Introducing cell-free DNA noninvasive testing in a Down syndrome public health screening program: a budget impact analysis.

BACKGROUND: Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma is a high accurate test for prenatal screening for Down syndrome. Although it has been reported to be cost effective as a contingent test, evidence about its budget impact is lacking. OBJECTIVE: To evaluate, using computer simulations, the budget impact of implementing NIPT as a contingent test in the Quebec Program of screening for Trisomy 21. METHODS: A semi-Markov analytic model built to simulate the budget impact of implementing NIPT into the current Quebec Trisomy 21 public Prenatal Screening, Serum Integrated prenatal screening (SIPS). Comparisons were made for a virtual population similar to that of expected Quebec pregnant women in 2015 in terms of size and age. Data input parameters were retrieved from a thorough literature search and in government databases, especially data from Quebec Program of screening for Trisomy 21. The 2015-2016 fiscal year budget impact was estimated from the Quebec healthcare system perspective and was expressed as the difference in the overall costs between the two alternatives (SIPS minus SPS + NIPT). RESULTS: Our study found that, at a baseline cost for NIPT of CAD$ 795, NIPT as a second-tier test offered to high-risk women identified by current screening program (SIPS + NIPT) may be affordable for Quebec health care system. Compared to the current screening program, it would be implemented at a neutral cost, considering a modest annual savings of $ 80,432 (95% CI $ 79, $ 874-$ 81,462). Results were sensitive to the NIPT costs and the uptake-rate of invasive diagnostic tests. CONCLUSION: Introducing NIPT as a contingent test in the Quebec Trisomy 21 screening program is an affordable strategy compared to the current practice. Further research is needed to confirm if our results can be reproduced in other healthcare jurisdictions.

Cell-free DNA noninvasive prenatal screening for aneuploidy versus conventional screening: A systematic review of economic evaluations.

Although noninvasive prenatal testing (NIPT) for aneuploidies using cell-free fetal DNA in maternal blood has been reported to have a high accuracy, only little evidence about its cost-effectiveness is available. We systematically reviewed and assessed quality of economic evaluation studies published between January 1, 2009 and January 1, 2016 where NIPT was compared to the current screening practices consisting of biochemical markers with or without nuchal translucency (NT) and/or maternal age. We included 16 studies and we found that, at current level of NIPT prices, contingent NIPT provide the best value for money, especially for publicly funded screening programs. NIPT as first-line test was found not cost-effective in the majority of studies. The NIPT unit cost, the risk cut-offs for current screening practice, the screening uptake rates (first- and second-line screening) as well as the costs and uptake rates of invasive diagnostic screening were the most common uncertain variables. The overall quality of included studies was fair. Considering a possible drop in prices and an ongoing NIPT expansion to include other chromosomes abnormalities other than T21, T18, T13 and sex chromosomes aneuploidies, future research are needed to examine the potential cost-effectiveness of implementing NIPT as first-line test.

Cost effectiveness of newborn screening for cystic fibrosis: a simulation study.

BACKGROUND: Early detection of cystic fibrosis (CF) by newborn screening (NBS) reduces the rate of avoidable complications. NBS protocols vary by jurisdiction and the cost effectiveness of these different protocols is debated. OBJECTIVE: To compare the cost effectiveness of various CF NBS options. METHODS: A Markov model was built to simulate the cost effectiveness of various CF-NBS options for a hypothetical CF-NBS program over a 5-year time horizon assuming its integration into an existing universal NBS program. NBS simulated options were based on a combination of tests between the two commonly used immunoreactive trypsinogen (IRT) cutoffs (96th percentile and 99.5th percentile) as first tier tests, and, as a second tier test, either a second IRT, pancreatic-associated protein (PAP) or CFTR mutation panels. CFTR mutation panels were also considered as an eventual third tier test. Data input parameters used were retrieved from a thorough literature search. Outcomes considered were the direct costs borne by the Quebec public health care system and the number of cases of CF detected through each strategy, including the absence of screening option. RESULTS: IRT-PAP with an IRT cutoff at the 96th percentile is the most favorable option with a ratio of CAD$28,432 per CF case detected. The next most favorable alternative is the IRT1-IRT2 option with an IRT1 cutoff at the 96th percentile. The no-screening option is dominated by all NBS screening protocols considered. Results were robust in sensitivity analyses. CONCLUSION: This study suggests that NBS for cystic fibrosis is a cost-effective strategy compared to the absence of NBS. The IRT-PAP newborn screening algorithm with an IRT cutoff at the 96th percentile is the most cost effective NBS approach for Quebec.

Assessment of the prevalence of the 985A>G MCAD mutation in the French-Canadian population using allele-specific PCR.

Inherited deficiency of medium-chain acyl-CoA dehydrogenase (MCAD) is a severe, sometimes fatal disorder. A single mutation in the MCAD gene, 985A>G, is involved in approximately 90% of cases. To evaluate the relevance of implementing a systematic population-based screening program in the province of Quebec using a biochemical test, we measured the prevalence of this mutation in a set of anonymous newborn samples from the Quebec City area, a region where the majority of its inhabitants are French-Canadians. An allele-specific polymerase chain reaction assay was designed and used to detect the mutation in 7143 DNA samples obtained from consecutive anonymous newborns. Pools of eight DNA samples were genotyped in parallel for the same mutation to validate this pooling strategy. The allelic frequency of the MCAD 985A>G mutation was found to be 0.71% and the carrier frequency 1:71 (95% confidence interval 1:55 to 1:98). This estimate predicts a homozygous frequency of 1:19,837. Ninety-nine heterozygous carriers and one homozygous individual were identified out of 7143 samples. There was 100% concordance between the individual and pooled analyses, and the pooling strategy reduced the total genotyping costs by approximately 70%. The carrier frequency estimated for this population is similar to other northwestern European populations and would support implementation of systematic newborn screening (such as tandem mass spectrometry screening) for this disease. Pooling DNA samples followed by genotyping appears to be cost-effective for estimating prevalence of rare mutations.

Hereditary hemochromatosis screening: effect of mutation penetrance and prevalence on cost-effectiveness of testing algorithms.

Screening for hereditary hemochromatosis, although largely discussed, is not yet implemented in clinical practice. We evaluated the cost-effectiveness of 165 hemochromatosis population-screening algorithms involving two or three of several screening tests by developing a computer program that simulates all possible screening scenarios. Input data comprised government estimates of health services data and costs and a virtual population with user-defined demographic characteristics (including variable HFE mutation frequencies and penetrance values). We show that when C282Y homozygote prevalence is set at 3:1000, population screening appears cost-effective when penetrance of the biochemical phenotype is >0.70. When only hepatocellular carcinoma and cirrhosis are considered as the cost-driving complications, population-based screening is not significantly more cost-efficient than no screening, but life expectancy of individuals identified with hereditary hemochromatosis and treated is still improved by 7 years. Among the 165 screening algorithms tested in 91 different virtual populations of one million individuals, biochemical tests usually perform better as the initial test than genetic testing. Indeed, the genetic testing is most cost-effective as the final confirmatory test. Finally, for most combinations of prevalence and penetrance of HFE, one screening algorithm--unbound iron-binding capacity + transferrin saturation--appeared robust enough to be always within the top 5 most cost-effective strategies.

Work status after workers' compensation claims for upper limb musculoskeletal disorders.

AIM: To provide information on employment status after workers' compensation (WC) claims for musculoskeletal disorders of the limbs (MSDs). METHODS: Two-year follow up of the workers who filed a WC claim for MSDs in 1996 in the Pays de la Loire region. Of the 701 eligible workers, 514 workers (70%) participated. Information was requested by means of a mailed questionnaire about the characteristics of the MSDs and job status at the time of the WC claim and two years later. RESULTS: Two years after the WC claim, 65% of the claimants had returned to work in the same company, often without any ergonomic improvement, 12% had retired or had left employment voluntarily, and 18% had been dismissed. The risk of dismissal was associated with three factors: being older than 45 years, having two or more MSDs at claim, and working in the cleaning services sector.

Does motivation mediate influence of social factors on educational consequences?

Yamauchi, Kumagai, and Kawasaki (7) reported results from two separate regression analyses showing that perceived control and motivation were both significant predictors of self-regulated learning strategies among Japanese high school students. In the present article, it is proposed that integrating perceived control, motivation, and self-regulated learning strategies into a single motivational sequence would result in theoretical and applied benefits.

High throughput and economical mutation detection and RFLP analysis using a minimethod for DNA preparation from whole blood and acrylamide gel electrophoresis.

We report a simple, rapid, and high throughput method which allows the simultaneous processing of multiple whole blood samples for routine DNA purification and analysis. The method is based on a microscale DNA preparation and digestion using minimal amounts of reagents and handling. The amount of material necessary for a Southern blot analysis (5-7 micrograms) is obtained from 200 microliters of whole blood. All steps involved in DNA preparation and restriction digestion are processed in a single 1.5-ml Eppendorf tube. DNA preparation is performed using a salting out procedure with a proteinase K digestion step but no phenol/chloroform extraction. Restricted fragments are separated by electrophoresis through polyacrylamide slab gels followed by electrotransfer to nylon membranes. By varying the electrophoresis parameters (V/cm or duration), fragments of interest up to 12 kb length can be separated with high resolution. At least 80 samples can be processed at once per DNA preparation, and multiples of this number depend on the available equipment. This economical and rapid method allows routine DNA analysis for mutation or RFLP detection to be performed on a large scale which is a mandatory feature in any DNA-based population screening program. In addition, the DNA purified by the minimethod can be used as an economical source for PCR analysis.