risk-tailored screening for prostate cancer: A benefit-harm and cost-effectiveness modelling study.
Callender Tom et al. PLoS medicine 2019 Dec (12) e1002998 (Posted: Dec 21, 2019 4PM)

Based on the results of this modelling study, offering screening to men at higher risk could potentially reduce overdiagnosis and improve the benefit–harm tradeoff and the cost-effectiveness of a prostate cancer screening program. The optimal threshold will depend on societal judgements of the appropriate balance of benefits–harms and cost-effectiveness.


Cost-effectiveness of Active Identification and Subsequent Colonoscopy Surveillance of Lynch Syndrome Cases.
Peterse Elisabeth F P et al. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2019 Oct (Posted: Oct 23, 2019 9AM)


Cost-effectiveness of risk-stratified colorectal cancer screening based on polygenic risk – current status and future potential
SK Naber et al, JNCI SPectrum, October 17, 2019 (Posted: Oct 18, 2019 8AM)

This cost-effectiveness analysis shows that currently, colorectal cancer screening based on polygenic risk is unlikely to be cost effective compared to uniform screening. This is expected to change with a?>?0.05 increase in AUC value, a?>?30% reduction in polygenic testing costs, or a?>?5% increase in adherence with screening.


The predicted impact and cost-effectiveness of systematic testing of people with incident colorectal cancer for Lynch syndrome.
Kang Yoon-Jung et al. The Medical journal of Australia 2019 Oct (Posted: Oct 16, 2019 9AM)


Systematic review of the evidence on the cost-effectiveness of pharmacogenomics-guided treatment for cardiovascular diseases
Ye Zhu, et al. Genetics in Medicine, October 8, 2019 (Posted: Oct 10, 2019 8AM)

The study conducted a systematic review using multiple databases from inception to 2018. The study found mixed evidence on the cost-effectiveness of PGx in CVD care. Supportive evidence exists for clopidogrel–CYP2C19 and warfarin–CYP2C9/VKORC1, but evidence is limited in other drug–gene combinations. Gaps persist, including unclear explanation of perspective and cost inputs, underreporting of study design elements.


A Cost-effectiveness Analysis of Multigene Testing for All Patients With Breast Cancer
L Sun et al, JAMA Oncology, October 3, 2019 (Posted: Oct 04, 2019 9AM)

In this cost-effectiveness microsimulation modeling study incorporating data from 11 836 women, unselected BRCA1/BRCA2/PALB2 testing at breast cancer diagnosis was extremely cost-effective compared with BRCA1/BRCA2 testing based on clinical criteria or family history for UK and US health systems.


Cost-effectiveness of population genomic screening.
Veenstra David L et al. Genetics in medicine : official journal of the American College of Medical Genetics 2019 Jul (Posted: Jul 17, 2019 8AM)


Generic Cost-Effectiveness Models: A Proof of Concept of a Tool for Informed Decision-Making for Public Health Precision Medicine.
Snyder Susan R et al. Public health genomics 2019 Jun 1-11 (Posted: Jun 16, 2019 8AM)


Cost-effectiveness of newborn screening for severe combined immunodeficiency.
Van der Ploeg Catharina P B et al. European journal of pediatrics 2019 May 178(5) 721-729 (Posted: May 01, 2019 8AM)


Clinical and Cost Effectiveness of Two “New” Lynch Syndrome Case Finding Protocols in Endometrial Cancer Population Contrasted with the IHC-based Protocol
JM Gudgeon et al, BioRXIV, April 18, 2019 (Posted: Apr 21, 2019 6PM)


Should women with a BRCA1/2 mutation aged 60 and older be offered intensified breast cancer screening? - A cost-effectiveness analysis.
Phi Xuan-Anh et al. Breast (Edinburgh, Scotland) 2019 Mar 4582-88 (Posted: Mar 27, 2019 9AM)


Preventive Genomic Screening of Young Adults Could be Cost-Effective, Australian Research Suggests
Genomeweb, February 20, 2019 (Posted: Feb 21, 2019 9AM)


Population genomic screening of all young adults in a health-care system: a cost-effectiveness analysis.
Zhang Lei et al. Genetics in medicine : official journal of the American College of Medical Genetics 2019 Feb (Posted: Feb 20, 2019 11AM)


Clinical impact and cost-effectiveness of a 176-condition expanded carrier screen
KA Beauchamp et al, Genetics in Medicine, February 14,, 2019 (Posted: Feb 14, 2019 10AM)


An economic model of the cost-utility of pre-emptive genetic testing to support pharmacotherapy in patients with major depression in primary care.
Sluiter Reinier L et al. The pharmacogenomics journal 2019 Jan (Posted: Jan 23, 2019 1PM)


Cost Effectiveness of the Oncotype DX Genomic Prostate Score for Guiding Treatment Decisions in Patients With Early Stage Prostate Cancer.
Chang Eric M et al. Urology 2018 Dec (Posted: Jan 02, 2019 4PM)


Cost-Effective But Unaffordable: The CAR-T Conundrum.
Leech Ashley A et al. Journal of the National Cancer Institute 2018 Dec (Posted: Dec 30, 2018 9AM)


Cost-Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Pediatric Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia.
Sarkar Reith R et al. Journal of the National Cancer Institute 2018 Dec (Posted: Dec 30, 2018 9AM)


Cost-Effectiveness of a Pharmacogenetic Test to Guide Treatment for Major Depressive Disorder.
Groessl Erik J et al. Journal of managed care & specialty pharmacy 2018 Aug 24(8) 726-734 (Posted: Nov 07, 2018 11AM)


Cost-Effectiveness and Budget Impact of Lumacaftor/Ivacaftor in the Treatment of Cystic Fibrosis.
Vadagam Pratyusha et al. Journal of managed care & specialty pharmacy 2018 Oct 24(10) 987-997 (Posted: Sep 26, 2018 10AM)


Using "Big Data" in the Cost-Effectiveness Analysis of Next-Generation Sequencing Technologies: Challenges and Potential Solutions.
Wordsworth Sarah et al. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research 2018 21(9) 1048-1053 (Posted: Sep 19, 2018 9AM)


Gene therapy in hemophilia A: a cost-effectiveness analysis.
Machin Nicoletta et al. Blood advances 2018 Jul 2(14) 1792-1798 (Posted: Aug 01, 2018 10AM)


Clinical Impact and Cost-Effectiveness of a 176-Condition Expanded Carrier Screen
KA Beachamp et al, BioRXIV, July 2018 (Posted: Jul 24, 2018 1PM)


Cost-effectiveness and Benefit-to-Harm Ratio of Risk-Stratified Screening for Breast Cancer A Life-Table Model
N Pashayan et al, JAMA Oncology, Juy 5, 2018 (Posted: Jul 05, 2018 11AM)


QALYs in 2018—Advantages and Concerns
PJ Neumann et al, JAMA May 2018 (Posted: May 28, 2018 10AM)


A population-based cost-effectiveness study of early genetic testing in severe epilepsies of infancy.
Howell Katherine B et al. Epilepsia 2018 May (Posted: May 17, 2018 1PM)


BRCA mutation carrier detection. A model-based cost-effectiveness analysis comparing the traditional family history approach and the testing of all patients with breast cancer.
Norum Jan et al. ESMO open 2018 3(3) e000328 (Posted: Apr 25, 2018 9AM)


The role of cost-effectiveness analysis in precision medicine and public health genomics.
S Grosse, CDC slide presentation, Mar 2018 (Posted: Apr 20, 2018 10AM)


Cardiovascular Genetic Risk Testing for Targeting Statin Therapy in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Cost-Effectiveness Analysis.
Jarmul Jamie et al. Circulation. Cardiovascular quality and outcomes 2018 Apr 11(4) e004171 (Posted: Apr 18, 2018 10AM)


Cost-effectiveness of Genome and Exome Sequencing in Children Diagnosed with Autism Spectrum Disorder.
Yuen Tracy et al. Applied health economics and health policy 2018 Apr (Posted: Apr 18, 2018 10AM)


Cost-Effectiveness Analyses of the 21-Gene Assay in Breast Cancer: Systematic Review and Critical Appraisal.
Wang Shi-Yi et al. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2018 Apr JCO2017765941 (Posted: Apr 18, 2018 10AM)


more


Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.
TOP