Cost Avoidance and Outcome Improvement by Implementing a Test Utilization Strategy for Molecular Microbiology Tests

Test utilization is an essential strategy in the clinical laboratory, especially with increasing numbers of tests and health care costs. We designed a triage system for molecular microbiology tests ordered from 2007 through 2010 to assess their appropriateness before they were sent out to a reference laboratory for testing. The number of tests ordered and approved and the number with positive results were calculated during the study period. Cost avoidance was subsequently calculated. A total of 13,839 tests were ordered, averaging 3,335 tests/year. The overall approval rate was 76%, ranging from 72% in 2007 to 81% in 2010. With the exception of cytomegalovirus (CMV) and BK virus PCR, the numbers of all tests decreased in 2010 compared to 2007. The total savings over 4 years was $374,791, with an average cost avoidance of $93,698/year. Pathologists and microbiologists should design a utilization system for laboratory testing to avoid unnecessary cost and improve patient care.     

Novel LAMB3 mutations cause non‐syndromic amelogenesis imperfecta with variable expressivity

The field of genetics is evolving rapidly, significantly expanding the number of clinically useful genetic tests. The cost of genetic testing has created an increasing burden on public health care budgets. In Canada, funding bodies have responded by developing independent systems. Key individuals in each province and territory participated in a semi‐structured interview regarding the process in their jurisdiction to approve funding for referred out genetic testing and their decision‐making criteria. Two themes were identified: the importance of clinical utility in decision‐making and the utilization of genetic specialists as gate keepers. Allocation of a specific budget appears to be associated with some fiscal responsibility. Collaboration between provincial and territorial bodies may lead to a more unified approach across Canada.     

An MLPA‐Based Strategy for Discrete CNV Genotyping: CNV‐miRNAs as an Example

Copy number variation (CNV) has become well recognized in recent years. It has been estimated that common CNVs account for approximately 10% of the human genome and that they overlap hundreds of genes and other functional genetic elements. Although substantial progress in genome‐wide CNV analysis has been made recently, there is still a need for a method that allows precise genotyping of selected CNVs. Here, we describe a novel strategy for CNV genotyping, taking advantage of the general principles of the multiplex ligation‐dependent probe amplification (MLPA) method and short oligonucleotide probes, allowing easy custom design and generation of assays for almost any genomic region of interest. As a proof‐of‐concept, we developed two assays covering 17 candidate CNV regions that overlap human miRNA genes. Extensive quality control analysis demonstrated high reproducibility and reliability of the genotypes determined using our method. Detailed analysis of identified CNVs revealed that they are highly differentiated among the HapMap populations. The main advantages of the developed strategy include the simplicity of the assay design, its flexibility in terms of the selection of genomic regions, and its low cost (<$1–$10/genotype, depending on scale of experiment). These advantages make the presented strategy attractive for large‐scale genetic analyses.     

Correlation of HTLV‐1 Tax genetic diversity with HTLV‐1 associated myelopathy/tropical spastic paraparesis progression and HTLV‐1a genotypes in an HTLV‐1 endemic region in Argentina

The oncoprotein Tax was characterized genetically from a large cohort of human T‐cell lymphotropic virus type 1 (HTLV‐1) seropositive individuals from the most endemic region of HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV‐1 infection in Argentina, the province of San Salvador de Jujuy. Sixteen HAM/TSP patients and 47 HTLV‐1 healthy carriers were evaluated. Six Tax genetic polymorphisms were identified and observed in 70.8% of healthy carriers and 62.5% of HAM/TSP patients. Tax genetic polymorphisms were not associated with clinical status but A8344C polymorphism statistically provide a borderline protective effect of HAM/TSP outcome. Nucleotide diversity in healthy carriers was 0.00549, whereas HAM/TSP virus population revealed a low diversity of 0.00379, suggests a positive selection for Tax protein conservation in this group. It is concluded that tax genetic polymorphisms do not increase the risk of developing HAM/TSP in this endemic region. However, in spite of the low prevalence of HTLV‐1aB genotype, statistical analysis revealed an important correlation of tax genetic signatures with HTLV‐1aA trans‐continental subgroup. J. Med. Virol. 82:1438–1441, 2010. © 2010 Wiley‐Liss, Inc.     

Implementation of a registry and open access genetic testing program for inherited retinal diseases within a non‐profit foundation

The Foundation Fighting Blindness is a 50‐year old 501c(3) non‐profit organization dedicated to supporting the development of treatments and cures for people affected by the inherited retinal diseases (IRD), a group of clinical diagnoses that include orphan diseases such as retinitis pigmentosa, Usher syndrome, and Stargardt disease, among others. Over $760 M has been raised and invested in preclinical and clinical research and resources. Key resources include a multi‐national clinical consortium, an international patient registry with over 15,700 members that is expanding rapidly, and an open access genetic testing program that provides no cost comprehensive genetic testing to people clinically diagnosed with an IRD living in the United States. These programs are described with particular focus on the challenges and outcomes of establishing the registry and genetic testing program.     

Utilization and cost effectiveness of standardized testing for screening and confirmation of drugs of abuse in urine

Screening and confirmation testing for drugs of abuse in urine (DAU) represent areas for potential reduction of laboratory workload and attendant cost savings. Following a careful review of the dinical needs of the underlying veteran patient population served by 7 medical facilities in the Boston area, DAU test ordering frequencies, positive rates for several screening panels and the associated confirmation tests, DAU panel standardization, and confirmation testing only by request were introduced. These changes were all reviewed and approved by the clinician users of DAU testing at each institution before the changes were implemented. Before standardization of DAU screening panels, 59,835 DAU screening requests were done at a cost of $216,005; following standardization, there was 47% decrease in DAU screening utilization (27,876) and costs ($100,633). Before implementation of a DAU confirmation by request only policy, 5,331 confirmation tests were done at a cost of $111,502; after institution of the confirmation policy, there was 95% decrease in confirmation tests (5,080) and costs ($105,826). DAU panel standardization and DAU confirmation by request only have resulted in substantial reductions of laboratory workload and costs in a veterans population and may serve as a model for other patient populations with perhaps similar outcomes.     

Clinical pathology consultation improves coagulation factor utilization in hospitalized adults

Coagulation factor replacement can effectively treat or prevent most hemophilia complications, but it is expensive. Although published data describe how to achieve therapeutic goals through cost-effective selection and dosing of replacement products, criteria are not universally known or followed. A review of our institution's experience revealed overdosing of coagulation factors in the majority of patients treated during a 12-month period, at a cost that approached $700,000. Consequently, we established mandatory clinical pathology consultation before releasing such factors. In the subsequent 30 months, 32 adults received 64 courses of treatment. For patients with hemophilia A, the mean cost per admission was reduced by approximately 27% (total savings, $61,536). For patients with factor VIII inhibitor, there was an approximate 6% cost reduction (total savings, $47,292). The combined savings was $108,828. The mean plasma factor level achieved during the intervention period was 84% +/- 55% compared with 117% +/- 58% for the preintervention period (P = .008). Neither the number of treatment (factor transfusion) days nor the number of RBC transfusions changed significantly. Our data support that pathology consultation yields consistent and appropriate therapy and improves resource utilization.     

Fine‐needle aspiration of primary osseous lesions: A cost effectiveness study

Fine‐needle aspiration (FNA) is not widely used in the work‐up of osseous lesions because of concerns regarding its high incidence of nondiagnostic specimens. Although several studies have shown that FNA is less expensive than surgical biopsy, the authors are aware of only one prior study evaluating the cost effectiveness of FNA, which includes the cost of incisional or core needle biopsies necessary to establish a diagnosis when the initial FNA was noncontributory. A computerized search of the pathology records of three medical centers was performed to obtain all FNAs of primary osseous lesions. For each FNA case, all subsequent core needle, incisional or excisional biopsies were recorded as was the result of the definitive operative procedure. The cost of obtaining the definitive diagnosis was calculated for each case including the cost of FNA, imaging guidance utilized, and cost of subsequent surgical biopsy when necessary. The cost of an alternate approach using only surgical biopsy was calculated. The average per patient costs of these two protocols were compared. A total of 165 primary bone tumors underwent FNA. One hundred six of these yielded a definitive cytologic diagnosis. In 59 cases, FNA yielded a result insufficient for definitive therapy necessitating surgical biopsy. FNA investigation of the 165 bone lesions cost 575,932 (average of 3,490 per patient). Surgical biopsy alone would have cost 5,760 per patient. FNA resulted in a cost savings of 2,215 per patient. Diagn. Cytopathol. 2010 © 2009 Wiley‐Liss, Inc.     

The case of Powhatan Correctional Center/Virginia Department of Corrections and Virginia Commonwealth University/Medical College of Virginia.

OBJECTIVE: To implement a cost/benefit analysis of telemedicine subspecialty care provided between the Powhatan Correctional Center (PCC) of the Virginia Department of Corrections (Corrections) and the Medical College of Virginia campus of Virginia Commonwealth University (MCV/VCU). METHODS: We evaluated the costs and benefits of the implementation of telemedicine for HIV-positive inmates. Benefits included dollar savings in transportation and medical reimbursement. Costs included those of operating the telemedicine system and of medical care. Non-dollar benefits included implementing more consistent and timely treatment of inmates and reducing security risk. RESULTS: Over the 7-month study period, the total number of HIV consults by telemedicine was 165. The Department of Corrections was able to achieve transportation and medical savings of $35,640 and $21,123, respectively. The operating costs for the telemedicine services totaled $42,277. The net benefit, which is the difference between cost savings and total operating costs, was $14,486. CONCLUSION: Telemedicine increased access to care for HIV-positive inmates and generated cost savings in transportation and care delivery.     

The utilization of pre‐implantation genetic testing in the absence of governance: a real‐time experience

To create a diagnostic document describing the utilization of pre‐implantation genetic testing (PGT) in the absence of monitoring and regulation. Retrospective cohort study of couples undergoing PGT between 2004 and 2007 in Lebanon. The clinical indications for 192 PGT cycles performed during the study period were gender selection (96.3%), chromosomal aneuploidy (3.1%), and balanced translocation (0.5%). When gender selection was sought, the selection of a son was desired in 94.1% of cases. Of couples undergoing PGT for sex selection, 16.2% were childless, 8.6% had one child of the opposite gender, 28.1% had two same‐gender children, 29.7% had three same‐gender children, and 11.9% had four or more. Our findings demonstrate the morally questionable consequences of self‐regulated systems in which physicians are the sole gatekeepers of norms and ethics.     

Patient satisfaction and cancer‐related distress among unselected Jewish women undergoing genetic testing for BRCA1 and BRCA2

Metcalfe KA, Poll A, Llacuachaqui M, Nanda S, Tulman A, Mian N, Sun P, Narod SA. Patient satisfaction and cancer‐related distress among unselected Jewish women undergoing genetic testing for BRCA1 and BRCA2. It is not known to what extent participation in a genetic testing program for BRCA1 and BRCA2, which does not include an extensive pre‐test counselling session, influences cancer‐related distress, cancer risk perception and patient satisfaction. Unselected Jewish women in Ontario were offered genetic testing for three common Jewish BRCA mutations. Before testing and 1‐year post‐testing, the women completed questionnaires which assessed cancer‐related distress, cancer risk perception, and satisfaction. A total of 2080 women enrolled in the study; of these, 1516 (73%) completed a 1‐year follow‐up questionnaire. In women with a BRCA mutation, the mean breast cancer risk perception increased from 41.1% to 59.6% after receiving a positive genetic test result (p = 0.002). Among non‐carriers, breast cancer risk perception decreased slightly, from 35.8% to 33.5% (p = 0.08). The mean level of cancer‐related distress increased significantly for women with a BRCA mutation, but did not change in women without a mutation; 92.8% expressed satisfaction with the testing process. The results of this study suggest that the majority of Jewish women who took part in population genetic screening for BRCA1 and BRCA2 were satisfied with the delivery of genetic testing and would recommend testing to other Jewish women. However, women with a BRCA mutation experienced increased levels of cancer‐related distress.     

A cost savings approach to SPRED1 mutational analysis in individuals at risk for neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a clinically diagnosed autosomal dominant disorder requiring routine clinical management, particularly during the pediatric years. An overlapping disorder, Legius syndrome, at times is clinically indistinguishable from NF1 and results in a small percentage of individuals being mischaracterized. Distinguishing these two entities is increasingly important for prognosis, reproductive planning, and clinical management. The goal of our study was to evaluate the cost impact of genetic testing for patients with solely pigmentary findings. The costs of genetic testing in patients aged 1.5–18 years were modeled using a simulated population, assuming the clinical management approach of a single NF1 clinic. Two genetic testing algorithms (SPRED1 testing alone, and NF1 mutation analysis with reflex to SPRED1) were compared against a baseline of no genetic testing. The cost for SPRED1 mutation analysis for each individual meeting NF1 diagnostic criteria without neoplastic or boney manifestation, when compared to the no‐testing approach with routine follow‐up mutations between the ages of 10 and 14 years, was minimal (range of $4–$16). Based on the clinical practice of one NF1 clinic, we found that the cost difference to perform SPRED1 mutation analysis on individuals who meet diagnostic criteria for NF1 without neoplastic or boney manifestation were minimal. Therefore it is important that “when to test decisions” remain a physician/patient discussion, as individual benefits may be greatest at a different age than when it is most cost efficient. © 2013 Wiley Periodicals, Inc.     

Influence of individual differences in disease perception on consumer response to direct‐to‐consumer genomic testing

Individuals who undergo multiplex direct‐to‐consumer (DTC) genomic testing receive genetic risk results for multiple conditions. To date, research has not investigated the influence of individual differences in disease perceptions among consumers on testing outcomes. A total of 2037 participants received DTC genomic testing and completed baseline and follow‐up surveys assessing disease perceptions and health behaviors. Participants were asked to indicate their most feared disease of those tested. Perceived seriousness and controllability of the disease via lifestyle or medical intervention were assessed. Participants most frequently reported heart attack (19.1%) and Alzheimer's disease (18.6%) as their most feared disease. Perceived seriousness and control over the feared disease both influenced response to DTC genomic testing. Greater perceived seriousness and diminished perceived control were associated with higher, but not clinically significant levels of anxiety and distress. In some cases these associations were modified by genetic risk. No significant associations were observed for diet, exercise and screening behaviors. Individual differences in disease perceptions influence psychological outcomes following DTC genomic testing. Higher perceived seriousness may make a consumer more psychologically sensitive to test results and greater perceived control may protect against adverse psychological outcomes. Findings may inform development of educational and counseling services.     

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     

Perceptions of genetic counseling services in direct‐to‐consumer personal genomic testing

To describe consumers' perceptions of genetic counseling services in the context of direct‐to‐consumer personal genomic testing is the purpose of this research. Utilizing data from the Scripps Genomic Health Initiative, we assessed direct‐to‐consumer genomic test consumers' utilization and perceptions of genetic counseling services. At long‐term follow‐up, approximately 14 months post‐testing, participants were asked to respond to several items gauging their interactions, if any, with a Navigenics genetic counselor, and their perceptions of those interactions. Out of 1325 individuals who completed long‐term follow‐up, 187 (14.1%) indicated that they had spoken with a genetic counselor. The most commonly given reason for not utilizing the counseling service was a lack of need due to the perception of already understanding one's results (55.6%). The most common reasons for utilizing the service included wanting to take advantage of a free service (43.9%) and wanting more information on risk calculations (42.2%). Among those who utilized the service, a large fraction reported that counseling improved their understanding of their results (54.5%) and genetics in general (43.9%). A relatively small proportion of participants utilized genetic counseling after direct‐to‐consumer personal genomic testing. Among those individuals who did utilize the service, however, a large fraction perceived it to be informative, and thus presumably beneficial.     

Cost analysis of a neonatal point-of-care monitor

A hypothetical model using a base case and sensitivity analyses compared averted and incurred costs of in-line monitoring with neonatal intensive care unit satellite laboratory testing. Data were obtained retrospectively for 1 year from 50 consecutive critically ill premature neonates weighing less than 1,000 g at birth whose blood tests were performed in-line and processed at the satellite laboratory. Averted costs included phlebotomies, satellite blood testing, and transfusions; incurred costs included in-line monitor rental, nursing time, and daily monitor validation. In-line monitoring led to cost savings of $324 per neonate and a benefit/cost ratio (BCR) of 1.23 in our base case. Sensitivity and scenario analyses addressed uncertainty and led to a BCR variation of 0.41 to 2.48. Compared with satellite laboratory testing, in-line monitoring of critically ill neonates may generate cost savings through reduced laboratory analysis expense, less phlebotomy loss, and fewer blood transfusions for hospitals with high laboratory cost structures. Because most cost savings result from offsetting indirect costs (eg, building space and hospital overhead) that are of a longer term nature, short-run cost savings are less likely to be realized.     

Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability

PurposeThis study investigated whole-exome sequencing (WES) yield in a subset of intellectually disabled patients referred to our clinical diagnostic center and calculated the total costs of these patients’ diagnostic trajectory in order to evaluate early WES implementation.MethodsWe compared 17 patients’ trio-WES yield with the retrospective costs of diagnostic procedures by comprehensively examining patient records and collecting resource use information for each patient, beginning with patient admittance and concluding with WES initiation. We calculated cost savings using scenario analyses to evaluate the costs replaced by WES when used as a first diagnostic tool.ResultsWES resulted in diagnostically useful outcomes in 29.4% of patients. The entire traditional diagnostic trajectory average cost was $16,409 per patient, substantially higher than the $3,972 trio-WES cost. WES resulted in average cost savings of $3,547 for genetic and metabolic investigations in diagnosed patients and $1,727 for genetic investigations in undiagnosed patients.ConclusionThe increased causal variant detection yield by WES and the relatively high costs of the entire traditional diagnostic trajectory suggest that early implementation of WES is a relevant and cost-efficient option in patient diagnostics. This information is crucial for centers considering implementation of WES and serves as input for future value-based research into diagnostics.Genet Med 18 9, 949–956.     

Cost‐effectiveness and cost‐utility of cognitive therapy,rational emotive behavioral therapy,and fluoxetine (prozac) in treating depression: a randomized clinical trial

Cost‐effectiveness and cost‐utility of cognitive therapy (CT), rational emotive behavioral therapy (REBT), and fluoxetine (Prozac) for major depressive disorder (MDD) were compared in a randomized clinical trial with a Romanian sample of 170 clients. Each intervention was offered for 14 weeks, plus three booster sessions. Beck Depression Inventory (BDI) scores were obtained prior to intervention, 7 and 14 weeks following the start of intervention, and 6 months following completion of intervention. CT, REBT, and fluoxetine did not differ significantly in changes in the BDI, depression‐free days (DFDs), or Quality‐Adjusted Life Years (QALYs). Average BDI scores decreased from 31.1 before treatment to 9.7 six months following completion of treatment. Due to lower costs, both psychotherapies were more cost‐effective, and had better cost‐utility, than pharmacotherapy: median $26.44/DFD gained/month for CT and $23.77/DFD gained/month for REBT versus $34.93/DFD gained/month for pharmacotherapy, median $/QALYs=$1,638, $1,734, and $2,287 for CT, REBT, and fluoxetine (Prozac), respectively. © 2008 Wiley Periodicals, Inc. J Clin Psychol 65:1–17, 2009.     

Consecutive medical exome analysis at a tertiary center: Diagnostic and health‐economic outcomes

The utility of whole exome analysis has been extensively demonstrated in research settings, but its clinical utility as a first‐tier genetic test has not been well documented from diagnostic and health economic standpoints in real‐life clinical settings. We performed medical exome analyses focusing on a clinically interpretable portion of the genome (4,813 genes) as a first‐tier genetic test for 360 consecutive patients visiting a genetics clinic at a tertiary children's hospital in Japan, over a 3‐year period. Bioinformatics analyses were conducted using standard software. A molecular diagnosis was made in 171 patients involving a total of 107 causative genes. Among these 107 causative genes, 57 genes were classified as genes with potential organ‐specific interventions and management strategies. Clinically relevant results were obtained in 26% of the total cohort and 54% of the patients with a definitive molecular diagnosis. Performing the medical exome analysis at the time of the initial visit to the tertiary center, rather than after visits to pertinent specialists, brain MRI examination, and G‐banded chromosome testing, would have reduced the financial cost by 197 euros according to retrospective calculation under multiple assumption. The present study demonstrated a high diagnostic yield (47.5%) for singleton medical exome analysis as a first‐tier test in a real‐life setting. Medical exome analysis yielded clinically relevant information in a quarter of the total patient cohort. The application of genomic testing during the initial visit to a tertiary medical center could be a rational approach to the diagnosis of patients with suspected genetic disorders.     

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.