Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluations

PurposeThere is considerable evidence regarding the efficacy and effectiveness of BRCA genetic testing programs, but whether they represent good use of financial resources is not clear. Therefore, we aimed to identify the main health-care programs for BRCA testing and to evaluate their cost-effectiveness.MethodsWe performed a systematic review of full economic evaluations of health-care programs involving BRCA testing.ResultsNine economic evaluations were included, and four main categories of BRCA testing programs were identified: (i) population-based genetic screening of individuals without cancer, either comprehensive or targeted based on ancestry; (ii) family history (FH)-based genetic screening, i.e., testing individuals without cancer but with FH suggestive of BRCA mutation; (iii) familial mutation (FM)-based genetic screening, i.e., testing individuals without cancer but with known familial BRCA mutation; and (iv) cancer-based genetic screening, i.e., testing individuals with BRCA-related cancers.ConclusionsCurrently BRCA1/2 population-based screening represents good value for the money among Ashkenazi Jews only. FH-based screening is potentially very cost-effective, although further studies that include costs of identifying high-risk women are needed. There is no evidence of cost-effectiveness for BRCA screening of all newly diagnosed cases of breast/ovarian cancers followed by cascade testing of relatives, but programs that include tools for identifying affected women at higher risk for inherited forms are promising. Cost-effectiveness is highly sensitive to the cost of BRCA1/2 testing.ConclusionsGenet Med 18 12, 1171–1180.     

Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways: A scoping review and recommended methods

PurposeMethodological challenges have limited economic evaluations of genome sequencing (GS) and exome sequencing (ES). Our objective was to develop conceptual frameworks for model-based cost-effectiveness analyses (CEAs) of diagnostic GS/ES.MethodsWe conducted a scoping review of economic analyses to develop and iterate with experts a set of conceptual CEA frameworks for GS/ES for prenatal testing, early diagnosis in pediatrics, diagnosis of delayed-onset disorders in pediatrics, genetic testing in cancer, screening of newborns, and general population screening.ResultsReflecting on 57 studies meeting inclusion criteria, 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.ConclusionOur frameworks can guide the design of model-based CEAs and ultimately foster robust evidence for the economic value of GS/ES.     

Which Lynch syndrome screening programs could be implemented in the “real world”? A systematic review of economic evaluations

PurposeLynch syndrome (LS) screening can significantly reduce cancer morbidity and mortality in mutation carriers. Our aim was to identify cost-effective LS screening programs that can be implemented in the “real world.”MethodsWe performed a systematic review of full economic evaluations of genetic screening for LS in different target populations; health outcomes were estimated in life-years gained or quality-adjusted life-years.ResultsOverall, 20 studies were included in the systematic review. Based on the study populations, we identified six categories of LS screening program: colorectal cancer (CRC)–based, endometrial cancer–based, general population–based, LS family registry–based, cascade testing–based, and genetics clinic–based screening programs. We performed an in-depth analysis of CRC-based LS programs, classifying them into three additional subcategories: universal, age-targeted, and selective. In five studies, universal programs based on immunohistochemistry, either alone or in combination with the BRAF test, were cost-effective compared with no screening, while in two studies age-targeted programs with a cutoff of 70 years were cost-effective when compared with age-targeted programs with lower age thresholds.ConclusionUniversal or <70 years–age-targeted CRC-based LS screening programs are cost-effective and should be implemented in the “real world.”     

The views of people with a lived experience of deafness and the general public regarding genetic testing for deafness in the reproductive setting: A systematic review

PurposeGenes associated with nonsyndromic hearing loss are commonly included in reproductive carrier screening panels, which are now routinely offered in preconception and prenatal care in many countries. However, there is debate whether hearing loss should be considered a medical condition appropriate for screening. This systematic review assessed research on opinions of those with a lived experience of deafness and the general public regarding genetic testing for deafness in the reproductive setting.MethodsSearch of 5 online databases yielded 423 articles, 20 of which met inclusion criteria. We assessed the quality of each study, extracted data, and performed thematic analysis on qualitative studies.ResultsMost studies indicated interest in the use of prenatal diagnosis for deafness. However, there were mixed views, and sometimes strongly held views, expressed regarding the reproductive options that should be available to those with an increased chance of having a child with deafness. Studies were small, from a limited number of countries, and most were too old to include views regarding preimplantation genetic testing.ConclusionThere is a broad range of views regarding the use of reproductive options for deafness. Further research is essential to explore the benefits and harms of including nonsyndromic hearing loss genes in carrier screening.     

Benefits,harms, and costs of newborn genetic screening for hypertrophic cardiomyopathy: Estimates from the PreEMPT model

PurposePopulation newborn genetic screening for hypertrophic cardiomyopathy (HCM) is feasible, however its benefits, harms, and cost-effectiveness are uncertain.MethodsWe developed a microsimulation model to simulate a US birth cohort of 3.7 million newborns. Those identified with pathogenic/likely pathogenic variants associated with increased risk of HCM underwent surveillance and recommended treatment, whereas in usual care, individuals with family histories of HCM underwent surveillance.ResultsIn a cohort of 3.7 million newborns, newborn genetic screening would reduce HCM-related deaths through age 20 years by 44 (95% uncertainty interval [UI] = 10-103) however increase the numbers of children undergoing surveillance by 8127 (95% UI = 6308-9664). Compared with usual care, newborn genetic screening costs $267,000 per life year saved (95% UI, $106,000 to $919,000 per life year saved).ConclusionNewborn genetic screening for HCM could prevent deaths but at a high cost and would require many healthy children to undergo surveillance. This study shows how modeling can provide insights into the tradeoffs between benefits and costs that will need to be considered as newborn genetic screening is more widely adopted.     

Experiences and attitudes of hereditary cancer screening patients in a consumer directed testing model

BackgroundSince 2015, the Information is Power initiative has offered free and reduced cost hereditary cancer screening to the North Alabama population with a consumer-initiated model. Patients received pre-test and post-test education through a genetic counseling video. Positive results also received a call from a genetic counselor.ObjectiveWe surveyed past Information is Power patients to assess if video education and electronic result delivery addressed the needs of a hereditary cancer screening population.MethodsAn electronic survey was sent out to Information is Power patients who opted into research contact. The survey assessed participant knowledge, satisfaction with result delivery, and perceived uncertainty after receiving test results.Results213 participants completed the survey. Eighteen percent of participants would have preferred individual communication with a genetics specialist about their results. Over 99 % of survey participants correctly interpreted a positive result, while 73 % correctly interpreted a negative result. Overall, participants were certain about the impact of their genetic test results.Practice ImplicationsThese findings support a model of population genetic testing and genetic counseling that is sustainable while meeting the educational needs of most participants. Observed misconceptions surrounding a negative result should be highlighted in future population screening patient resources to meet patient needs.     

Systematic review of the evidence on the cost-effectiveness of pharmacogenomics-guided treatment for cardiovascular diseases

PurposeTo examine the evidence on the cost-effectiveness of implementing pharmacogenomics (PGx) in cardiovascular disease (CVD) care.MethodsWe conducted a systematic review using multiple databases from inception to 2018. The titles and abstracts of cost-effectiveness studies on PGx-guided treatment in CVD care were screened, and full texts were extracted.ResultsWe screened 909 studies and included 46 to synthesize. Acute coronary syndrome and atrial fibrillation were the predominantly studied conditions (59%). Most studies (78%) examined warfarin–CYP2C9/VKORC1 or clopidogrel–CYP2C19. A payer’s perspective was commonly used (39%) for cost calculations, and most studies (46%) were US-based. The majority (67%) of the studies found PGx testing to be cost-effective in CVD care, but cost-effectiveness varied across drugs and conditions. Two studies examined PGx panel testing, of which one examined pre-emptive testing strategies.ConclusionWe 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 critical to economic evaluations, and limited examination of PGx panel and pre-emptive testing for their cost-effectiveness. This review identifies the need for further research on economic evaluations of PGx implementation.     

Systematic review of outcomes in studies of reproductive genetic carrier screening: Towards development of a core outcome set

PurposeCurrent practice recommendations support the widespread implementation of reproductive genetic carrier screening (RGCS). These consensus-based recommendations highlight a research gap, with findings from current studies being insufficient to meet the standard required for more rigorous evidence-based recommendations. This systematic review assessed methodological aspects of studies on RGCS to inform the need for a core outcome set.MethodsWe conducted a systematic search to identify peer-reviewed published studies offering population-based RGCS. Study designs, outcomes, and measurement methods were extracted. A narrative synthesis was conducting using an existing outcome taxonomy and criteria used in the evaluation of genetic screening programs as frameworks.ResultsSixty-five publications were included. We extracted 120 outcomes representing 24 outcome domains. Heterogeneity in outcome selection, measurement methods and time points of assessment was extensive. Quality appraisal raised concerns for bias. We found that reported outcomes had limited applicability to criteria used to evaluate genetic screening programs.ConclusionDespite a large body of literature, diverse approaches to research have limited the conclusions that can be cumulatively drawn from this body of evidence. Consensus regarding meaningful outcomes for evaluation of RGCS would be a valuable first step in working towards evidence-based practice recommendations, supporting the development of a core outcome set.     

Providing genetic testing and genetic counseling for Parkinson’s disease to the community

PurposeTo evaluate the feasibility and impact of offering genetic testing and counseling to patients with Parkinson's disease (PD), with the potential to enroll in gene-targeted clinical trials and improve clinical care.MethodsA multicenter, exploratory pilot study at 7 academic hospital sites in the United States tracked enrollment and randomized participants to receive results and genetic counseling at local sites or by genetic counselors, remotely. Follow-up surveys measured participant/provider satisfaction, knowledge, and psychological impact.ResultsFrom September 5, 2019 to January 4, 2021, 620 participants were enrolled and 387 completed outcome surveys. There were no significant differences in outcomes between local and remote sites, with both arms reporting high knowledge and satisfaction scores (>80%). Notably, 16% of those tested had reportable PD gene variants (pathogenic/likely pathogenic/risk allele).ConclusionLocal clinicians, as well as genetic counselors, with educational support as needed, can effectively return genetic results for PD as we observed favorable outcome measures in both groups. Increasing access to PD genetic testing and counseling is urgent; this can inform future efforts to integrate genetic testing and counseling into clinical care for all those with PD.     

Cost savings through molecular diagnosis for hereditary hemorrhagic telangiectasia

PurposeHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder of vascular development resulting in direct connections between the arterial and venous systems, bypassing capillaries. Symptoms and signs can appear throughout life and marked intrafamilial variability confounds diagnosis based purely on clinical criteria. We set out to determine the impact of genetic testing on the cost of screening for HHT in at-risk relatives.MethodsWe performed economic modeling of idealized pedigrees following two scenarios: repeated clinical screening until an HHT diagnosis could be either affirmed or excluded, and mutation testing in the proband, followed by genetic testing of at-risk relatives and clinical monitoring of only those relatives who test positive for the familial mutation.ResultsBased on actual reimbursement data from our region’s largest health insurer, the molecular diagnostic model saved over $22,000 for a family with four relatives at risk for the initial diagnostic work-up. For a cohort of 100 probands, the total savings for the molecular diagnostic model over a reasonable period of follow-up was greater than $9 million.ConclusionIn this idealized setting in which all probands and at-risk relatives accepted molecular testing, the economic advantages of genetic screening over repeated clinical screening are substantial.Genet Med 2012:14(6):604–610     

Universal tumor screening in a population with MSH6- and PMS2-associated Lynch syndrome

PurposeUniversal screening for Lynch syndrome (LS) on resected colorectal carcinomas (CRCs) and endometrial carcinomas (ECs) was implemented in Iceland in 2017 using immunohistochemistry (IHC) for mismatch repair (MMR) proteins. We examined the efficacy of the universal screening algorithm to detect LS and the diagnostic accuracy of MMR IHC by comparing results with a population-based genotype database.MethodsAll patients diagnosed with CRC or EC per the Icelandic Cancer Registry from 2017 to 2019 who had tumor MMR IHC performed were included. Pathology reports and patient charts were reviewed. MMR IHC stains were crossmatched with genotyping results obtained from the deCODE database.ResultsIHC staining was done on 404 patients with CRC and 74 patients with EC. A total of 61 (15.1%) patients with CRC and 15 (20.3%) patients with EC were MMR-deficient. MMR IHC had 88.9% sensitivity in identifying patients with LS and a positive predictive value of 10.7%. Only 50% of individuals were appropriately referred for genetic testing, leading to underdiagnosis of LS.ConclusionUniversal screening for LS using MMR protein IHC in CRC and EC accurately identified patients appropriate for genetic testing in a population with MSH6 and PMS2 LS predominance. Because of lack of referral to genetic counseling, only 50% of patients with LS were identified through the screening algorithm.     

Risk and uncertainty: Shifting decision making for aneuploidy screening to the first trimester of pregnancy

PurposeThe clinical introduction of first trimester aneuploidy screening uniquely challenges the informed consent process for both patients and providers. This study investigated key aspects of the decision-making process for this new form of prenatal genetic screening.MethodsQualitative data were collected by nine focus groups that comprised women of different reproductive histories (N = 46 participants). Discussions explored themes regarding patient decision making for first trimester aneuploidy screening. Sessions were audio recorded, transcribed, coded, and analyzed to identify themes.ResultsMultiple levels of uncertainty characterize the decision-making process for first trimester aneuploidy screening. Baseline levels of uncertainty existed for participants in the context of an early pregnancy and the debate about the benefit of fetal genetic testing in general. Additional sources of uncertainty during the decision-making process were generated from weighing the advantages and disadvantages of initiating screening in the first trimester as opposed to waiting until the second. Questions of the quality and quantity of information and the perceived benefit of earlier access to fetal information were leading themes. Barriers to access prenatal care in early pregnancy presented participants with additional concerns about the ability to make informed decisions about prenatal genetic testing.ConclusionsThe option of the first trimester aneuploidy screening test in early pregnancy generates decision-making uncertainty that can interfere with the informed consent process. Mechanisms must be developed to facilitate informed decision making for this new form of prenatal genetic screening.     

Effects of genetic risk information on children's psychosocial wellbeing: A systematic review of the literature

PurposeAs advances in research have made a growing number of genetic tests available, clinicians will increasingly be faced with making decisions about when offering genetic testing services to children is appropriate. A key factor in such decisions involves determining whether knowledge of genetic health risks might have an impact on children's psychosocial wellbeing.MethodsWe conducted a systematic review of the literature using five online databases to identify studies that assessed the impact of communicating nondiagnostic carrier or presymptomatic genetic test results to children.ResultsA total of 17 articles met the inclusion criteria for this review. These studies used a wide range of methodologies to explore carrier and predictive testing. Although there was little quantitative evidence that receiving genetic test results led to a significant impact on children's psychosocial wellbeing, it was found that methodological inconsistencies, small samples, and reliance on assessments most appropriate for psychopathology make any firm conclusions about the impact of genetic testing on children premature.ConclusionCurrently, there is insufficient evidence to inform a nuanced understanding of how children respond to genetic testing. This suggests a strong need for further research that uses rigorous approaches to address children's emotional states, self-perception, and social wellbeing.     

Precision medicine for developmental and epileptic encephalopathies in Africa—strategies for a resource-limited setting

PurposeSub-Saharan Africa bears the highest burden of epilepsy worldwide. A presumed proportion is genetic, but this etiology is buried under the burden of infections and perinatal insults in a setting of limited awareness and few options for testing. Children with developmental and epileptic encephalopathies (DEEs) are most severely affected by this diagnostic gap in Africa, because the rate of actionable findings is highest in DEE-associated genes.MethodsWe tested 234 genetically naive South African children diagnosed with/possible DEE using gene panels, exome sequencing, and chromosomal microarray. Statistical comparison of electroclinical features in children with and children without candidate variants was performed to identify characteristics most likely predictive of a positive genetic finding.ResultsOf the 41 (of 234) children with likely/pathogenic variants, 26 had variants supporting precision therapy. Multivariate regression modeling highlighted neonatal or infantile-onset seizures and movement abnormalities as predictive of a positive genetic finding. We used this, coupled with an emphasis on precision medicine outcomes, to propose the pragmatic “Think-Genetics” strategy for early recognition of a possible genetic etiology.ConclusionOur findings emphasize the importance of an early genetic diagnosis in DEE. We designed the Think-Genetics strategy for early recognition, appropriate interim management, and genetic testing for DEE in resource-constrained settings.     

An intervention strategy to improve genetic testing for dilated cardiomyopathy in a heart failure clinic

PurposeDespite its clinical implications in screening and therapy, genetic testing in dilated cardiomyopathy (DCM) is underused. This study evaluated implementing a practice intervention in a heart failure clinic to automate and streamline the process of genetic testing.MethodsEligible patients with DCM were compared for frequency of pretest genetic education and testing during pre- and postintervention periods. The intervention comprised automated prescheduling of a cardiovascular genomics e-consult that served as a placeholder for downstream, pretest education, testing, and post-test review of genetic results.ResultsPatients with DCM were more likely to undergo pretest genetic education after intervention than before intervention (33.5% vs 14.8%, P < .0001). Similarly, patients with DCM were more likely to undergo genetic testing after intervention than before intervention (27.3% vs 13.0%, P = .0006). The number of patients who were diagnosed to have likely pathogenic or pathogenic genetic variants were 2 of 21 (9.5%) and 6 of 53 (11.1%) before and after intervention, respectively, and variants were present in the following genes: FLNC, TTN, DES, LMNA, PLN, and TNNT2.ConclusionAn intervention strategy in a heart failure clinic to increase the rates of pretest genetic education and testing in eligible patients with DCM was feasible and efficacious and may have important implications for the management of DCM.     

Maternal cell-free DNA–based screening for fetal microdeletion and the importance of careful diagnostic follow-up

BackgroundNoninvasive prenatal screening (NIPS) by next-generation sequencing of cell-free DNA (cfDNA) in maternal plasma is used to screen for common aneuploidies such as trisomy 21 in high risk pregnancies. NIPS can identify fetal genomic microdeletions; however, sensitivity and specificity have not been systematically evaluated. Commercial companies have begun to offer expanded panels including screening for common microdeletion syndromes such as 22q11.2 deletion (DiGeorge syndrome) without reporting the genomic coordinates or whether the deletion is maternal or fetal. Here we describe a phenotypically normal mother and fetus who tested positive for atypical 22q deletion via maternal plasma cfDNA testing.MethodsWe performed cfDNA sequencing on saved maternal plasma obtained at 11 weeks of gestation from a phenotypically normal woman with a singleton pregnancy whose earlier screening at a commercial laboratory was reported to be positive for a 22q11.2 microdeletion. Fluorescence in situ hybridization and chromosomal microarray diagnostic genetic tests were done postnatally.ConclusionNIPS detected a 22q microdeletion that, upon diagnostic workup, did not include the DiGeorge critical region. Diagnostic prenatal or postnatal testing with chromosomal microarray and appropriate parental studies to determine precise genomic coordinates and inheritance should follow a positive microdeletion NIPS result.     

Diagnostic accuracy of rapid nucleic acid tests for group A streptococcal pharyngitis: systematic review and meta-analysis

BackgroundAcute pharyngitis is one of the most common conditions in outpatient settings and an important source of inappropriate antibiotic prescribing. Rapid antigen detection tests (RADTs) offer diagnosis of group A streptococcus at the point of care but have limited sensitivity. Rapid nucleic acid tests (RNATs) are now available; a systematic review of their accuracy is lacking.ObjectivesTo evaluate the accuracy of RNATs in patients with pharyngitis; to explore test-level and study-level factors that could explain variability in accuracy; and to compare the accuracy of RNATs with that of RADTs.Data sourcesMEDLINE, Embase, Web of Science (1990–2020).Study eligibility criteriaCross-sectional studies and randomized trials.ParticipantsPatients with pharyngitis.Index test/s and reference standardsRNAT commercial kits compared with throat culture.MethodsWe assessed risk of bias and applicability using QUADAS-2. We performed meta-analysis of sensitivity and specificity using the bivariate random-effects model. Variability was explored by subgroup analyses and meta-regression.ResultsWe included 38 studies (46 test evaluations; 17 411 test results). RNATs were most often performed in a laboratory. The overall methodological quality of primary studies was uncertain because of incomplete reporting. RNATs had a summary sensitivity of 97.5% (95% CI 96.2%–98.3%) and a summary specificity of 95.1% (95% CI 93.6%–96.3%). There was low variability in estimates across studies. Variability in sensitivity and specificity was partially explained by test type (p < 0.05 for both). Sensitivity analyses limited to studies with low risk of bias showed robust accuracy estimates. RNATs were more sensitive than RADTs (13 studies; 96.8% versus 82.3%, p 0.004); there was no difference in specificity (p 0.92).ConclusionsThe high diagnostic accuracy of RNATs may allow their use as stand-alone tests to diagnose group A streptococcus pharyngitis. Based on direct comparisons, RNATs have greater sensitivity than RADTs and equal specificity. Further studies should evaluate RNATs in point-of-care settings.     

The use of fault reporting of medical equipment to identify latent design flaws

Background and purposePoor device design that fails to adequately account for user needs, cognition, and behavior is often responsible for use errors resulting in adverse events. This poor device design is also often latent, and could be responsible for “No Fault Found” (NFF) reporting, in which medical devices sent for repair by clinical users are found to be operating as intended. Unresolved NFF reports may contribute to incident under reporting, clinical user frustration, and biomedical engineering technologist inefficacy. This study uses human factors engineering methods to investigate the relationship between NFF reporting frequency and device usability.Material and methodsAn analysis of medical equipment maintenance data was conducted to identify devices with a high NFF reporting frequency. Subsequently, semi-structured interviews and heuristic evaluations were performed in order to identify potential usability issues. Finally, usability testing was conducted in order to validate that latent usability related design faults result in a higher frequency of NFF reporting.ResultsThe analysis of medical equipment maintenance data identified six devices with a high NFF reporting frequency. Semi-structured interviews, heuristic evaluations and usability testing revealed that usability issues caused a significant portion of the NFF reports. Other factors suspected to contribute to increased NFF reporting include accessory issues, intermittent faults and environmental issues. Usability testing conducted on three of the devices revealed 23 latent usability related design faults.ConclusionsThese findings demonstrate that latent usability related design faults manifest themselves as an increase in NFF reporting and that devices containing usability related design faults can be identified through an analysis of medical equipment maintenance data.     

Effect of genomic drift of influenza PCR tests

BackgroundNucleic acid amplification assays have become the method of choice for influenza (Flu) testing due to superior accuracy and faster turnaround time. Although assays are designed to detect highly conserved genomic targets, mutations can influence test sensitivity. Most of the circulating viruses in the United States during the 2014–2015 season were associated with significant genetic drift; however, the effect on testing was unknown.Objectives and study designWe compared the performance of Prodesse ProFlu+/ProFAST+ (PFlu/PFAST), FilmArray Respiratory Panel (RP), cobas^® Influenza A/B test (cIAB), and Xpert^® Flu (Xpt) in a retrospective analysis of consecutive nasopharyngeal specimens received for a two-week period during the winter of 2015. Furthermore, limits of detection (LOD) were determined with six isolates of Flu.ResultsOf the 275 specimens, 63 were positive for FluA by PFAST, 60 were positive by RP, 58 were positive by cIAB and 52 were positive by Xpt. Only a subset of 135 specimens was tested by PFlu, of which 32 were positive. The sensitivity/specificity for PFAST, RP, cIAB, Xpt and PFlu was 100/99.1%, 96.7/99.5%, 91.8/99.1%, 85.2%/100%, and 75.6%/98.9%, respectively. LOD analyses demonstrated assay performance variations were strain associated. Specifically, PFlu’s and cIAB’s LODs were higher with A/Texas/50/2012-like and A/Switzerland/9715293/2013-like strains, while Xpt’s highest LOD was with the Swiss strain.ConclusionsStrain-associated assay performance variation is known to occur with other Flu test methods; hence, it is not surprising that such variation would be observed with molecular tests. Careful monitoring and reporting for strain-associated variances are warranted for all test methods.     

Models of communication for polygenic scores and associated psychosocial and behavioral effects on recipients: A systematic review

PurposeThis study aimed to systematically review current models for communicating polygenic scores (PGS) and psycho-behavioral outcomes of receiving PGSs.MethodsOriginal research on communicating PGSs and reporting on psycho-behavioral outcomes was included. Search terms were applied to 5 databases and were limited by date (2009-2021).ResultsIn total, 28 articles, representing 17 studies in several disease settings were identified. There was limited consistency in PGS communication and evaluation/reporting of outcomes. Most studies (n = 14) presented risk in multiple ways (ie, numerically, verbally, and/or visually). Three studies provided personalized lifestyle advice and additional resources. Only 1 of 17 studies reported using behavior change theory to inform their PGS intervention. A total of 8 studies found no evidence of long-term negative psychosocial effects up to 12 months post result. Of 14 studies reporting on behavior, 9 found at least 1 favorable change after PGS receipt. When stratified by risk, 7 out of 9 studies found high PGS was associated with favorable changes including lifestyle, medication, and screening. Low-risk PGS was not associated with maladaptive behaviors (n = 4).ConclusionPGS has the potential to benefit health behavior. High variability among studies emphasizes the need for developing standardized guidelines for communicating PGSs and evaluating psycho-behavioral outcomes. Our findings call for development of best communication practices and evidence-based interventions informed by behavior change theories.