Drug wars about macular degeneration

4 October 2018 by

jcm-04-00343-g004-1024Bayer Plc v NHS Darlington Clinical Commissioning Groups (CCG) and others [2018] EWHC 2465 (Admin) – read judgment

This judicial review concerned whether it was lawful for NHS clinical commissioning groups to adopt a policy for offering the drug Avastin to patients suffering from “wet” (or neo-vascular) age-related macular degeneration (AMD).  Avastin, although not licensed for ophthalmic use, at £28 per injection is significantly cheaper than the licensed alternatives (£816 and £551 respectively per injection). The Royal College of Ophthalmologists has estimated that the NHS-wide saving of switching to Avastin was at least £102 million p.a.

Bayer and Novartis (with their drugs licensed for AMD) therefore had considerable financial interests in setting aside this policy. They sought review of the commissioning groups’ policy.  The manufacturer of Avastin (Roche) was an interested party. The drug is widely used in other countries for neo-vascular AMD.  The General Medical Council had issued guidance saying that doctors could prescribe off-label medicines provided they were satisfied that there was sufficient evidence or experience of using the medicine to demonstrate its safety and efficacy.

There were essentially six issues before the court.

Whipple J dismissed the claim for judicial review.

 

Background 

For those not familiar with health and medicines regulation, [37] – [66] of the judgment explains the various public bodies involved. Perhaps the key ones are

  • the National Institute for Clinical Excellence (NICE), an NHS body which formulates guidelines on investigations, treatment and medicines;
  • the European Medicines Agency (EMA, an EU body set up by the Medicines Directive), for the moment based in London;
  • the Medicines and Healthcare products Regulatory Agency (MHRA), the EMA’s domestic counterpart.

 

Reasoning 

There were essentially six issues which lay at the heart of this challenge.

1. Did the EMA have exclusive competence to determine whether Avastin is effective and/or clinically effective for ophthalmic use?
2. Could treating clinicians lawfully choose Avastin on grounds of cost?
3. Was Avastin safe for ophthalmic use?
4. Was there a mature and established market in Avastin prepared for ophthalmic use?
5. Was Avastin an unlicensed medicine or an off-label use of a licensed medicine?
6. What was the relevant test by which the lawfulness of the policy was to be judged, in domestic law?

Whipple J answered these as follows

1. Competence: Domestic authorities, specifically NICE and the CCGs, had exclusive competence to assess whether Avastin was clinically effective in treating wet AMD. The EMA and the MHRA had exclusive competence to determine whether to recommend that a medicine should be granted a marketing authorisation for any particular purpose, but could not consider whether to grant a marketing authorisation for ophthalmic use until the manufacturer of Avastin asked for that. However,  EU legislation did not envisage that the national healthcare authorities should be prohibited from considering the efficacy or safety of Avastin to treat wet AMD. As Whipple J put it at [144].

That seems to me to be an absurd proposition. It would give unbounded power to the pharmaceutical companies to decide which medicines to make available for which purposes. That is not what the Directive envisages or provides; and that would be seriously detrimental to the wider public interest in maintaining a cost-effective public health system. To the contrary, in my judgment, it is for the national healthcare authorities – exclusively, in this case – to assess the efficacy, risk and overall clinical effectiveness (including issues of cost and safety) of a medicine like Avastin which is proposed for use outside its marketing authorisation. This is not a unique situation. The domestic authorities find themselves “alone” in the assessment of any medicine which is proposed for use outside of its marketing authorisation. This is commonplace, for example, in paediatric medicine where medicines are often, necessarily, used outside of their marketing authorisation.

2. Relevance of cost: As a matter of construction, the GMC guidance did not prohibit a clinician from prescribing an unlicensed drug simply because there were licensed alternatives. The guidance positively required clinicians to take cost into account ([151-152])

3. Safety: The claimants argued that Avastin was not safe or not as safe as their drugs. But this was contrary to NICE’s view, and NICE possessed the institutional competence and expertise to reach a view on Avastin’s safety. The court could not go beyond its guidance, which settled the issue of safety.

4. Avastin was widely used to treat ophthalmic conditions.

5. Unlicensed/off-label? The issue is whether Avastin was an unlicensed medicine or an off-label use of a licensed medicine. The claimants relied upon the MHRA’s views that it was an unlicensed medicine. The defendants said that the CJEU law had changed since this guidance, and it was in any event only guidance. The judge agreed – it was an off-label use – and invited the MHRA to review its position.

6. Legal test as to lawfulness of the policy: The battle lines on the law were these.

The claimants said that the policy intended the large-scale supply of an unlicensed drug and was therefore simply unlawful; the legal test was whether the policy, if followed, (i) lead to unlawful acts; (ii) permit unlawful acts or (iii) encourage unlawful acts: [193].

The defendants said the question was whether the policy was capable of lawful implementation.

The judge, at [196], agreed with the defendants, subject to some degree of realism as to whether the lawful forms of supply were not simply a tiny part of the anticipated supply.

Lawfulness of the different modes

Having decided question 6, the judge proceeded to consider the different modes in which the drug might be supplied in practice. Her conclusion [238} was that each mode at least might be lawful.

Remaining grounds of challenge

The judge then related these conclusions to the remaining various grounds of challenge.

She was unimpressed by an argument that the policy fundamentally undermined the objective of the Medicine Directive 2001/83.

The scheme and purpose of the Directive did not extend to protecting the commercial interests of pharmaceutical companies in a case such as the instant one with unusual facts and enormous jeopardy to the public purse [245].

The policy did not undermine patients’ access to NICE-recommended treatments. The other drugs were still available as options [248-249].

The last ground was that the policy was accompanied by inaccurate and misleading leaflets for patients. The judge concluded that this was not capable of challenge; the leaflets concerned were in draft form, and had not been issued yet.

Hence she concluded that the policy was lawful.

 

Conclusion

A robust and clear judgment on a case which was capable if it had been lost of costing the NHS over £100 million a year. But given the sums at stake, and that Avastin has already troubled the CJEU in cases from Germany and Italy (twice), this may not be the end of the story,

The conclusion ((6) above) on the right legal approach to potential unlawfulness is of particular interest and of potential wider application.

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