SB, R (on the application of) v NHS England, Court of Appeal - Administrative Court, August 08, 2017, [2017] EWHC 2000 (Admin)

Resolution Date:August 08, 2017
Issuing Organization:Administrative Court
Actores:SB, R (on the application of) v NHS England

Case No: CO/5243/2016

Neutral Citation Number: [2017] EWHC 2000 (Admin)




Royal Courts of Justice

Strand, London, WC2A 2LL

Date: 8/08/2017

Before :


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Between :

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Ian Wise QC and Stephen Broach (instructed by Hodge Jones & Allen LLP) for the Claimant

Jenni Richards QC (instructed by Blake Morgan LLP) for the Defendant

Hearing dates: 18 and 19 July 2017

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JudgmentMrs Justice Andrews:


  1. The Claimant (``S'') is a severely autistic 7½ year old child, with an associated severe learning disability, whose autism was first diagnosed when he was 3. He attends a specialist school. He is non-verbal, and does not socialise with other children. He displays violent and challenging behaviour, and is difficult to manage. S also suffers from Phenylketonuria (``PKU''). PKU is a rare inherited metabolic condition, present from birth, which inhibits the ability to digest protein. The condition prevents the body from breaking down an amino acid called phenylalanine, which consequently builds up in the blood.

  2. Professor Anita MacDonald is a consultant dietician in Inherited Metabolic Disorders at Birmingham Children's Hospital, and part of the team there that has been treating S since July 2015. She was also the clinical lead for the clinical reference group that advised the Defendant in respect of the formulation of its Clinical Commissioning Policy: ``The use of Sapropterin in children with Phenylketonuria'' (``the CCP''). It is her evidence that increasing blood phenylalanine is clearly associated with decreased cognitive function, especially in children under 12 years old (when the brain is continuing to develop). There is a probability of an IQ less than 85 at blood phenylalanine over 400 ìmol/L. Poorly controlled blood phenylalanine levels are also associated with the occurrence of white matter abnormalities in the brain. Even well-controlled patients have IQs that are 5 to 7 points lower than their unaffected siblings, although generally within the normal range of 92 to 102.

  3. The higher the concentration of phenylalanine in the blood, the worse the impairment is likely to be. This is not simply a logical deduction, but the subject of scientific consensus. In a study published in 2007 by Waisbren and others (``Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis'') a meta-analysis was carried out examining the correlation between IQ and phenylalanine levels reported in 40 different publications. Among the conclusions drawn was that a difference of 100 ìmol/L between birth and 6-12 years predicted a difference in IQ between 1.3 to 3.1 points in patients whose phenylalanine levels ranged from 423-750 ìmol/L. That study was among the evidence presented to the Defendant by the clinical reference group and used when formulating the CCP.

  4. Without treatment, most children with PKU develop profound and irreversible intellectual disability, delayed speech, seizures and behavioural abnormalities. Other adverse outcomes include impaired executive function, reduced processing speed, attention problems, and impaired fine motor skills.

  5. The objective of any treatment is to ensure that blood phenylalanine levels are maintained consistently within a safe range. If levels are consistently above that range, there is a risk of long term cognitive impairment. For children under 12 the upper limit of the range is 360 ìmol/L (although in England the slightly lower figure of 350 ìmol/L has been used, the difference is immaterial for the purposes of the present claim). The link between cognitive impairment, and phenylalanine levels above the upper limit of the range is well documented. By way of example, in another of the studies referred to by Professor MacDonald (which again was among those considered when the CCP was formulated) Huijbredts and others: ``Sustained attention and inhibition of cognitive interference in treated phenylketonuria'' (2002), the authors found that 38 children with PKU with concurrent blood phenylalanine levels in excess of 360 ìmol/L performed significantly worse in several tests targeting executive function than matched controls, whereas children with PKU whose phenylalanine was 360 ìmol/L or less performed as well as the control group and better than the children whose phenylalanine level exceeded that figure.

  6. There is a consensus that, for an optimal outcome, treatment should start as early as possible and that strict control of blood phenylalanine levels is of primary importance, particularly during the first years of life. Patients with PKU are diagnosed by newborn screening, and treatment will commence by the age of 14 days when blood phenylalanine levels are consistently above 360 ìmol/L.

  7. The standard treatment for PKU is dietary management. This involves restricting the amount of natural protein consumed, often to only 10%-20% of the amount contained in a normal diet, coupled with the taking of a supplement (a protein substitute) to promote normal growth and development. With the exception of fruit and some vegetables, there are few foods that can be eaten without severe limitation. The carefully supervised dietary management of a child with PKU aims to provide enough protein and phenylalanine for adequate growth, but not too much that the levels go too high. Regular blood tests are used to monitor the levels of blood phenylalanine. Dietary adherence is essential, but problematic, and provides a huge burden to families. It can be difficult to achieve, especially as the child gets older. It is recommended that the diet is continued for life.

  8. S has two siblings who also suffer from PKU, but they are not autistic. In their case, it has been possible to implement a dietary regime that successfully manages the condition. However, the extreme severity of S's autism and the way in which it affects his behaviour has made it increasingly difficult to control his consumption of protein and to ensure that he takes his supplements as he should. S dislikes low protein foods and refuses to eat them; he becomes obsessed with certain foods, and when he is unable to eat the things he wants, he becomes very distressed. Attempts to restrict his consumption of foods that he does like which are too rich in protein, such as custard, will result in severe emotional outbursts, sometimes accompanied by violence towards himself or others.

  9. S has tried and rejected almost all types of protein substitute, and although he currently takes one in the form of a dry powder, the amount he will consume from day to day is inconsistent, and much of it goes to waste. He does not understand why he is not allowed to eat the same food as his parents or other children, or why he needs to take the supplement. He is highly unpredictable in what he will and will not accept. His parents, specialist teachers and treating clinicians have done their best to manage his condition in highly challenging circumstances, and the tireless dedication of his parents is something to which the Court must pay tribute: but despite their efforts his levels of phenylalanine are regularly above the levels that are considered safe. Even when kept inside the target range, they are usually only just inside the upper limit.

  10. In S's case, higher levels of phenylalanine in the blood appear to correlate with increased emotional volatility, though it is not possible to definitively attribute certain behaviour to the amount of phenylalanine in his blood rather than to his autism. Both may be contributing factors and one may exacerbate the other. However, when his phenylalanine levels are high he has severe temper tantrums, and exhibits unacceptable disruptive behaviour, described in detail by Professor MacDonald, by one of S's former teachers, Mrs Leaf, and by S's father in their witness statements. He also becomes restless at night and has poor sleeping patterns. Because of the severity of S's autism, he is intolerant of invasive medical procedures, so intubation is not a practical option. Even if it were, it would cause him unacceptable psychological harm.

  11. By this claim for judicial review S, by his father and litigation friend, seeks to challenge a series of decisions made by the Defendant refusing an application made on S's behalf by one of his treating consultants, Dr Santra, through the individual funding request (``IFR'') process, for funding to treat S with sapropterin dihydrochloride. For ease of reference, I shall refer to that drug by its trademarked brand name, ``Kuvan''. In simple terms, for patients who are responsive, Kuvan reduces the level of phenylalanine in the blood, thus making the patient more protein tolerant and enabling them to eat more ``normal'' foods. In those who respond to Kuvan, the diet is likely to be relaxed and the dietary supplement reduced by 50%. The use of special low protein foods will be decreased or even stopped altogether. Kuvan significantly ameliorates the effects of PKU: however, even in a responsive patient there still has to be some dietary management, and the patient will still have to take supplements (albeit a smaller amount). The European Commission granted a marketing authorisation for Kuvan, valid throughout the European Union, on 2 December 2008.

  12. The group of patients who are responsive to Kuvan are those with ``mild to moderate'' PKU; around 20% of children with the condition aged 4 and above. S's treating clinicians believe that S falls within that group, although the question whether he will be responsive to Kuvan can only be answered definitively if he undergoes a clinical trial. The manufacturers offer a free trial of the drug, but quite understandably the treating clinicians consider that it would...

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