Newborn Screening and Treatment of Phenylketonuria: Projected Health Outcomes and Cost-Effectiveness

Abstract

The objective of this study was to evaluate the cost-effectiveness of newborn screening and treatment for phenylketonuria (PKU) in the context of new data on adherence to recommended diet treatment and a newly available drug treatment (sapropterin dihydrochloride). A computer simulation model was developed to project outcomes for a hypothetical cohort of newborns with PKU. Four strategies were compared: (1) clinical identification (CI) with diet treatment; (2) newborn screening (NBS) with diet treatment; (3) CI with diet and medication (sapropterin dihydrochloride); and (4) NBS with diet and medication. Data sources included published literature, primary data, and expert opinion. From a societal perspective, newborn screening with diet treatment had an incremental cost-effectiveness ratio of $6400/QALY compared to clinical identification with diet treatment. Adding medication to NBS with diet treatment resulted in an incremental cost-effectiveness ratio of more than $16,000,000/QALY. Uncertainty analyses did not substantially alter the cost-effectiveness results. Newborn screening for PKU with diet treatment yields a cost-effectiveness ratio lower than many other recommended childhood prevention programs even if adherence is lower than previously assumed. Adding medication yields cost-effectiveness results unlikely to be considered favorable. Future research should consider conditions under which sapropterin dihydrochloride would be more economically attractive.

A Review of Disparities and Unmet Newborn Screening Needs over 33 Years in a Cohort of Mexican Patients with Inborn Errors of Intermediary Metabolism

“…Mortality by disease was also assessed for all illnesses. An analysis excluding conditions with the same mortality rate as that observed in the general population, such as HPA/PKU or 3-methylcronyl-CoA carboxylase deficiency (MCC) [ 33 , 34 ], was performed to avoid bias. Kaplan‒Meier survival curves were generated for disorders with the highest mortality rates.…”

How longitudinal observational studies can guide screening strategy for rare diseases

“…Furthermore, different treatment options and adherence rates need to be considered in economical evaluations. For instance, a recent study demonstrated that NBS for PKU was cost‐effective with low phenylalanine diet even if adherence rates were lower than previously assumed, but not with sapropterin dihydrochloride medication 119 . In analogy, the implementation of highly costly gene therapies and other advanced therapy medicinal products for (future) NBS target diseases will require a careful evaluation of economic consequences from a societal perspective, particularly if other therapies are already available.…”

“…For instance, a recent study demonstrated that NBS for PKU was cost-effective with low phenylalanine diet even if adherence rates were lower than previously assumed, but not with sapropterin dihydrochloride medication. 119 In analogy, the implementation of highly costly gene therapies and other advanced therapy medicinal products for (future) NBS target diseases will require a careful evaluation of economic consequences from a societal perspective, particularly if other therapies are already available. In conclusion, fair evaluation of NBS programs is a true challenge and can succeed only if (1) NBS is understood as a complex system, (2) meaningful indicators and endpoints are chosen, (3) robust clinical health data from NBS and pre-NBS cohorts are available, and (4) different perspectives are integrated into the analysis.…”

Hyperphenylalaninemias genotyping: Results of over 60 years of history in Lombardy, Italy

“…Variants in DNAJC12 gene have also been recently described as causing possible hyperphenylalaninemia 14–16 . Usually, patients with HPA are detected through newborn screening for phenylketonuria (PKU) and defined as affected by milder to more severe forms (PKU/HPA) depending on serum phenylalanine levels, 3 which is due to a remarkable allelic variability accounting for different related patterns of phenylalanine hydroxylase residual enzymatic activity (EC 1.14.16.1) 4–6 . Prompt and correct identification/prediction of the hyperphenylalaninemia subtype represent the most important task on a clinical standpoint in order to set appropriate treatments, including in most cases a tailor‐made dietary intervention according to patients' needs, metabolic control and Phe tolerance 7,8 .…”