Cost analysis of reflexive versus selective molecular testing for indeterminate thyroid nodules.

BACKGROUND: Molecular testing is now commonly used to refine the diagnosis of indeterminate thyroid nodules. The purpose of this study is to compare the costs of a reflexive molecular testing strategy to a selective testing strategy for indeterminate thyroid nodules. METHODS: A Markov model was constructed to estimate the annual cost of diagnosis and treatment of a real-world cohort of patients with cytologically indeterminate thyroid nodules, comparing a reflexive testing strategy to a selective testing strategy. Model variables were abstracted from institutional clinical trial data, literature review, and the Medicare physician fee schedule. RESULTS: The average cost per patient in the reflexive testing strategy was $8,045, compared with $6,090 in the selective testing strategy. In 10,000 Monte Carlo simulations, diagnostic thyroid lobectomy for benign nodules was performed in 2,440 patients in the reflexive testing arm, compared with 3,389 patients in the selective testing arm, and unintentional observation for malignant nodules occurred in 479 patients in the reflexive testing arm, compared with 772 patients in the selective testing arm. The cost of molecular testing had the greatest impact on overall costs, with $1,050 representing the cost below which the reflexive testing strategy was cost saving compared with the selective testing strategy. CONCLUSION: In this cost-modeling study, reflexive molecular testing for indeterminate thyroid nodules enabled patients to avoid unnecessary thyroid lobectomy at an estimated cost of $20,600 per surgery avoided.

Use of point-of-care molecular tests reduces hospitalization and oseltamivir administration in children presenting with influenza-like illness.

Influenza is associated with increased morbidity, healthcare costs, hospitalization rates, and mortality in children. Rapid immunochromatography assay (ICA), a test with low sensitivity, is often used as point-of-care (POC) test. Recently, the rapid syndromic molecular test FilmArray has become available. This observational study aims to evaluate whether the use of FilmArray would decrease the use of antivirals and hospitalization rates among children presenting to the emergency room (ER) with influenza-like illness (ILI) symptoms. Nasopharyngeal swabs were prospectively collected from children, aged 0-16 years, presenting with ILI at the ER of a tertiary hospital during the peak endemic period. Patients were allocated to be tested by either FilmArray or ICA. The use of antivirals and hospitalization rates were noted. Logistic regression models were used to investigate the impact of testing methods on decision-making. Overall, 80 children were included (mean age: 5 years). Admissions were more likely to occur if an ICA test was performed (OR, 3.16; 95% CI, 1.01-9.82; p = .046). Oseltamivir administration was more likely among children who had undergone the ICA test (OR, 4.67; 95% CI, 1.06-20.43; p = .041). The implementation of rapid molecular test had no impact on complementary diagnostic testing or antibacterial prescription. The use of FilmArray significantly reduced both hospitalization and oseltamivir administration in children. Further knowledge on the use of POC tests is required to improve current management of children presenting with ILI and decrease associated healthcare costs.

Challenges in the clinical implementation of precision medicine companion diagnostics.

INTRODUCTION: The pace of biomarker discovery has increased exponentially over the last few years, ushering in an era of precision medicine (PM) with a growing arsenal of treatments tailored to specific patient populations. To accurately identify patients, companion diagnostics (CDx) are developed and launched alongside these treatments. However, even with a timely launch of therapies and CDx tests, patients are not guaranteed optimal access to these tests because of the inefficiencies embedded within the clinical diagnostic testing landscape supporting PM. AREAS COVERED: This commentary describes implementation challenges facing CDx tests and delaying clinical uptake. We also assess the 'siloed thinking' perpetuating these challenges and propose steps toward resolution. Our research is based on published literature and findings from the Diaceutics proprietary patient testing database. EXPERT OPINION: The clinical and economic ecosystem underpinning the diagnostic journey of patients remains severely underdeveloped. Patients are denied suitable therapies because of delayed identification or failings in real-world testing deployment. Progress is needed in clinical collaborations, integrator platforms, economic value sharing, and ownership of the patient testing journey to PM. We need to consider that better precision testing will deliver an equal or greater outcome to patients than new precision treatments alone.

Point-of-Care Intrapartum Group B Streptococcus Molecular Screening: Effectiveness and Costs.

OBJECTIVE: To assess outcomes and costs associated with around-the-clock point-of-care intrapartum group B streptococcus (GBS) polymerase chain reaction (PCR) screening. METHODS: Intrapartum PCR screening was implemented in 2010. Intrapartum PCR was compared with antenatal culture screening in an uncontrolled, single institution, preintervention and postintervention study. The study periods included 4 years before and 6 years after the intervention, commencing in 2006 and concluding in 2015. The primary outcome measure was rate of early-onset neonatal GBS disease. Secondary outcomes included length of stay, days of antibiotics, and costs. RESULTS: During the 4 years of antenatal culture screening, 11,226 deliveries were recorded compared with 18,835 in the 6 years of intrapartum GBS PCR screening, corresponding to 11,818 and 18,980 live births, respectively. During the antenatal culture period, 3.8% of term deliveries did not undergo GBS testing compared with 0.1% during the intrapartum PCR period (P<.001). Between the two periods, the rate of proven early-onset GBS disease cases decreased from 1.01/1,000 to 0.21/1,000 (P=.026) and probable early-onset GBS disease cases from 2.8/1,000 to 0.73/1,000 (P<.001); the risk ratio for both was 0.25, 95% CI (0.14-0.43). Total days of hospital and antibiotic therapy for early-onset GBS disease declined by 64% and 60%, respectively, with no significant difference for average length of stay or antibiotic duration preintervention and postintervention. The yearly cost of delivery and treatment of newborns with GBS infection was reduced from $41,875±6,823 to $11,945±10,303 (P<.001). The estimated extra cost to avoid one early-onset GBS disease was $5,819. CONCLUSION: Point-of-care intrapartum GBS PCR screening was associated with a significant decrease in the rate of early-onset GBS disease and antibiotic use in newborns. The additional PCR costs were offset in part by the reduction in early-onset GBS disease treatment costs.

Real-world utilization of molecular diagnostic testing and matched drug therapies in the treatment of metastatic cancers.

AIMS: To assess the frequency of biopsies and molecular diagnostic testing (human DNA/RNA analysis), anti-cancer drug use (genomically-matched targeted therapy [GMTT], unmatched targeted therapy [UTT], endocrine therapy [ET], and chemotherapy [CT]), and medical service costs among adults with metastatic cancer. METHODS: Adults diagnosed with metastatic breast, non-small cell lung (NSCLC), colorectal, head and neck, ovarian, and uterine cancer (2010Q1-2015Q1) were identified in the OptumHealth Care Solutions claims database and followed from first metastatic diagnosis for ≥1 month and until the end of data availability. Utilization was assessed for each cancer cohort (all and patients aged ≥65 years); per-patient-per-month (PPPM) medical service costs were assessed for all patients. Testing frequency estimates were applied to Surveillance, Epidemiology, and End Results Program data to estimate the number of untested patients (2010-2014). RESULTS: Patients with metastatic cancer (n = 8,193; breast [n = 3,414], NSCLC [n = 2,231], colorectal [n = 1,611], head and neck [n = 511], ovarian [n = 275], and uterine [n = 151]) were 63 years old (mean), with 11.1-22.2 months of observation. Biopsy and molecular diagnostic testing frequencies ranged from 7% (uterine) to 73% (ovarian), and from 34% (head and neck) to 52% (breast), respectively. Few were treated with GMTT (breast, 11%; NSCLC, 9%; colorectal, 6%). Treatment with UTT ranged from 0.7% (uterine) to 21% (colorectal). Biopsy, diagnostic testing, and anti-cancer drug therapy were less frequent for those ≥65 years. Medical service costs (PPPM, mean) ranged from $6,618 (head and neck) to $9,940 (ovarian). The estimated number of untested new patients with metastatic cancer was 636,369 (all) and 341,397 (≥65). LIMITATIONS: In addition to the limitations of claims analyses, diagnostic testing frequency may be under-estimated if patients underwent testing prior to study inclusion. CONCLUSIONS: The low frequency of molecular diagnostic testing suggests there are opportunities to better inform management of patients with advanced cancer, particularly decisions to treat with GMTT.

Point-Counterpoint: Meningitis/Encephalitis Syndromic Testing in the Clinical Laboratory.

INTRODUCTIONSyndromic panels were first FDA cleared for detection of respiratory pathogens in 2008. Since then, other panels have been approved by the FDA, and most recently, the FilmArray meningitis/encephalitis panel (BioFire, Salt Lake City, UT) has become available. This assay detects 14 targets within 1 h and includes pathogens that typically cause different manifestations of infection, although they infect the same organ system. Several studies have reported both false-positive and false-negative results with this test, and all agree that the cost is significant. As with other panels, health care systems have adopted different strategies for offering this assay. Some have implemented strategies to limit the use of the test to certain patient populations, others have elected not to offer the test, and others have elected not to offer the test and instead request that providers order specific PCRs for the pathogens that best fit the patient's symptoms. In this Point-Counterpoint, Jennifer Dien Bard of the Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, and of the Keck School of Medicine at the University of Southern California explains why laboratories should offer these assays without restriction. Kevin Alby of the University of Pennsylvania explains the concerns about the use of these assays as first-line tests and why some limitations on their use might be appropriate.

Biopsy Procedures and Molecular Testing Utilization and Related Costs in Patients with Metastatic Lung Cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene rearrangements are key therapeutic targets for biomarker-driven treatment with an EGFR or ALK tyrosine kinase inhibitor (TKI) in patients with metastatic non-small cell lung cancer (NSCLC). To appropriately guide treatment decisions, since 2011, the National Comprehensive Cancer Network and the American Society of Clinical Oncology therefore recommend EGFR and ALK analysis in tumor samples obtained at the time of diagnosis in patients with non-squamous NSCLC. Currently, there are limited data on utilization patterns and cost of biopsy procedures and biomarker tests in patients with metastatic NSCLC who receive an EGFR or ALK TKI. OBJECTIVES: To (a) describe utilization patterns and costs associated with biopsy procedures and biomarker testing in patients with NSCLC who received erlotinib or crizotinib between 2009 and 2012 and (b) investigate the timing of these procedures relative to the erlotinib or crizotinib index date. METHODS: Adult patients with metastatic lung cancer were identified by ICD-9-CM diagnostic codes within the Truven Health Analytic MarketScan database. Patients were included in the analysis if they had an index erlotinib or crizotinib claim between January 1, 2009, and September 30, 2012 (index period) and were continuously enrolled for ≥ 12 months before the index claim. Because there is no specific ICD-9-CM diagnostic code for NSCLC, patients with metastatic lung cancer who received erlotinib or crizotinib were considered to have metastatic NSCLC. Using CPT and ICD-9-CM codes, lung biopsy procedures performed during the 24 months before or 12 months after the index claim date were identified. For every patient, biomarker testing claims for EGFR and ALK were identified using the molecular pathology stacked CPT code during the 2 months before or 1 month after the index date. The frequency of claims for biopsy procedures and biomarker testing was analyzed descriptively. The overall summary measures for biomarker testing, especially frequency of EGFR testing in patients receiving erlotinib, was also described as before and after 2011, the year when biomarker testing became part of the guidelines. Per patient and overall costs for biopsy procedures and biomarker testing were calculated from payer and patient perspectives. RESULTS: Of the 4,926 identified patients, 4,801 (97.5%) received erlotinib, and 125 (2.5%) received crizotinib. Biopsy procedure claims were identified for 3,579 (72.7%) patients, including 3,503 (73.0%) erlotinib recipients and 76 (60.8%) crizotinib recipients. Biomarker testing claims were identified for 675 (13.7%) patients, including 634 (13.2%) erlotinib recipients and 41 (32.8%) crizotinib recipients. Overall, most biomarker testing procedures (476 of 741) were identified in 435 (of 675) patients after year 2011. Also, among erlotinib recipients, percentage of patients receiving EGFR testing was increased over the index period. Per patient mean (SD) numbers of biopsy procedures and biomarker tests were 1.2 (1.1) and 0.2 (0.4), respectively. In the outpatient setting, per patient mean (SD) cost per biopsy procedure was $1,223 ($1,899) from the payer perspective and $60 ($147) from the patient perspective, whereas in the inpatient setting, it was $8,163 ($18,712) and $180 ($691), respectively. Among patients receiving at least 1 biomarker test, the per patient mean (SD) cost for the overall population was $891 ($1,062) and $43 ($229); for erlotinib recipients, it was $906 ($1,084) and $42 ($228); and for crizotinib recipients, it was $664 ($576) and $55 ($243) in payer and patient perspectives, respectively. CONCLUSIONS: This study provides insight into the use and cost of biopsy and biomarker testing procedures in patients with metastatic NSCLC. The low frequency of biomarker testing highlights the need for more awareness of testing to guide treatment decisions in these patients. Costs associated with biopsy procedures and biomarker testing provide insight into the economic impact on metastatic NSCLC patients treated with targeted therapy. DISCLOSURES: This study was sponsored by Merck & Co. Shinde is a study manager working for Merck under contract with AllSourcePPS, an Agile 1 company in Huntington Beach, California. Cao and Kothari are employees of Merck & Co., Kenilworth, New Jersey. Study concept and design were contributed primarily by Shinde and Kothari. Data analysis was performed by Cao. Data interpretation was performed by Shinde, Cao, and Kothari. Shinde wrote the manuscript with assistance from Cao and Kothari. The revision was completed primarily by Shinde and Kothari.

Molecular testing patterns in metastatic non-small cell lung cancer.

OBJECTIVES: Identification of oncogene mutations and gene rearrangements in individuals with non-small cell lung cancer (NSCLC) can help identify candidates for targeted therapy. This study examined whether clinicians are ordering molecular testing for patients with metastatic NSCLC (mNSCLC) prior to therapy initiation. STUDY DESIGN: Members from a national health plan with lung cancer and metastatic disease were followed retrospectively. METHODS: Members were identified in medical claims data from January 1, 2010, to December 31, 2012, if they had 2 or more claims for lung cancer (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 162.xx) and metastatic disease (≥ 1 claim with ICD-9-CM code 196.xx-198.xx) who were continuously enrolled in a fully insured plan 180 days prior to index date. Patients were excluded if they had a history of chemotherapy used primarily in small cell lung cancer, or a medical claim associated with an unrelated malignancy. The timing of molecular testing was compared with the start of chemotherapy and targeted therapy, if applicable. RESULTS: A total of 2623 patients presumed to have mNSCLC were included for analysis; of whom, 52.5% were male with a mean age of 72.5 years (SD = 8.2 years). A total of 1597 (60.9%) patients had a Current Procedural Terminology code associated with molecular testing at any time in their claims history. Of the 733 patients with molecular testing and chemotherapy or targeted therapy claims, testing occurred prior to systemic therapy initiation in 651 (88.8%; 95% CI, 86.1%-90.9%) patients. The median time between testing and therapy initiation was 38 days (interquartile range = 23-69 days). CONCLUSIONS: Assessment of oncogene mutations and gene rearrangements in mNSCLC routinely occurs prior to treatment initiation as suggested by analyses of claims data from a large US health plan. Validation using patient medical records is needed.

Real-world performance of a microarray-based rapid diagnostic for Gram-positive bloodstream infections and potential utility for antimicrobial stewardship.

The Verigene Gram-positive blood culture assay (BC-GP) is a microarray-based rapid diagnostic test, which includes targets for 12 bacterial species and 3 resistance determinants. We prospectively compared the diagnostic accuracy of the BC-GP to routine microbiologic methods and evaluated the potential of the BC-GP for antimicrobial stewardship programs. A total of 143 consecutive patients with Gram-positive bacteremia were included in the analysis. BC-GP correctly identified 127/128 (99.2%) of organisms from monomicrobial blood cultures and 9/14 (64.3%) from polymicrobial, including all methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Stewardship interventions were possible in 51.0% of patients, most commonly stopping or preventing unnecessary vancomycin or starting a targeted therapy. In Monte Carlo simulations, unnecessary antibiotics could be stopped at least 24 hours earlier in 65.6% of cases, and targeted therapy could be started at least 24 hours earlier in 81.2%. BC-GP is a potentially useful test for antibiotic stewardship in patients with Gram-positive bacteremia.

Cost-effectiveness of molecular testing for thyroid nodules with atypia of undetermined significance cytology.

CONTEXT: Novel molecular diagnostics, such as the gene expression classifier (GEC) and gene mutation panel (GMP) testing, may improve the management for thyroid nodules with atypia of undetermined significance (AUS) cytology. The cost-effectiveness of an approach combining both tests in different practice settings in North America is unknown. OBJECTIVE: The aim of the study was to determine the cost-effectiveness of two diagnostic molecular tests, singly or in combination, for AUS thyroid nodules. DESIGN AND SETTING: We constructed a microsimulation model to investigate cost-effectiveness from US (Medicare) and Canadian healthcare system perspectives. PATIENTS: Low-risk patients with AUS thyroid nodules were simulated. INTERVENTIONS: We examined five management strategies: 1) routine GEC; 2) routine GEC + selective GMP; 3) routine GMP; 4) routine GMP + selective GEC; and 5) standard management. MAIN OUTCOME MEASURES: Lifetime costs and quality-adjusted life-years were measured. RESULTS: From the US perspective, the routine GEC + selective GMP strategy was the dominant strategy. From the Canadian perspective, routine GEC + selective GMP cost and additional CAN$24 030 per quality-adjusted life-year gained over standard management, and was dominant over the other strategies. Sensitivity analyses reported that the decisions from both perspectives were sensitive to variations in the probability of malignancy in the nodule and the costs of the GEC and GMP. The probability of cost-effectiveness for routine GEC + selective GMP was low. CONCLUSIONS: In the US setting, the most cost-effective strategy was routine GEC + selective GMP. In the Canadian setting, standard management was most likely to be cost effective. The cost of these molecular diagnostics will need to be reduced to increase their cost-effectiveness for practice settings outside the United States.

Clinical requests for molecular tests: the 3-step evidence check.

Laboratory tests performed by molecular methods are increasing in volume and complexity at an unprecedented rate. Molecular tests have a broad set of applications, and most recently have been advocated as the mechanism by which providers can further tailor treatments to the individual patient. As the momentum behind molecular testing continues to increase, pathology practices may find themselves unprepared for the new wave of molecular medicine. This special article has been developed in an effort to provide pathologists who have limited molecular training with a simple and quick algorithm for determining whether a requested molecular test is appropriate for a patient. Additional recommendations for a more intensive and proactive review and management of molecular requests also are included. The principles discussed can easily be applied to requests for any test, including those not using molecular methods, which would be sent to an outside reference laboratory. This special article was developed from a Webinar for the College of American Pathologists targeting education for pathologists about the transformation of pathology practice in the new molecular and digital age.

[Bacterial identification methods in the microbiology laboratory]. / Métodos de identificación bacteriana en el laboratorio de microbiología.

In order to identify the agent responsible of the infectious process and understanding the pathogenic/pathological implications, clinical course, and to implement an effective antimicrobial therapy, a mainstay in the practice of clinical microbiology is the allocation of species to a microbial isolation. In daily routine practice microbiology laboratory phenotypic techniques are applied to achieve this goal. However, they have some limitations that are seen more clearly for some kinds of microorganism. Molecular methods can circumvent some of these limitations, although its implementation is not universal. This is due to higher costs and the level of expertise required for thei implementation, so molecular methods are often centralized in reference laboratories and centers. Recently, proteomics-based methods made an important breakthrough in the field of diagnostic microbiology and will undoubtedly have a major impact on the future organization of the microbiology services. This paper is a short review of the most noteworthy aspects of the three bacterial identification methods described above used in microbiology laboratories.

Use and limitations of malaria rapid diagnostic testing by community health workers in war-torn Democratic Republic of Congo.

BACKGROUND: Accurate and practical malaria diagnostics, such as immunochromatographic rapid diagnostic tests (RDTs), have the potential to avert unnecessary treatments and save lives. Volunteer community health workers (CHWs) represent a potentially valuable human resource for expanding this technology to where it is most needed, remote rural communities in sub-Saharan Africa with limited health facilities and personnel. This study reports on a training programme for CHWs to incorporate RDTs into their management strategy for febrile children in the Democratic Republic of Congo, a tropical African setting ravaged by human conflict. METHODS: Prospective cohort study, satisfaction questionnaire and decision analysis. RESULTS: Twelve CHWs were trained to safely and accurately perform and interpret RDTs, then successfully implemented rapid diagnostic testing in their remote community in a cohort of 357 febrile children. CHWs were uniformly positive in evaluating RDTs for their utility and ease of use. However, high malaria prevalence in this cohort (93% by RDTs, 88% by light microscopy) limited the cost-effectiveness of RDTs compared to presumptive treatment of all febrile children, as evidenced by findings from a simplified decision analysis. CONCLUSIONS: CHWs can safely and effectively use RDTs in their management of febrile children; however, cost-effectiveness of RDTs is limited in zones of high malaria prevalence.

[More adequate use of laboratory services--economical aspects]. / Riktigere bruk av laboratorietjenester--økonomiske aspekter.

BACKGROUND: There has been a substantial increase in reimbursement for outpatient laboratory services in recent years. This article gives an overview of the use of such laboratory services and discusses measures for improved efficiency. MATERIAL AND METHODS: We have analysed reimbursement to the specialist health care for the period 2002-04. RESULTS: In the period 2002-04 the reimbursement to public laboratories increased by 42%. There has been a substantial growth in all reimbursements groups, especially for "General analysis for molecular biological methods" (236%). Reimbursement to private laboratories have increased by 24%, similar to the increase in general clinical chemistry. There has been a trend towards using the expensive reimbursement groups more often, especially for public laboratories. There is substantial variation in the use of laboratory services between the health regions. DISCUSSION: Our results indicate that the growth and variation in the use of laboratory services cannot be explained by deteriorated health or more illness in the population. The variation indicates that the use of laboratory services is not optimal. Establishment of a national laboratory system within specialized health care may contribute to a more knowledge-based use of laboratory services.

[Cost-effectiveness evaluation of predictive molecular diagnostics using the example of hereditary non-polyposis colorectal cancer (HNPCC)]. / Kosteneffektivitätsbewertung Prädiktiver Molekulardiagnostik am Beispiel des Hereditären Nichtpolypösen Kolorektalkarzinoms (HNPCC).

STUDY OBJECTIVE: Four different diagnostic strategies, with and without various molecular diagnostic tests, are compared and contrasted not only by years gained and the cost of therapy and diagnosis, but also by the cost-effectiveness of the diagnostic strategies. METHODOLOGY: A fictitious cohort of 100,000 people, whose genetic pre-disposition leading to the development of colorectal cancer corresponds to a representative average amongst the current population, will be studied from their 1st to their 85th year. This data will be then put through Markov models specifically developed for the study. At the end of the Markov process, it will then be possible to compile a cost-effectiveness report in regard to the various diagnostic and treatment strategies. RESULTS: A tiered diagnosis (with family case history, micro-satellite instability, molecular diagnostic diagnosis of an index person and subsequent genetic analysis of all people at risk) represents the most cost-effective method at a rate of euro 3,867 per year gained. The cost-effectiveness of a purely clinical diagnosis has a rate of euro 4,397 per year gained and is followed by the cost of direct gene testing of people at risk from families at risk at a rate of euro 6,208. The worst level of cost-effectiveness, with a rate of euro 15,705, was shown by nationwide gene screening. The incremental cost-effectiveness of Strategy IV and Strategy II is euro 124,168 per gained year. CONCLUSIONS: With the scenarios put forward we can show that a 65% reduction in gene test costs is necessary in order for a cost-effective nationwide gene screening for HNPCC to take place. The break-even level, however, depends only on a few cost-effectiveness drivers such as screening and therapy costs, proportion of HNPCC of all colorectal cancer and discounting rate. Should these changes (e.g., through a restructured medical environment), then we would see such a change in the break-even cost of a gene test and that a cost-effective nationwide gene screening could be made plausible. In a final evaluation of the use of predictive molecular diagnostics, other dimensions (such as possible psychological problems and discriminatory risks) apart from cost-effectiveness should also be included.

Utilization and diagnostic yield of neurogenetic testing at a tertiary care facility.

BACKGROUND: Institutions face increasing charges related to molecular genetic testing for neurological diseases. The literature contains little information on the utilization and performance of these tests. METHODS: A retrospective utilization review was performed to determine the diagnostic yield of neurogenetic tests ordered during calendar year 2005 at a large academic medical center in the western United States. RESULTS: Overall, a relevant mutation was identified in 30.2% of the 162 patients tested and in 21.5% of the 121 probands, defined as patients for whom no mutation has been previously identified in a family member. Patients with muscle weakness (n = 65) had a mutation detected in 26.2% of all patients and 23.5% of probands (n = 51), with an estimated testing cost per positive result of $3190. Patients tested for neuropathy (n = 36) had a mutation detected in 27.8% of patients and 22.6% of probands (n = 31), with an estimated cost per positive result of $5955. Patients with chorea (n = 25) had a positive result obtained in 68% of patients and 71.4% of probands (n = 7); the estimated cost per positive test was $440. Other diagnostic categories evaluated include ataxias (n = 18; yield, 11.1%; $7620 per positive), familial stroke or dementia syndromes (n = 8; yield, 12.5%; $6760 per positive), and multisystem mitochondrial disorders (n = 10; yield, 20%; $6485 per positive). CONCLUSIONS: Expert clinicians at a tertiary care center who ordered neurogenetic tests obtained a positive result in 21.5% of patients without previously identified familial mutations. These results can be used for comparison and to help establish utilization guidelines for neurogenetic testing.

Effectively managing your reference laboratory relationship.

Clinical laboratories use reference laboratories for laboratory services that they, themselves, routinely are unable to provide, often for economic and/or competency-related reasons. Decisions on reference laboratory providers usually are based upon reputation, quality of service, depth of test menu, other value-added services, testing frequency and turnaround time, price, client services support, information technology support, and logistics. The referring laboratory also is faced with the challenge of how to manage physician ordering patterns and their requests for esoteric testing. This is particularly important and problematic in cases of questionable medical necessity, high cost, or both. This article attempts to address this dilemma and how best to manage the utilization of expensive esoteric tests, particularly in the face of little or no reimbursement for these services by payers and health plans.