IMD WATCH
THE COSTS OF A SPECIAL DIET In a health service concerned with limited resources, cost effectiveness is a consideration, as well as clinical effectiveness. This article will consider ‘the critical requirements’ for a very low-protein diet in inherited metabolic disease (IMD), specifically highlighting the diet in PKU. This includes outlining why this investment is needed and why an understanding of the cost is required. There are a few inborn errors of metabolism for which treatment is a very low-protein diet supplemented with a protein substitute or replacement. PKU is one of these conditions. Patients are required to consume specialist prescription-only protein substitutes and low phenylalanine (Phe) foods. Treatment is lifelong.1,2 Women with PKU who are pregnant, or who are planning a pregnancy, need to take particular care to manage their condition, as high Phe levels can damage their unborn child. There are other IMDs for which a low-protein diet is indicated, such as homocystinuria (HCU), tyrosinemia and maple syrup urine disease (MSUD). Patients with IMDs on ultra-lowprotein diets are supervised and monitored by Specialist Centres across the UK, commissioned centrally.3 The specialist dietary products are prescription only, are not available commercially and are approved by the Advisory Committee on Borderline Substances (ACBS). Patients require a regular and consistent supply of a large number of prescribed products as part of the synthetic diet, otherwise metabolic control is compromised. There are an estimated 10,000 patients attending metabolic clinics. We do not know how many patients are on a very low-protein diet requiring prescribable products, but it is estimated that, in the UK, 2500 patients with PKU are on a diet and a further 60 to 70 new diagnoses of PKU occur every year.
The rationale of PKU treatment is to achieve strict blood control to prevent any brain damage or impairment in children4-7 and avoid the reduced life chances via reductions in IQ. When treatment is compromised, it is clear that children with PKU have lower IQs than their non-PKU siblings.8,9 Historically, the diet was thought necessary only for children, since the evidence base on PKU in adulthood was ‘work in progress’. The accumulated evidence is now clear that adults with uncontrolled blood Phe levels are compromised in their executive function, their mental health and their psychosocial outcomes.10-14 There is international agreement and recommendation that lifelong treatment is essential.1,2 PRESCRIPTIONS PART 1 - PROTEIN SUBSTITUTE USE IN PKU
Protein substitutes are the lynchpin of a very low Phe diet, as the patients’ protein/nitrogen and micronutrient requirements must be met.15,16 The products should be taken at least three times daily, every day of a patient’s life following diagnosis and, thus, a range of palatable products are essential.17,18 A reminder: the nutrients being substituted are macro as well as micronutrients, thus, daily doses of substitutes are high, eg, 80 tablets per day for a 55kg woman. There have been considerable efforts in the last 30 years to develop these products to aid optimum safety,
Suzanne Ford, Dietary Advisor to NSPKU Suzanne Ford is a Metabolic Dietitian working with Adults at North Bristol NHS Trust and also for the National Society of Phenylketonuria (NSPKU).
Professor Anita MacDonald, OBE Consultant Dietitian in IMD, Birmingham Children's Hospital One of the UK’s top paediatric dietitians, Anita’s specialism lies with inherited metabolic disorders.
REFERENCES Please visit the Subscriber zone at NHDmag.com
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IMD WATCH Table 1: Food portions that provide 1g of protein, ie, 1 exchange/50mg phenylalanine Cow’s milk
30mL
Jacket or boiled potatoes
80g
Single cream
40mL
Roast potatoes
55g
Double cream
60mL
Chips
45g
Yoghurt
20g
Broad beans
20g
Rice - boiled
45g
Peas (fresh, frozen and tinned)
25g
Rice - raw
15g
Spring greens (boiled)
35g
Table 2: Cost of low phenylalanine diet for an adult with PKU (calculated Dec 2018) Daily requirement 60g protein equivalent from protein substitute Based on the average cost of 3 brands
Cost per annum £11,617
Weekly requirement
Daily requirement 80g protein equivalent from protein substitute Based on the average cost of 3 brands
Cost per annum £15,489
Weekly requirement
114g low-protein bread per day (800g/week)
£416
114g low-protein bread per day (800g/week)
£416
500g low-protein flour per week
£364
500g low-protein flour per week
£364
400ml low-protein milk per day (14 cartons per week)
£927
400ml low-protein milk per day (14 cartons per week)
£927
250g pasta per week
£224
250g pasta per week
£224
1 pizza base per week
£224
1 pizza base per week
£224
£265
100g sausage mix/burger mix per week
£265
100g sausage mix/burger mix per week Total cost
£14,037
tolerance, efficacy and palatability. Most protein substitute products contain micronutrients and, more recently, have added docosahexaenoic acid - for use in pregnancy as well as infants and children.19 Finally, as well as reducing protein or micronutrient deficiencies, the protein substitutes provide protection (through provision of amino acids) against high blood Phe levels by reducing catabolism and promoting anabolism. Protein substitute range and product development A wide range of protein substitutes should be available for patients with IMDs such as PKU, as it is well established that patients struggle to fully adhere to protein substitutes due to their low palatability. A patient's age-related and clinical needs must be met, eg, infancy, weaning, childhood, pregnancy, both higher and lower calorie formulae subject to growth needs.20 Pre36
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Total cost
£17,909
prepared liquid protein substitutes and formulae have some clinical advantages to powders and there is a variety of different presentations available to patients.21,22 Protein substitute choices (for people with PKU) have recently expanded to include glycomacropeptide (GMP) powders and liquids. These are reported to have high levels of patient acceptability (reduced acidity compared to amino acids and a lower osmolarity, so reduced osmolar effects on the gut). However, in some areas, GPs and CCG exceptions panels have declined to support people with PKU by declining to fund GMP products to their patients, despite much clinical evidence to support them.29-31 Future development of better protein substitutes to improve acceptability and adherence is essential for better outcomes in PKU, as is the support of prescribers for these products.
Table 3: Cost of low phenylalanine diet for children with PKU (calculated Dec 2018) 3-year-old child weighing 14kg Daily requirement 40g protein equivalent from protein substitute* Based on the average cost of 2 brands
Cost per annum £8251
Weekly requirement
7-year-old child weighing 22kg Daily requirement 50g protein equivalent from protein substitute Based on the average cost of 2 brands
Cost per annum £9526
Weekly requirement
40g low-protein bread per day (280g/week)
£145
80g low-protein bread per day (560g/week)
£290
250g low-protein flour per week
£182
500g low-protein flour per week
£364
600ml low-protein milk per day (21 cartons per week)
£1391
400ml low-protein milk per day (14 cartons per week)
£927
125g pasta per week
£112
250g pasta per week
£224
0.5 pizza base per week
£112
1 pizza base per week
£224
50g sausage mix/burger mix per week
£133
100g sausage mix/burger mix per week
£265
Total cost
£10,326
Total cost
£11,820
* Protein substitute gels/pastes are used for children usually up to four years. These are more expensive because the demand for these is smaller than for liquid protein substitutes.
PRESCRIPTIONS PART 2 - LOW-PROTEIN PRODUCTS
Specialist low-protein products are needed to provide variety and bulk to children and adults, as their products are not available in supermarkets nor in health food as glutenfree products now are. If low-protein products are used insufficiently, then energy intake is compromised and endogenous Phe is released through catabolism, or the individual is hungry and is likely to eat higher protein food choices, resulting in loss of metabolic control. Scottish research (done before gluten-free food prescription was questioned), outlines the negative experiences and obstructions which people with PKU have experienced when attempting to access prescribable low-protein products.23 It is not uncommon for patients or parents to feel humiliated and frustrated by either the system or by staff within primary care and when no food is accessible, a hungry and uncontrolled patient is the result. Table 1 illustrates the level of restrictions involved in this diet – it is not possible for most patients to maintain metabolic control without prescribable foods,24 as hunger would be overwhelming. Most of the people with PKU
recently completing an NSPKU survey,25 were prescribed fewer than 10 PKU exchanges, or 10g protein, per day. An example of food providing 1g protein is listed in Table 1. Unlike diabetes, epilepsy or hypothyroidism, inborn errors of metabolism are not part of the medical exemptions for paying prescription charges. Many adults with PKU who are on diet use a prepayment certificate for their treatments (currently £104 for 12 months), though in Scotland and Wales, prescriptions are free. COST OF THE LOW-PROTEIN DIET TO THE NHS
The overall cost is in the region of £12,000£18,000 per year, with the overall cost varying subject to the age of the patient and their size, as protein substitutes are prescribed in a weight dependent manner. COST COMPARISON OF OTHER TREATMENTS FOR IMDS
As researchers develop pharmacological solutions for IMDs, it is important to compare cost effectiveness with each different treatment approach, so this is one reason for an accurate picture of the cost of dietary treatment. In the future, it is possible that enzyme chaperone, www.NHDmag.com February 2019 - Issue 141
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IMD WATCH Table 4: Guideline low-protein product amounts per month (NSPKU 2017)26 Age of patient with PKU
Recommended maximum number of low-protein items to prescribe each month
4 months to 3 years
15 units
4-6 years
25 units
7-10 years
30 units
11-18 years
50 units
Adults
50 units
Pre-pregnancy/ pregnancy
50 units
Table 5: Prescribable low-protein food groups and units ACBS prescribable foods
Definition of one unit
Pasta
1 box (500g)
Bread/bread rolls
1 packet
Flour mix/cake mix
1 packet (500g)
Breakfast cereals
1 packet
Pasta snack pots
4 snack pots
Pizza bases
2 pizza bases
Sausage/burger mixes
4 sachets
Biscuits
1 packet (150g)
Energy supplements, eg, Vitabite and Chocotino
1 packet
Cakes
6 x 40g
Egg replacer
1 packet
Dessert mixes
6 sachet
Low-protein spreads
1 tub
enzyme substitution therapies, probiotics with enzymes and similar, could reduce or completely negate the need for dietary treatment. Price comparisons, therefore, may occur in the future so that the full economic impact of new treatments can be judged. At the time of writing, an enzyme chaperone molecule called sapropterin dihydrochloride, marketed as Kuvan, is under consideration for commissioning for PKU and this would be an alternative or an adjunct to dietary treatment of PKU in the UK.
WHAT ARE THE CURRENT PRESSURES?
On 28th November 2018, NHS England published Prescribing Gluten Free Foods in Primary Care: Guidance for CCGS,27 which changes the law about the obligations to patients with coeliac disease. There are similarities in the types of products, but there is one significant difference: if you are on a low-protein diet you cannot buy low-protein products in a supermarket. Primary care staff are likely to be more familiar with what gluten-free prescriptions are about, who they are for and the recent restrictions in gluten-free prescriptions than the existence of metabolic disorders and treatment with low-protein foods (and protein substitute) via primary care as outlined by NHS Specialist Commissioning guidelines, so difficulties are anticipated. Currently, time is taken up of NHS primary and tertiary care staff, as well as patient and carers in sorting out confusion about prescriptions in PKU and breaks in treatment do occur as outlined in interim results of a patient prescriptions registry.28 CONCLUSION
There are several challenges to ensure that patients with IMDs receive effective treatment delivered with continuity – this includes patients with PKU. At the time of writing, dietary treatment is the only treatment for many of these patients. Innovative ways could exist for better access to prescribable products for metabolic patients and there have already been small projects in the UK working on this, though not in metabolic disorders. However, all involved in the pathways of metabolic treatments need to appreciate both the costs involved and the necessity of treatment.
For NSPKU supporting documents, please visit www.nspku.org and click on leaflets to download, including: • Supporting Patients with PKU in the GP Surgery: A Guide for GP Administrative Staff • Information for Pharmacists • Prescription Guidelines Also: Follow NSPKU on Twitter @NSPKU www.NHDmag.com February 2019 - Issue 141
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