Access to clinically indicated genetic tests for pediatric patients with Medicaid: Evidence from outpatient genetics clinics in Texas

PurposeLittle is known about how Medicaid coverage policies affect access to genetic tests for pediatric patients. Building upon and extending a previous analysis of prior authorization requests (PARs), we describe expected coverage of genetic tests submitted to Texas Medicaid and the PAR and diagnostic outcomes of those tests.MethodsWe retrospectively reviewed genetic tests ordered at 3 pediatric outpatient genetics clinics in Texas. We compared Current Procedural Terminology (CPT) codes with the Texas Medicaid fee-for-service schedule (FFSS) to determine whether tests were expected to be covered by Medicaid. We assessed completion and diagnostic yield of commonly ordered tests.ResultsAmong the 3388 total tests submitted to Texas Medicaid, 68.9% (n = 2336) used at least 1 CPT code that was not on the FFSS and 80.7% (n = 2735) received a favorable PAR outcome. Of the tests with a CPT code not on the FFSS, 60.0% (n = 1400) received a favorable PAR outcome and were completed and 20.5% (n = 287) were diagnostic. The diagnostic yield of all tests with a favorable PAR outcome that were completed was 18.7% (n = 380/2029).ConclusionMost PARs submitted to Texas Medicaid used a CPT code for which reimbursement from Texas Medicaid was not guaranteed. The frequency with which clinically indicated genetic tests were not listed on the Texas Medicaid FFSS suggests misalignment between genetic testing needs and coverage policies. Our findings can inform updates to Medicaid policies to reduce coverage uncertainty and expand access to genetic tests with high diagnostic utility.     

Randomized prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test

PurposeTo evaluate the diagnostic yield and clinical relevance of clinical genome sequencing (cGS) as a first genetic test for patients with suspected monogenic disorders.MethodsWe conducted a prospective randomized study with pediatric and adult patients recruited from genetics clinics at Massachusetts General Hospital who were undergoing planned genetic testing. Participants were randomized into two groups: standard-of-care genetic testing (SOC) only or SOC and cGS.ResultsTwo hundred four participants were enrolled, 202 were randomized to one of the intervention arms, and 99 received cGS. In total, cGS returned 16 molecular diagnoses that fully or partially explained the indication for testing in 16 individuals (16.2% of the cohort, 95% confidence interval [CI] 8.9–23.4%), which was not significantly different from SOC (18.2%, 95% CI 10.6–25.8%, P = 0.71). An additional eight molecular diagnoses reported by cGS had uncertain relevance to the participant’s phenotype. Nevertheless, referring providers considered 20/24 total cGS molecular diagnoses (83%) to be explanatory for clinical features or worthy of additional workup.ConclusioncGS is technically suitable as a first genetic test. In our cohort, diagnostic yield was not significantly different from SOC. Further studies addressing other variant types and implementation challenges are needed to support feasibility and utility of broad-scale cGS adoption.     

Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test

PurposeGenetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use.MethodsWe prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing.ResultsWGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24%; P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A.ConclusionWGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort.     

Factors influencing parental decision about genetics evaluation for their deaf or hard-of-hearing child

PurposeTo identify factors that are associated with why parents of deaf children who have had GJB2/GJB6 testing as part of a genetics research study do or do not take their children for genetics evaluation.MethodsSelf-administered questionnaire was completed by parents of a deaf child participating in a GJB2/GJB6 testing study.ResultsA total of 30 parents (representing 24 children) completed the questionnaire; 11 of 24 children (46%) underwent a genetics evaluation. Compared with parents who did not take their child for a genetics evaluation, those who did were more likely to (1) have supportive pediatricians, (2) feel it was important or would be helpful to their child, (3) recall the recommendation for evaluation, (4) have family members who wanted the child to have an evaluation, and (5) be Hispanic or Asian. Genetic test results, knowledge of genetics evaluation, psychosocial factors, language concerns, or structural factors were not substantively associated with attending a genetics evaluation.ConclusionParental perceptions, family environment, and pediatricians play a role in decisions regarding genetics evaluation. Because genetic testing for deafness likely will occur outside of traditional genetics clinics and without comprehensive genetics evaluation, efforts to increase pediatricians' awareness of the usefulness of genetics evaluation may be essential to ensure appropriate care for deaf and hard-of-hearing children as recommended by the American College of Medical Genetics.     

Direct-to-consumer genetic testing: An assessment of genetic counselors' knowledge and beliefs

PurposeDirect-to-consumer genetic testing is a new means of obtaining genetic testing outside of a traditional clinical setting. This study assesses genetic counselors' experience, knowledge, and beliefs regarding direct-to-consumer genetic testing for tests that would currently be offered in genetics clinics.MethodsMembers of the National Society of Genetic Counselors completed a web-administered survey in February 2008.ResultsResponse rate was 36%; the final data analysis included 312 respondents. Eighty-three percent of respondents had two or fewer inquiries about direct-to-consumer genetic testing, and 14% had received requests for test interpretation or discussion. Respondents believed that genetic counselors have a professional obligation to be knowledgeable about direct-to-consumer genetic testing (55%) and interpret results (48%). Fifty-one percent of respondents thought genetic testing should be limited to a clinical setting; 56% agreed direct-to-consumer genetic testing is acceptable if genetic counseling is provided. More than 70% of respondents would definitely or possibly consider direct-to-consumer testing for patients who (1) have concerns about genetic discrimination, (2) want anonymous testing, or (3) have geographic constraints.ConclusionResults indicate that genetic counselors have limited patient experiences with direct-to-consumer genetic testing and are cautiously considering if and under what circumstances this approach should be used. Genet Med 2011:13(4):325–332.     

Estimating the burden and economic impact of pediatric genetic disease

PurposeTo identify the economic impact of pediatric patients with clinical indications of genetic disease (GD) on the US health-care system.MethodsUsing the 2012 Kids’ Inpatient Database, we identified pediatric inpatient discharges with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes linked to genetic disease, including well-established genetic disorders, neurological diseases, birth defects, and other physiological or functional abnormalities with a genetic basis. Cohort characteristics and health-care utilization measures were analyzed. Discharges with a GD-associated primary diagnosis were used to estimate the minimum burden; discharges with GD-associated primary or secondary codes established the maximum burden.ResultsOf 5.85 million weighted discharges, 2.6–14% included GD-associated ICD-9-CM codes. For these discharges, mean total costs were $16,000–77,000 higher (P < 0.0001) in neonates and$12,000–17,000 higher (P < 0.0001) in pediatric patients compared with background, corresponding to significantly higher total charges and lengths of stay. Aggregate total charges for suspected GD accounted for $14 to $57 billion (11–46%) of the “national bill” for pediatric patients in 2012.ConclusionPediatric inpatients with diagnostic codes linked to genetic disease have a significant and disproportionate impact on resources and costs in the US health-care system.     

The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders

PurposeThe purpose of this study was to assess the diagnostic yield of the traditional, comprehensive clinical evaluation and targeted genetic testing, within a general genetics clinic. These data are critically needed to develop clinically and economically grounded diagnostic algorithms that consider presenting phenotype, traditional genetics testing, and the emerging role of next-generation sequencing (whole-exome/genome sequencing).MethodsWe retrospectively analyzed a cohort of 500 unselected consecutive patients who received traditional genetic diagnostic evaluations at a tertiary medical center. We calculated the diagnosis rate, number of visits to diagnosis, genetic tests, and the cost of testing.ResultsThirty-nine patients were determined to not have a genetic disorder; 212 of the remaining 461 (46%) received a genetic diagnosis, and 72% of these were diagnosed on the first visit. The cost per subsequent successful genetic diagnosis was estimated at $25,000.ConclusionAlmost half of the patients were diagnosed using the traditional approach, most at the initial visit. For those remaining undiagnosed, next-generation sequencing may be clinically and economically beneficial. Estimating a 50% success rate for next-generation sequencing in undiagnosed genetic disorders, its application after the first clinical visit could result in a higher rate of genetic diagnosis at a considerable cost savings per successful diagnosis.Genet Med16 2, 176–182.     

Clinical impact of genomic testing in patients with suspected monogenic kidney disease

PurposeTo determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease.MethodsWe performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia.ResultsES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%).ConclusionIn this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.     

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology

PurposeImplementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation.MethodsWe studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene–based testing) and WES simultaneously.ResultsOur unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted.ConclusionOur data support such a use of WES in pediatric neurology for disorders of presumed genetic origin.Genet Med advance online publication 23 March 2017     

The value of genetic testing: beyond clinical utility

ObjectiveTo assess the value of genetic testing from the perspective of the Department of Veterans Affairs (VA) clinical leadership.MethodsWe administered an Internet-based survey to VA clinical leaders nationwide. Respondents rated the value (on a 5-point scale) of each of six possible reasons for genetic testing. Bivariate and linear regressions identified associations between value ratings and environmental, organizational, provider, patient, and encounter characteristics.ResultsRespondents (n = 353; 63% response rate) represented 92% of VA medical centers. Tests that inform clinical management had the highest value rating (58.6%), followed by tests that inform disease prevention (56.4%), reproductive options (50.1%), life planning (43.9%), and a suspected (39.9%) or established (32.3%) diagnosis. Factors positively associated with high value included a culture that fosters adoption of genomics, specialist versus primary care provider, genetic tests available on laboratory menus, availability of genetic testing guidelines, clinicians knowing when to request genetics referrals, and availability of genetics professionals.ConclusionOur results demonstrate the varied value of genetic testing from the perspective of clinical leadership within a health-care system. Engaging organizational leadership in understanding the various reasons for genetic testing and its value beyond clinical utility may increase adoption of genetic tests to support patient-centered care.Genet Med advance online publication 15 December 2016     

Eligibility criteria in private and public coverage policies for BRCA genetic testing and genetic counseling

PurposeCoverage policies for genetic services for hereditary cancers are of interest because the services influence cancer risk reduction for both persons with cancer and their family members. We compared coverage policies for BRCA genetic testing and genetic counseling among selected payers in the United States to illuminate eligibility criteria variation that may explain differential access by insurance type. We compared these policies with policies for breast cancer screening with magnetic resonance imaging to consider whether payers apply a unique policy approach to genetic services.MethodsWe conducted a case study of large private and public payers selected on number of covered lives. We examined coverage policies for BRCA genetic testing, genetic counseling, and screening with magnetic resonance imaging and the eligibility criteria for each. We compared eligibility criteria against National Comprehensive Cancer Network guidelines.ResultsEligibility criteria for BRCA testing were related to personal history and family history of cancer. Although private payers covered BRCA testing for persons with and without cancer, the local Medicare carrier in our study only covered testing for persons with cancer. In contrast, Arizona's Medicaid program did not cover BRCA testing. Few payers had detailed eligibility criteria for genetic counseling. Private payers have more detailed coverage policies for both genetic services and screening with magnetic resonance imaging in comparison with public payers.ConclusionDespite clinical guidelines establishing standards for BRCA testing, we found differences in coverage policies particularly between private and public payers. Future research and policy discussions can consider how differences in private and public payer policies influence access to genetic technologies and health outcomes.     

Insurance denials and diagnostic rates in a pediatric genomic research cohort

PurposeThis study aimed to assess the amount and types of clinical genetic testing denied by insurance and the rate of diagnostic and candidate genetic findings identified through research in patients who faced insurance denials.MethodsAnalysis consisted of review of insurance denials in 801 patients enrolled in a pediatric genomic research repository with either no previous genetic testing or previous negative genetic testing result identified through cross-referencing with insurance prior-authorizations in patient medical records. Patients and denials were also categorized by type of insurance coverage. Diagnostic findings and candidate genetic findings in these groups were determined through review of our internal variant database and patient charts.ResultsOf the 801 patients analyzed, 147 had insurance prior-authorization denials on record (18.3%). Exome sequencing and microarray were the most frequently denied genetic tests. Private insurance was significantly more likely to deny testing than public insurance (odds ratio = 2.03 [95% CI = 1.38-2.99] P = .0003). Of the 147 patients with insurance denials, 53.7% had at least 1 diagnostic or candidate finding and 10.9% specifically had a clinically diagnostic finding. Fifty percent of patients with clinically diagnostic results had immediate medical management changes (5.4% of all patients experiencing denials).ConclusionMany patients face a major barrier to genetic testing in the form of lack of insurance coverage. A number of these patients have clinically diagnostic findings with medical management implications that would not have been identified without access to research testing. These findings support re-evaluation of insurance carriers’ coverage policies.     

Private payer coverage policies for exome sequencing (ES) in pediatric patients: trends over time and analysis of evidence cited

PurposeExome sequencing (ES) is being adopted for neurodevelopmental disorders in pediatric patients. However, little is known about current coverage policies or the evidence cited supporting these policies. Our study is the first in-depth review of private payer ES coverage policies for pediatric patients with neurodevelopmental disorders.MethodsWe reviewed private payer coverage policies and examined evidence cited in the policies of the 15 largest payers in 2017, and trends in coverage policies and evidence cited (2015–2017) for the five largest payers.ResultsThere were four relevant policies (N = 5 payers) in 2015 and 13 policies (N = 15 payers) in 2017. In 2015, no payer covered ES, but by 2017, three payers from the original registry payers did. In 2017, 8 of the 15 payers covered ES. We found variations in the number and types of evidence cited. Positive coverage policies tended to include a larger number and range of citations.ConclusionWe conclude that more systematic assessment of evidence cited in coverage policies can provide a greater understanding of coverage policies and how evidence is used. Such assessments could facilitate the ability of researchers to provide the needed evidence, and the ability of clinicians to provide the most appropriate testing for patients.     

Utilization of genetic tests: analysis of gene-specific billing in Medicare claims data

PurposeWe examined the utilization of precision medicine tests among Medicare beneficiaries through analysis of gene-specific tier 1 and 2 billing codes developed by the American Medical Association in 2012.MethodsWe conducted a retrospective cross-sectional study. The primary source of data was 2013 Medicare 100% fee-for-service claims. We identified claims billed for each laboratory test, the number of patients tested, expenditures, and the diagnostic codes indicated for testing. We analyzed variations in testing by patient demographics and region of the country.ResultsPharmacogenetic tests were billed most frequently, accounting for 48% of the expenditures for new codes. The most common indications for testing were breast cancer, long-term use of medications, and disorders of lipid metabolism. There was underutilization of guideline-recommended tumor mutation tests (e.g., epidermal growth factor receptor) and substantial overutilization of a test discouraged by guidelines (methylenetetrahydrofolate reductase). Methodology-based tier 2 codes represented 15% of all claims billed with the new codes. The highest rate of testing per beneficiary was in Mississippi and the lowest rate was in Alaska.ConclusionsGene-specific billing codes significantly improved our ability to conduct population-level research of precision medicine. Analysis of these data in conjunction with clinical records should be conducted to validate findings.Genet Med advance online publication 26 January 2017     

Genetics educational needs in China: physicians’ experience and knowledge of genetic testing

PurposeThe aims of this study were to explore the relationship between physicians’ knowledge and utilization of genetic testing and to explore genetics educational needs in China.MethodsAn anonymous survey about experience, attitudes, and knowledge of genetic testing was conducted among physicians affiliated with Peking Union Medical College Hospital during their annual health evaluation. A personal genetics knowledge score was developed and predictors of personal genetics knowledge score were evaluated.ResultsSixty-four physicians (33% male) completed the survey. Fifty-eight percent of them had used genetic testing in their clinical practice. Using a 4-point scale, mean knowledge scores of six common genetic testing techniques ranged from 1.7 ± 0.9 to 2.4 ± 1.0, and the average personal genetics knowledge score was 2.1 ± 0.8. In regression analysis, significant predictors of higher personal genetics knowledge score were ordering of genetic testing, utilization of pedigrees, higher medical degree, and recent genetics training (P < 0.05). Sixty-six percent of physicians indicated a desire for specialized genetic services, and 84% reported a desire for additional genetics education.ConclusionThis study demonstrated a sizable gap between Chinese physicians’ knowledge and utilization of genetic testing. Participants had high self-perceived genetics educational needs. Development of genetics educational platforms is both warranted and desired in China.Genet Med17 9, 757–760.     

Differential use of available genetic tests among primary care physicians in the United States: results of a national survey

PurposeThis study assesses primary care physicians' experience ordering and referring patients for genetic testing, and whether minority-serving physicians are less likely than those serving fewer minorities to offer such services.MethodsSurvey of a random sample of 2000 primary care physicians in the United States (n = 1120, 62.3% response rate based on eligible respondents) conducted in 2002 to assess what proportion have (1) ever ordered a genetic test in general or for select conditions; (2) ever referred a patient for genetic testing to a genetics center or counselor, a specialist, a clinical research trial, or to any site of care.ResultsNationally, 60% of primary care physicians have ordered a genetic test and 74% have referred a patient for genetic testing. Approximately 62% of physicians have referred a patient for genetic testing to a genetics center/counselor or to a specialist, and 17% to a clinical trial. Minority-serving physicians were significantly less likely to have ever ordered a genetic test for breast cancer, colorectal cancer, or Huntington disease, or to have ever referred a patient for genetic testing relative to those serving fewer minorities.ConclusionsReduced utilization of genetic tests/referrals among minority-serving physicians emphasizes the importance of tracking the diffusion of genomic medicine and assessing the potential impact on health disparities.     

Psychiatrists' attitudes,knowledge, and experience regarding genetics: a preliminary study

PurposeThis study is the first survey of a random national sample of US psychiatrists to assess attitudes, knowledge, and clinical experience regarding genetics. We hypothesized that clinicians with more recent genetics training would demonstrate more positive attitudes and greater genetics knowledge and experience than those with less recent training.MethodsA probability sample of US psychiatrists (n = 93) was invited to participate in a mail survey regarding genetic medicine.ResultsForty-five psychiatrists completed the survey (response rate = 48%). All believed that genetics strongly or moderately influenced a person's mental health. Respondents expressed positive attitudes toward incorporating genetics into psychiatric practice, but most did not have recent genetics training or experience in referring patients to genetic counselors or ordering genetic tests. Psychiatrists who had genetics training within the previous 5 years had more experience in providing genetic services.ConclusionsThis survey identified areas of strength (positive attitudes about providing genetic services, belief in the heritability of mental illness) and future targets for educational intervention (general genetics, information about testing and counseling resources). The association between recent training and a greater level of clinical genetics experience suggests that educational efforts may be successful in preparing psychiatrists to provide genetic services in the future.     

A structured genetics rotation for pediatric residents: an important educational opportunity

PurposeAs the integral role of genetics in health and disease becomes increasingly understood, pediatricians must incorporate genetic principles into their care of patients. Structured exposure to genetics during residency may better equip future pediatricians to meet this goal.MethodsPediatric interns in the Johns Hopkins pediatric residency program have the option to spend one week immersed in clinical genetics by attending outpatient clinics and seeing inpatient consults. A pretest assessing clinical genetics knowledge is given before the rotation and compared with an identical post-test. Interns have a “scavenger hunt” to introduce genetic resources useful to pediatricians and complete a logbook of patient experiences. An evaluation is completed at the end of the rotation.ResultsSince the selective started in July 2016, 50 interns have participated. Average pretest score was 2.5/5 compared with a post-test score of 4.3/5, p < 0.0001. Interns saw on average ten patients and four different diagnoses. Overall evaluation was 4.4 on a 5-point scale, 5 being “excellent.”ConclusionThis experience suggests that a structured rotation in genetics provides pediatric interns with an opportunity to learn basic clinical genetics knowledge and skills and see patients whom they may otherwise not encounter during residency.     

Genetics professionals are key to the integration of genetic testing within the practice of frontline clinicians

PurposeGenetic tests have become widely available. We sought to understand the use of genetic tests in the practice of frontline clinicians within the United States Department of Veterans Affairs (VA).MethodsWe administered a web-based survey to clinicians at 20 VA facilities. Physicians, nurse practitioners, physician assistants, and pharmacists were eligible. We excluded genetics providers and clinicians not seeing patients. We used multiple logistic regression to evaluate the associations between clinician characteristics and experience with genetics.ResultsThe response rate was 11.3% (1207/10,680) and of these, 909 respondents were eligible. Only 20.8% of the respondents reported feeling prepared to use genetic tests and 13.0% of the respondents were currently ordering genetic tests; although, it was usually only 1 or 2 a year. Delivery of genetic tests without involving genetics providers was preferred by only 7.9% of the respondents. Characteristics positively associated with currently ordering genetic tests included practice in clinical and research settings, believing improving genetics knowledge could alter their practice, feeling prepared to use genetic tests, and referral of at least 1 patient to genetics in the past year.ConclusionMost VA clinicians don’t feel prepared to use genetic tests. Those with genetic testing experience are more likely to consult genetics providers. The demand for genetics providers should increase as frontline clinicians use genetic tests in their practice.