“…With nationwide CF NBS underway, the research climate shifted from one focused on identifying the benefits of screening to one focused on identifying the best screening methodology. [5][6][7] Although wide variations in screening methods and cutoff values currently exist throughout the United States and across the world, 6,8 almost all algorithms begin by evaluating IRT 1 levels by using a dried blood specimen collected between 1 and 5 days of age with the second tier being either a second IRT or DNA analysis for CF transmembrane conductance regulator (CFTR) mutations. 9 Further testing and referrals are then made based on the particular screening method in use by the state.…”
WHAT'S KNOWN ON THIS SUBJECT: Although it has been shown that cystic fibrosis newborn screening is beneficial, the strategies vary widely, and there has been uncertainty about the costs and consequences of different algorithms and whether screening methods/decisions should be based on assumed cost differences.
WHAT THIS STUDY ADDS:This study contributes by offering a comparison of both costs, assessed comprehensively, and the consequences associated with the 2 most popular screening methodologies, immunoreactive trypsinogen/immunoreactive trypsinogen and immunoreactive trypsinogen/DNA, by using a decision-tree framework allowing variation in the model parameters.abstract OBJECTIVES: Because cystic fibrosis can be difficult to diagnose and treat early, newborn screening programs have rapidly developed nationwide but methods vary widely. We therefore investigated the costs and consequences or specific outcomes of the 2 most commonly used methods.
METHODS:With available data on screening and follow-up, we used a simulation approach with decision trees to compare immunoreactive trypsinogen (IRT) screening followed by a second IRT test against an IRT/DNA analysis. By using a Monte Carlo simulation program, variation in the model parameters for counts at various nodes of the decision trees, as well as for costs, are included and applied to fictional cohorts of 100 000 newborns. The outcome measures included the numbers of newborns given a diagnosis of cystic fibrosis and costs of screening strategy at each branch and cost per newborn.
RESULTS:Simulations revealed a substantial number of potential missed diagnoses for the IRT/IRT system versus IRT/DNA. Although the IRT/IRT strategy with commonly used cutoff values offers an average overall cost savings of $2.30 per newborn, a breakdown of costs by societal segments demonstrated higher out-of-pocket costs for families. Two potential system failures causing delayed diagnoses were identified relating to the screening protocols and the follow-up system.
CONCLUSIONS:The IRT/IRT screening algorithm reduces the costs to laboratories and insurance companies but has more system failures. IRT/DNA offers other advantages, including fewer delayed diagnoses and lower out-of-pocket costs to families. Pediatrics 2012;129:e339-e347 AUTHORS:
“…With nationwide CF NBS underway, the research climate shifted from one focused on identifying the benefits of screening to one focused on identifying the best screening methodology. [5][6][7] Although wide variations in screening methods and cutoff values currently exist throughout the United States and across the world, 6,8 almost all algorithms begin by evaluating IRT 1 levels by using a dried blood specimen collected between 1 and 5 days of age with the second tier being either a second IRT or DNA analysis for CF transmembrane conductance regulator (CFTR) mutations. 9 Further testing and referrals are then made based on the particular screening method in use by the state.…”
WHAT'S KNOWN ON THIS SUBJECT: Although it has been shown that cystic fibrosis newborn screening is beneficial, the strategies vary widely, and there has been uncertainty about the costs and consequences of different algorithms and whether screening methods/decisions should be based on assumed cost differences.
WHAT THIS STUDY ADDS:This study contributes by offering a comparison of both costs, assessed comprehensively, and the consequences associated with the 2 most popular screening methodologies, immunoreactive trypsinogen/immunoreactive trypsinogen and immunoreactive trypsinogen/DNA, by using a decision-tree framework allowing variation in the model parameters.abstract OBJECTIVES: Because cystic fibrosis can be difficult to diagnose and treat early, newborn screening programs have rapidly developed nationwide but methods vary widely. We therefore investigated the costs and consequences or specific outcomes of the 2 most commonly used methods.
METHODS:With available data on screening and follow-up, we used a simulation approach with decision trees to compare immunoreactive trypsinogen (IRT) screening followed by a second IRT test against an IRT/DNA analysis. By using a Monte Carlo simulation program, variation in the model parameters for counts at various nodes of the decision trees, as well as for costs, are included and applied to fictional cohorts of 100 000 newborns. The outcome measures included the numbers of newborns given a diagnosis of cystic fibrosis and costs of screening strategy at each branch and cost per newborn.
RESULTS:Simulations revealed a substantial number of potential missed diagnoses for the IRT/IRT system versus IRT/DNA. Although the IRT/IRT strategy with commonly used cutoff values offers an average overall cost savings of $2.30 per newborn, a breakdown of costs by societal segments demonstrated higher out-of-pocket costs for families. Two potential system failures causing delayed diagnoses were identified relating to the screening protocols and the follow-up system.
CONCLUSIONS:The IRT/IRT screening algorithm reduces the costs to laboratories and insurance companies but has more system failures. IRT/DNA offers other advantages, including fewer delayed diagnoses and lower out-of-pocket costs to families. Pediatrics 2012;129:e339-e347 AUTHORS:
“…The screening panel should include more rather than less mutations to avoid disproportionate number of missed screened cases (false negatives) in USA ethnic minorities. In order to capture a high percentage of cases involving ethnic minorities, full sequencing of the CFTR gene is required (Ross, 2008). Kammesheidt et al (2006) have shown the feasibility of temporal temperature gradient electrophoresis-based full sequence analysis and targeted sequencing from DNA in newborn blood specimens which can increase the identification of mutations in ethnic minorities.…”
Section: Irt/dna and Irt/dna/irt Protocols In Neonatal Screeningmentioning
confidence: 99%
“…Children whose sample has at least one mutation or whose sample has a very high initial IRT measurement are asked to provide a second sample for a second IRT measurement. Only those with an elevated IRT levels on the second sample undergo sweat testing (Ross, 2008). Corbetta et al (2002) assessed the performance of IRT/DNA/IRT based on IRT followed by direct CFTR gene analysis (based on a panel of up to 31 mutations) in hypertrypsinaemic newborn infants in Italy.…”
Section: Irt/dna and Irt/dna/irt Protocols In Neonatal Screeningmentioning
confidence: 99%
“…The main benefits of the IRT/DNA/IRT protocol over a single IRT/DNA methodology is that they reduce the number of children who need to undergo sweat testing, and the number of parents who are informed of their child's carrier status and need genetic counselling (Ross, 2008). However, the main disadvantage of the IRT/DNA/IRT protocol is its complexity and the anxiety generated for families who have to wait for the result of a second IRT (McCormick et al, 2002).…”
Section: Irt/dna and Irt/dna/irt Protocols In Neonatal Screeningmentioning
confidence: 99%
“…Some ethnic minority children with rare mutations may still be detected to the extent that the IRT/DNA/IRT method employs the safeguard of recommending sweat testing of children with a very high IRT measurement even if no mutations are detected. Modeling in different ethnic communities using different DNA panels would be necessary to determine whether the costs of the extra laboratory testing are outweighed by the benefits achieved by reducing the number of children who need to undergo sweat testing and genetic counselling (Ross, 2008).…”
Section: Irt/dna and Irt/dna/irt Protocols In Neonatal Screeningmentioning
Fifty years after the advent of state newborn screening (NBS) programs for a metabolic condition, there is evidence that the decision to mandate universal screening can reduce health disparities. When in-hospital screening for phenylketonuria began in the early 1960s, most hospitals simply added the procedure to the list of routine clinical practices for newborns, such as giving vitamin K. For a variety of reasons, including fear of missed cases, advocates managed to get state governments involved. By the late 1960s, most states required screening of all or almost all newborns. 1 Although these advocates and state legislators did not describe their actions as addressing population-level health disparities, they believed that it was unfair for some infants to bear the consequences of late diagnosis of phenylketonuria simply because they were born in a hospital that did not provide the test. By making NBS for phenylketonuria universally available, they reduced the impact of unequal access to a new and effective therapeutic intervention-one cause of health disparities based on income, location, education, and race/ethnicity. 2 Recent reports from states that perform NBS for severe combined immune deficiency (SCID) confirm this hypothesis. This is a rare condition that is typically diagnosed when an infant or young child has 1 or more unusual infections. Bone marrow transplantation is highly effective to treat this condition, and outcomes are better when performed in the newborn period. In 2010 SCID was added to the Recommended Uniform Screening Panel (RUSP), the list of conditions recommended for NBS by the US Secretary of Health and Human Services. Early reports of NBS for SCID have revealed that SCID is much more common in black and Hispanic individuals than previously suggested by clinical referrals to
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