Insurance Reimbursement for Special Foods and Phenylalanine Levels in Patients With PKU in China.

Importance: Recent changes in China's social medical insurance reimbursement policy have impacted the financial burden of patients with phenylketonuria (PKU) for special foods. However, whether this policy change is associated with their blood phenylalanine (PHE) concentration is unclear. Objective: To investigate the association between the reimbursement policy and blood PHE concentration in patients with PKU. Design, Setting, and Participants: This cohort study measured the blood PHE concentrations of 167 patients with PKU across 4 newborn screening centers in China from January 2018 to December 2021. The reimbursement policy for special foods for patients with PKU at 2 centers was canceled in 2019 and restored from 2020 onwards. In contrast, the other 2 centers consistently implemented the policy. Data were analyzed from September 10 to December 6, 2023. Exposures: The implementation and cancelation of the reimbursement policy for special foods of patients with PKU. Main Outcomes and Measures: The blood PHE concentration was regularly measured from 2018 to 2021. A 1-sided Z test was used to compare the mean of the blood PHE concentration between different years. Results: Among 167 patients with PKU (mean [SD] age, 84.4 [48.3] months; 87 males [52.1%]), a total of 4285 measurements of their blood PHE concentration were collected from 2018 to 2021. For patients at the center that canceled the reimbursement policy in 2019, the mean (SD) of the blood PHE concentrations in 2019 was 5.95 (5.73) mg/dL, significantly higher than 4.84 (4.11) mg/dL in 2018 (P < .001), 5.06 (5.21) mg/dL in 2020 (P = .006), and 4.77 (4.04) mg/dL in 2021 (P < .001). Similarly, for patients at the other center that canceled the policy in 2019, the mean (SD) of the blood PHE concentrations in 2019 was 5.95 (3.43) mg/dL, significantly higher than 5.34 (3.45) mg/dL in 2018 (P = .03), 5.13 (3.15) mg/dL in 2020 (P = .003), and 5.39 (3.46) mg/dL in 2021 (P = .03). On the contrary, no significant difference was observed between any of the years for patients at the 2 centers that consistently implemented the policy. Conclusions and Relevance: In this cohort study of patients with PKU from multiple centers, the implementation of the reimbursement policy for special foods was associated with controlling the blood PHE concentration. Special foods expenditure for patients with PKU should be included in the scope of long-term social medical insurance reimbursement.

Comparison of Cost Analysis in Patients with Tetrahydrobiopterin-Responsive and Non-Responsive Phenylketonuria in Turkey.

Phenylketonuria is an inherited metabolic disorder that leads to neurobehavioral dysfunction. The main treatment is a low-phenylalanine diet and/or the cofactor tetrahydrobiopterin. Regular outpatient follow-up care and measurement of the phenylalanine levels in the blood are required. We aimed to analyze the economic burden of phenylketonuria on families and the state. The patients with phenylketonuria were divided into three groups according to their treatment: a low-phenylalanine diet group (n = 50), a tetrahydrobiopterin group (n = 44), and a group taking tetrahydrobiopterin together with the diet (n = 25). A comparative cost analysis was carried out. The annual economic burden to the state was calculated to average EUR 18,801 ± 15,345 and was lowest in the diet group, then in the tetrahydrobiopterin group, and highest in the tetrahydrobiopterin + diet group (p < 0.001). Out-of-pocket costs amounted to EUR 1531 ± 1173 per year, and indirect losses averaged EUR 2125 ± 1930 per year for all families. The economic loss was significantly lower in the families taking tetrahydrobiopterin than in the other groups (p = 0.001). The combined use of medical nutrition and BH4 treatments has been shown to increase the economic burden on the state. Reimbursing low-protein products and increasing the number of patients eligible for financial allowances may reduce the economic burden on families.

Prevalence, characteristics, and costs of diagnosed homocystinuria, elevated homocysteine, and phenylketonuria in the United States: a retrospective claims-based comparison.

BACKGROUND: Classical homocystinuria (HCU), an inborn error of homocysteine metabolism, has previously been estimated to affect approximately 1 in 100,000-200,000 people in the United States (US). HCU is poorly detected by newborn screening, resulting in underestimates of its prevalence. This study compared characteristics, healthcare use and costs, and projected prevalence between patients with diagnosed HCU, elevated total homocysteine (tHcy), and diagnosed phenylketonuria (PKU). METHODS: Patients in the MarketScan® Research Databases were identified with strictly-defined HCU (> 2 diagnoses, including 1 ICD-10), broadly-defined HCU (> 1 ICD-10), elevated tHcy (> 20 µmol/L) without an HCU diagnosis, or > 1 ICD-9/ICD-10 PKU diagnosis during 1/1/2010-12/31/2016 (first qualifying claim = index). Demographics and healthcare utilization and costs per patient per month (PPPM) were compared between all cohorts, frequencies of comorbidities and medications were compared between HCU and elevated tHcy patients, and healthcare provider types were assessed among HCU patients. The prevalence of patients meeting each cohort definition was projected to the United States (US) population. RESULTS: Patients with strictly-defined (N = 2450) and broadly-defined (N = 6613) HCU, and with elevated tHcy (N = 2017), were significantly older than PKU patients (N = 5120) (57 vs. 56 vs. 53 vs. 18 years; p < 0.05). Vitamin D deficiency, hyperlipidemia, folic acid/B vitamins, and lipid-lowering medications, among others, were more common among diagnosed HCU patients vs. those with elevated tHcy (all p < 0.05). Rates of healthcare utilization were generally higher among HCU and elevated tHcy patients, compared to PKU, though total healthcare costs were similar between groups. Most HCU patients (~ 38%) received their index diagnosis from a primary care physician; very few (~ 1%) had any claim from a geneticist during their enrollment. The age-adjusted national prevalence of HCU was projected at 31,162 (95% CI: 30,411 - 31,913; ~ 1 in 10,000 of the US population) using the broad definition. CONCLUSIONS: The actual prevalence of HCU may be > 10 times prior estimates, at 1 in 10,000 in the US, and this study suggests that HCU is not being diagnosed until later in life. Improvements to newborn screening, detection in young children, and physician education regarding HCU among patients may be necessary to alleviate the burden of this genetic disease.

Characteristics, comorbidities, and use of healthcare resources of patients with phenylketonuria: a population-based study.

Background: Phenylketonuria is a well-known disease, yet the characteristics of the affected population and their use of healthcare resources have not been comprehensively evaluated. Patient characteristics and use of resources are subjects of interest for most governments, especially for a disease included in newborn screening programs. Objective: The aim of this study was to determine characteristics and use of healthcare resources of patients with phenylketonuria in the region of Catalonia. Methods: Records of 289 patients admitted with phenylketonuria between 2007 and 2017 were extracted from the PADRIS database that includes admission data from primary care centers, hospitals (inpatient and outpatient care), extended care facilities, and mental health centers. Results: The patient population was composed of 140 male patients and 149 female patients, and 102 patients were registered via newborn screening during the study period. Patients were admitted on average 2.19 times per year, mostly into primary care centers which concentrated the largest portion of direct medical expenses. Similar percentages of urgent and scheduled admissions were registered both in primary care and hospitals. Annual direct medical cost of treating patients with phenylketonuria was €667 per patient. Finally, 66.80% of the patients suffered from chronic conditions affecting two or more systems, likely to correspond to a wide variety of conditions. Conclusions: Altogether, phenylketonuria patient demographics and direct medical costs in Catalonia have been revised. Patients diagnosed with phenylketonuria appeared 1.3-times more likely to suffer from chronic conditions in distinct organ systems, which is expected to have an effect on their use of healthcare resources. These results support the need to adapt and improve the healthcare system, taking multimorbidity into consideration in an effort to control the medical expenses derived.

Admissions and Cost of Hospitalisation of Phenylketonuria: Spanish Claims Database Analysis.

BACKGROUND: Phenylketonuria is a well-known rare disease included in the neonatal screening of many countries. Therefore, there are few published data on the admissions and costs of phenylketonuria in Spain. OBJECTIVE: The objective of this study was to assess the number of admissions and the economic burden of phenylketonuria in Spain. METHODS: Patients with phenylketonuria were identified from a Spanish database containing data from public and private healthcare centres from 1997 to 2015. The parameters obtained were characteristics of the patients, type of admissions, readmissions, discharges, length of stay, medical service, annual number of visits, annual number of patients, visit-associated costs and patient-associated costs. RESULTS: Five hundred and ninety-four patients with phenylketonuria were identified: 48.32% were male with a mean (standard deviation) age of 4.50 (10.23) years. The hospital admissions were divided into emergency visits (55.94%) and scheduled visits (43.92%). The majority of patients were discharged home (98.86%). The mean (standard deviation) duration of stay was 4.04 (4.98) days. The number of admissions per year ranged between 13 and 88, with an average of 1.18 admissions per patient per year. Finally, the mean cost per visit increased from €1064.91 to €3709.40, and the mean cost per patient increased from €1818.90 to €4239.32 from 1999 to 2015. CONCLUSIONS: The access to economic and social data on phenylketonuria in Spain has been updated. The number of admissions in Spain between 1997 and 2015 and healthcare costs between 1999 and 2015 were calculated. There were 24 admissions as a result of a phenylketonuria diagnosis in 2015 and the mean healthcare cost per patient was €4239.32. This information can help to adapt and improve each healthcare system to take into consideration rare diseases.

Prevalence of comorbid conditions among adult patients diagnosed with phenylketonuria.

BACKGROUND: Phenylalanine hydroxylase (PAH) deficiency, otherwise known as phenylketonuria (PKU), is an inborn error of metabolism that requires treatment to be initiated in the newborn period and continued throughout life. Due to the challenges of treatment adherence and the resulting cumulative effects of high and labile blood phenylalanine, PKU exerts a significant burden of disease. Retrospective studies using large databases allow for unique perspectives on comorbidities associated with rare diseases. An evaluation of comorbidities across various organ systems is warranted to understand the disease burden in adult patients. OBJECTIVES: The aim of this insurance claim-based observational study was to assess the prevalence of comorbid conditions across various organ systems (e.g. dermatological, renal, respiratory, gastrointestinal, hematological, and others) among adult PKU patients compared with matched controls from the general population. METHODS: This retrospective, case-controlled study selected patients from United States insurance claims databases from 1998 to 2014 using International Classification of Diseases, Ninth Revision (ICD-9) codes for diagnosis of PKU. The date of first diagnosis during the study period was index date and this was not necessarily the first time the patient was diagnosed with PKU. Cases were matched with a 1:5 ratio with general population (non-PKU controls) on age, sex, race, geographic location, duration of time in the database and insurance type. Prevalence and prevalence ratio (PR) calculations for comorbidities across various organ systems among adults (≥20 years old) with PKU were compared with the general population (non-PKU controls). The conditions were selected based on complications associated with PKU and feedback from clinicians treating PKU patients. RESULTS: A total of 3691 PKU patients and 18,455 matched, non-PKU controls were selected, with an average age of 35 years. The mean healthcare costs incurred by the PKU patients during baseline, were approximately 4 times that of the controls ($4141 vs $1283; p < .0001). The prevalence rates of comorbidities across various organ systems during the follow-up period were significantly higher for those with PKU than in the control group. After adjusting for baseline characteristics, the adjusted prevalence ratios (PR) of 15 conditions studied (asthma, alopecia, urticaria, gallbladder disease, rhinitis, esophageal disorders, anemia, overweight, GERD, eczema, renal insufficiency, osteoporosis, gastritis/esophagitis and kidney calculus) were all above PR = 1.24 and significantly higher for the PKU cohort (p ≤ .001). The highest adjusted PR were for renal insufficiency with hypertension (PR [95% CI]: 2.20 [1.60-3.00]; p < .0001) and overweight (PR [95%CI]: 2.06 [1.85-2.30]; p < .0001). CONCLUSIONS: The prevalence of selected comorbidities across several organ systems is significantly higher among PKU patients than for general population controls. Regular screening for common co-morbidities may be warranted as part of PKU management.

Dietary patterns, cost and compliance with low-protein diet of phenylketonuria and other inherited metabolic diseases.

BACKGROUND/OBJECTIVES: Phenylketonuria (PKU) and several other inherited metabolic diseases (IMD) require a lifelong low-protein diet (LPD), otherwise they lead to many health complications. LPDs, however, carry a significant economic burden for patients and their families. The objective of this study was to explore the costs of low-protein foods (LPFs) necessary for LPD as well as dietary patterns and compliance towards an LPD. SUBJECTS/METHODS: A detailed questionnaire was created in cooperation with National Association of PKU and other IMD (NSPKU), and consequently sent to all NSPKU members treated with an LPD (n=303). A total of 184 respondents from the Czech Republic were included in the study (174 had PKU, 10 had other IMD). RESULTS: The average daily consumption of LPF was equal to 411.7 g (PKU) and 345.6 g (other IMD), which corresponds to energy value of 5558 kJ and 4438 kJ, respectively, per patient per day. Patients mostly consumed low-protein flour (≈30% of energy intake), pasta (≈18%), basic pastry (≈15%) and sweets (≈10%). The average monthly costs of LPDs were equal to [euro ]130 (PKU) and [euro ]129 (other IMD) per patient per month. The compliance with LPD was decreasing with increasing age (P<0.0001). CONCLUSIONS: This is the largest study examining costs and dietary patterns of LPDs in patients with PKU and the first study of this kind in other IMD patients requiring an LPD. The study clearly showed that an LPD carries a very high economic burden for families, which may lead to less LPD compliance and potential severe health consequences.

Household financial burden of phenylketonuria and its impact on treatment in China: a cross-sectional study.

BACKGROUND: Phenylketonuria (PKU) is a rare inborn disease, which, untreated, leading to severe neurobehavioral dysfunction. Considering its complexity, the management of PKU may bring a formidable economic burden to parents and caregivers. It is still unknown what the out-of-pocket expenses are for a patient with PKU in China. This paper explores the household financial burden of classical PKU and its impact on Chinese families in a quantitative manner for the first time. METHODS: A non-interventional and observational study was conducted at the China-Japan Friendship Hospital, one of the national centers for inherited metabolic disorders in China. The medical and non-medical household financial burdens were consolidated into a questionnaire to evaluate the out-of-pocket costs (OOPCs) of PKU treatment and follow-up. FINDINGS: The total OOPCs were USD$3766.1 (0y), USD$3795.2 (1-2 ys), USD$4657.7 (3-4 ys), USD$5979.9 (5-8 ys), and USD$5588.7 (9 ys and older) for PKU patients of different age groups. The median economic burden of classical PKU was 75.0 % of total annual family income (range 1.0-779.1 %), and 94.4 % of the families exceeding the threshold considered as catastrophic expenditure. There was a negative correlation between the financial burden and the proportion of time when Phe concentrations were in the desired target range (120-250 µmol/L) in 0-4-ys group (r = -0.474, p = 0.026). CONCLUSIONS: The management of PKU is associated with a severe financial burden on patients' families, which may lead to insufficient treatment or variation of blood Phe concentration. The current reimbursement policies are as yet inadequate. A national reimbursement system targeting treatment practices for PKU patients and other rare diseases across China is imperative.

An Economic Evaluation of Neonatal Screening for Inborn Errors of Metabolism Using Tandem Mass Spectrometry in Thailand.

BACKGROUND: Inborn errors of metabolism (IEM) are a rare group of genetic diseases which can lead to several serious long-term complications in newborns. In order to address these issues as early as possible, a process called tandem mass spectrometry (MS/MS) can be used as it allows for rapid and simultaneous detection of the diseases. This analysis was performed to determine whether newborn screening by MS/MS is cost-effective in Thailand. METHOD: A cost-utility analysis comprising a decision-tree and Markov model was used to estimate the cost in Thai baht (THB) and health outcomes in life-years (LYs) and quality-adjusted life year (QALYs) presented as an incremental cost-effectiveness ratio (ICER). The results were also adjusted to international dollars (I$) using purchasing power parities (PPP) (1 I$ = 17.79 THB for the year 2013). The comparisons were between 1) an expanded neonatal screening programme using MS/MS screening for six prioritised diseases: phenylketonuria (PKU); isovaleric acidemia (IVA); methylmalonic acidemia (MMA); propionic acidemia (PA); maple syrup urine disease (MSUD); and multiple carboxylase deficiency (MCD); and 2) the current practice that is existing PKU screening. A comparison of the outcome and cost of treatment before and after clinical presentations were also analysed to illustrate the potential benefit of early treatment for affected children. A budget impact analysis was conducted to illustrate the cost of implementing the programme for 10 years. RESULTS: The ICER of neonatal screening using MS/MS amounted to 1,043,331 THB per QALY gained (58,647 I$ per QALY gained). The potential benefits of early detection compared with late detection yielded significant results for PKU, IVA, MSUD, and MCD patients. The budget impact analysis indicated that the implementation cost of the programme was expected at approximately 2,700 million THB (152 million I$) over 10 years. CONCLUSION: At the current ceiling threshold, neonatal screening using MS/MS in the Thai context is not cost-effective. However, the treatment of patients who were detected early for PKU, IVA, MSUD, and MCD, are considered favourable. The budget impact analysis suggests that the implementation of the programme will incur considerable expenses under limited resources. A long-term epidemiological study on the incidence of IEM in Thailand is strongly recommended to ascertain the magnitude of problem.

Cost-benefit analysis of hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency: for consideration of expanded newborn screening in Hong Kong.

OBJECTIVES: To evaluate the cost-benefit of implementing an expanded newborn screening programme for hyperphenylalaninemias due to 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency in Hong Kong. SETTING: Regional public hospitals in Hong Kong providing care for cases of inborn errors of metabolism. METHODS: Implementational and operational costs of a new expanded mass spectrometry-based newborn screening programme were estimated. Data on various medical expenditures for the mild and severe phenotypic subtypes were gathered from a case cohort diagnosed with PTPS deficiency from 2001 to 2009. Local incidence from a previously published study was used. RESULTS: Implementation and operational costs of an expanded newborn screening programme in Hong Kong were estimated at HKD 10,473,848 (USD 1,342,801) annually. Assuming a birthrate of 50,000 per year and an incidence of 1 in 29,542 live births, the medical costs and adjusted loss of workforce per year would be HKD 20,773,207 (USD 2,663,232). Overall the annual savings from implementing the programme would be HKD 9,632,750 (USD 1,234,968). CONCLUSIONS: Our estimates show that implementation of an expanded newborn screening programme in Hong Kong is cost-effective, with a significant annual saving for public expenditure.

The time consuming nature of phenylketonuria: a cross-sectional study investigating time burden and costs of phenylketonuria in the Netherlands.

BACKGROUND: Phenylketonuria (PKU) is a rare inborn error of metabolism that affects the ability of patients to metabolise phenylalanine (Phe). Lifelong management of blood Phe levels is required in order to avoid the complications associated with PKU. This constitutes a severely protein restricted diet, and regular monitoring of Phe levels. Management of PKU may be costly and time-consuming for adult patients or caregivers of PKU-affected children. A cross-sectional study was performed with patients or their caregivers in the Netherlands to gain insight into the personal time burden and cost of living with PKU. METHODS: A systematic literature review was performed to identify all aspects of PKU management that may pose a financial or time burden on patients or caregivers. Findings were confirmed through interviews with PKU experts and feedback from patients and caregivers, and consolidated into a questionnaire that aimed to evaluate the impact of each of these factors. Early and continuously treated adult patients and caregivers from seven metabolic centres were recruited to complete the questionnaire online. RESULTS: 22 adult patients and 24 caregivers participated in the study. Managing a Phe-restricted diet represented an extra time burden of 1 h and 24 min for caregivers and 30 min for adult patients per day. Caregivers reported a significantly higher time burden than adult patients. The median total out-of-pocket cost (OOPC) for patients was €604 annually, with 99% of expenditure on low-protein food products. Greater disease severity was significantly associated with increased OOPC and time burden for both adult patients and caregivers. CONCLUSIONS: Management of PKU is associated with a considerable time burden for both caregivers of children with PKU and adult patients. Caregivers of PKU-affected children reported a significantly higher time burden than adult patients. The OOPC of caregivers and patients was mainly driven by the expenditure on low protein food.

Costs and outcomes over 36 years of patients with phenylketonuria who do and do not remain on a phenylalanine-restricted diet.

BACKGROUND: To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. METHOD: A computer-based model was constructed depicting the management of PKU patients over the first 36 years of their life, derived from patients suffering from this metabolic disorder in The Health Improvement Network database (a nationally representative database of patients registered with general practitioners in the UK). The model was used to estimate the incidence of co-morbidities and the levels of healthcare resource use and corresponding costs over the 36 years. RESULTS: Patients who remained on a phenylalanine-restricted diet accounted for 38% of the cohort. Forty-seven per cent of patients discontinued their phenylalanine-restricted diet between 15 and 25 years of age. Of these, 73% remained off diet and 27% restarted a restricted diet at a mean 30 years of age. Fifteen per cent of the cohort had untreated PKU. Eleven per cent of patients who remained on a phenylalanine-restricted diet for 36 years received the optimum amount of prescribed amino acid supplements. Patients had a mean 12 general practitioner visits per year and one hospital outpatient visit annually, but phenylalanine levels were only measured once every 18 to 24 months. The mean NHS cost (at 2007/08 prices) of managing a PKU sufferer over the first 36 years of their life was estimated to range between £21 000 and £149 000, depending on the amount of prescribed nutrition they received. CONCLUSION: The findings suggest that the majority of patients with PKU were under-treated. The NHS cost of patient management should not be an obstacle to encouraging patients to remain on a restricted diet until further information becomes available about the long-term clinical impact of stopping such a diet. Nevertheless, patients require counselling and managed follow up regardless of the choices they make about their diet.

[Risk-sharing scheme in Israel--Kuvan as an allegory].

Healthcare systems worldwide are dealing with the uncertainty characterizing new and expensive health technoLogies, particularly aspects involving drug effectiveness and the extent and doses required for utilization. Reducing this uncertainty can be achieved mainly by using either coverage with evidence development methods or risk-sharing schemes (RSS). In 2011, the first phenylketonuria (PKU) risk-sharing scheme was set up in Israel, through the public funding health services updating process. This was done in order to ensure that people with PKU could access PKU sole treatment--sapropterin dihydrochloride, Kuvan. The apparent effectiveness of the treatment, on one hand, and the uncertainty regarding the number of patients and average treatment dosage, on the other hand, dictated the RRS. This scheme determined a ceiling number of tablets to be funded by the insurer, above this ceiling the manufacturer would finance Kuvan. Furthermore, it was agreed that after 3 years Kuvan would be brought to the public committee for updating reimbursement decisions. It is inevitable that risk sharing and conditional coverage agreements will become a common practice in the reimbursement process in the future. This will allow competent authorities and pharmaceutical companies to build clinical experience and other required data with medicines which might normally not be eLigible for reimbursement. Before it becomes the common practice in Israel, the RSS for Kuvan, process and outcomes, should be monitored and analyzed by the Ministry of Health, to ensure patients access to treatment, the effective collection of the research data and the effective interaction between Israel's four health funds and the manufacturer.

Cultural aspects in the management of inborn errors of metabolism.

European Health Care Systems have not yet accommodated both previous and current migration waves. Children from immigrant families, especially children with chronic conditions, are particularly affected from the shortcomings in medical care. One condition, phenylketonuria (PKU), is an inborn error of metabolism (IEM) which results in intellectual disability unless treated with a lifelong phenylalanine (Phe) restricted diet. In our PKU clinic, patients from families who previously had emmigrated from the geographic area of Turkey to Austria, exhibited worse blood Phe control and cognitive development than comparable patients from native Austrian families. Using structured and semi-structured interviews, questionnaires, and illness narratives, we identified language, psychosocial, economic, educational and cultural barriers as factors influencing adherence to treatment. Our findings led us to conclude that access to interpreter services, exploration of the socio-cultural background and of family ecology, as well as bi-directional communication and medical decision making according to the "best interest of the child" principle, may improve outcomes in patients requiring complex treatment and care.

Diet in phenylketonuria: a snapshot of special dietary costs and reimbursement systems in 10 international centers.

BACKGROUND AND AIMS: To gather exploratory data on the costs and reimbursement of special dietary foods used in the management of phenylketonuria (PKU) from ten international specialist PKU centers. METHODS: Experts from each center provided data on retail costs of the three most frequently used phenylalanine-free protein substitutes and low-protein foods at their center; reimbursement of protein substitutes and low-protein foods; and state monetary benefits provided to PKU patients. RESULTS: The mean annual cost of protein substitutes across 4 age groups (2 y, 8 y, 15 y and adults) ranged from €4273 to €21,590 per patient. The cost of low-protein products also differed; the mean cost of low-protein bread varied from €0.04 to €1.60 per 100 kcal. All protein substitutes were either fully reimbursed or covered by health insurance. However, reimbursement for low-protein products varied and state benefits differed between centers. CONCLUSIONS: The variation in the cost and reimbursement of diet therapy and the level of additional state benefits for PKU patients demonstrates the large difference in expenditure on and access to PKU dietary products. This highlights the inequality between healthcare systems and access to special dietary products for people with PKU, ultimately leading to patients in some countries receiving better care than others.

Cost effectiveness of establishing a neonatal screening programme for phenylketonuria in Libya.

BACKGROUND: Inborn errors of metabolism (IEM) are a significant cause of morbidity and mortality in North Africa and the Middle East. With the evident success of neighbouring countries in initiating neonatal screening for IEM, the Libyan Authorities are now considering introducing neonatal screening for phenylketonuria (PKU) in Libya in the first instance, with the prospect of expanding the programme to cover other IEM in the future. OBJECTIVE: To estimate the cost effectiveness of neonatal screening for PKU compared with no neonatal screening in Libya. METHODS: A decision model was constructed to estimate the cost effectiveness of neonatal screening for PKU, from the perspective of Libyan society. Healthcare resource use and other input parameters were based on expert opinion. RESULTS: The expected discounted cost to Libyan society of screening over 15 years and managing ∼374 patients with detected PKU over their lifetime was estimated to be $US213.6 (95% CI 211.9, 214.3) million (year 2007-8 values). The current expected discounted cost of managing these same PKU patients over their lifetime as a result of not screening was estimated to be $US321.2 (95% CI 318.0, 322.7) million. Hence, screening would save Libyan society $US107.6 (95% CI 105.5, 109.1) million over the lifetime of PKU patients and lead to an additional 6947 life-years (95% CI 6837, 7056). The expected cost per undiscounted life-year gained was estimated to be -$US15,500 (95% CI -16,600, 1100). There would be a 90% return on investment in the screening programme since society would gain $US1.9 for every $US1 invested. Probabilistic sensitivity analysis demonstrated that the screening programme has a 0.95 probability of being cost effective even at a willingness-to-pay threshold of $US4000 per life-year gained. CONCLUSIONS: Within the model's limitations, neonatal screening for PKU appears to offer Libyan society a strategy that is cost effective compared with no neonatal screening.

Phenylketonuria management from an European perspective: a commentary.

Phenylketonuria is discussed from an European perspective, addressing the need of common definitions of terms commonly used, the need of a world-wide guideline on the diagnosis and treatment of phenylketonuria, the differences between existing European guidelines, and day-to-day care, further directives for the near future, and changing the concept from compliance to concordance, in which patients have a more clearly defined responsibility.

[Financial justification of investments into special diet for patients with phenylketonuria].

INTRODUCTION: Phenylketonuria is a genetic disorder of metabolism of amino acid phenylalanine, which results in the absence of phenylalanine hydroxylase, an enzyme that catalyzes the conversion of phenylalanine into tyrosine. It is an autosomal recessive disorder. Screening for phenylketonuria in Voivodina started in 2003. Screening data are shown in this paper. Treatment of phenylketonuria is based on a strict, life long, low protein diet with the controlled phenylalanine intake. Diet must start early, in the first weeks of life. The aim of the diet is to reduce natural protein intake and to cover protein needs by special phenylalanine free protein products. There is a big variety of formulas found available on the market for treatment of phenylketonuria. All of them are free of phenylalanine and very expensive. DISCUSSION: Till May 2005 there was no refunding for these products in our country. According to the decision made by the Provincial Secretariat for Health, providing all children with protein supplement in their first year of life started at the Institute for Child and Youth Healthcare. In September 2007 the Republic Fund for Health Insurance started to refund protein supplement and low protein products for all children up to the age of 18 years. CONCLUSION: Besides all technical and organizational difficulties associated with this work, this paper also shows how, by good prevention of phenylketonuria complications, much more money can be saved than it has been invested, even in countries with low amounts of money allocated for this purpose (in absolute figures).